Molecular Clinical Genetics and Gene Therapy Alan W. Flake
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Molecular Clinical Genetics and Gene Therapy Alan W. Flake
The topics of this chapter are broad in scope and outside the realm of a classic core education in pediatric surgery. However, both molecular genetics and gene therapy will be of increasing clinical importance in all medical specialties, including pediatric surgery, in the near future. A few conservative predictions include improvements in the diagnostic accuracy and prediction of phenotype, the development of new therapeutic options for many disorders, and the optimization of pharmacotherapy based on patient genotype, but there are many other possible uses. The goal here is to provide an overview of recent developments that are relevant or potentially relevant to pediatric surgery.
MOLECULAR CLINICAL GENETICS Although hereditary disease has been recognized for centuries, only relatively recently has heredity become the prevailing explanation for numerous human diseases. Before the 1970s, physicians considered genetic diseases to be relatively rare and irrelevant to clinical care. With the advent of rapid advances in molecular genetics, we currently recognize that genes are critical factors in virtually all human diseases. Although an incomplete indicator, McKusick's Mendelian Inheritance in Man has grown from about 1500 entries in 1965 to 10,000 in 2000, documenting the acceleration of knowledge in human genetics. 44 Even disorders that were once considered to be purely acquired, such as infectious diseases, are now recognized to be influenced by genetic mechanisms of inherent vulnerability and genetically driven immune system responses. Despite this phenomenal increase in genetic information and the associated insight into human disease, there remains a wide gap between the identification of genotypic abnormalities that are linked to phenotypic manifestations in humans and any practical application to patient treatment. With the notable exceptions of genetic counseling and prenatal diagnosis, molecular genetics presently has little impact on the daily practice
of medicine or, more specifically, on the practice of pediatric surgery. The promise of molecular genetics cannot be denied, however. IdentifYing the fundamental basis of human disorders and of individual responses to environmental, pharmacologic, and disease-induced perturbations is the first step toward understanding the downstream pathways that may have a profound impact on clinical therapy. The ultimate application of genetics would be the correction of germline defects for affected individuals and their progeny. Although germline correction remains a future fantasy fraught with ethical controversy,56 there is no question that molecular genetics will begin to impact clinical practice in myriad ways within the next decade. A comprehensive discussion of the field of molecular genetics is beyond the scope of this chapter, and there are many sources of information on the clinical genetics of pediatric surgical disorders.
Human Molecular Genetics and Pediatric Surgical Disease The rapid identification of genes associated with human disease has revolutionized the field of medical genetics, providing more accurate diagnostic, prognostic, and potentially therapeutic tools. However, increased knowledge is always associated with increased complexity. Whereas the classic model assumed that the spread of certain traits in families is associated with the transmission of a single molecular defect-with individual alleles segregating into families according to Mendel's lawstoday's model recognizes that very few phenotypes can be satisfactorily explained by a mutation at a single gene locus. The phenotypic diversity recognized in disorders that were once considered monogenic has led to a reconceptualization of genetic disease. Although mendelian models are useful for identifying the primary cause of familial disorders, they appear to be incomplete as models of the true physiologic and cellular nature of defects. 15 .66 ,71 Numerous disorders that were initially
Ability to predict phenotype from genotype • Higher •
Multifactorial
X3l.5 2 This is undoubtedly only one of many approaches that will use site-specific integration in the future and should, if successful, negate the risk of insertional mutagenesis. Finally, a critical issue for in vivo gene transfer with integrating vectors in individuals of reproductive age is the potential for germline transmission, with alteration of the human genome. The risk of this event is poorly defined at present and is most likely extremely low, although in some circumstances (e.g., fetal gene transfer), it could be increased. 56 Although still not technically possible, the intentional site-specific correction of defects in the germline would be the ultimate in gene therapy. However, even if the technology becomes available, the intentional alteration of the human genome raises profound ethical and societal questions that will need to be thoroughly addressed before its application. The considerations are similar to those for insertional mutagenesis, so many of the approaches mentioned earlier for gene targeting and reduction of the potential for insertional mutagenesis are applicable here as well.
Overview of the Current Status of Gene Transfer At present it is clear that viral vectors are the best available vehicle for efficient gene transfer into most tissues. Several gene therapy applications have shown promise in early-phase clinical trials. Although the adverse events noted in the XSCID trial have dampened enthusiasm, this still represents the first successful treatment of a disease by gene therapy. The treatment of hemophilia B using rAAV is also promising. 32 ,41 The next few years are likely to bring advances in the treatment of certain types of cancer using conditionally replicating oncolytic viruses and in the treatment of vascular and coronary artery disease using viral vectors that express angiogenic factors. In the future, new disease targets are likely to become approachable through the fusion of viral vectormediated gene transfer with other technologies such as RNA interference, a powerful tool to achieve gene silencing, Such vectors could be useful in developing therapy for a range of diseases, such as dominantly inherited genetic disorders, infectious diseases, and cancer, Advances in the understanding of viral vector technology and DNA entry into cells and nuclei will likely lead to the development of more efficient nonviral vector systems that may rival viral vectors in efficiency and have superior safety, Gene vector systems of the future may be very different from those in use today and will ultimately provide efficient delivery of target-specific, regulated, transgene expression for an appropriate length of time.
REFERENCES 1. Acton JD, Wilmott RW: Phenotype of CF and the effects of possible modifier genes. Paediatr Respir Rev 2001;2: 332-339. 2, Arnie! J, Lyonnet S: Hirschsprung disease, associated syndromes, and genetics: A review,J Med Genet 2001;38:729-739,
Ethical Considerations Donna A. Caniano and Carolyn Ells
In his classic text The Surgeon and the Child, Potts noted that "the satisfaction of correcting a deformity in a newborn infant lies in the fact that all his life lies before him. Parents hope for miracles, but are grateful for the best that can be given by a mere human being."lg This profound statement underscores the essence of pediatric surgery, whether repairing a major congenital anomaly, treating a devastating traumatic injury, or resecting a malignancy. Each endeavor offers the pediatric surgeon the joy of providing a child with relief of suffering and the potential for a full and productive life. The ethical challenges faced by pediatric surgeons encompass the basic moral principles of medical practice, issues that are distinctive to the profession of surgery, and other factors that are unique to the care of infants and children. In this chapter we review some of the basic ethical concepts and responsibilities pertinent to pediatric surgical ethics. We also address some new areas of ethical and surgical controversy, including the operative management of children with morbid obesity and sex assignment surgery in infants with intersex conditions.
PEDIATRIC SURGICAL mHICS What is distinctive about surgical ethics flows first from what is distinctive about the relationship between surgeons and their patients. Little" has identified five pillars that mark the moral domain of the surgeon-patient relationship: rescue, proximity, ordeal, aftermath, and presence. These factors may be present in other therapeutic relationships as well, but they have a special intensity in surgery. The term rescueacknowledges the elements of surrender and dependency that patients and their families experience when surgery is pursued. To be rescued from a serious threat, patients open themselves up to invasive and traumatic surgcal remedies over which they have little control. Surgeons and patients and their families (parents in most pediatric surgical encounters) need to work together to confront and negotiate the patient's surrender and dependency within the context of the surgeon's power. Proximity refers to surgeons' acknowledgment of the close, intimate interactions they have with their patients. Remarkably, surgeons explore the inner bodies of their
patients, an aspect of the encounter that differs from other medical interactions. Surgeons see and touch, and incise and suture, parts of patients that the patients themselves can barely imagine. Proximity privileges surgeons with knowledge and an understanding of suffering that patients cannot reciprocate. Patients cannot know their surgeons in this intimate way, nor can they know themselves in the way that their surgeons come to know them. Surgeons must realize that surgery is an ordeal for patients; it is an extreme experience that must be endured. Little" has emphasized that surgical patients forgo their autonomy, acknowledge dependency, place trust, face risk, confront embodiment and mortality, lose control over time and space, and experience alienation, pain, fear, discomfort, suffering, and boredom. Depending on the surgical procedure, the patient's sense of personal identity may be irrevocably challenged or changed. In the aftmath of surgery, surgeons must recognize that some patients may have difficulties long after their immediate recovery. Physical and emotional scars, discomfort, risks, and other types of suffering can be reminders of a past illness or injury and signs of vulnerability to future illness or injury. Understanding the aftermath of surgery can help surgeons understand threats to their patients' existential experiences, as well as to their own. In pediatric surgery, aftermath takes on a unique aspect in its dual nature, affecting the child-patient and the parents, both of whom experience the consequences of the surgical encounter. Presence is both a virtue and a duty for surgeons. They must be a visible and engaged presence throughout the entire surgical experience. In pediatric surgery, this professional obligation extends to the long-term follow-up of their patients, often into young adulthood. For example, pediatric surgeons may be the only specialistswho understand the potential long-term complications and functional difficulties that may arise from major neonatal reconstructive operations in the gastrointestinal and hepatobiliary systems. Meeting this duty requires a patient-centered approach to care in which each patient, and his or her particular situation and experience, guides the surgeon in nurturing the surgical relationship and promoting the patient's interests.
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Surgeons bring to the surgical relationship the values and ethical principles of their profession, which give priority to the interests and well-being of their patients. 111 Surg-icnl ethic^, McCullough et a1.'2 present patients' rights related to the surgical encounter, each of which implies a key professional value. They remind us that patients have the right "not to be killed intentionally or negligently by the surgeon, not to be harmed by intent or negligence of the surgeon ... not to be deceived by the surgeon ... to be adequately informed about the risks and benefits of surgery, to be treated by a knowledgeable, competent practitio~ler,to have his or her health and well-being more highly valued than the surgeon's ow11econornic inierest, and to decide whether to accept treatlneilt under the conditions described."" In pediatric surgery, the professional commitment to fi~llyirlform patients, to enable them to choose treatment or nontreatrnent, and to not deceive them typically requires third parties (in most cases, their parents) to speak, understand, and consent on behalf of infants, children, arid adolescents. Although parents are usually the surrogate decision makers for their children, courtappointed guardians or other spokespersons may fulfill this role, depending on relevant laws. In somejurisdictions, and in certain specific circumstances, adolescent patients may be granted authority to make their own decisions about the health care they receive. This situation is particularly applicable to adolescents with chronic illnesses, such as sickle cell disease, cystic fibrosis, and advanced malignancies. However, when an adolescent's consent to or refusal of surgery is in direct opposition to parental wishes, the assistance of social services and legal counsel may be required. Including the family or surrogate decision makers in the surgical relationship is necessary notjust to authorize (or refuse) surgery on behalf of patients. Providing patient-centered care requires an understanding that the patient lives in a family context, which defines, in part, who he or she is as an individual. It also requires acknowledging the greater vulnerability of minor patients who have less of a voice-or often no voice-in treatment decisions and little or no understanding of the surgical process. These patients must be provided with the support they need to optimize their care and the protection they need in light of their vulnerability. Extending the surgical relationship to others helps the surgeon understand the patient and make recommendations that are in the patient's best interests, and it allows others to share in providing the support that these young patients require. One ethical challenge routinely faced by pediatric surgeons (and surrogate decision makers) is determining the interests of patients whose moral characters and values are not yet substantially (much less fully) formed. The character traits, goals, values, and preferences of minor patients should be factored into plans for their care, but judgment is needed to determine what weight to give them. Pediatric surgeons should have in their armamentarium various approaches to ethical decision making and problem solving. Baylis and Canianol advocate a team approach to difficult ethical problems encountered in the surgical treatment of infants and children. This approach acknowledges that contemporary health care in tertiary pediatric
hospitals relies on several teams: the patient-parent unit, the nursing and allied health care members, and the surgical-medical professionals. The health care team for any given patient must unite around a common moral language and an understanding of the ethical issues relative to the particular situation. For example, the caregivers and decision makers for an extremely premature neonate with multiple congenital anomalies must have practical and cognitive knowledge about the pertinent ethical issues. The team or team leaders must have the capacity to elucidate the values and goals that are important to the parents and other involved family mernbers. The values of the parents and Family assume particular relevance when their cultural or religious background differs from that of the health care team in substantive ways. For instance, certain cultural practices may dictate that the authority for medical decision making resides with individuals other than the parents, such as grandparents or community elders. Finally, the team must decide on a specific decision-making method. Several maxims apply to difficult ethical problems in pediatric surgery: (1) good ethics begin with good facts; (2) rational people may hold opposing and irreconcilable views; (3) generally, the best decisions are those developed by consensus; (4) most decisions do not need to be made in haste; and (5) in cases of severe neonatal and pediatric illness, most decisions are painful, and many do not have happy solutions. Most ethical dilemmas arise when there is a dispute or disagreement between the surgical-medical professionals and the patient-parents. These disagreements usually center on what constitutes the best interests of the patient (e.g., continued life with the burdens of severe disability) and what describes an acceptable quality of life for the patient. Glover and %aniano7have outlined a process for ethical decision making that involves several components, including identifying the decision makers, gathering all the medical-surgical facts with the best available prognostic indications, clarifying the relevant values from the "stakeholders" (usually the parents or close family members, in the case of infants), defining all available treatment and nontreatment options, evaluating all options and making recommendations (usually the responsibility of the pediatric surgeon), and achieving a consensus resolution (an ethics consultant or mediator may be useful in cases of significant dispute). Some of these approaches are addressed later in this chapter, when we discuss some of the newer ethical challenges faced by pediatric surgeons.
INNOVATION AND RESEARCH Most citizens of progressive societies place great value on innovation in all areas, including medicine. To achieve advances and technical improvements in pediatric surgery, the profession has relied on the individual and collective innovation of its members. Society expects surgeons to pursue innovation and to develop new therapies and treatment techniques. Patients gravitate toward new operations that offer a presumed benefit, as witnessed by the rapid conversion from open to laparoscopic
CHAPTER
cholecystectomy 2 decades ago. Patients also give great latitude to their surgeons in allowing, or even expecting, them to modify or refine traditional surgical techniques as necessary to complete an operation. McKneallyls observed that individual surgeons are usually acknowledged for their original thinking and technical accomplishments by having operations named in their honor. Numerous operations in pediatric surgery carry the names of those surgeons who first described them, including Ladd's procedure for midgut volvulus and the Duhamel pullthrough for Hirschsprung's disease. In contrast to other areas of medicine, in which randomized clinical trials precede the introduction of new drugs and treatments, the field of surgery has been free to develop new operations without stringent legal and professional regulations.Ulthough some notable procedures, such as pneumatic reduction of intussusception and the Swenson pull-through for Hirschsprung's disease, were tested in animal models, most operations in pediatric surgery are piloted and perfected on patients. New operations are typically introduced by means of a presentation at a professional meeting of pediatric surgeons and subsequent publication in a peer-reviewed journal. The pediatric surgeon who developed the operation usually reports on his or her experience, in terms of complications and outcomes, in patients treated at a single institution with a variable period of follow-up. Reasons given for adopting operations in humans without rigorous scrutiny include the following: (1) suitable animal models may be lacking for the particular anatomic condition; (2) the new operation represents an extension of standard, accepted techniques applied in a novel manner; (3) the new operation is meant to benefit an individual patient rather than to learn something; (4) professional standards are lacking for the introduction of new operations; (5) it is often unclear when an operation should undergo clinical trials; and (6) the current system has worked reasonably well for patients in terms of safety and presumed benefit. In fact, numerous operations have been abandoned either because they did not achieve the desired outcome (e.g., sympathectomy for Hirschsprung's disease) or because they had unacceptably high morbidity and mortality rates (e.g.,jejunoileal bypass for morbid obesity). Research is considered to be a systematic investigation designed to develop or contribute generalizable knowledge. In pediatric surgery, an operation may be performed in a novel way to treat a single patient; thus, in a strict sense, such an operation is not research. But, as is often the case, subsequent operations are performed on additional patients, data are collected, and the novel procedure is presented and published. What began as a treatment for a single patient has crossed over into clinical research, making it subject to the ethical standards for human investigation. In 1966 Beecher published a seminal article in the Nnu England Journal of Mdicine detailing several examples of medical and surgical treatments that had been published in respected journals yet violated the ethical norms of informed consent and safety.* Although the Nuremberg trials following World War I1 had unveiled the horrors of unethical human experimentation,
14
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mainstream medical research in the United States was largely unregulated, and examples of unethical research practices were problematic. Beecher's report galvanized the public to demand, and the federal government to reqiire, institutional review to ensure the-ethical acceptability of all research (medical, behavioral, and surgical) on human subjects. Through the National Research Act of 197'4, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research convened a group of respected clinical scientists, physicians, and experts in ethics, religion, and law to review the basic principles that should characterize the conduct of research involving human subjects and to develop guidelines to ensure the conduct of ethical research. The commission issued its summary statement, the Belmont Report," in 1979. The report identified the principles of respect for persons (which it divided into respect for autonomy and protection of the vulnerable), beneficence, and.justice as particularly relevant to research ethics. These principles have subsequently become important in clinical practice as well, although their application differs. Within the Belmont Report were two features of critical importance to pediatric surgeons: the role of informed consent for research subjects, and the protection that must be accorded when research is performed on vulnerable subjects, such as children. Parents and society expect that pediatric surgeons will be conservative guardians in surgical innovation, relying on a long tradition of generally safe operations and of progress in ameliorating the effects of congenital anomalies. Levinel0 has described some newly introduced procedures as nonvalidated, a term that acknowledges the ethical and medical hazards of novel o~erations.which may be obscured by the terminology of innovation. For both pediatric surgeons and parents, the concept of a nonvalidated operation is more transparent and honest; it embodies the fact that the proposed operation has not been subjected to rigorous clinical investigation. The presumption that a given novel operation is superior to its traditional counterpart is, in reality, a presumption only if it lacks an empirical basis. Clinical trials of a nonvalidated operation may reveal that it is superior to, equal to, or worse than conventional procedures. For example, the recent National 1nstit;tes of Healthfunded clinical trial of fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia was stopped after the enrollment of 24 patients because survival was unexpectedly higher for the infants who received standard care (planned delivery and postnatal care at a tertiary center) compared with those undergoing the fetal intervention." Lacking rigorous scrutiny, the current system of surgical innovation may hinder the determination of an optimal surgical therapy for a given condition. A compelling argument can be made that pediatric surgeons have an ethical obligation to participate in well-designed prospective, multi-institutional clinical trials that seek to establish the best operations or treatments for their patients.Vatients and their families have a right to expect pediatric surgeons to practice competent surgical care that includes the best proven surgical treatments
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and operations. When pediatric surgeons perform nonvalidated operations on their patients, no matter how well intentioned, they may be providing treatments that are not optimal, because they have not been rigorously tested.
BARlATRlC SURGERY Obesity among children and adolescents is recognized as a major public health concern in many developed countries. In the United States, obesity affects about 16% of children, one third of whom are considered morbidly obese. Although the causes of this trend are not fully apparent, the decline in physical activity and the high-calorie diets of American children are likely contributing factors. Obesity in children and adolescents has significant ramifications for the individual and for public health. Because obesity is associated with serious conditions such as hyperlipidemia, hypertension, and type 2 diabetes, the financial and social costs are high. The adverse psychological factors associated with obesity in children and adolescents have not been well studied, but these may have considerable social and financial costs as well. Health care professionals and the broader social community share concerns about the effects of obesity on children and adolescents, in part because of the serious ramifications for their physical and mental health and long-term well-being. Treatment for morbid obesity includes medical and surgical approaches. The range of success with these approaches varies, and research is needed to better assess them, particularly in a pediatric population. Medical therapy that includes a comprehensive program of exercise and diet has not been successful in adults over the long term. Few children's hospitals have developed comprehensive medical obesity programs; thus, there is scant evidence in the pediatric literature about the outcomes of such programs. For adults with morbid obesity, surgical therapy is quite popular because it has been successful in achieving weight reduction with acceptable morbidity and mortality rates. Based on the good results in the adult population, it is not surprising that pediatric surgeons are being asked by the public-in particular, eager patients and their parents-to provide bariatric surgery for children and adolescents with morbid obesity (see Chapter 78). Roux-en-Y gastric bypass and gastric banding, both performed laparoscopically, are the two bariatric operations performed most frequently in adults in North America and Europe. Although both achieve weight loss, gastric banding does not alter the anatomy and is reversible; gastric bypass alters the anatomy in an essentially irreversible manner. Gastric bypass is very effective in achieving weight loss not only because it reduces the size of the stomach but also because it causes malabsorption. Long-term studies in adults indicate that gastric banding is somewhat less effective in achieving major weight loss but is successful in reducing the comorbid conditions of hypertension and diabetes.
There are some ethical concerns about bariatric surgery that pediatric surgeons should consider.9 Both operations are currently nonvalidated therapies for pediatric patients, and neither safety nor efficacy has been proved by multi-institutional clinical trials in this population. Patients and their surrogate decision makers should understand the nonvalidated nature of these operations before they make an informed choice to have a bariatric operation. Moreover, pediatric surgeons performing these operations should participate, whenever possible, in well-designed clinical studies that seek to define the safety, efficacy, and long-term outcomes of these surgeries in pediatric patients with morbid obesity. As with other nonvalidated treatments, research evaluating the safety and efficacy of bariatric procedures should be designed in a way that does not interfere with the therapeutic objectives of patients. Because of insufficient research and the relatively recent history of bariatric surgery (isolated case reports in adolescents), the risks and potential benefits of these operations are difficult to assess. Although early results have shown these operations to be safe for adolescents, the long-term outcomes are unknown. The gastric bypass operation raises concerns about chronic nutritional issues, such as vitamin deficiencies, and possible adverse effects over a lifetime. An additional concern is that patients must comply with prescribed dietary restrictions and undergo medical surveillance indefinitely. It is generally well recognized that patients tend to forgo regular checkups over the long term, particularly if they have no physical complaints. Because the long-term risks of these operations for adolescents are unknown, subtle aberrations in physiology that would be detected by close medical supervision might go unnoticed and undiagnosed until they cause serious consequences. Risks alone do not render a therapy unethical. The ethical assessment of risks involves taking into account the gravity of the risks, the probability that they will occur, and the potential benefits that patients may experience. The potential benefits should be assessed in light of the available evidence and the particular patient's situation. Where there are gaps in research, pediatric surgeons should draw on evidence from the adult population and extrapolate to adolescent patients, as their experience and expertise deem appropriate. In the informed choice process, pediatric surgeons should be honest with patients and their surrogate decision makers about what is known, what is unknown, and the reasoning behind their recommendations regarding a bariatric operation for a particular patient. For children or adolescents with morbid obesity, bariatric surgery may be viewed as a quick and easy "fix" compared with nonsurgical means of achieving weight loss. Quick and easy solutions are certainly desirable, but if nonsurgical means or less invasive procedures are (or prove to be) safer or more effective, or if they protect important options for children and adolescents (e.g., the ability to make important decisions about their health, bodies, and lives in the future), pediatric surgeons should be wary about agreeing to perform bariatric surgery. Pediatric surgeons, in their role as child advocates, have
CHAPTER
a professional responsibility to encourage a more balanced reflection and assessment of the therapeutic options for morbid obesity. In general, surgeons should be hesitant to operate on patients who are not capable of making their own informed decisions when the surgery can be safely delayed until they are capable of making such decisions. This is especially true when the surgery has irreversible effects and the safety and efficacy of the surgery are unknown. Pediatric surgeons must consider not only whether bariatric surgery is a potential therapeutic option for a particular patient but also whether it is the best option for a particular patient. Although the choice to have or forgo surgery is ultimately up to the patient and his or her surrogate decision makers, the surgeon's recommendations are usually an important factor. For some patients, this may mean recommending a less effective but reversible surgical technique or delaying a decision about surgery until the patient is older and pursuing medical therapy in the meantime.
SEX ASSIGNMENT SURGERY A variety of conditions in infancy, including ambiguous genitalia, cloacal exstrophy, and penile agenesis: may lead pediatric surgeons to consider sex assignment surgery. During the past decade, the traditional medical and surgical management of newborns with genital ambiguity has become controversial, with individuals who were "reconstructed" in infancy challenging the appropriateness of their treatment and questioning the success of their outcomes. Through advocacy organizations such as the Intersex Society of North America and the Androgen Insensitivity Support Group, adults with intersexuality (most of whom had sex assignment surgery in infancy and childhood) have publicly voiced their extreme dissatisfaction with several aspects of their medical and surgical care. Intersex is the term now used bv medical wrofessionals and the public to refer to congenital conditions that result in nonstandard male or female genital anatomy. A primary assumption underlying sex assignment surgery is that having nonstandard genitalia will cause psychological harm and that this harm can be avoided or reduced by performing surgery to normalize the appearance of the genitals, so that the child can be raised in the gender thaital ~)hascoi'~.c.s~iscitation. Similarly, tllc s~~rvival rate f0r ()lit-of-hospital cardiac arrest in children is only half' that of' adlllts.1' Although part of this discrepancy results fi-on1 the diilkl-ent causes of cardiac arrest in children and adults, ~mfamiliarity and inadequate training with childr-en also (,ontributes to poor outcome. The fhi1ur.e rate fiw resl~scitationinterventions in the field is twice as high in cllildrcn as in adults; the failure rate {Or prehospit;il cndolr;~c.llcal intubation in children is close to 5O'%.li Unt:nrnili;~rity with pediatric resuscitation skills is undcrstandahlc; although trauma is the most common indication fiw pediatric ambulance transport, it accounts fi)r lcss than 10'%1of'total paramedic patient volume in most metropolitan areas. The most important objectives for emergency pcrsonnel in the field are:
1. Recognition and treatment of' immediate lift-threatening dysfu~lction. 2. Assessment of the mechanism of trauma and extent of injuries. 3. Documentation of pertinent medical d;~t;i. 4. Triage to an appropriate-level pediatric trii1111l;ifi~cility. Added to these are the challenges of comfi)rting a tei-rified and hurt child as well as the distraught pa~.cnts. Thus, the paramedic's task can be forniidahle. Consequently, prehospital personnel fi~nctionbest by adopting strict protocols to treat in-jured children. The priorities and techniques associated with pediatric field resuscitation are similar to those for emergency department care described later.
Prehospital Care Systematic management is essential to an injured child's sulvi11al. The resuscitation process begins when emergency transport personnel first encounter the child in the field. The fate of any child can turn o n the decisions and interventions that ti-anspil-e during these first crucial moments. The inj~u-y-acijusteddeath rate for children is
Primary Survey and Treatment of Life-Threatening Injuries When an injured child encounters medical personnel, whether in the field o r in the emergency room, events should transpire in a rapid sequence designed to
CHAPTER
15
recognize and treat acute injuries. This systematic approach allows the standardization of diagnostic and treatment decisions so that individual variations in patterns of injury do not prevent caregivers from recognizing and treating subtle injuries that can have a profound impact on outcome. This systematic framework comprises a primary survey, a resuscitation phase, and a definitive secondary survey. The primary survey is the initial process of identifying and temporizing injuries that are potentially life threatening and follows the ABCDE sequence: airway, breathing, circulation, disability, and exposure. The system relies on simple observations to assess physiologic derangement and immediate intervention to prevent death.
Airway and Cervical Spine Control Provision of airway control is perhaps the least controversial of all priorities in pediatric trauma management. The inability to establish and maintain a child's airway, leading to hypoxia and inadequate ventilation, continues to be a common cause of cardiorespiratory arrest and death. Significant clinical hypoxia is suspected when oxygen saturation is less than 95%. Assessment of the airway includes inspection of the oral cavity; manual removal of debris, loose teeth, and soft tissue fragments; and aspiration of blood and secretions with mechanical suction. If a child is neurologically intact, phonates normally, and is ventilating without stridor or distress, invasive airway management is unnecessary. Airway patency can be improved in a spontaneouslybreathing child by the use ofjaw-thrust or chin-lift maneuvers. An airway that is unsecured because of coma, combativeness, shock, or direct airway trauma requires endotracheal intubation. A nasopharyngeal or oropharyngeal airway can improve management during bag-mask ventilation, but this is a temporizing measure until definitive control is established. In most cases, orotracheal intubation with in-line cervical spine stabilization is the preferred approach to airway control. Although nasotracheal intubation is recommended in nonapneic adults with potential cervical spine injuries, this approach is not indicated and is poorly tolerated in children. Pediatric ainvay anatomy is unique and affects management technique. The child's larynx is anatonlically higher and more anterior than in the adult, necessitating an upward angulation of the laryngoscope to place the endotracheal tube properly. Removing the anterior half of the rigid cervical collar allows access to the neck for gentle cricoid pressure. The pediatric epiglottis is shorter, less flexible, and tilted posteriorly over the glottic inlet. Because of this, direct control of the epiglottis with a straight blade is usually necessary for proper visualization of the vocal cords. The vocal cords themselves are fragile and easily damaged. The narrowest point in the pediatric ainvay is the subglottic trachea at the cricoid ring, as opposed to the glottis in adult patients. Therefore, passage of the endotracheal tube through the vocal cords does not guarantee safe advancement into the trachea or avoidance of subglottic injury. Appropriate endotracheal tube selection is an important part of pediatric resuscitation. The internal diameter can range from 3.0 to 3.5 mm in newborns to 4.5 mm at 1 to 2 years of age. After 2 years of age, the internal diameter can
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be estimated by the following formula: Internal diameter = Age/4 + 4. Approximating the diameter of the patient's little finger is also useful. Because of the narrow subglottic trachea, an uncuffed endotracheal tube is indicated in children 8 years of age or younger (Fig. 15-2).1 1-13 The technique of intubation depends on the urgency of establishing an airway. In a hypotensive, hypoxemic, comatose child, orotracheal intubation is accomplished without delay as an integral part of the resuscitation. In a more elective situation, more attention is given to adequate preoxygenation by bag-mask ventilation with 100% oxygen and premedication. Thoracic trauma can preclude intubation or make attainment of adequate oxygen saturation impossible. Inducing hypocarbia (carbon dioxide partial pressure [Pac:02]30 to 35 mm Hg) by hyperventilation is advantageous. Following preoxygenation using mask ventilation, children should receive atropine sulfate (0.01 to 0.02 mg/kg) to ensure that the heart rate remains high during intubation. It is important to maintain an adequate heart rate because this is directly proportional to cardiac output; stroke volume does not change much in children. Also, children should be premedicated with intravenous sedatives and muscle relaxants. Appropriate sedatives include short-acting barbiturates such as thiopental sodium (5.0 mg/kg) if volume status is normal or a benzodiazepine such as midazolam (0.1 mg/kg) if hypovolemia is suspected. Muscle relaxation is achieved with short-acting nondepolarizing agents (vecuronium bromide 0.1 mg/kg) or shorter-acting depolarizing agents (succinylcholine chloride 1.0 mg/kg) . The presence of burns and devitalized tissue precludes the use of succinylcholine because of the risk of hyperkalemia. Continuous monitoring of an intubated child with end-tidal Co, and pulse oximetry is essential. In the rare case when tracheal intubation is not possible as a consequence of oral or maxillof'acial trauma or congenital anomaly, a surgical airway is indicated. A surgical cricothyrotomy is the preferred approach in children older than 10 years. The cricothyroid membrane is easily exposed through a transverse skin incision to accommodate placement of a small, uncuffed endotracheal tube. Morbidity is lower than with an emergency tracheostonly because of the superficial location of the cricothyroid membrane. The cricothyrotomy should be converted to a formal tracheostomy when the child is stabilized, to avoid subglottic stenosis. In small children, the cricoid cartilage is a delicate structure and provides the rnajority of support to the trachea. Injury of this membrane during emergency cricothyrotomy can lead to significant morbidity and lifelong laryngotracheomalacia. To avoid this complication, children younger than 10 years should undergo needle cricothyrotomy andjet insu!Tlation of the trachea. A 16- to 18gauge intraverious catheter is used to access the tracheal lumen through the cricothyroid ine~nbraneand is connected to a 100% oxygen source at a high flow rate of 10 to 12 L,/miiiute. Needle-jet ventilation is limited ill children by the hypercarbia that occurs ill approximately 30 minutes; therefore, this method is effective fi)r only a short time. Following stabilization of' the child, endotracheal intubation or formal tracheostorny is necessary.1"
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. .. .,.y -
i
.
F -
End
nx and supraglottic space are anterior and angled cephalad compared with the
position in adults. A posterior neck roll optimizes visualization of the vocal cords in children. B, The tongue is large relative to the space in a child's oral cavity. The tongue should be moved to one side of the oral cavity to facilitate exposure of the posterior pharynx and supraglottic area. C,The laryngoscope blade is inserted from the right side of the mouth and slides back along the vallecula. 0, With the blade in the proper position and the child's neck slightly extended in the sniffing position, lifting the handle (positions 1, 2, 3) raises the epiglottis and brings the vocal cords into direct vision. E, In all except newborns, the straight blade should be placed over the epiglottis to lift it, along with the base of the tongue, to expose the larynx. A stylet with the tip curved within the endotracheal tube facilitates successful intubation. The endotracheal tube is held in place while the laryngoscope is removed and secured after verification of bilateral breath sounds. (From Eichelberger MR: Pediatric Trauma, Prevention, Acute Care, Rehabilitation. St. Louis, Mosby, 1993.)
Breathing Compromised breathing and ventilation in an injured child are usually the result of either head injury (impaired spontaneous ventilatory drive) or thoracic injury (impaired lung expansion). Recognition of a head injury is usually obvious, but recognition of a thoracic
injury that impairs lung expansion requires a detailed survey. The potential seriousness of these injuries is underscored by the fact that mortality rates for thoracic trauma in children approach 25%.14 Following thoracic trauma, air, fluid, or viscera can compromise the pleural space. Compression of the pulmonary parenchyma can result in impaired gas exchange sufficient
CHAPTER
15
to produce respiratory distress. In the case of traumatic rupture of the diaphragm, loss of muscular integrity also has a direct effect on lung expansion. The child's mediastinum is extremely mobile; as pressure increases in the pleural space, the mediastinum is displaced to the opposite side, causing compression of the contralatera1 lung. The distortion of mediastinal vascular structures, along with elevated intrathoracic pressure, can result in a critical reduction in venous return. Loss of chest wall integrity from flail chest impairs ventilation and oxygenation. Consequently, paradoxical chest wall movement occurs during inspiration, preventing complete lung expansion; assisted positive-pressure breathing is the best treatment. Because of the flexible nature of a child's chest, the force required to fracture multiple ribs is enormous and is transmitted to the underlying lung parenchyma, resulting in a pulmonary contusion. Regions of parenchymal hemorrhage and edema impair ventilationperfusion matching, and the decrease in pulmonary compliance can dramatically increase the work of breathing; both can precipitate ventilatory failure. Recognition of ventilatory compromise is usually not difficult, especially with a high index of suspicion. The sound of air movement at the mouth and nares is assessed, as are the rate, depth, and effort of respirations. On inspection, asymmetrical excursion of the chest wall suggests a ventilatory abnormality. Percussion elicits dullness or hyperresonance, depending on the presence of fluid or air in the pleural space, and breath sounds are decreased. With tension hemopneumothorax, mediastinal shift can be detected by tracheal deviation, displacement of the point of maximal cardiac impulse, and distended neck veins caused by impaired venous return. Mechanical ventilatory failure is life threatening and requires immediate treatment during the primary survey. All children require supplemental oxygen by nasal cannula, mask, or endotracheal tube. Endotracheal intubation and assisted ventilation are sufficient to treat hypoventilation due to head injury, pain from rib fractures, flail chest, and pulmonary contusions. Simple hemopneumothorax may be well tolerated with supplemental oxygen until tube thoracostomy can be performed after the primary survey (Fig. 15-3). In cases of hemopneumothorax that results in compromised ventilation or hypotension, tube thoracostomy is required, often combined with endotracheal intubation and intravenous access for rapid fluid infusion. If tension is present, the hemodynamic derangements can be minimized by needle thoracostomy in the second intercostal space at the midclavicular line, followed by thoracostomy tube placement. A chest tube of adequate caliber to evacuate blood and air should be inserted into the pleural cavity. The narrow intercostal space of a small child usually limits the size of the tube, but the largest-caliber tube that can be placed should be used. The tube is placed in the midaxillary line at the nipple level (fourth or fifth intercostal space) to avoid intra-abdominal placement through an elevated diaphragm. The tube is directed posterior and cephalad, to evacuate both blood and air, and is connected to a Pleurovac closed-suction drainage system set at -15 cm H 2 0 (see Fig. 15-3).Persistent hemorrhage
Accident Victims and Their Emergency Management
269
from a thoracostomy tube is uncommon in children; however, drainage of 1 to 2 mL/kg per hour is a sign of significant ongoing bleeding from a vascular or mediastinal injury that may require thoracotomy to identify and control the source. When endotracheal intubation has been performed, the child's fraction of oxygen in inspired air should be loo%, with a tidal volume of 10 to 12 cc/kg at a rate of 15 to 20 cycles/minute. Oxygenation and ventilation should be manipulated to maintain an arterial oxygen ~ tension (PO?) greater than 80 mm Hg and a P C Oof 30 to 35 mm Hg, with a positive end-expiratory pressure not to exceed 5 cm H 2 0 . The goal is to prevent secondary brain injury by optimizing oxygenation and cerebral perfusion by minimizing intracranial pressure (ICP). Children with head trauma are best managed by moderate hyperventilation and hypocarbia (Pco, 30 to 35 mm Hg) to reduce ICP.6,13,18
Circulation and Vascular Access The third priority in the primary survey is the rapid assessment of circulation and the establishment of venous access. Seriously injured children often have normal vital signs, even with significantly decreased circulating volume; their cardiovascular reserve delays the early hemodynamic signs of hypovolemia until relatively late in the resuscitation phase. A high index of suspicion based on the mechanism of injury and continuous careful scrutiny of physiologic parameters and clinical signs are necessary to minimize morbidity. A reliable sign of adequate perfusion is normal mental status. As the child is resuscitated, clinical signs of the efficacy of resuscitation should be monitored. Improvement in the following parameters is consistent with hemodynamic stability and success of resuscitation:
1. 2. 3. 4. 5.
Slowing of the heart rate (20 mm Hg). Return of normal skin color and peripheral perfusion. Increased warmth of extremities. Clearing of the sensorium (improving Glasgow Coma Scale score). 6. Increased systolic blood pressure (>80 mm Hg). 7. Urinary output of 1 to 2 mL/kg per hour in infants and 1 mL/kg per hour in adolescents.
After establishment of an adequate airway, provision of venous access in a hypovolemic child is often a challenge. Two functioning catheters are best in all cases of significant injury. Optimally, venous access should be achieved above and below the diaphragm, given the potential for extravasation of resuscitation fluids from occult intra-abdominal venous injuries. Nevertheless, in children, any peripheral venous access is useful. Two attempts should be made to place large-bore peripheral lines in the upper extremities. If percutaneous placement is unsuccessful, insertion of an intraosseous line is useful in a child younger than 6 years (see later). In children older than 6 years, a venous cutdown performed at the ankle is best. The greater saphenous vein is easily exposed through short transverse incisions 0.5 to 1 cm proximal and anterior to the medial malleolus.
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, Thoracostomy tube insertion. A, An incision is made in the midaxillary line just below the nipple in a male or inframammary fold in a female (fourth intercostal space). B, The dissection is carried out in a cephalad direction subcutaneously over two ribs. A long subcutaneous track is preferable in a child to minimize air leak around the tube. C, The fourth intercostal space is the ideal place for thoracostomy tube placement. 17, The entrance into the pleural space should be made just over and superior to the rib to avoid injury to intercostal vessels. E, Lateral view of the technique. (From Eichelberger MR: Pediatric Trauma, Prevention, Acute Care, Rehabilitation. St. lmuis, Mosby, 1993.)
T h e exposed vein is suspended over a silk ligature, and t h e largest appropriate i~ltravenouscatheter is introduced r vision. Transection o r i n t o t h e vessel lume11 ~ u l d e direct ligation o f t h e vein is n o t necessary (Fig. 15-4). Central vexlous catheterization can result i n significant complications, s u c h as laceration o f t h e subclavian o r femoral artery, rnakirlg it a less useful technique. T h e femoral r o u t e is preferred because o f ease o f access. I f subclavian v e n o u s access is necessary, t h e child should b e placed i n t h e T r e n d e l e n b u r g position with t h e head maintained i n a neutral position without t h e placement o f a posterior shoulder roll. T h i s positio~i provides
optimal cross-sectional area o f t h e subclavian vein i n b o t h children a n d adults.12 An intraosseous line is a simple, reliable, and safe route for t h e administration o f fluids, blood products, a n d medications. T h e t e c h n i q u e is applicable i n children 6 years o f age and younger because t h e marrow is well perfused i n early childhood. T h e preferred site for intraosseous i n s e r t i o n is t h r o u g h t h e flat a n t e r o m e dial surface o f t h e tibia, about 2 t o 3 c m below t h e tibia1 plateau. T h e needle is angled 60 degrees f r o m horizontal a n d pointed toward t h e foot. T h e cortex is penetrated, and t h e marrow cavity is detected b y aspirating
CHArTeu
15
blood arid particulate material. Alternative sites include the midline distal femur, 3 cm above the condyles directed cephalad i r i sinall children, arid the distal tibia above the 111edi;llrnalleolus or the proximal humerus in adolescents, although the need for an intraosseous line is I :ti e in this age group. Specially designed intraosseous needles shot~ldhe available in the pediatric resuscitation roo111to facilitate this maneuver; however, a 1 4 to lcgauge needle can be used. The coinplication rate is low, but potential coniplications include osteomyelitis, cellulitis, fi-actwe,growth plate injury, fat embolism, and compartment syndrome. As soon as vascnlar access is established, fluid resuscitation with ;I bolus of fluid is begun. Generally, isotonic cryst;~lloidsolution, such as lactated Ringer's solution, is ;~dniinistei-cd in 20 mI,/kg increments. If evidence of
Accident Victims arid T h e i r Emergency M a ~ ~ a g e ~ l ~ r ~271 lt
hypovolemia persists after 40 mI,/kg has been given, tl-ansfi~sionof ABO-matched packed red blood cells is initiated in a bolt~sof' 10 1n1Jkg. Packed red blood cells have the advantages of raising colloid oncotic pressure and effecting a AOI-crapid and sustained intravascula~expansion than ciystalloid. In addition, the red blood cell provides hemoglobin to increase oxygcn carrying capacity. All fluids (crystalloid, colloid, and blood) should be warmed during iiifi~sion.This is accolnl)lishcd by microwaving crystalloid solutions oi- using a warrning device. It is important to reassess the child's I-csponsct o I-csnscitation contirlually. to characterile the nati11-cand extent of the injuries, and to avoid the coniplic;jtions of cxccssive fluid resuscitation. As pel-fi~sionis restored, the rate of fluid infusion is gradually reduced to avoid unnecessary fluid administra6on. Puliiionary c d e ~ n ararely occurs i n
a
-
(;rc;~tcrs;lplw~io~isv\'c.i~i c.;~nnulatiotl
A, 3 mm) between the probe and the aorta, double contour of the aortic wall, and US signal between the aorta and the visceral pleura. The sensitivity for diagnosing traumatic rupture of the aorta by TEE was 100% in this report; the specificity was 75%. The authors proposed that TEE be done in all cases of severe chest trauma. TEE is also useful in cases with equivocal findings on CT or aortography to avoid an unnecessary thora~otomy.~~ Once the diagnosis is proved, treatment options include open repair, endovascular stent-graft, or even nonoperative observation in some cases. Aortic surgery carries a significant risk of complications, including intracranial hypertension, which may exacerbate bleeding; left ventricular strain; renal failure; and spinal cord ischemia. Heparin may increase the likelihood of bleeding at remote sites of injury. A small intimal flap may heal spontaneously, but surgical repair through a left posterolateral thoracotomy is the treatment of choice, after the patient has been stabilized (the bleeding at other locations should be repaired first). Surgery can be safely delayed pending repair or control of associated severe injuries to the CNS, extensive burns, septic or contaminated wounds, solid organ injuries likely to bleed with heparinization, and respiratory failure." In such cases, beta blockade to control mean arterial blood pressure and ICU monitoring are essential until repair can be safely accomplished. Esmolol is the preferred beta blocker. Cardiopulmonary bypass (usually left heart bypass) should always be available during repair in case the injury extends to the aortic root. The left lung should be collapsed and retracted. Care is required when dissecting the aorta for cross-clamping to avoid injury to the branches that supply the spinal cord and injury to the vagus nerve and its recurrent branch. Some partial tears can be repaired primarily; however, repair usually requires placement of a woven Dacron graft, especially when the tear is circumferential. There are three basic ways to perform the operation: 1. Clamp and sew. 2. Intraoperative shunt. 3. Mechanical circulatory support. The simplest is to clamp and sew without a shunt or cardiopulmonary bypass. This is the fastest method
and requires the shortest cross-clamp time; it is adequate if the injury is not too extensive. Razzouk et a1.68 reported that the clamp-and-sew technique is feasible in the majority of patients without increased mortality or spinal cord injury. Kwon et a1.43concur that the clamp technique does not increase mortality or morbidity. However, others strongly disagree. Hochheiser et al." reported a lower incidence of postoperative paraplegia after repair with mechanical circulatory support. Another option is intraoperative shunting with a heparin-bonded shunt. This may reduce the risk of ischemic damage to the spinal cord without the risks of systemic heparinization; however, there are no controlled studies to prove this. The third method is to use mechanical circulatory support during the repair. The most common choice is cardiopulmonary bypass from the left superior pulmonary vein or left atrium to the femoral artery.56 Femoralfemoral bypass with direct perfusion of the distal descending thoracic aorta has also been used. Some authorities believe that cardiopulmonary bypass reduces the risk of paraplegia, but it requires systemic heparinization, which can increase the incidence of intracranial hemorrhage.44 The rate of paraplegia after repair of traumatic rupture of the aorta is about 5% to 10%. Individual variations in spinal cord blood supply, crossclamp time, and intraoperative hypotension are important determinants of spinal cord injury. There have been several recent reports of transfemoral stent insertion (endovascular stent-grafts) for injuries to the thoracic aorta in adults. Early results indicate that the outcome may be better than with standard open repair. Three case series have had remarkably low incidences Endovascular stent-grafts have been of paraplegia.15,39,60 reported in a small series of children, but there are no reports of long-term results.38 Only 1 of 13 patients in Eddy's report,17a populationbased study that included prehospital deaths, survived traumatic rupture of the aorta. In contrast, DelRossi et al.13 reported a '75% survival rate in a clinical series. Three of the 21 survivors in DelRossi's series were paraplegic after repair, but two later recovered. DelRossi found no evidence to support one technique of repair over the others. However, Fabian et a1.Z1 reported that the clamp-andsew technique is more likely than repair with bypass to result in paraplegia, especially if the cross-clamp time is longer than 30 minutes. As is true for many types of injury, outcome also depends on associated injuries.44 Hormuth et a1.33reported excellent overall results in a series of 11 children with thoracic aortic injuries. They repaired isthmus injuries with left heart bypass and direct perfusion of the distal thoracic aorta, and arch injuries were repaired with hypothermic arrest.
Chylothorax Injury to the thoracic duct, though rare, causes chylothorax. Most cases resolve spontaneously with nutritional support (total parenteral nutrition or elemental diet with medium-chain triglycerides). Occasionally, ligation of the thoracic duct is necessary.
CHAPTER
Traumatic Asphyxia Traumatic asphyxia, a clinical syndrome that is unique to children, occurs with sudden compression of the abdomen or chest (or both) against a closed glottis.76 This event causes a rapid rise in intrathoracic pressure, which is transmitted to all the veins that drain into the valveless superior vena cava. Extravasation of blood occurs into the skin of the upper half of the body, the sclerae, and possibly the brain. The brain may also be damaged by hypoxia during and after the injury. The clinical features of this disorder include seizures, disorientation, petechiae in the upper half of the body and conjunctivae, and respiratory failure (Fig. 16-10). Treatment is supportive, and most patients recover uneventfully.
Penetrating Injuries The initial management of penetrating injuries is the same as for blunt trauma: clear the airway, give oxygen and intravenous fluids, carefully assess the patient, and obtain a plain chest radiograph in every case. An attempt should be made to determine the path of the injury by marking the entry and exit wounds on the plain films. Endotracheal intubation and chest tube insertion should be done as needed during the initial resuscitation. It is important to consider the possibility of a concomitant abdominal injury with any wound below the nipple line. Bronchoscopy is indicated for suspected injury to the major airways; esophagoscopy and water-soluble contrast studies are indicated for suspected
16
Thoracic Injuries
291
esophageal wounds. Echocardiography can be used in stable patients to diagnose suspected heart injuries. Treatment is also the same as described for blunt trauma. Most patients do not require thoracotomy. The most common indications for surgery are massive bleeding, massive air leak, and pericardial tamponade. Penetrating injuries are more likely to involve the heart, especially with anterior wounds medial to the midclavicular line. These injuries may cause pericardial tamwonade or, if the wericardium has a defect. exsanguinating hemorrhage into the chest. Shock is a clear indication for urgent thoracotomy in cases of penetrat, management of ing wounds to the chest. ~ o w e v e i the patients with wounds near the heart who present with normal physiologic parameters is problematic. The most conservative and safest approach is to take all such patients to the operating room for a subxiphoid pericardial window, followed by thoracotomy through a median sternotomy, if necessary. Recent reports suggest that early echocardiography may be a sensitive test for occult cardiac injuries and that this technique can be used to select patients who require a pericardial window, thereby In minimizing unnecessary invasive proced~res.~0.~7,62 one report, only patients with pericardial effusions on echocardiography underwent subxiphoid pericardial window; if blood was found, a median sternotomy followed. Patients with normal echocardiographs were observed clinically. Harris et a1.Z8 reported a large experience with penetrating cardiac injuries and recommended cardiac US to diagnose these injuries in stable patients. When an operation is required for a penetrating cardiac injury, a Foley catheter through the defect may control the bleeding temporarily to facilitate suture of the defect. Median sternotomy is best for known cardiac injuries.
COMPLICATIONS There is little information in the literature on the morbidity of chest injuries or the complications after surgical management of thoracic injuries in children. The two most common postoperative complications are pulmonary atelectasis and pneumonia. The most serious is paraplegia, which occurs in 5% to 10% of cases of injury to the thoracic aorta.
OUTCOME
Traumatic asphyxia. This child, injured in an auto accident, was restrained but still suffered a severe compression injury of the chest. In addition to petechial hemorrhages over his upper torso, he had 48 hours of mental confusion, indicating that his brain suffered hemorrhage as w l l .
The risk for death from thoracic injury varies with the type of injury and the number and severity of associated injuries, particularly to the CNS. Roux and Fisher71 reported a series of 100 consecutive children with motor vehicle-related chest trauma in South Africa. Ninety-one pedestrians constituted the largest subgroup. The eight patients who died had a mean injury severity score of 34, compared with a score of 25 among the survivors. Seven of the eight children who died had fatal head injuries. Thus, in children with blunt injuries to the chest, the severity of injury and the presence of concomitant head injuries are the main determinants
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of survival. In children, death from thoracic injury tends to occur in the first few days after the injury, usually from other injuries and not from respiratory failure or sepsis, as is the case in adults. The overall mortality for chest injuries was 15% in the NPTR-virtually identical to most adult series.l2 Mortality increases with each individual chest injury: 30% for a ruptured diaphragm, 40% for cardiac injury; and 50% for injury to a major vessel. The morbidity among survivors is remarkably low. DiScala'4 reported that 90% of survivors in the NPTR had no impairment at the time of discharge.
12. 13. 14. 15. 16.
SUMMARY The following points summarize the management of thoracic injuries in children:
1. Most thoracic injuries can be diagnosed by a combination of clinical assessment and plain chest radiographs. 2. Most heal with supportive treatment and tube thoracostomy drainage. 3. Life-threatening thoracic injuries are relatively uncommon. 4. A few thoracic injuries require surgery, but even the most severe can be managed successfully if they are recognized and treated expeditiously.
REFERENCES
17. 18. 19. 20.
21.
22. 23.
1. American College of Surgeons: Advanced Trauma Life Support Program for Physicians. Chicago, American College of Surgeons, 1993. 2. Banks E, Chun J, Weaver F: Chronic innominate artery dissection after blunt thoracic trauma: Case report. J Trauma 1995;38:975. 3. Bergman K, Spence L, Wesson D, et al: Thoracic vascular injuries: A post mortem study. J Trauma 1990;30:604. 4. Bertrand S, Laquay N, El Rassi I, et al: Tricuspid insufficiency after blunt chest trauma in a nine-year-old child. Eur J Cardiothorac Surg 1999;16:587. 5. Bhende MS, Thompson AE: Evaluation of an end-tidal COP detector during pediatric cardiopulmonary resuscitation. Pediatrics 1995;95:395. 6. Blackmore CC, Zweibel A, Mann FA: Determining risk of traumatic aortic injury: How to optimize imaging strategy. AJR Am J Roentgen01 2000;174:343. 7. Bokhari F, Brakenridge S, Nagy K, et al: Prospective evaluation of the sensitivity of physical examination in chest trauma. J Trauma 2003;54:1255. 8. Bonadio WA, Hellmich T, Wisconsin M: Post-traumatic pulmonary contusion in children. Ann Emerg Med 1989;8:1050. 9. Brandt M, Luks FI, Spigland NA, et al: Diaphragmatic injury in children. J Trauma 1992;32:298. 10. Carillo EH, Guin BJ, Ali AT, et al: Transthoracic ultrasonography is an alternative to subxiphoid ultrasonography for the diagnosis of hemopericardium in penetrating precordial trauma. Am J Surg 2000;179:34. 11. Chen MY, Miller PR, McLaughlin CA, et al: The trend of using computed tomography in the detection of acute
24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34.
thoracic aortic and branch vessel injury after blunt thoracic trauma: A single-center experience over 13 years. J Trauma 2004;56:783. Cooper A, Barlow B, DiScala C, String D: Mortaliw and truncal injury: The pediatric ' J ~ e d i a t rSurg 1994:29:33. DelRossi AJ, Cernaianu AC, Madden LD, et al: Traumatic disruptions of the thoracic aorta: Treatment and outcome. Surgery 1990;108:864. DiScala C: Biannual Report. National Pediatric Trauma Registry, 1995. Dunham MB, Zygun D, Petrasek P, et al: Endovascular stent grafts for acute blunt aortic injury. J Trauma 2004; 56:1173. Dyer DS, Moore EE, Ilke DN, et al: Thoracic aortic injury: How predictive is mechanism and is chest computed tomography a reliable screening tool? A prospective study of 1561 patients. J Trauma 2000;48:682. Eddy AC, Rusch VW, Fligner CL, et al: The epidemiology of traumatic rupture of the thoracic aorta in children: A 13-year review. J Trauma 1990;30:989. End A, Rodler S, Oturanlar D, et al: Elective surgery for blunt cardiac trauma. J Trauma 1994;37:798. Eren S, Balci AE, Ulku R, et al: Thoracic firearm injuries in children: Management and analysis of prognostic factors. Eur J Cardiothorac Surg 2003;23:888. Exadaktylos AK, Sclabas G, Schmid SW, et al: Do we really need routine computed tomography scanning in the primary evaluation of blunt chest trauma in patients with "normal" chest radiograph? J Trauma 2001;51:1173. Fabian TC, Richardson JD, Croce MA, et al: Prospective study of blunt aortic injury: Multi-center trial of the American Association for the Surgery of Trauma. J Trauma 1997;42:374. Fernandez L, Radhakrishna J, Gordon RT, et al: Thoracic BB injuries in pediatric patients. J Trauma 1995;38:384. Frame SB, Thompson TC: Blunt cardiac injuries. Adv Trauma Crit Care 1995;10:15. GarciaV, Gottschall CS, Eichelberger MR, et al: Rib fractures in children: A marker of severe trauma. J Trauma 1990;30:695. Gavant ML, Menke PG, Fabian T, et al: Blunt traumatic aortic rupture: Detection with helical CT of the chest. Radiology 1995;197:125. Gittleman MA, Gonzalea-del-ReyJ, Brody AS, et al: Clinical predictors for the selective use of chest radiographs in pediatric blunt trauma evaluations. J Trauma 2003;55:670. Hall A, Johnson K: The imaging of paediatric thoracic trauma. Paediatr Respir Rev 2002;3:241. Harris DG, Bleeker CP, Pretorius J, et al: Penetrating cardiac injuries-current evaluation and management of the stable patient. S Afr J Surg 2001;39:90. Harris GJ, Soper RT: Pediatric first rib fractures. J Trauma 1990;30:343. Hirsch R, Landt Y, Porter S, et al: Cardiac troponin I in pediatrics: Normal values and potential use in the assessment of cardiac injury. J Pediatr 1997;130:853. Hochheiser GM, Clark DE, Morton JR: Operative technique, paraplegia, and mortality after blunt traumatic aortic injury. Arch Surg 2002;137:434. Holmes JF, Sokolove PE, Brant WE, et al: A clinical decision rule for identifying children with thoracic injuries after blunt torso trauma. Ann Emerg Med 2002;39:492. Hormuth D, Cefali D, Rouse T, et al: Traumatic disruption of the thoracic aorta in children. Arch Surg 1999; 134:759. Horton TG, Cohn SM, Heid MP, et al: Identification of trauma patients at risk of thoracic aortic tear by mechanism of injury. J Trauma 2000;48:1008.
CHAPTER
35. HothJ, Scott MJ, Bullock TK, et al: Thoracotomy for blunt trauma: Traditional indications may not apply. Am Surg 2003;69:1108. 36. Hu J, Wall MJ Jr, Estrera AL, et al: Surgical management of traumatic pulmonary injury. Am J Surg 2003; 186:620. 37. Janson JT, Harris DG, Pretorius J, et al: Pericardial rupture and cardiac herniation after blunt chest trauma. Ann Thorac Surg 2003;75:754. 38. Karmay-Jones R, Hoffer E, Meissner M, et al: Management of traumatic rupture of the thoracic aorta in pediatric patients. Ann Thorac Surg 2003;75:1513. 39. Kasirajan K, Heffernan D, Langsfield M: Acute thoracic aortic trauma: A comparison of endoluminal stent grafts with open repair and nonoperative management. Ann Vasc Surg 2003;17:589. 40. Kleinman P, Mark SE, Spevak MR, et al: Fractures of the rib head in abused infants. Radiology 1992;185:119. 41. Knudtson JL, Dort JM, Helmer SD, et al: Surgeon-performed ultrasound for pneumothorax in the trauma suite. J Trauma 2004;56:527. 42. Kulshrestha P, Munshi I, Wait R: Profile of chest trauma in a level I trauma center. J Trauma 2004;57:576. 43. Kwon CC, Gill IS, Fallon WF, et al: Delayed operative intervention in the management of traumatic descending thoracic aortic rupture. Ann Thorac Surg 2002;74:1888. 44. Langanay T, Verhoye JP, Corbineau H, et al: Surgical treatment of acute traumatic rupture of the thoracic aorta-timing reappraisal? Eur J Cardiothorac Surg 2002;21:282. 45. Langer JC, Winthrop AL, Wesson DE, et al: Diagnosis and incidence of cardiac injury in children with blunt thoracic trauma. J Pediatr Surg 1989;24:1091. 46. Le Bret F, Rue1 P, Rosier H, et al: Diagnosis of traumatic mediastinal hematoma with transesophageal echocardiography. Chest 1994;105:373. 47. Lomoschitz FM, Eisenhuber E, Linnau KF, et al: Imaging of chest trauma: Radiological patterns of injury and diagnostic algorithms. Eur J Radiol 2003;48:61. 48. Magid N, Glass T: A "hole in a r i b as a sign of child abuse. Pediatr Radiol 1990;20:334. 49. Mandavia DP, Joseph A: Bedside echocardiography in chest trauma. Emerg Med Clin North Am 2004;22:601. 50. Manson D, Babyn PS, Palder S, et al: CT of blunt chest trauma in children. Pediatr Radiol 1995;23:1. 51. Maron BJ, Gohman TE, Kyle SB, et al: Clinical profile and spectrum of commotio cordis. JAMA 2002;287:1142. 52. Matthews BD, Bui H, Harold KL, et al: Laparoscopic repair of traumatic diaphragmatic injuries. Surg Endosc 2003; 17:254. 53. Meller JL, Little AG, Shermeta DW: Thoracic trauma in children. Pediatrics 1984;74:813. 54. Melton SM, Kerby JD, McGiffin D, et al: The evolution of chest computed tomography for the definitive diagnosis of blunt aortic injury: A single-center experience. J Trauma 2004;56:243. 55. Mirvis SE, Shanmuganathan K: MR imaging of thoracic trauma. Magn Reson Imaging Clin N Am 2000;8:91. 56. Moore EE, Burch JM, Moore JB: Repair of the torn descending thoracic aorta using the centrifugal pump for partial left heart by-pass. Ann Surg 2004;240:38. 57. Nagy K, Lohmann C, Kim DO, et al: Role of echocardiography in the diagnosis of occult penetrating cardiac injury. J Trauma 1995;38:859. 58. Nakayama DK, Ramenofsky ML: Chest injuries in childhood. Ann Surg 1989;210:770. 59. Nakayama DK, Rowe MI: Intrathoracic tracheobronchial injuries in childhood. Int Anesthesiol Clin 1988;26:42.
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60. Ott MC, Stewart TC, Lawlor DK, et al: Management of blunt thoracic aortic injuries: Endovascular stent versus open repair. J Trauma 2004;56:565. 61. Parker MS, Matheson TL, Rao AV, et al: Making the transition: The role of helical CT in the evaluation of potentially acute thoracic injuries. AJR Am J Roentgen01 2001;176:1267. 62. Patel AN, Brennig C, CotnerJ, et al: Successful diagnosis of penetrating cardiac injury using surgeon performed ultrasonography. Ann Thorac Surg 2003;76:2046. 63. Patel HN, Hahn D, Comess KA: Blunt chest trauma: Role of intravascular and transesophageal echocardiography in cases of abnormal thoracic aortogram. J Trauma 2003;55:330. 64. Peterson RJ, TepasJ 3rd, Edwards FH, et al: Pediatric and adult thoracic trauma: Age-related impact on presentation and outcome. Ann Thorac Surg 1994;58:14. 65. Place RJ, Cavanaugh DG: Computed tomography to diagnose pericardial rupture. J Trauma 1995;38:882. 66. Powell RW, Gill EA, Jurkovich GJ, et al: Resuscitative thoracotomy in children and adolescents. Am Surg 1988;54:188. 67. Pross M, Manger T, Mirow L, et al: Laparoscopic management of late-diagnosed major diaphragmatic rupture. J Laparoendosc Adv Surg Tech A 2003;10:111. 68. Razzouk AJ, Gundry SR, Wang N, et al: Repair of traumatic aortic rupture: A 25-year experience. Arch Surg 2000; 135:913. 69. Reinoso-Barbero F, Sanabria P, Bueno J, et al: Highfrequency ventilation for a child with traumatic bronchial rupture. Anesth Analg 1995;81:183. 70. Renton J, Kincaid S, Ehrlich PF: Should helical CT scanning of the thoracic cavity replace the conventional chest x-ray as a primary assessment tool in pediatric trauma? An efficacy and cost analysis. J Pediatr Surg 2003;38:793. 71. Roux P, Fisher RM: Chest injuries in children: An analysis of 100 cases of blunt chest trauma from motor vehicle accidents. J Pediatr Surg 1992;27:551. 72. Rowan KR, Kirkpatrick AW, Liu D, et al: Traumatic pneumothorax detection with thoracic US: Correlation with chest radiography and CT-initial experience. Radiology 2002;227:305. 73. Rubin GD: CT angiography of the thoracic aorta. Semin Roentgen01 2003;38:115. 74. RuDusky BM: Myocardial contusion culminating in a ruptured pseudoaneurysm of the left ventricle-a case report. Angiology 2003;54:359. 75. Salehian 0,Mulji A: Tricuspid valve disruption and ventricular septa1 defect secondary to blunt chest trauma. Can J Cardiol 2004;20:231. 76. Sarihan H, Abes M, Akyazici R, et al: Traumatic asphyxia in children. J Cardiovasc Surg (Torino) 1997;38:93. 77. Scorpio RS, Wesson DE, Smith CR, et al: Blunt cardiac injuries in children: A postmortem study. J Trauma 1996; 41:306. 78. Shabb BR, Taha M, Nabbout G, et al: Successful delayed repair of a complete transection of the right mainstem bronchus in a five-year-old girl: Case report. J Trauma Injury Infect Crit Care 1995;38:964. 79. Shorr R, Crittenden M, Indeck M, et al: Blunt thoracic trauma: analysis of 515 patients. Ann Surg 1987;206:200. 80. SwaanenburgJC, KlaaseJM, DeJongste MJ, et al: Troponin I, troponin T, CKMB-activity and CKMB-mass as markers for the detection of myocardial contusion in patients who experienced blunt trauma. Clin Chim Acta 1998; 272: 171. 81. Sybrandy KC, Cramer MJ, Burgersdijk C: Diagnosing cardiac contusion: Old wisdom and new insights. Heart 2002;89:485.
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82. Taskinen SO, Salo,JA, Halttunen PE, et al: Tracheobronchial rupture due to blunt chest trauma: A follow-up study. Ann Thorac Surg 1989;48:846. 83. Tatou E, Steinmetz E, Jazayeri S, et al: Surgical outcome of traumatic rupture of the thoracic aorta. Ann Thorac Surg 2000;69:70. 84. Tellez DW, Hardin WD Jr, Takahashi M, et al: Blunt cardiac injury in children. J Pediatr Surg 1987;22:1123. 85. Thomas P, Saux P, Lonjon T, et al: Diagnosis by video-assisted thoracoscopy of traumatic pericardial rupture with delayed luxation of the heart: Case report. J Trauma 1995;38:967.
86. Wang JN, Tsai YC, Chen SL, et al: Dangerous impactcommotio cordis. Cardiology 2000;93:124. 87. Williams RL, Connolloy PT: In children undergoing chest radiography what is the specificity of rib fractures for non-accidental injury? Arch Dis Child 2004;89:490. 88. Wilson A, Wall MJ Jr, Maxson R, et al: The pulmonary hilum twist as a thoracic damage control procedure. Am J Surg 2003;186:49. 89. Worthy S, Kang EY, Hartman TE, et al: Diaphragmatic rupture: CT &dings in 11 patients. ~adidlogy-1995; 194:885.
Abdominal Trauma Steven Stylianos and Richard H. Pearl
Who could have imagned the influence of Simpson's 1968 publication on the successful nonoperative treatment of select children presumed to have splenic injury?142Initially suggested in the early 1950s by Warnsborough, then chief of general surgery at the Hospital for Sick Children in Toronto, the era of nonoperative management of splenic injury began with the report of 12 children treated between 1956 and 1965. The diagnosis of splenic injury in this select group was made by clinical findings, along with routine laboratory and plain radiographic findings. Keep in mind that this report predated ultrasonography (US), computed tomography (CT), or isotope imaging. Subsequent confirmation of splenic injury was made in one child who required laparotomy years later for an unrelated condition, when it was found that the spleen had healed in two separate pieces. Nearly 4 decades later, the standard treatment of hemodynamically stable children with splenic injury is nonoperative, and this concept has been successfully applied to most blunt injuries of the liver, kidney, and pancreas as well. Surgical restraint is now the norm. based on an increased awareness of the anatomic patterns and physiologic responses of injured children. Our colleagues in adult trauma care have slowly acknowledged this success and are applying many of the principles learned in pediatric trauma to their patients.7g A recent review of the National Pediatric Trauma Registry (NPTR) indicates that 8% to 12% of children suffering blunt trauma have an abdominal injury.z8 Fortunately, more than 90% of them survive. Although abdominal injuries are 30% more common than thoracic injuries, they are 40% less likely to be fatal. The infrequent need for laparotomy in children with blunt abdominal injury has created a debate regarding the role of pediatric trauma surgeons in their treatment. Recent analyses of the NPTR and the National Trauma Data ~ a n emphasize k the overall "surgical" nature of pediatric trauma patients, with more than 25% of injured children requiring operative intervention.l.141 Clearly, a qualified pediatric trauma surgeon would be the ideal coordinator bf such care. Few surgeons have extensive experience with massive abdominal solid organ injuries requiring immediate surgery. It is imperative that surgeons familiarize themselves with current treatment algorithms for life-threatening
abdominal trauma. Important contributions have been made in the diagnosis and treatment of children with abdominal injury by radiologists and endoscopists. The resolution and speed of CT, the screening capabilities of focused abdominal sonography for trauma (FAST), and the percutaneous, angiographic, and endoscopic interventions of nonsurgeon members of the pediatric trauma team have all enhanced patient care and improved outcomes. This chapter focuses on the more common blunt injuries and unique aspects of care in children. Renal and genitourinary injuries are covered separately in Chapter 18.
DIAGNOSTIC MODALITIES The initial evaluation of an acutely injured child is similar to that of an adult. Plain radiographs of the cervical spine, chest, and pelvis are obtained after the initial survey and evaluation of the ABCs (airway, breathing, and circulation). Other plain abdominal films add little to the acute evaluation of pediatric trauma patients. As imaging modalities have improved, treatment algorithms have changed significantly in children with suspected intra-abdominal injuries. Prompt identification of potentially life-threatening injuries is now possible in the vast majority of children.
Computed Tomography CT has become the imaging study of choice for the evaluation of injured children owing to several advantages. CT is now readily accessible in most health care facilities; it is a noninvasive, accurate method of identifying and qualifying the extent of abdominal injury; and it has reduced the incidence of nontherapeutic exploratory laparotomy. Use of intravenous contrast is essential, and "dynamic" methods of scanning have optimized vascular and parenchymal enhancement. The importance of a contrast "blush" in children with blunt spleen and liver injury continues to be debated and is discussed later (Fig. 17-1).3Wead CT, if indicated, should be performed first without contrast, to avoid concealing a hemorrhagic
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A ,
B
A, Abdominal computed tomography scan demonstrating a significant injury to the right hepatic lobe with intravenous contrast "blush." This patient had successful angiographic embolization and avoided operation. B, Abdominal computed tomography scan demonstrating a significant injury to the spleen with intravenous contrast "blush" (arrow). The patient remained hemodynamically stable and avoided operation.
brain injury. Enteral contrast for enhancement of the gastrointestinal (GI) tract is generally not required in the acute trauma setting and can lead to aspiration. Not all children with potential abdominal injuries are candidates for CT evaluation. Obvious penetrating injury often necessitates immediate operative intervention. A hemodynamically unstable child should not be taken out of an appropriate resuscitation room for the performance of CT. These children may benefit from an alternative diagnostic study, such as peritoneal lavage or FAST, or urgent operative intervention. The greatest limitation of abdominal CT in trauma is the inability to reliably identify intestinal rupture.flJ5 Findings suggestive but not diagnostic of intestinal perforation are pneumoperitoneum, bowel wall thickening, free intraperitoneal fluid, bowel wall enhancement, and dilated A high index of suspicion should exist for the presence of bowel injury in a child with intraperitoneal fluid and no identifiable solid organ injury on CT.lZ7The diagnosis and treatment of bowel injury are reviewed in detail later.
Focused Abdominal Sonography for Trauma Clinician-performed sonography for the early evaluation of an injured child is currently being evaluated to determine its optimal use. Examination of Morrison's pouch; the pouch of Douglas; the left flank, including the perisplenic anatomy; and a subxiphoid view to visualize the pericardium is the standard four-view FAST examination (Fig. 17-2). This bedside examination may be a good rapid screening study, particularly in patients too unstable to undergo an abdominal CT scan. Early reports have found FAST to be a helpful screening tool in children, with a high specificity (95%)but low sensitivity (33%) in
.
Schematic of a focused abdominal sonography for trauma (FAST) examination, with emphasis on views of the subxiphoid, right upper quadrant and Morrison's pouch, left upper quadrant and left paracolic region, and pelvic region and pouch of Douglas. (Original illustration by Mark Mazziotti, MD.)
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identifying intestinal injury,lObnda lack of identifiable free fluid does not exclude a significant injury. FAST may be useful in decreasing the number of CT scans performed for "low-likelihood" injuries. Repetition of the study may be necessary, depending on clinical correlation, and the finding of free fluid in itself is not an indication for surgical intervention. Recently, a simple scoring system for quantifylng the amount of hernoperitoneum has been shown to be predictive of the need for laparotomy in a small series of children after blunt abdominal trauma.lo1Prospective validation of such a FAST score is necessary.
Diagnostic Peritoneal Lavage and Laparoscopy Diagnostic peritoneal lavage (DPL) has been a mainstay in trauma evaluation for more than 3 decades. However, its utility in pediatric trauma is limited. Because up to 90% of solid organ injuries do not require surgical intervention, the finding of free blood in the abdomen by DPL has limited clinical significance. Hemodynamic instability and the need for ongoing blood replacement are the determinants for operation in patients with solid organ injury in the absence of blood in the abdominal cavity. Additionally, the speed and accuracy of CT have further decreased the'indications for DPL in pediatric trauma. The sensitivity of CT in diagnosing solid organ injuries and more subtle injuries to the duodenum, pancreas, and intestines continues to improve. This has relegated DPL to the evaluation of patients with clinical findings suggestive of bowel injury and no definitive diagnosis on CT. In this setting, the presence of bile, food particles, or other evidence of GI tract perforation is diagnostic. Recent literature has suggested that laparoscopy can both diagnose and, in some cases, allow definitive surgical management without laparotomy, further limiting the usefulness of DPL. In a study from Dundee, Scotland, comparing DPL and laparoscopy, both tests were highly sensitive (loo%), but laparoscopy had a higher specificity (94% versus 83%).Z9 Large prospective trials using laparoscopy in adults have demonstrated increased diagnostic accuracy, decreased nontherapeutic laparotomy rates, and a significant decrease in hospital length of stay, with an attendant reduction in costs. For example, in a report from the University of Tennessee, 55% of patients with abdominal trauma avoided laparotomy after laparoscopic e~aluation.3~ Similar work from Jacobi Medical Center in New York City revealed a direct relationship between a reduction in negative laparotomies and increased use of laparoscopy for diagnosis and rnanagement.l26 Multiple adult studies have shown the utility of laparoscopy not only in trauma evaluation but also in the definitive management of related injuries. Repairs of gastric and intestinal perforation, bladder rupture, liver laceration, diaphragmatic injury, and splenic injury have all been reported.21J28J40The extent of feasible operations is directly related to the surgeon's skill with advanced laparoscopic techniques and the patient's overall stability. At the Children's Hospital of Illinois, our two most recent handlebar injuries causing bowel perforation were successfully treated laparoscopically.As with elective abdominal surgery, the role of laparoscopy in trauma will increase substantially as trauma centers redirect their training of
17
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297
residents to this modalitv and as more ~ediatriccenters report outcome studies for laparoscopic trauma management in ~hildren.2O>~~,Q
SOLID ORGAN INJURIES Spleen and Liver The spleen and liver are the organs most commonly injured in blunt abdominal trauma, with each accounting for one third of the injuries. Nonoperative treatment of isolated splenic and hepatic injuries in stable children has been universally successful and is now standard practice. However, there is great variation in the management algorithms used by individual pediatric surgeons. Review of the NPTR and recent surveys of the American Pediatric Surgical Association (APsA) membership confirm the wide disparity in practice.",'" Controversy also exists regarding the utility of CT grading and the finding of contrast blush as a predictor of outcome in liver and spleen injury.49,82,89,106Several recent studies reported contrast blush in 7% to 12% of children with blunt spleen injury (see Fig. 17-1).2"76,wThe rate of operation in the "blush" group approached or exceeded 20%. The authors emphasized that CT blush was worrisome but that most patients could still be managed successfully without operation. The role of angiographic embolization in pediatric spleen injury has yet to be determined. Recently the APSA Trauma Committee analyzed a contemporary multi-institution database of 832 children treated nonoperatively at 32 centers in North America from 1995 to 1997 (Table 17-1). 135 Consensus guidelines
Grade I
Grade II
Grade Ill Grade lV
(n = 116) (n = 341) (n = 275) (n =ZOO) Admitted to ICU (%) No. hospital days (mean) No. hospital days (range) Transfused (%) Laparotomy (%) Follow-up imaging (%) Activity.restriction (mean wk) Activity restriction (range wk)
55.0
54.3
72.3
85.4
4.3
5.3
7.1
7.6
1-7
2-9
3-9
410
1.8 0 34.4
5.2 1.0 46.3
10.1* 2.77 54.1
26.6* 12.67 51.8
5.1
6.2
7.5
9.2
2-6
2-8
4-12
6-12
*Grade Ill vs grade IV, p < 0.014. tGrade Ill vs grade IV, p < 0.0001. CT, computed tomography; ICU, intensive care unit. From Stylianos S, APSATrauma Committee: Evidence-based guidelines for resource utilization in children with isolated spleen or liver injury. J Pediatr Surg 2000;35:164-169.
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Grade l Grade I1 Grade Ill Grade lV ICU days Hospital stay (days) Predischarge imaging Postdischarge imaging Activity restriction (wk)*
0 2 None None 3
0 3 None None 4
0 4 None None 5
1 5 None None
6
CT, computed tomography; ICU, intensive care unit. *Return to full-contact, competitive sports (e.g., football, wrestling, hockey, lacrosse, mountain climbing) should be at the discretion of the individual pediatric trauma surgeon. The proposed guidelines for return to unrestricted activity include "normal" age-appropriateactivities. From Stylianos S, APSA Trauma Committee: Evidence-basedguidelines for resource utilization in children with isolated spleen or liver injury. J Pediatr Surg2000; 35: 164-169.
on intensive care unit (ICU) stay, length of hospital stay, use of follow-up imaging, and physicai activity restriction for clinically stable children with isolated spleen or liver injuries (CT grades I to IV) were defined based on this analysis (Table 17-2). The guidelines were then applied prospectively in 312 children with liver or spleen injuries treated nonoperatively at 16 centers from 1998 to 2000.l36 Patients with other minor injuries such as nondisplaced, were noncomminuted fractures or soft tissue injuries ., included as long as the associated injuries did not influence the variables in the study. The patients were grouped by severity of injury defined by CT grade. Compliance with the proposed -guidelines was analyzed for -age, organ injured, and injury grade. All patients were followed for 4 months after injury. It is imperative to emphasize that these proposed bidelines askme hemodynakic stability. The extremely low rates of transfusion and operation document the stability of the study patients. Specific guideline compliance was 81% for ICU stay, 82% for length of hospital stay, 87% for follow-up imaging, and 78% for activity restriction. There was a significant improvement in compliance from year 1 to year 2 for ICU stay (77% versus 88%, P < 0.02) and activity restriction (73% versus 87%, P < 0.01). There were no differences in compliance by age, gender, or organ injured. Deviation from the guidelines was the surgeon's choice in 90% of cases and patient-related in 10%. Six patients (1.9%) were readmitted, although none required operation. Compared with the previously studied 832 patients, the 312 patients managed prospectively by the proposed guidelines had a significant reduction in ICU stay (P< 0.0001), hospital stay (P < 0.0006), follow-up imaging ( P < 0.0001), and interval of physical activity restriction ( P < 0.04) within each grade of injury. From these data it was concluded that prospective application of specific treatment guidelines based on injury severity resulted in conformity in patient management, improved utilization of resources, and validation of guideline safety. Significant reductions in ICU stay,
hospital stay, follow-up imaging, and activity restriction were achieved without adverse sequelae when compared with the retrospective database. The attending surgeon's decision to operate for spleen or liver injury is best based on evidence of continued blood loss, such as low blood pressure, tachycardia, decreased urine output, and falling hematocrit unresponsive to crystalloid and blood transfusion. The rates of successful nonoperative treatment of isolated blunt splenic and hepatic injury now exceed 90% in most pediatric trauma centers and in adult trauma centers with a strong pediatric commitment (H. N. Loworn, personal communication) .87,135.'3" A study of more than 100 patients from the NPTR indicated that nonoperative treatment of spleen or liver injury is indicated even in the presence of associated head injury if the patient is hemodynamically stable.63 Rates of operative intervention for blunt spleen or liver injury were similar with and without an associated closed head injury. Not surprisingly, adult trauma services have reported excellent survival rates for pediatric trauma patients; however, an analysis of treatment for spleen and liver injuries reveals alarmingly high rates of operative treatThis discrepancy in operative rates ment.42,64,87,113 emphasizes the importance of disseminating effective guidelines, because the majority of seriously injured children are treated outside of dedicated pediatric trauma centers. Mooney and Forbess8reviewed the New England Pediatric Trauma Database in the 1990s and identified 2500 children with spleen injuries. Two thirds were treated by nonpediatric trauma surgeons, and two thirds were treated in nontrauma centers. After allowing for multiple patient- and hospital-related variables, the authors found that the risk of operation was reduced by half when a surgeon with pediatric training provided care to children with spleen injuries. In a similar review using the KIDS 2000 administrative data set, Rothstein et al.lI4 found that despite adjustment for hospital- and patient-specific variables, children treated at an adult general hospital had a 2.8 greater chance ( P < 0.003), and those treated at a general hospital with a pediatric unit had a 2.6 greater chance ( P < 0.013), of undergoing splenectomy than those cared for at a freestanding pediatric hospital. Adult trauma surgeons caring for injured children must consider the anatomic, immunologic, and physiologic differences between pediatric and adult trauma patients and incorporate these differences into their treatment protocols. The major concerns are related to the potential risks of increased transfusion requirements, missed associated injuries, and increased length of hospital stay. Each of these concerns has been shown to be without merit.78,86,90,95,104,118,133
Associated Abdominal Injuries Advocates of surgical intervention for splenic trauma cite their concern about missing associated abdominal injuries if no operation is performed. Morse and Garciago reported successful nonoperative treatment in 110 of 120 children (91%) with blunt splenic trauma, of whom 22 (18%) had associated abdominal injuries. Only 3 of
CHAPTER
A
17
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299
B
A, Splenic pseudoaneurysm after (arrows) nonoperative treatment of blunt splenic injury. B, Successful angiographic embolization (arrozus show occlusion of ruptured vessels). a
these 120 patients (2.5%) had GI injuries, and each was discovered at early celiotomy done for a specific indication. There was no morbidity from missed injuries or delayed surgery. Similarly, a review of the NPTR from 1988 to 1998 revealed 2977 patients with solid abdominal visceral injuries; only 96 (3.2%) had an associated hollow visceral injury.95 Higher rates of hollow visceral injury were observed in assaulted patients and in those with multiple solid visceral injuries or pancreatic injuries. Differences in mechanism of injury may account for the much lower incidence of associated abdominal injuries in children with splenic trauma. There is no justification for an exploratory celiotomy solely to avoid missing potential associated injuries in children.
Complications of Nonoperative Treatment
liver injury.l3,40 These rare occurrences lead to caution when determining a minimum safe interval before the resumption of unrestricted activities. Routine follow-up imaging studies have identified pseudocysts and pseudoaneurysms following splenic injury (H. N. Loworn, personal c o m m u n i ~ a t i o n ) .Splenic ~~~~~ pseudoaneurysms often cause no symptoms and appear to resolve with time. The true incidence of self-limited, posttraumatic splenic pseudoaneurysms is unknown because routine follow-up imaging after successful nonoperative treatment has been largely abandoned. Once identified, the actual risk of s ~ l e n Gdseudoaneurvsm nmture is also unclear. Angiographic embolization techniques can successfully treat these lesions, obviating the need for open surgery and loss of splenic parenchyma (Fig. 17-3).Splenic pse~d6cystscan achieve enormous size, leading to and GI disturbance (Fig. 17-4). Simple percutaneous aspiration leads to a high recurrence rate. Laparoscopic excision and marsupialization are highly effective (Fig. 17-5).
Nonoperative treatment protocols have been the standard for most children with blunt liver and spleen injuries for the past 2 decades. This cumulative experience has allowed us ;o evaluate both the benefits and the risks of the non-operative approach. Fundamental to the success of a nonoperative strategy is the early, spontaneous cessation of hemorrhage. Transfusion rates for children with isolated spleen or liver injuries have fallen below lo%, confirming the lack of continued blood loss in the majority of patients.7".8'.87.13".'"6 Despite many favorable observations, isolated reports of significant delayed hemorrhage with adverse outcomes continue to appear.13,40,46J23 Shilyansky et a1.lz3 reported two children with delayed hemorrhage 10 days after blunt liver injury. Both children had persistent right upper quadrant and right shoulder pain despite normal vital signs and stable hematocrits. The authors recommended continued inhouse observation until symptoms resolve. Other reports a Computed tomography scan of post-traumatic have described patients with significant bleeding 38days after grade I1 spleen injury and 24 days after grade IV splenic pseudocyst.
CHAPTER
A
.
17
Abdominal Trauma
299
B
-
A, Splenic pseudoaneurysm after ( a m s )nonoperative treatment of blunt splenic injury. B, Successful angiographic embolization (arrou~s show occlusion of ruptured vessels).
these 120 patients (2.5%) had GI injuries, and each was discovered at early celiotomy done for a specific indication. There was no morbidity from missed injuries or delayed surgery. Similarly, a review of the NPTR from 1988 to 1998 revealed 2977 patients with solid abdominal visceral injuries; only 96 (3.2%) had an associated hollow visceral injury.95 Higher rates of hollow visceral injury were observed in assaulted patients and in those with multiple solid visceral injuries or pancreatic injuries. Differences in mechanism of injury may account for the much lower incidence of associated abdominal injuries in children with splenic trauma. There is no justification for an exploratory celiotomy solely to avoid missing potential associated injuries in children.
Complications of Nonoperative Treatment
liver injury.lS4O These rare occurrences lead to caution when determining a minimum safe interval before the resumption of unrestricted activities. Routine follow-up imaging studies have identified pseudocysts and pseudoaneurysms following splenic injury (H. N. Loworn, personal communication).41.g* Splenic pseudoaneurysms often cause no symptoms and appear to resolve with time. The true incidence of self-limited, posttraumatic splenic pseudoaneurysms is unknown because routine follow-up imaging after successful nonoperative treatment has been largely abandoned. Once identified, the actual risk of splenic pseudoaneurysm rupture is also unclear. Angiographic embolization techniques can successfully treat these lesions, obviating the need for open surgery and loss of splenic parenchyma (Fig. 17-3).Splenic pseudocysts can achieve enormous size, leading to pain and GI disturbance (Fig. 174). Simple percutaneous aspiration leads to a high recurrence rate. Laparoscopic excision and marsupialization are highly effective (Fig. 17-5).
Nonoperative treatment protocols have been the standard for most children with blunt liver and spleen injuries for the past 2 decades. This cumulative experience has allowed us io evaluate both the benefits and the risks of the non-operative approach. Fundamental to the success of a nonoperative strategy is the early, spontaneous cessation of hemorrhage. Transfusion rates for children with isolated spleen or liver injuries have fallen below lo%, confirming the lack of continued blood loss in the majority of patient~.7"."2.87.~35,~36 Deswite many favorable observations, isolated reports of significant delayed hemorrhage with adverse outcomes continue to appear.13,40,46,123 Shilyansky et al.123 reported two children with delayed hemorrhage 10 days after blunt liver injury. Both children had persistent right upper quadrant and right shoulder pain despite normal vital signs and stable hematocrits. The authors recommended continued inhouse observation until symptoms resolve. Other reports Computed tomography scan of post-traumatic have described patients with significant bleeding 38days after grade I1 spleen injury and 24 days after grade IV splenic pseudocyst.
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A , -
B
A, Laparoscopic view of splenic pseudocyst capsule. B, Appearance of cyst wall after laparoscopic aspiration and before marsupialization.
Sequelae of Damage-Control Strategies Even the most severe solid organ injuries can be treated without surgery if there is a prompt response to resuscitation.lo8 In contrast, emergency laparotomy, embolization, or both are indicated in patients who are hemodynamically unstable despite fluid and red blood cell transfusion. Most spleen and liver injuries requiring operation are amenable to simple methods of hemostasis using a combination of manual compression, direct suture, topical In young chilhemostatic agents, and mesh ~rapping.l~2~2 dren with significant hepatic injury, the sternum can be divided rapidly to expose the suprahepatic or intrapericardial inferior vena cava, allowing for total hepatic vascular isolation (Fig. 17-6).150 Children can tolerate periods of vascular isolation for 30 minutes or longer as long as their blood volume is replenished. With this exposure, the liver and major perihepatic veins can be isolated and the bleeding controlled, permitting direct suture repair or ligation of the offending vessel. Although the cumbersome and dangerous technique of atriocaval shunting has been largely abandoned, newer endovascular balloon catheters can be useful for temporary vascular occlusion to allow access to the juxtahepatic vena ~ a v a . ~ The early morbidity and mortality of severe hepatic injuries are related to the effects of massive blood loss and replacement with large volumes of cold blood products. The consequences of prolonged operations with massive blood product replacement include hypothermia, coagulopathy, and acidosis. Although the surgical team may keep pace with blood loss, life-threatening physiologic and metabolic consequences are inevitable, and many of these critically ill patients are unlikely to survive once their physiologic reserves have been exhausted. A multiinstitutional review identified exsanguination as the cause of intraoperative death in 82% of 537 patients at eight academic trauma centers.57 The mean pH was 7.18 and the mean core temperature was 32°C before death.
Moulton et al.Y3reported survival in only 5 of 12 (42%) consecutive operative cases of retrohepatic vascular or severe parenchymal liver injury in children. Maintenance of physiologic stability during the struggle for surgical control of severe bleeding is a formidable challenge even for the most experienced surgical team, particularly when hypothermia, coagulopathy, and acidosis occur. This triad creates a vicious circle in which each derangement exacerbates the others, and the
.
Total hepatic vascular isolation with occlusion of the porta-, supra-, and infrahepatic inferior vena cava and supraceliac aorta (optional). (Original illustration by Mark Mazziotti, MD.)
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17
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301
physiologic and metabolic consequences often preclude completion of the procedure. Lethal coagulopathy from dilution, hypothermia, and acidosis can rapidly occur.145 Experimental studies have defined the alterations in proPhase 1 Abbreviated laparotomy for exploration and anticoagulant enzyme processes, platelet activation, Control of hemorrhage and contamination and platelet adhesion defects with varying degrees of Packing and temporary abdominal wall closure hypothermia.14' The infusion of activated recombinant Aggressive ICU resuscitation Phase 2 Core rewarming factor VII in patients with massive hemorrhage has been Optlmizatlon of volume and oxygen delivery promising in several case reports.68 Correction of coagulopathy Increased emphasis on physiologic and metabolic Planned reoperation(s) for packing change Phase 3 stability in emergency abdominal operations has led to Definitive repair of injuries the development of staged, multidisciplinary treatment Abdominal wall closure plans, including abbreviated laparotomy, perihepatic packing, temporary abdominal closure, angiographic embolization, and endoscopic biliary stenting.5,32a45.69J4g ICU, intensive care unit. Asensio et aL6 reported on 103 patients with mostly penetrating grade IV or V hepatic injuries treated between have been proposed beyond the conventional vital signs 1991 and 1999. Mean blood loss was estimated at 9.4 L, and urine output, including serum lactate, base deficit, and mean volume infusion in the operating room was mixed venous oxygen saturation, and gastric mucosal 15 L. Packing of the hepatic injuries was used in 50% of pH. Once a patient is rewarmed, coagulation factors are patients at the first operation. Forty percent of patients Eeplaced, and oxygen delivery is optimized, he or she can who survived the initial operative control of hemorrhage be returned to the operating room for pack removal and had postoperative angiographic embolization (Fig. 17-7). definitive repair of injuries. A review of nearly 700 adult Survival was 63% in grade IV patients and 24% in grade V patients, emphasizing the lethality of such injuries patients treated by abdominal packing from several instidespite a well-choreographed, staged, multidisciplinary tutions demonstrated hemostasis in 80%, survival of 32% to 73%, and abdominal abscess rates of 10% to 40%.26,53 approach. Trauma surgeons treating critically injured Although abdominal packing with planned reoperation children must familiarize themselves with these lifesaving has been used with increasing frequency in adults during techniaues. Abbreviated laparotomy with packing for hemostasis, the past 2 decades, there is little published experience in children.30,36,5"80~115,13'L~134.'38Nevertheless, we believe allowing resuscitation before planned reoperation, is an that this technique has a place in the management of chilalternative in unstable patients in whom further blood dren with massive intra-abdominal bleeding, especially loss would be untenable. This "damage-control" philosoafter blunt trauma. phy is a systematic, phased approach to the management The ~ J ~three 3 We reported a 3-year-old child who required abdomiof exsanguinating trauma p a t i e n t ~ . ~ , ~ phases of damage control are detailed in Table 17-3. nal packing for a severe liver injury, making closure of the &though controversial, several resuscitative end points abdomen impossible.138A Silastic "silo" was constructed
A
.
B
-
A, Hepatic artery angiogram in a patient with persistent hemorrhage after initial damage-control laparotomy. The bleeding vessel is identified (curved arrow). B, Successful embolization was performed.
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to accommodate the bowel until the packing could be removed. The patient made a complete recovery. The combined technique of packing and a silo allowed time for correction of the hypothermia, acidosis, and coagulopathy, without compromise of respiratory mechanics. One review reported 22 infants and children (age 6 days to 20 years) with refractory hemorrhage who were treated with abdominal packing.134The anatomic site of hemorrhage was the liver or hepatic veins in 14, retroperitoneum or pelvis in 7, and pancreatic bed in 1. Primary fascia1 closure was accomplished in 12 patients (55%), and temporary skin closure or prosthetic material was used in the other 10. Packing controlled hemorrhage in 21 of 22 patients (95%). Removal of the packing was possible within 72 hours in 18 patients (82%). No patient rebled after the packing was removed; however, 2 patients died with the packing in place. Seven patients (32%) developed an abdominal or pelvic abscess, and all were successfully drained by laparotomy (6 patients) or percutaneously (1 patient); 6 of the 7 patients with abdominal sepsis survived. Overall, 18 patients (82%) survived. Two deaths were due to multisystem organ failure, one to cardiac failure from complex cardiac anomalies, and one to exsanguination after blunt traumatic liver injury. There were no differences in the volume of intraoperative blood product transfusion, time to initiate packing, physiologic status, or type of abdominal closure between survivors and nonsurvivors. Although the success of abdominal packing is encouraging, it may contribute to significant morbidity, such as intra-abdominal sepsis, organ failure, and increased intra-abdominal pressure. Intra-abdominal packs are contaminated by skin and gut flora, but these organisms are not those implicated in subsequent patient sepsis.48 Adams et a1.2 evaluated fluid samples from 28 patients with abdominal packing and found peritoneal endotoxin and mediator accumulation even when cultures were sterile. The authors concluded that laparotomy pad fluid accumulating after damage-control laparotomy can contribute to neutrophil dysfunction by enhancing neutrophil respiratory burst and inhibiting neutrophil responses to specific chemotactic mediators needed to fight infection. Thus, the known propensity of such patients to both intraabdominal and systemic infection may be related to changes in neutrophil receptor status and effector function related to the accumulation of inflammatory mediators in the abdomen. Early washout, repetitive packing, and other efforts to minimize mediator accumulation deserve consideration. It is essential to emphasize that the success of the abbreviated laparotomy and planned reoperation depends on an early decision to employ this strategy before irreversible shock occurs. When employed as a desperate, lastditch resort after prolonged attempts at hemostasis have failed, abdominal packing has been uniformly unsuccessful. Physiologic and anatomic criteria have been identified as indications for abdominal packing. Most of these focus on intraoperative parameters, including pH (-7.2), core temperature (16 seconds), in a patient with profuse hemorrhage requiring large volumes of blood product transfusion.
The optimal time for re-exploration is controversial, because neither the physiologic end points of resuscitation nor the increased risk of infection with prolonged packing are well defined. The obvious benefits of hemostasis provided by packing are also balanced against the potential deleterious effects of increased intra-abdominal pressure on ventilation, cardiac output, renal function, mesenteric circulation, and intracranial pressure. Timely alleviation of the secondary abdominal compartment syndrome may be a critical salvage maneuver for patients. Temporary abdominal wall closure at the time of packing can prevent the abdominal compartment syndrome. We recommend temporary abdominal wall expansion in all patients requiring packing until hemostasis is obtained and visceral edema subsides. A staged operative strategy for unstable trauma patients represents advanced surgical care and requires sound judgment and technical expertise. Intra-abdominal packing for control of exsanguinating hemorrhage is a lifesaving maneuver in highly selected patients in whom coagulopathy, hypothermia, and acidosis render further surgical procedures unduly hazardous. Early identification of patients likely to benefit from abbreviated laparotomy techniques is crucial for success.
Abdominal Compartment Syndrome The abdominal compartment syndrome is a term used to describe the deleterious effects of increased intra-abdominal pressure.l16 The syndrome includes respiratory insufficiency from worsening ventilation-perfusion mismatch, hemodynamic compromise from preload reduction due to inferior vena cava compression, impaired renal function from renal vein compression, decreased cardiac output, intracranial hypertension from increased ventilator pressures, splanchnic hypoperfusion, and abdominal wall overdistention. The causes of intra-abdominal hypertension in trauma patients include hernoperitoneum, retroperitoneal or bowel edema, and use of abdominal or pelvic packing. The combination of tissue injury and hemodynamic shock creates a cascade of events, including capillary leak, ischemia-reperfusion,and release of vasoactive mediators and free radicals, which combine to increase extracellular volume and tissue edema. Experimental evidence indicates that there are significant alterations in cytokine levels in the presence of sustained intra-abdominal pressure elevation.100J12 Once the combined effects of tissue edema and intra-abdominal fluid exceed a certain level, abdominal decompression must be considered. The adverse effects of abdominal compartment syndrome have been acknowledged for decades; however, abdominal compartment syndrome has only recently been recognized as a life-threatening but potentially treatable The incidence of this complication has increased markedly in recent years due to -high-volume resuscitation protocols. Measurement of intra-abdominal pressure can be useful in determining the contribution of abdominal compartment syndrome to altered physiologic Intra-abdominal presand metabolic parameter~.~g,fl.s4 sure can be determined by measuring bladder pressure. This involves instilling 1 mL/kg of saline into the Foley
CHAPTER
catheter and connecting it to a pressure transducer or manometer via a three-way stopcock. The symphysis pubis is used as the zero reference point, and the pressure is measured in centimeters of water or millimeters of mercury. Intra-abdominal pressures in the range of 20 to 35 cm H 2 0 or 15 to 25 mm Hg have been identified as an indication to decompress the abdomen. Many prefer to intervene according to alterations in other physiologic and metabolic parameters rather than a specific pressure measurement. Chang et al.19 reported 11 adult trauma patients with abdominal compartment syndrome in whom abdominal decompression using pulmonary artery catheters and gastric tonometry improved preload, pulmonary function, and visceral perfusion. Anecdotally, decompressive laparotomy has been used successfully to reduce refractory intracranial hypertension in patients with isolated brain injury without overt signs of abdominal compartment ~ y n d r o m e . ~ j Experience with abdominal decompression for abdominal compartment syndrome in children is limited.31,34,97,122.134,138 Nonspecific abdominal CT findings in children with abdominal compartment syndrome include narrowing of the inferior vena cava, direct renal compression or displacement, bowel wall thickening with enhancement, and a rounded appearance of the a b d ~ m e n .Neville ~~ et al?7 reported the use of patch abdominoplasty in 23 infants and children, only 3 of whom were trauma patients. These authors found that patch abdominoplasty for abdominal compartment syndrome effectively decreased airway pressures and oxygen requirements. Failure to respond with a decrease in airway pressures or fraction of inspired oxygen was an ominous sign in their series. Several authors have found that abdominal decompression resulted in decreased airway pressures, increased oxygen tension, and increased urine output in children with abdominal compartment syndrome.31,97J22 Many materials have been suggested for use in temporary patch abdominoplasty, including Silastic sheeting, Gore-Tex sheeting, intravenous bags, cystoscopy bags, ostomy appliances, and various mesh materials (Fig. 17-8). The vacuum-pack technique, used successfully in adults, seems pr0mising.~,~~J39
A I
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Bile Duct Injury Nonoperative management of pediatric blunt liver injury is highly successful but is complicated by a 4% risk of persistent bile leakage.lOJ17 Radionuclide scanning is recommended when biliary tree injury is suspected.120 Delayed views may show a bile leak even if early views are normal. Several reports have highlighted the benefits of endoscopic retrograde cholangiopancreatography (ERCP) with placement of transampullary biliary stents for biliary duct injury following blunt hepatic trauma. Although ERCP is invasive and requires conscious sedation, it can pinpoint the site of injury and allow treatment of the injured ducts without open surgery (Fig. 17-9).Endoscopic transampullary biliary decompression is a recent addition to the treatment options for patients with persistent bile leakage. The addition of sphincterotomy during ERCP for persistent bile leakage following blunt liver injury has been advocated to decrease intrabiliary pressure and encourage internal decompre~sion.2',9"12~It is important to note that endoscopic biliary stents may migrate or become obstructed and require specific treatment.
INJURIES TO THE DUODENUM AND PANCREAS In contrast to the liver and spleen, injuries to the duodenum and pancreas are much less frequent, accounting for less than 10% of intra-abdominal injuries in children sustaining blunt trauma. Isolated duodenal and pancreatic injuries occur in approximately two thirds of cases, with combined injuries to both organs occurring in the remainder. The severity of the duodenal or pancreatic injury and associated injuries determines the necessity for operative versus nonoperative management. The "protected" retroperitoneum both limits the chance of injury and increases the difficulty of early diagnosis. Added to this diagnostic dilemma is the frequency of associated intra-abdominal or multisystem injuries, which can mask subtle physical and radiographic diagnostic signs of injury to the duodenum and pancreas.
B A, Abdominal wall expansion with Silastic sheeting. B, Abdominal wall expansion with a Gore-Tex patch.
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A
B
, A, Endoscopic retrograde cholangiopancreatography demonstrating several bile leaks after blunt liver injury. B, Endoscopic view of transarnpullary biliary stent.
Duodenum In a report on blunt duodenal rupture, Ballard et reviewed a &year statewide (Pennsylvania) experience. Of 103,864 patients registered from 28 trauma centers, blunt injury to the duodenum occurred in 206 (0.2%),of whom only 30 (14%) had full-thickness rupture. The mechanism of iniury was car crash in 70%, which included both adults
number were interpreted as ndrma~.~ o r t a l i 6was 50% transection Complete transection with 2 cm devascularization Avulsion of renal hilum that devascularizes kidney
Bladder lnjury Scale I Hematoma Laceration II Laceration Ill Laceration IV Laceration V Laceration
Contusion, intramural hematoma Partial thickness Extraperitoneal bladder wall laceration 1 2 cm Extraperitoneal (>2 cm) or intraperitoneal (12 cm) bladder wall lacerations lntraperitoneal bladder wall laceration >2 cm Intra- or extraperitoneal bladder wall laceration extending into the bladder neck or ureteral orifice (trigone)
Urethral lnjury Scale l Contusion II Stretch injury Ill Partial disruption IV Complete disruption V Complete disruption
321
Blood at urethral meatus; urethrography normal Elongation of urethra without extravasation on urethrography Extravasation of urethrographic contrast medium at injury site, with contrast visualized in the bladder Extravasation of urethrographic contrast medium at injury site without visualization in the bladder; 2 cm urethral separation, or extension into the prostate or vagina
--
*Advance one grade for multiple injuriesto the same organ. tBased on most accurate assessment at autopsy, laparotomy, or radiologic study. From Moore EE, Shackford SR, Pachter HL, et al: Organ injury scaling: Spleen, liver, and kidney. J Trauma 1989;29:1664
Grade
.
- Artist's rendition of the American Association for the Surgery of Trauma grading system for genitourinary tract trauma. (Reproduced with permission from Coburn M: Genitourinary trauma. In Moore E, Feliciano DV, Mattox KL [eds]: Trauma, 5th ed. New York, McGraw-Hill, 2004.)
to this possibility. Placement of a Foley catheter or irrigation or replacement of an existing Foley catheter should remediate the problem. Although it is generally suggested that patients maintain a decreased level of activity until the microscopic or gross hematuria resolves, there are no evidence-based guidelines in the literature addressing appropriate length or type of activity restrictions for renal trauma. The period of time at which healing is adequate to allow return to full activity without risk has not yet been defined. Prospective studies are warranted. Although there is little controversy regarding management of the lower grade, less complex renal injuries in hemodynamically stable patients or the management of high grade, complex renal injuries in hemodynamically unstable patients, the management of those with intermediate injuries remains less well defined. Although the AAST grading scale appears to have some predictive value on the need for surgery, indications for surgery are based more on hemodynamic stability of the patient and associated injuries, rather than on grade of renal injury based on imaging criteria. The only absolute indication for surgery is hemodynamic instability with ongoing bleeding and transfusion requirements. Radiographic signs of
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ongoing renal bleeding include an expanding or unconwith major renal lacerations with a devitalized fragment tained retroperitoneal hematoma or complete avulsion after blunt abdominal trauma, Husmann and associof the mai; renal artery or vein with extravasation as ate@ found that renal exploration and surgical repair significantly improves the prognosis only in those demonstrated by CT or arteriography.g4 Although significant renal injury with urinary patients with concomitant intraperitoneal injuries. extravasation has in the past been considered a relative, Therefore, operative exploration of the kidney should be considered in children-with major blunt renal injuries if not absolute. indication for renal exdoration, more with a devascularized segment in association with intesrecent studies would suggest that most of these types tinal perforation or complex pancreatic injury to reduce of injuries can be successfully managed nonoperatively in the hemodynamically stable patient.120~148,161~171the incidence of serious infectious com~lications. Nonoperative management of hemodynamically Matthews and associates120reported spontaneous resolution of urinary extravasation in 27 of 31 patients (87%), stable children with complex higher grade blunt renal injury has become the standard of care in most centers. while the remaining 4 patients required ureteral stents ~ o s t . ~ e d i a t rand i c adult series report successful nonopdue to ~ersistentextravasation. Similarly, ,. Russell and erative management of even the most complex injuries, coworkers171 reported management of 15 pediatric including shattered but perfused kidneys and complex patients with grade IV renal injuries with urinary lacerations with extensive verinewhric hematoma and extravasation-9 patients (60%) required observation urinary extravasation.6J71 Proponents of nonoperative only; 1 required emergent partial n&phrectomy due to management of these patients note that in the absence hypotension and ongoing bleeding; and 5 developed of prospective studies comparing immediate explourinomas, 2 of whom were treated with percutaneous ration versus expectant management, no reliable data drainage and 3 of whom required ureteral stents. are available to suggest that surgery done early in the ~ l t h o u g hcomplications can occur with nonoperative course of injury reduces the long- or short-term complimanagement, most complications associated with urinary cations. The risk for nephrectomy associated with extravasation are easily treated by percutaneous drainage171 immediate exploration is avoided, and delayed surgery or endoscopic stent pla~ement,120,161,1~~ thereby achieving higher rates of renal salvage. is only necessary in 0% to 13% of With recent advances in interventional radiology techPatients with major renal trauma associated with niques and equipment, the need for delayed open enteric or pancreatic injury may be at increased risk for surgery has diminished significantly.78 An algorithm serious infectious complications, such as perinephric for the management of renal injuries in children is abscess and infected urinoma. In a study comparing presented in Figure 18-2. nonoperative versus surgical management of patients
* PK-1
Kidney all grades injury
i"l
Observation
Exploration
Persistent gross hematuria Persistent transfusion requirement Expanding abdominallflank mass Persistent fever
I
Repeat CT scan I
;4 Nephrectomy
Enlarging urinoma
Enlarging hematoma
Angiography Selective emb~lizations~~ C4, 93,184
Percutaneous drainage171 Cysto~copy/stenting'20.~6~~ In Exploration if unresponsive to above
-
-
Algorithm for the management of renal injuries in children.
CHAPTER
Collective review of 10 retrospective pediatric series of blunt renal trauma published over the past 13 years (1991-2004)* consists of 668 patients with the following grades of injury: grade I (342); grade I1 (46); grade I11 (64); grade IV (85); grade V (24); grades IV and V (16); grades I and I1 (50); grades I to 111 (18); and grades I1 and 111 (23). Operative intervention for renal injury was required in 45 patients (6.7%),including 31 nephrectomies (4.6%), 11 partial nephrectomies (1.6%), 1 renorrhaphy, and 2 nephrostomies. All patients with grades I and I1 renal injuries were successfully managed nonoperatively. Only 2 patients with grade I11 renal injuries required operative intervention: 1with nephrectomy and 1 with a partial nephrectomy. Forty-one of 125 (33%) children with grade IV and V renal injuries required operative intervention, including 30 nephrectomies (13 grade IV, 15 grade V, 2 grades IV and V); 10 partial nephrectomies (8 grade lV, 1 grade V, and 1 grades IV and V), 1 renorrhaphy (grades IV and V), and 2 nephrostomies (grades IV and V). The indication for operative intervention in almost all cases was hemodynamic instability with ongoing bleeding, with most requiring emergent operations within 24 hours of admission. The percentage of patients requiring operative intervention for renal injury ranged from 1.7%"2 to 12.7%,118 with the vast majority being those with highgrade (IV to V) complex injuries. Nonoperative management was successful in 93% of all patients with blunt renal trauma, 97% of those with grade 111 renal injuries, 75% of those with grade IV renal injuries, and 33% of those with grade V renal injuries.
Penetrating Injuries Penetrating renal injuries are rare in children. Although most gunshot wounds to the abdomen will require abdominal exploration, retroperitoneal dissection and exploration isindicated only if preoperative or intraoperative assessment suggests a major renal injury with extravasation outside of Gerota's fascia, there is suspicion for significant nonurologic retroperitoneal injury -(great vessels, duodenum, pancreas, colon), and/or inspection reveals an expanding or pulsatile retroperitoneal hematoma.lgl McAninch and c0workersl2~ classified gunshot wounds involving the kidney into five categories: (1) contusions (18.4%), (2) minor lacerations (13.8%), (3) major lacerations (50.5%), (4) vascular injuries (6.9%), and (5) lacerations combined with vascular injury (10.3%). The majority of patients had multiple injuries, with 95% requiring associated procedures. The nephrectomy rate was 13.8%. Although many of the kidneys rembved were potentially salva&able, most were removed because of the patient's precarious hemodynamic status. For renal-proximity stab wounds, nonoperative treatment is appropriate in hemodynamically stable patients without associated injuries who have been staged approHowever, a high index priately by triple-contrast CT.68,198 of suspicion for missed ureteral and other associated injuries must be maintained if a nonoperative pathway is chosen. *See references 7,8, 21, 43, 112, 118, 158, 171, 174, and 179.
18
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323
In a retrospective review by McAninch and coworkers,l27 55% of renal stab wounds and 24% of renal gunshot wounds were successfully managed nonoperatively with an acceptable complication rate. In the hemodynamically unstable patient with penetrating trauma or those with a retroperitoneal hematoma at laparotomy, a oneshot IVP may be useful to identify renal injury and confirm the presence and function of two renal units to further guide management.
Renovascular Injuries
Major renovascular injuries are rare in children. Carroll and c0lleagues3~and Turner and associates1g0reported penetrating trauma as a cause of renovascular injiries in 64% and 68% of their patients, respectively. Conversely, Cass and coworkers39 identified blunt external trauma as the cause of renovascular injury in 76% of patients. Regardless of the mechanism, these patients tend to have high injury severity scores, large transfusion requirements, and associated life-threatening multisystem injury,31,39J79the management of which supersedes that of renal injury. Knudson and colleagues105 reported that factors associated with a poor outcome after renovascular injuries include blunt trauma, grade V injury, and attempted arterial repair. Grade V injuries are frequently associated with severe major parenchymal injuries, which contribute to poor function of the revascularized kidney. Patients with grade V injuries with severe parenchymal disruption may be better served by immediate nephrectomy, provided that a functional contralateral kidney is present. Bruce and associatesZ3 compared 12 patients with blunt renal artery injuries who underwent operative intervention (9 nephrectomies; 3 revascularizations) with 16 patients who were managed nonoperatively, 1 of whom underwent endovascular stent placement. They concluded that nonoperative management of unilateral blunt renal artery injuries is safe and often successful, with a 6% risk of developing post-traumatic renovascular hypertension. . The pathogenesis of renovascular injuries due to blunt trauma is thought to be caused by rapid deceleration, which results in stretching of the renal vasculature, disru~tionof the arterial intimar and arterial thr0mbosis.3~ Blunt arterial injury occurs more commonly on the left side than on the right side31,33,34,190because the right renal artery is longer than the left and may be better able to withstand the stretching " caused bv d e ~ e l e r a t i o n . ~ ~ Although hematuria may be absent or microscopic in 13% to 56% of patients with renovascular injuries,3l,39,65,128,179 most hatients have other symptoms or signs that raise suspicion for a major renal injury and prompt further diagnostic imaging.31J7g Renovascular injury is suggested on CT by (1) lack of renal enhancement or excretion, often in the Dresence of normal renal contour; (2) vein enhancement; (3) central hematoma; (4) abrupt cutoff of an enhanced renal artery; and (5) nonopacification of the pelvicaliceal ~vstem.31,~79 The approach to this type of injury depends on the time to diagnosis, the type and extent of the vascular injury, and the extent of the associated i n j ~ r i e s . ~ ~ J O ~ J ~ ~
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artery injury or solitary kidney~.~~,~6J60 Repair of the right renal vein may be difficult owing to its An algorithm for short length and proximity to the inferior vena cava. the management of renovascular injuries is presented in Nonetheless, injuries to the main renal vein can be Figure 18-3. r e ~ a i r e din mosi cases.31Laceration of the left renal vein at its origin can be managed by ligation because collatComplications eral circulation supplied by gonadal and adrenal veins Although most renal injuries in children can be managed usually allows for adequate venous drainage.31~83 Segmental arteries are difficult to repair and may best nonoperatively, nonoperative management is not withbe managed by ligation with accompanying partial out complications. If a nonoperative course is chosen, nephrectomy if the area of infarction encompasses more the patient must be carefully monitored. Falling blood than 15% of the kidney.g0However, others suggest that counts, ongoing transfusion requirements, and persistent nonoperative management should be considered in any gross hematuria may be indicative of ongoing bleeding. patient with segmental artery occlusion that is not associA repeat CT scan or arteriogram is warranted. An arteriogram may be especially useful since some injuries ated with uncontrolled retroperitoneal hemorrhage, with ongoing bleeding may be amenable to selective extensive urinary extravasation,o r other intra-abdominal embolization to control the bleeding. Indeed, the sucindications for $urgev. This management strategy has been associated with an acceptably low incidence of cess of nonoperative management may be enhanced by com~lications.~~3~ angiographic embolization in select patients.G4 However, Arterial repair is most appropriate and most sucprofuse bleeding not amenable to embolization requires cessful for renovascular injuries caused by penetrating emergent operative exploration. trauma. Notwithstanding occasional reports of successful Prolonged ileus, fevers, and expanding abdominal/ revascularization in patients 19 hours after injury,82the flank mass or discomfort may be indicative of persistent urinary extravasation or urinoma, which is the most success of the procedure greatly diminishes after 8 hours ~ ~ ~ , ~ ~and ~ coworkersg9 common complication after renal trauma. Russell and of renal i s ~ h e m i a . 3 1 , 6 9 , 8 2 ,Ivatury associates171reported that about two thirds of all urinoreviewed 40 penetrating renovascular injuries and mas in children will spontaneously resolve. Accordingly, concluded that salvage of a kidney with a renovascular small, noninfected, stable collections require no treatinjury is determined primarily by the nature and extent ment other than observation, whereas larger, expanding of associated injuries. Furthermore, they reported that collections may be managed by percutaneous drainage171 while attempts at renal artery repair are often futile, or endoscopic placement of ureteral ~tents.~20J61J~~ renal vein injuries are more amenable to repair and Broad-spectrum antibiotics are also administered intrahave a better prognosis. Nephrectomy, however, remains the procedure of choice in the hemodynamically unstavenously. Delayed renal bleeding is unusual and most commonly ble patient with multiple trauma. occurs within 2 weeks of injury. However, Teigen and Blunt injuries to the main renal artery are associated with ,l~~ reported two children who developed maslowest success rate for complete renal p r e ~ e r v a t i o n . 3 ~ J ~ ~coworkers184 Haas and associates85 reviewed the management of sive life-threatening hemorrhage several weeks after the initial injury diagnosed by arteriography and successfully 12 patients with complete renal artery occlusibn secondary to blunt trauma. Renal artery revascularization was treated by percutaneous transcatheter embolization. Perinephric abscesses may be associated with ileus, attempted in 5 patients with a median warm ischemia time of 5 hours (range: 4.5 to 36 hours). Although four high fevers, and sepsis. CT is diagnostic. Most of these of five revascularizationswere deemed technically successabscesses are successfully treated with intravenous broad-spectrum antibiotics and percutaneous drainage. ful at the time of operation, 3 patients demonstrated no function and 1 showed minimal function on postoperaMultiloculated abscesses not amenable to percutaneous tive renal function scans. Two patients required delayed drainage may require operative drainage. nephrectomy due to complications, and of the 7 patients Late complications may include hydronephrosis, who underwent nonoperative management, 3 patients arteriovenous fistula, pseudoaneurysm, pyelonephritis, developed significant hypertension requiring nephreccalculus formation, and delayed renal hypertension. Posttraumatic arteriovenous fistula and pseudoaneurysm may tomy for blood pressure control. Based on these results, be successfully managed by percutaneous endovascular the authors are unable to advocate emergency revascularization for unilateral renal artery occlusion in the embolization.ll6Jfl The incidence of renal hypertension Dresence of a normal functional conhalateral kidney after trauma is quite low, occurring in fewer than 5% of patient~.85,141~142~~9~ The incidence is thought to be even unless the patient is hemodynamically stable and warm lower in children. Although hypertension usually occurs ischemia time is less than 5 hours. Patients with unianywhere from 2 weeks to several months after lateral injury, complete arterial thrombosis, extensive i n j ~ r y , ~ ~long-term , ~ ~ 2 , ~follow-up ~~ is essential because associated injuries, and a prohibitively long period of onset may be delayed up to 10 to 15 years after injury.IG0 renal ischemia may be managed either by primary nephrectomy or expectant nonoperative management depending on the hemodynamic stability of the patient. Follow-UplOutcomes There are reports of successful endovascular stenting Evidence-based guidelines for follow-up of children for traumatic renal artery dissection and thrombosis after renal injury are conspicuously lacking in the literain both children134 and adults.23~flIAn attempt should be made to revascularize all patients with bilateral renal ture. In a retrospective study, Abdalati and associates1
I
CHAPTER
18
Fienovascular injury
I
Genitourinary Tract Trauma
325
4 Unstable
f5 Exploration
Observation Consider angiographyl endovascular stentZ4.I l l s 134
25 Nephrectomy
I
Kidney appears salvageable
Kidney appears unsalvageable
I
I
I
Attempt revascularization
-
25 Nephrectomy
.
Algorithm for the management of renovascular trauma in children.
correlated initial CT grading of renal injury with frequency of complications and time course of healing in 35 patients. From this study, they concluded that grades I and I1 injuries healed completely and required clinical but not radiologic follow-up. Grade I11 injuries were associated with the highest risk of complications (30%),with healing taking up to 4 months to complete. Thus, it was recommended that grade I11 injuries be followed by sequential imaging with CT, scintigraphy, and/or ultrasound for 3 to 4 months until complete healing was documented. Grade IV injuries were often associated with some degree of renal loss and required radiologic follow-up to assess complications and residual renal function. Although CT provides important information regarding healing and the presence of complications, quantitative dimercaptosuccinic acid (DMSA) scintigraphy is a more useful tool to assess residual renal function after injury.143A study by Keller and coworkers103evaluated the functional outcome of nonoperatively managed renal injuries in 17 children as measured by blood urea nitrogen (BUN), creatinine, blood pressure, and DMSA renal scan after radiographic evidence of complete healing. Similar to the findings of Abdalati and associates,l complete healing was documented radiographically within 3 months in all cases. They concluded that functional outcome correlates with injury grade, with grades I1 to IV injuries retaining near normal function and grade V injuries demonstrating significant loss of renal function due to scarring
and parenchymal volume loss. Despite diminished function on DMSA renal scans, all children were asymptomatic, normotensive, and had normal BUN and creatinine levels. Larger prospective clinical and radiologic outcome studies are warranted to further assess time to healing, incidence of complications, residual function, and longterm outcomes after renal trauma to provide the physician with a more evidence-based approach to appropriate follow-up and counseling for the injured child. At present, it is generally recommended that children with more severe renal injuries be followed with serial blood pressure monitoring and CT and DMSA at 3 to 6 months postinjury. Further imaging is also indicated for onset of any urologic symptoms or development of hypertension.
Operative Management of Renal Trauma Although most cases of renal trauma in children may be successfully managed nonoperatively, the surgeon should be familiar with techniques of operative management as well. As discussed previously, operative management of renal trauma is generally reserved for hemodynamically unstable patients or those patients with severe associated injuries. The patient is usually explored through a generous midline abdominal incision. Although traditionally it has been taught that the surgeon should first gain proximal control of the renal artery and vein before entering Gerota's fascia or the hematoma in order to reduce blood loss and decrease the nephrectomy rate,""
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this approach has recently been challenged. In both , ~ ~ a prospective, randomized retrospective s t ~ d i e s 4and clinical trials1 it was concluded that vascular control of the renal hilum before opening Gerota's fascia has no effect on the nephrectomy rate, transfusion requirements, or blood loss but does significantly prolong operative times by up to an hour or more. The nephrectomy rate appears to depend more on the degree of injury rather than on the type of renal vascular contr01.~ No matter what the approach, the kidney is exposed and vascular control is obtained at the hilum. With exsanguinating hemorrhage, rapid mobilization of the kidney with digital control of the hilum may be necessary. The left renal vein can be ligated because collateral drainage is provided by the left adrenal and gonadal veins. However, trauma to the right renal vein requires repair. Segmental arteries may be ligated and partial nephrectomy performed if the area of infarction encompasses more than 15% of the kidney.g0If the patient is hemodynamically stable, the kidney itself is salvageable, and the period of warm ischemia after injury is acceptable, renal artery repair and revascularization may be attempted. Otherwise, a nephrectomy should be performed. If it appears salvageable, the damaged kidney is debrided to viable tissue and intrarenal hematomas are evacuated. Hemostasis should be obtained with absorbable sutures placed in a figure-of-eight pattern. The open collecting system should be closed with fine, absorbable, monofilament sutures, because woven sutures may cut through renal tissue.1z6 Internal stents may be required if the ureter or renal pelvis has been injured. The renal capsule should be closed to approximate the renal margins. If the capsule is destroyed, the lacerated margins should be covered with omental pedicle grafts, retroperitoneal fat, or polyglycolic acid mesh.gOJ26 Approximation and covering of renal tissue aids in hemostasis and wound healing and prevents delayed bleeding and extravasation of urine.lZ6
Ureter Ureteral injury is uncommon and assumes secondary importance in children with potentially life-threatening injuries. Nonetheless, delays in diagnosis and treatment are associated with major morbidity and a significant risk for life-threatening urosepsis later during the course , 2 ~ , ~and ~ , ~colleague^^^ ~ reported the of i n j ~ r y . ~ ~Boone risk for urologic complications to be 13% when blunt UPJ disruption was diagnosed within 24 hours compared with 54% with delayed diagnosis. The risk for renal loss was 4.5% to 9% with early diagnosis compared with 32% to 33% with delayed diagnosis.'4,96 Ureteral trauma is classified by the anatomic location of the injury and by the extent of mural damage (see Blunt ureteral injuries are rare, occurring Table 18-1).144 in less than 1% of patients with blunt abdominal trauma. Direct injuries may result from crush injuries or severe hyperextension or flexion injuries. Direct compression against a transverse process or vertebral body has been described,'gg and an association with traumatic paraplegia has been noted.loOPatients with congenital ureteral
obstruction are also predisposed to injury of the collecting system.89 Surgical repair is unlikely to be successful if the underlying obstruction is not recognized and treated. Indirect mechanisms of ureteral injury in children include falls or rapid deceleration. As noted by Boone and colleagues,l4 the UPJ is particularly prone to disruption secondary to these mechanisms. Howerton and associates96 reviewed 54 cases of ureteral avulsion within 4 cm of the UPJ and found that this type of injury was three times more common in children than in adults. Similarly, the right kidney was injured three times more often than the left. Penetrating trauma involving the ureter occurs in approximately 4% of patients and is most often caused by a stab or gunshot wound. Although this type of injury is most commonly seen in adults, it occurs in a significant percentage of children as we11.l8I In the largest series to date, PerepBrayfield and coworkers1" reviewed 118 patients with gunshot wounds to the ureter managed by a variety of surgical procedures, depending on the location and severity of the defect. They reported a 20% incidence of comvlications and concluded that a high index of suspicion is necessary to avoid missing these injuries. Iatrogenic injuries to the ureter in children occur most cokmonlfduring ureteroscopic and percutaneous endourologic procedures. Open surgical procedures, such as those involving resection of an abdominal or pelvic tumor or colectomv. ,, mav, also be associated with ureteral trauma. Radiation injury is also occasionally encountered. The paucity of early signs and symptoms makes the nonoperative diagnosis of ureteral injuries difficult. Boone and colleagues14 encountered gross hematuria in 27% of patients with UPJ disruption, whereas an additional 26% of patients had microscopic hematuria with shock. Absence of hematuria was noted in about one third of patients. As reviewed by Brandes and coworkers,l6 23% to 37% of ureteral injuries reported in the literature have conspicuous absence of significant hematuria. Flank tenderness. ecchvmosis. and mass effect are encountered in only approximately 7% of patients with proximal ureteral injury.14 Patients occasionally present with anuria if the injury is bilateral or involves a solitarv kidnev. Imaging modalities for diagnosis of ureteral trauma include CT and IVP. Up to 75% of ureteral injuries are missed by IVP.'69'65 Ureteral injuries may be difficult to diagnose by CT as well. With the faster helical CT scanners currently in use, it is critical to obtain delayed images during the excretory phase (2 to 10 minutes) so that ureteral extravasation is not missed. Failure of opacification of the ureter should also raise suspicion for ureteral injury.187 Retrograde pyelography is quite sensitive and should be performed in hemodynamically stable patients suspected to have a ureteral injury. Delayed diagnosis of ureteral injury occurs in approximately half of patients owing to the subtle nature of the clinical findings, frequent absence of hematuria, lack of sensitivity of radiolbgic imaging techniques, and high incidence of multisystem injury with concomitant patient instability.14J6Wreteralinjuries may be heralded
CHAPTER
by sepsis, vascular collapse, or drainage of urine from surgical wounds. Periureteral fibrosis, phlegmon, and abscess are common. Other complications include obstruction from stenosis and renal failure. In contrast to management of renal injuries, nonoperative management has limited application for ureteral injuries. Minor ureteral injuries with limited extravasation may be managed nonoperatively with a retrograde stent. However, most patients with ureteral injuries fare better with early operative repair. If the diagnosis is delayed significantly, temporary stenting or percutaneous nephrostomy diversion followed by interval operative reconstruction may be indicated, owing to the increased inflammation, friability, and complications associated with attempts at repair more than 3 to 5 days after injury. The treatment of ureteral injuries is dictated primarily by the location and mechanism of injury, amount of tissue loss, and the condition of the local tissues. Ureteral injury associated with a severely damaged or shattered kidney is best managed by nephrectomy. In the absence of or with limited renal injury, attempts at primary ureteral repair should be attempted. Disruption of the UPJ is generally manageable by dismembered pyeloplasty. If damage to the renal pelvis is extensive, it should be surgically debrided and closed and ureteral continuity should be restored by ureterocalicostomy. Midureteral injuries are repaired by limited debridement to viable tissue and a spatulated end-to-end anastomosis using fine absorbable suture. Injuries to the pelvic ureter are often amenable to a simple ureteral reimplantation. Occasionally, a psoas hitch or Boari flap is required for ~ stents are used a tension-free a n a s t o m o ~ i s .Ureteral routinely. Patients with ureteral trauma from a bullet wound require that the ureter be debrided until the edges bleed freely. Intravenous fluorescein and a Wood's lamp are occasionally useful to predict viability. Peristalsis is not a reliable sign of viability. A spatulated end-to-end anastomosis is performed, and stenting is mandatory. Unstable patients with multiple injuries are best managed by exteriorization of the transected ureter as an intubated ureterostomy or by simple ureteral ligation with intraoperative or postoperative percutaneous nephrostomy. Simple ureteral ligation is also an excellent form of management for unstable patients in whom the length of the ureteral defect precludes primary repair. Definitive reconstruction of a long ureteral defect is done on an elective basis once the patient is stable.12J65J81 Options include renal mobilization (which can yield 3 to 5 cm) ,Is1 the Boari flap or psoas hitch,l5 and autotransplantation.12.193 Additionally, transureteroureterostomy and ileal interposition can be done.ls1 Delayed diagnosis associated with significant adjacent visceral injury (i.e., duodenal or pancreatic injury) may be particularly problematic. Such injuries are marginally amenable to reconstruction. Percutaneous antegrade ureteral stenting with later, elective surgical correction of stenosis or fistula, if encountered, is the preferred method of management.ls6 This may also be the best approach to management of ureteral injury associated with infected urinoma, abscess, delayed diagnosis, or ureteral contusions complicated by urinary extravasation.
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327
Bladder Anatomy Although the bladder in children is located in the extraperitoneal space of Retzius, it is considered an the bony pelvis grows, the intra-abdominal organ.5" bladder assumes a pelvic position and is increasingly protected from injury. The anatomic attachments of the bladder influence the pattern of injury seen after some forms of trauma. The bladder is bound laterally by the internal obturator muscles and the umbilical ligaments.53At its base the bladder is attached to the urogenital diaphragm. Denonvillier's or the rectovesical fascia binds it posteriorly. Unlike the rest of the bladder, the dome is mobile and di~tensib1e.l~~
Causes
The bladder may be injured by blunt or penetrating trauma. Although penetrating injury to the bladder can be caused by any injury to the lower abdomen, the most common cause of unintentional injury is i a t r o g e n i ~ . ~ ~ ~ ~ 2 Migration or erosion of drains, ventriculoperitoneal shunts, intrauterine devices, and Foley catheters are rare causes of unintentional injury to the bladder.25,50,53,202 Intentional penetrating injuries are most commonly caused by gunshot wounds, which are usually associated with other intra-abdominal injuries. Blunt trauma accounts for 80% of injuries to the bladder. The susceptibility of the bladder to injury is somewhat dependent on the amount of urine contained at the time of injury.154 Motor vehicle crashes are the most common cause of blunt trauma to the bladder.53 Pelvic fractures with sharp bony fragments may lacerate the bladder (usually near the bladder neck), and shearing forces can tear the bladder at its mooring~.~3J~l A forceful, direct blow to the abdomen may rupture the dome of the bladder, even without an associated pelvic fracture.53JsO Because of its relatively protected position within the pelvis, considerable blunt force is required to cause bladder injury. Not surprisingly, serious injuries to other intra-abdominal organs are seen in almost half of patients with bladder injuries.70While 75% to 95% of bladder injuries are associated with pelvic fractures,27,70,151,180only 4% to 20% of patients with pelvic fractures have concomitant bladder i n j ~ r i e s . l ~ , 2 ~ , ~ 2 , l ~ ~
Classification and Definitions Bladder injuries due to blunt trauma may be further classified as contusions, and extraperitoneal and intraperitoneal ruptures. Extraperitoneal bladder ruptures occur in 60% to 65% of cases; intraperitoneal ruptures occur in 25% of cases; and a combination of the two occurs in 10% to 15% of cases.95 The AAST grading scale for bladder injuries is shown in Table 18-1. Contusions are disruptions in the bladder muscularis without loss of continuity of the bladder wall, whereas ruptures are complete disruptions of the bladder Contusions typically resolve without intervention.
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Extraperitoneal bladder ruptures are usually assodeliberate evaluation of the patient. The weakest and Nineteen percent of ciated with pelvic fracture~.~2.~22~~ most mobile part of the bladder, the dome, is the most patients (mostly male) with extraperitoneal bladder common site of intraperitoneal rupture. This type of ruptures have a concomitant urethral injury, and 8% injury occurs more commonly in children."J2' have an associated intraperitoneal i n j ~ r y . ~ 3 , ~ ~ Intraperitoneal bladder ruptures are best managed by In contrast to extraperitoneal ruptures, intraperitoneal early operative repair. Protracted extravasation of urine ruptures are infrequently associated with pelvic fractures into the peritoneal cavity can lead to life-threatening (Fig. 18-4). These injuries are often caused by compresmetabolic, septic, and mechanical derangements.27.",92 Patients presenting more than 24 hours after intraperision (burst-type injury) from a suprapubic blow to a toneal rupture of the bladder may have elevated BUN, distended bladder or sudden, forceful de~eleration.~2~",l~~ creatinine, and potassium levels; a decreased serum Intraperitoneal ruptures most commonly occur at the sodium concentration; and a laboratory profile similar dome of the bladder, whereas extraperitoneal rupto that of patients with acute renal f a i l ~ r e . ~ z tures are usually caused by bony perforation or shearing f o r c e ~ . ~ ~infants ~ ~ V nand young children, the bladder The bladder should be approached through a lower midline abdominal incision to avoid lateral contained is an intraperitoneal organ, and if it is ruptured it will often cause intraperitoneal extravasation of urine.122 hematoma. If necessary, the rent in the dome of the Occasionally, bladder ruptures may result from an extenbladder can be widened to facilitate a thorough examsive hematoma of the bladder wall or, in neonates, ination of the inner aspect of the bladder. Associated from manipulation of an umbilical artery catheter.20Jj0 extraperitoneal tears can be closed from within by a single running layer of absorbable suture; however, the surgeon must ensure that the patency of the ureteral Management orifices is preserved. An intravenous injection of indigo carmine may help verify the location and Bladder Contusions integrity of the ureteral orifices. The dye should be seen effluxing from the ureteral orifices within 10 minutes. Most bladder contusions heal spontaneously without intervention. If the sacral innervation of the bladder is Lacerations extending into the bladder neck should be carefully repaired to reconstruct the sphincteric compointact, patients with bladder contusions have excellent nents and reduce the likelihood of later urinary outcomes. Patients with a large pelvic hematoma that causes considerable bladder distortion may have difficulty incontinence. Intraperitoneal bladder injuries are voiding and may benefit from Foley catheter drainage. repaired with absorbable suture in two layers. After the bladder is repaired, a closed-suction drain is placed and brought out through a separate stab incision. Intraperitoneal Rupture Although in the past most surgeons would insert a largeIntraperitoneal ruptures are frequently associated with bore suprapubic cystostomy tube instead of or in addition to a transurethral catheter for urinary drainage other significant injuries, necessitating a thorough and after repair of an intraperitoneal bladder rupture, more recent literature would suggest that transurethral catheter drainage is not only adequate, but preferable. For any degree of bladder injury, transurethral catheters are equally effective, are associated with fewer complications, and may be removed sooner than suprapubic catheters.Y5,18.i,192 Urinary drainage is generally maintained for 5 to 10 days. Most surgeons will obtain a cystogram before removal of the urinary drainage catheter to evaluate the integrity of the repair. If no extravasation is documented, then the urinary catheter and closed-suction drain can be removed.
Extraperitoneal Rupture
Voiding cystourethrography demonstrating intraperitoneal rupture of the bladder. The patient also had bilateral fractures of the superior ischial and inferior pubic rami.
The preferred management of extraperitoneal rupture is transurethral catheter drainage alone. This approach is safe and effective and obviates the need for bladder exploration, manipulation of the extraperitoneal hematoma, and converting a closed pelvic fracture into an open one. At times, the degree of extravasation of contrast medium may be alarming. However, because it is dependent not only on the size of the tear but also on the amount of contrast medium instilled,"g,55the degree of extravasation alone may not indicate the severity or extent of the tear in the bladder.'7.3"-"7," In most
CHAPTER
instances, the tear heals completely and transurethral catheter drainage is successful even with extensive Almost 90% of extraperiurinary extravasation.41~42~55 toneal bladder ruptures heal within 10 days and the remainder within 3 weeks.55 Operative intervention is rarely required.
Penetrating Injuries Because of the high likelihood of associated injuries, which often take priority in management, patients with penetrating injuries to the bladder generally require exploratory laparotomy. The peritoneal cavity is opened in the midline, and injuries to the intra-abdominal viscera and major vasculature are addressed first. Attention is then directed to the bladder, and the extent of injury is determined. All devitalized bladder tissue and debris from clothing or bony spicules are removed.27 The integrity of the ureters can be confirmed with intravenous injection of indigo carmine. A diligent search should be made for extravasation, and, if necessary, the ureters should be intubated. Bladder mobilization is unnecessary and invites precipitous bleeding. Large, nonexpanding hematomas should be left undisturbed. The bladder should be entered through the dome. Extraperitoneal defects should be closed intravesically with a single layer of running absorbable suture. A watertight closure is ideal but not essential. With adequate bladder drainage, even a tenuous closure can heal satisfactorily. Intraperitoneal defects should be closed in two layers with absorbable suture. Closed-suction drains are placed as previously described, and transurethral catheter drainage is maintained for 5 to 10 days.
Urethra Although urethral trauma is a secondary consideration in children with potential life-threatening trauma, such injuries account for a disproportionate degree of long-term morbidity. It remains unclear whether delayed or immediate repair is superior, and there are no prospective, randomized studies addressing the issue. The majority of the available data are based on retrospective series in adults. The only available pediatric series are limited by small numbers of patients. Data from adult studies may not be applicable to children owing to anatomic differences. For example, in contrast to adults, the posterior urethra is not protected by the prostate in children and may be injured at any level. Blunt trauma with disruption of the bony pelvis accounts for most posterior urethral injuries in children. About 5% of males with a fractured pelvis will also have an injury to the posterior urethra.153Of these cases, 10% to 20% will have an associated bladder rupture.55 Motor vehicle accidents account for 90% of urethral injuries, and the remaining 10% result from falls, crush injuries, or sporting injuries. A lateral pelvic force without pelvic fracture rarely results in urethral disruption. Penetrating injuries involving the posterior urethra including stab wounds, gunshot wounds, and iatrogenic causes are rare.
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Genitourinary Tract Trauma
329
Anterior urethral injuries are often encountered after straddle injuries, such as a fall astride a fence, kicks, or bicycle injuries. Penetrating trauma to the anterior urethra is rare but may be seen with gunshot or stab wounds. Urethral instrumentation, penile surgery, and injuries from sexual intercourse and masturbation may also result in anterior urethral trauma. The diagnosis of urethral trauma is relatively straightforward. Symptoms of urethral injury may include the inability to void or the sensation of voiding without passing urine. Blood at the urinary meatus or gross hematuria after trauma strongly suggests urethral injury. Physical examination of the penis, scrotum, and perineum may reveal swelling and ecchymosis. The integrity of and boundaries of Buck's, Colles', and Scarpa's fascias indicate the region injured. Digital rectal examination may reveal upward displacement of the prostate or a boggy mass. This, however, may be difficult to assess in young children, so urethral imaging is required to confirm the diagnosis. If there is suspicion of a urethral injury, blind passage of a transurethral urinary catheter should not be attempted because there is a risk of creating a false passage with the catheter and converting a partial disruption into a complete one. Retrograde urethrography is the imaging modality of choice for diagnosis of urethral trauma. Findings of elongation, filling defect, or extravasation indicate urethral injury. If urethral integrity is demonstrated by retrograde urethrography, the catheter is then advanced and a cystogram is performed to exclude concomitant bladder injury. Table 18-1 outlines the classification of urethral injuries that includes contusions, stretch injuries, partial disruptions, and complete disruptions. A filling defect caused by contusion and hematoma or an elongated urethra without extravasation on retrograde urethrography indicates grade I or I1 injury. Urethral extravasation with bladder continuity indicates partial disruption (grade 111).Urethral extravasation with no admission of contrast agent into the proximal urethra or bladder suggests complete disruption (grade IV). Spasm of the periurethral musculature can mimic complete disruption. Figure 18-5 provides an example of injury to the bulbous urethra.
, - . Extravasation of contrast from the bulbous urethra due to penoscrotal urethral disruption. The posterior membranous and prostatic urethra is intact.
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The long-term sequelae of urethral trauma can be devastating and may include impotence, retrograde ejaculation, incontinence, and urethral strictures. Some of these complications may be a direct consequence of the trauma itself or may be related to surgical attempts at repair. ~ - d i a ~ n o sof i s anterior urethral injury is suggested if the retrograde urethrogram reveals only minimal extravasation with good urethral continuity and if the patient is able to void. Grade I or I1 injuries to the anterior urethra usually heal spontanedusly without insertion of any indwelling urinary catheters, as long as the patient is able to void. Intermediary grade anterior urethral injuries may be managed by an indwelling transurethral Foley catheter, whereas more complex injuries are best managed in the initial stages by placement of a suprapubic catheter. Delayed urethral strictures occur~commonly,and most are. amenable to urethroplasty. Penetrating injuries to the anterior urethra may be managed by exploration and primary repair or suprapubic urinary diversion. Husmann and colleaguesg7 reviewed management of 17 patients with partial transection of the anterior urethra due to low-velocity gunshot wounds and concluded that patients were best managed by aggressive wound debridement, corporeal repair, primary suture repair of the urethra, and placement of a suprapubic catheter. Strictures developed much less frequently with this approach (1 of 8) compared with suprapubic diversion and transurethral catheter stenting (7 of 9). In Ehildren, the majority of posterior urethral injuries may be managed nonoperatively. Grade I or I1 injuries, which may allow spontaneous voiding, are managed without surgery and without an indwelling urinary catheter. Patients who are unable to void are managed by insertion of a small, transurethral Foley catheter. Grade I11 injuries with minimal extravasation may also be managed by passing a small, transurethral Foley catheter under fluoroscopic guidance immediately after the retrograde urethrogram. If the catheter does not pass easily, however, a suprapubic tube should be placed. Options for repair of more complex posterior urethral injuries include primary surgical repair with anastomosis of the disrupted urethral ends, delayed primary surgical repair, primary surgical catheter realignment, primary endoscopic and radiologic realignment, or suprapubic cystostomy with delayed urethroplasty. Primary surgical repair involves evacuation of the pelvic hematoma, mobilization of the prostate and urethra, and direct end-to-end anastomosis between the prostatic and membranous urethra. Problems with this approach include increased risk of uncontrolled bleedin;" d u e to exploration of the injury site with release of the tamponade effect of the hematoma; increased risk of impotence due to dissection of the periprostatic and periurethral tissues; and increased risk of incontinence due to damage to the intrinsic urethral sphincter mechanism by dissection, mobilization, and debridement of torn urethral ends.51,53,56,57~108~1g5 TO minimize these complications, Mundy150 advocated delaying primary surgical repair
until 7 to 10 days after injury once the patient was more stable, the operative view was less obscured by bleeding, and before the onset of fibrosis. Primary surgical catheter realignment was first introduced by Ormond and Cothran in 1934 with multiple variations in technique over the ensuing y e a r ~ . ~ ~ ~ ~ ~ 7 " 1 0 7 Despite not requiring direct suturing of the disrupted urethral ends, this technique still requires an open procedure with entry into and evacuation of pelvic hematoma with all of the attendant risks of primary surgical repair. More recently, innovative combined transurethral and transvesical endoscovic and interventional radiologic techniques have been introduced to achieve primary alignment without the risk of explor,~~,~~~-~~2,~~ ing the disrupted ~ r e t h r a . ~ 7 , 4 9 , ~ ~Furthermore, because there is no manipulation of periprostatic tissues and no additional trauma to the cavernous nerves, there should be no additional risk of erectile dysfunction other than that caused by the injury itself. These minimally invasive techniques have produced encouraging results so far, but clinical experience is limited to small series. Postoperative outcomes of these small series indicate that 88% to 100% of patients are continent, 14% to 39% of patients have some degree of erectile dysfunction, and about half require subsequent internal urethrotomies. Concerns about the impact of primary open surgical repair or catheter realignment on potency and urinary continence led to the introduction of an alternative treatment approach, namely suprapubic cystostomy with delayed urethroplasty. First advocated by Johanson of Sweden in 1953, no attempt is made to explore the urethra but rather the urinary stream is simply diverted via a suprapubic cystostomy tube. A stricture is considered inevitable and is repaired several months later. This approach has gained widespread acceptance and is considered a standard approach to the management of complex posterior urethral disruptions. Advantages of this approach include avoiding entry into a fresh pelvic hematoma with risk of blood loss and infection, speed and simplicity of suprapubic tube insertion, and decreased incidence of i m ~ o t e n c eand incontinence due to avoidance of dissection of the prostate and urethra.73 Disadvantages include prolonged need for a suprapubic tube with risk of infection and stone formation as well as the nearly 100% risk for urethral strictures, which may be quite complex and difficult to repair even in the delayed setting.Io7 Tunc and colleagueslsg reviewed 77 cases of delayed repair of traumatic posterior urethral injuries and demonstrated adequate urethral continuity in 9596, postoperative incontinence in 9%, and postoperative erectile dysfunction in 16%. They concluded that delayed posterior urethroplasty is a successful treatment option with acceptable morbidity. After extensive literature review regarding different approaches to management of complex hosterGr urethral injuries, Holevar and associates" concluded that these injuries may be treated with either primary endoscopic realignment or suprapubic cystostomy with delayed urethroplasty with similar results. Urethral trauma in females is rare."J" The usual mechanism of injury involves pelvic fracture incurred
CHAPTER
during a motor vehicle accident. Straddle injury occasionally results in damage to the urethra. Female urethral injuries may be distal avulsion from the perineal attachment or proximal disruptions and lacerations. The latter type of injury is characteristically associated with other pelvic injuries, including vaginal and bladder neck lacerations. Perry and colleagues159 reviewed the evaluation of urethral injuries in females with pelvic fractures. Blood at the vaginal introitus mandates a meticulous vaginal examination. The urinary meatus must also be carefully examined and its patency confirmed by passage of a catheter. However, it is important to note that catheters can often be passed into the bladder even in the presence of a significant urethral injury. Development of vulva1 edema after removal of the catheter warrants prompt investigation. Because urethrography in young girls is difficult and unreliable, urethroscopy is the preferred diagnostic modality. Delays in diagnosis of urethral injury in girls occur frequently and have devastating consequences.159Such injury is misdiagnosed in about 50% of cases and can result in life-threatening sepsis and necrotizing fasciitis. Therefore, one should have a low threshold for performing urethroscopy when urethral injury is suspected in a young girl. Treatment is dictated by the extent and location of injury. Urethral injuries that extend into the bladder neck require meticulous repair with reapproximation of the bladder outlet and urethra. Such injuries are encountered about two thirds of the time.121,122,126,129 Associated vaginal injuries are repaired primarily. Urethral crush injuries that do not involve the bladder neck are managed by extended transurethral Foley catheterization (6 to 8 weeks) or, if necessary, suprapubic catheter drainage. Significant long-term complications associated with pediatric female urethral trauma are common and include urethral stenosis, urethrovaginal fistula, incontinence, and vaginal s t e n ~ s i s . ~ ~ Clearly every effort must be made to promptly detect and aggressively manage this uncommon injury.
External Genitalia Girls Blunt genital trauma in girls is fairly common. The presenting symptoms are usually the presence of blood in the underpants or on the perineum shortly after injury.l17 Blunt genital trauma most commonly results from straddle injury. The most common types of injury, in decreasing order of frequency, are lacerations or contusions of the perineal body, vagina, labia, urethra, and rectum. Due to the extreme difficulty of performing a thorough genitourinary examination in an awake, uncomfortable, anxious, and embarrassed child, the majority of patients are best evaluated in the operating room under general anesthesia. Indeed, as many as 76% of patients will have more extensive injuries than can be appreciated in the emergency department.l17 Management of female genital trauma is dictated by the type and extent of injury. Necrotic, contused tissue
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should be debrided. Lacerations are primarily repaired after hemostasis is achieved. Absorbable sutures are used to preclude the need for removal. Urethroscopy and proctoscopy may be necessary to more thoroughly evaluate the injury.
Boys The most common injury to the penis is iatrogenic injury during circumcision.80 Complications of circumcision include penile amputation, urethral fistulization, laceration of the glans penis, and inaccurate removal of the foreskin resulting in phimosis degloving injury. Most of these injuries are avoidable with use of proper technique. Penile injury resulting from blunt or penetrating trauma is rare in children. Urethral lacerations should be managed as described in the previous section. The findings of an expanding hematoma, palpable corporal defect, and excessive bleeding suggest cavernosal injuries. When possible, these injuries should be repaired primarily.17Urinary diversion with a suprapubic tube is occasionally necessary.79 The preferred method of management of gunshot wounds with a limited extent of injury is debridement of superficial wounds, repair of the cavernosal defects, and primary repair of the urethral injury.87 Penile erectile dysfunction (impotence) can occur after blunt pelvic and perineal trauma.149The dysfunction results from shearing of the penile blood vessels in the pelvis. Penile revascularization may restore potency.119 Priapism may also occur after blunt trauma. For this disorder, selective angiography is helpful to diagnose the injury and to embolize the arteriovenous fistula causing the priapism. Doppler ultrasonography is also useful to characterize and localize the lesion.lS8 Injury resulting from zipper entrapment of the penis can be addressed, in many cases, in the emergency department but may require a general anesthetic for release of the penis.20° Penile strangulation injuries due to constricting bands are managed by removal of the constricting band in as atraumatic a manner as possible. In children, hair tourniquets are common sources of constriction and may be quite difficult to remove. Severe strangulation injuries may result in necrosis of the distal penile skin, glans, cavernosum, or urethra. Conservative debridement and urinary diversion may be required.48 Scrota1 injuries may result from penetrating trauma, blunt trauma, or both. High-resolution ultrasonography is very useful in the evaluation of these injuries.1° Ultrasonography of penetrating injuries can identify testicular rupture and extratesticular soft tissue abnormalities as well as the presence and location of foreign bodies.110 This technique is also useful in distinguishing less serious injuries, such as scrota1 hematomas, hydroceles, and hematoceles, from surgical emergencies, such as testicular rupture and infarction. It should be noted that epididymal rupture is not as easily identified on ultrasonography.l55 Patients with hematoceles should be considered for exploration to evacuate the blood from the tunica vaginalis testis because this approach reduces morbidity and hastens recovery. Testicular disruption is managed by debridement and primary c l ~ s u r e . ~
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196. Werkman HA, Jansen C, Klein JP, e t al: Urinary tract injuries in multiply-injured patients: A rational guideline for the initial assessment. Injury 22:471, 1991. 197. Wessel LM, Scholz S,Jester I, et al: Management of kidney injuries in children with blunt abdominal trauma. J Pediatr Surg 2000;35:1326. 198. Wessells H, McAninchJW, Meyer A, et al: Criteria for nonoperative treatment of significant penetrating renal lacerations. J Urol 157:24, 1997.
199. Whitesides E, Kozlowdki DL: Ureteral injury from blunt abdominal trauma: Case report. J Trauma 1994;36:745. 200. Wyatt JB, Scobie WG: The management of penile zipper entrapment in children. Injury 1994;25:59. 201. Yale-Loehr AJ, Kramer SS, Quinlan DM, et al: CT of severe renal trauma in children: Evaluation and course of healing with conservative therapy. AJR Am J Roentgen01 1989; 152:109. 202. Zakin D: Perforation of the bladder by the intrauterine device. Obstet Gynecol Surv 1984;39:59.
Musculoskeletal Trauma Richard S. Davidson and Michelle S. Caird
Musculoskeletal trauma is the most common medical emergency in children. The number of cases continues to increase in association with the popularity of motor vehicles, all-terrain vehicles, and power lawn mowers. In a child with multiple injuries, optimal treatment requires a cooperating team of medical professionals with diverse specialties who understand the priorities of each team member. As in all other pediatric specialties, it is important to remember that children are not "little adults." Priority management need not compromise complete patient management. This chapter reviews the important differences between the musculoskeletal systems of children and adults, and it highlights the principles of evaluation and management in children with musculoskeletal injuries. The treatment of high-priority musculoskeletal injuries is specifically discussed, including open fractures, compartment syndrome, femoral neck fractures, mangled extremities, spine trauma, and suspected child abuse. For details on the management of specific musculoskeletal fractures and injuries of childhood, readers should refer to textbooks on children's f r a c t ~ r e s . l ~ , 2 ~ 2 ~
MUSCULOSKELETAL SYSTEMS OF CHILDREN AND ADULTS Differences in the musculoskeletal anatomy and biomechanics of children and adults determine the unique patterns of musculoskeletal injury seen in childhood. Injuries to growing bones are a double-edged sword: they can have a remarkable capacity for healing and remodeling, but they are also subject to the problems of overgrowth and growth disturbance, which can have lifelong consequences.
Anatomy The major anatomic distinctions of skeletally immature bones are the physis and the periosteum. Each long bone in a child contains the epiphysis, physis, metaphysis, and diaphysis (Fig. 19-1). The epiphysis is the area beyond the physis, or primary growth plate, which contains the
articular cartilage. The secondary center of ossification arises within the epiphysis and progressively enlarges as the cartilage ossifies during skeletal maturation. The physis provides longitudinal growth and converts the newly formed cartilage into bone in the metaphysis. The diaphysis, or shaft, is surrounded by periosteum, which generates new bone and provides circumferential bone growth. By adulthood, the growth plate closes, and there is limited potential for remodeling.
Biomechanics Skeletally immature bones are porous, less brittle, and better able to tolerate deformation than are mature bones. Pores stop the progression of a fracture line but weaken the bone under a compressive force. As a result, a greater variety of fractures is seen in children than in adults. A child's bone can bend without fracture (Fig. 19-2); it can buckle under compression;it can fracture like a "green stick," with an incomplete crack on the tension side and a bend on the compression side; and it can fracture completely. The thick periosteum that surrounds the diaphysis of the bone can minimize or prevent displacement of diaphyseal fractures. The periosteum tears on the tension side of a fracture but often remains intact on the compression side. The intact periosteum can then function as a hinge or a spring, increasing deformity. Depending on the injury, the periosteum may simplify or complicate reduction of a fracture (Fig. 19-3). In the complex of bone, ligaments, and cartilage in a child, the physis is the weakest part and therefore is the most likely site of failure. An angular force to a joint in a young child is most likely to cause a fracture along the growth plate, whereas in an adolescent or an adult, a ligamentous injury or dislocation would occur. Frankel and Nordin15 provide extensive information on the biomechanics of bone. In a fall on an outstretched hand, a young child is unlikely to sprain a wrist; more commonly, a child sustains a fracture with a displaced distal radius growth plate. Similarly, instead of spraining an ankle, a child is more likely to sustain a physeal fracture of the distal fibula. Under low-energy forces, these injuries are unlikely to lead to growth disturbance.
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. - .
Anatomy of the child's bone.
Articular cartilage Epiphysis Ossification center Growth plate
Physis
Primary and secondary spongiosa
Metaphysis
Cancellous bone Diaphysis Compact bone
The Salter-Harris classification system of fractures involving the physis can guide proper management (Fig. 194).28 Type 1 fractures extend along the entire physis. Type 2 fractures involve part of the growth plate and part of the metaphysis; these fractures are seldom associated with growth arrest except when they occur in the distal femur
i
d
........ ............ ...... ....... ....... ...............
Bend
Buckle
Greenstick
,
- -
Fracture types in children. (From Rang M: Children's
Fractures. Philadelphia, JB Lippincott, 1974.)
and proximal tibia. Type 3 fractures involve part of the physis and pass across the epiphysis into the joint. Because of the possibility of incongruity of the joint, type 3 fractures often require open reduction and fixation. Type 4 fractures occur longitudinally, crossing the physis from the metaphysis into the epiphysis. This type of fracture is commonly associated with subsequent formation of a bony bar across the physis, which causes partial growth arrest with subsequent angulation. Open reduction and internal fixation are usually required for type 4 fractures, because joint incongruity and fusion across the physis are common. Type 5 fractures are diagnosed retrospectively, when all or part of the physis fails to grow. It is hypothesized that injury to the physis results from direct compression or local vascular insult. Growth disturbance may result in loss of longitudinal growth or angular deformities. Damage to the physis in high-energy injuries can lead to asymmetrical growth in any of the fracture types.
The physiologic differences between the musculoskeletal systems of children and adults are found in healing and remodeling. Growing bones are also at risk for the unique problems of overgrowth and growth disturbance. Healing in children is rapid and age dependent. A newborn may achieve clinically stable union of a fracture in 1 week, whereas a similar fracture in an adolescent may take 6 weeks to heal. In children, the rapid healing process partially results from the thick periosteum, which may form its own bone bridge. Except for displaced
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= closed hinge
-
.
A, In children, the intact periosteum of a fracture prevents reduction by traction. B, By retracing the path of injury, the fracture can be reduced. C, Closing the hinge. D, A cast with three-point molding holds the hinge closed and keeps the fracture reduced. (From Rang M: Children's Fractures. Philadelphia, JB Lippincott, 1974.)
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intra-articular fractures or fractures with gross soft tissue interposition, nonunion of fractures is rare in children. The bones of children have great potential for remodeling, but the limitations must be understood. Remodeling potential is better in younger patients, in deformities closer to the physes, and where angulation is in the plane of motion of the nearestjoint. Remodeling does not effectively correct angulation perpendicular to joint motion or rotation. These deformities should be reduced before healing begins (Fig. 19-5). Growth stimulation may follow fractures of long bones. This can be especially apparent in the lower extremity. The inequality in leg length that results from such stimulation is less important in children younger than 2 years and in adolescents. For children of other ages, an average l c m increase can be expected in femur fractures.11,29,3* Although discrepancies in leg length are unpredictable, it is often possible to reduce the ultimate inequality by allowing the fracture to heal with a 1-cm overlap in an otherwise anatomic alignment. Most of the growth stimulation occurs within the first year after injury, so follow-up visits for 1 year are recommended, even after uneventful healing. Damage to the physis can produce severe shortening, angular deformity, or both. Although this may be caused by the initial trauma, it can also result from failure to obtain anatomic reduction of a physeal fracture or from repeated or overzealous attempts at reduction (Fig. 19-6). When major (>2 cm) limb length discrepancies in the lower extremities are evident, treatment depends on the amount of remaining skeletal growth and the projected difference in limb lengths. Treatment may involve timed ablation of the growth plate on the normal limb, shortening osteotomy of the normal limb, or lengthening of the short limb. Angular deformities can also be addressed, taking into consideration the patient's skeletal age and the severity of the deformity.
EVALUATION OF MUSCULOSKELETAL INJURIES Clinical Assessment The initial assessment of children with multiple injuries may be difficult. Details of the incident may be missing, and the patient's history may be incomplete. The Advanced Trauma Life Support (ATLS) system of assessment involves a primary evaluation to identify and immediately address life-threatening injuries, followed by a secondary
Salter-Harris classification of epiphyseal fractures. Type 1 involves the entire physis. Type 2 involves part of the growth plate and part of the metaphysis. Type 3 involves part of the physis and passes across the epiphysis into the joint. Type 4 is longitudinal, crossing the physis from the metaphysis into the epiphysis. Type 5 is diagnosed retrospectively when the physis fails to grow. See text for clinical implications of each fracture type.
7
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TRAUM Slwen2year m with eigh~degrees of re'moq :
a forearm fracture over a 9period. A to C, An teroplOStC plane. D t o E Late ral plane
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Anteroposterior radiograph of the knees in a 13-year-old boy shows growth disturbance of the left distal femoral growth plate after a fracture (on right in photo).
children, cannot provide a history,judicial use of special diagnostic studies can be critical.
evaluation to find and treat other significant injuries. The injuries identified in the secondary evaluation must also be treated in a timely manner to prevent devastating lifelong consequences. Postponing the management of serious musculoskeletal injury for an extended period can be associated with a poor prognosis for return to normal function. The musculoskeletal examination begins with observation of the patient for sites of deformity, swelling, contusions, abnormal color, and open fractures. If a fracture is suspected, confirmatory diagnostic studies may be integrated into the complete physical examination. If such studies cannot be done, it must be assumed that a fracture exists, and the suspected site must be splinted until the fracture is confirmed or ruled out. Splinting may also reduce discomfort and limit further damage to soft tissue. A complete neurovascular examination is essential in any case of suspected limb or spine injury. When an uncooperative patient will not allow an adequate physical examination or, in the case of comatose patients or preverbal
A
-
.
Radiographic Assessment Plain radiography is the first and most widely used test to identify skeletal injury in children, but it can also be a major source of misdiagnosis in this age group. Cartilage, which makes up a large percentage of the child's skeleton, is radiolucent but can fracture. Ossification centers appear at different ages in different locations. The timing of their appearance a i d their location vary greatly and can suggest fractures. Confusion most frequently occurs in the elbow, knee, and cervical spine. Comparison of the injured and uninjured limbs can be useful. Plain radiographic soft tissue signs, such as the posterior fat pad-sign in elbow injuries, are associated with a high likelihood of underlying fracture (Fig. 19-7).30
B
Lateral elbow radiographs of a 2-year-old boy with a mildly displaced supracondylar humerus fracture and posterior fat pad sign (A) and a normal age-matched elbow (B).
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A number of imaging studies are available for the assessment of pediatric musculoskeletal injuries and are injury and age specific. Radiographs may confirm fractures. Ultrasonography is a readily available, noninvasive imaging test that can be used to evaluate the unossified epiphysis, especially in injuries about the elbow.8 Magnetic resonance imaging (MRI) may also be helpful, especially in evaluating the injured spine, but it may require general anesthesia in a young or uncooperative patient. Computed tomography (CT) scanning is useful in periarticular fractures in children approaching skeletal maturity. For exarnple, ankle physeal fractures in children with partially closed physes are best delineated with CT scan.22 Arteriography may be required to assess vascular injury associated with a fracture. Rarely, proximal tibia1 physeal fractures and distal humerus fractures through the supracondylar region can be associated with disruption of the blood supply to the distal limb. These injuries require emergent treatment, and an intraoperative arteriogram may also be needed. Joint aspiration can identify blood and fat, which indicate an intra-articular fracture that would not be identified on radiographs. Finally, arthrography and arthroscopy may define intra-articular injury to the cartilage and ligaments.
MANAGEMENT OF MUSCULOSKELETAL INJURIES Immediate Treatment Priority treatment cannot interfere with complete treatment of an injured child. Proper timing and coordination of management with other disciplines are imperative. Traction or splinting often adequately stabilizes the musculoskeletal injury until other tests and treatments have been completed. Immobilization may also reduce the need for pain medications, which can mask the symptoms of other disorders, such as intra-abdominal injuries, and inhibit diagnosis. Although there are many types of splints, ranging from plaster to traction bows, the basic principles of fracture management remain the same. The injured part should be splinted as it is found, and the joints above and below the injury should be immobilized without compromising the circulation of the soft tissues. Portable traction splints or custom-molded, well-padded plaster or fiberglass splints can be used in the initial management of fractures. Failure to immobilize the fracture can cause further soft tissue damage from sharp bone ends, crushing of entrapped neurovascular elements, or reopening of clotted vessels.
The choice of fixation method depends on the child's age, the location of the fracture, the presence and extent of soft tissue injury, and the presence of multitrauma. Metaphyseal undisplaced or impacted fractures are likely to heal faster than diaphyseal or displaced fractures. Fractures with devitalized bone or soft tissues take longer to heal. Radiographic evaluation in conjunction with clinical judgment and experience is needed when determining the healing time of fractures in children. Fragments of bone must be held together until they are sufficiently strong to withstand the forces specific to the bone. A satisfactory position must be obtained, without harming adjacent tissue, before the fracture becomes fixed. Fractures in newborns and infants begin to heal within a few days, but fractures in adolescents can be moved freely for 10 to 14 days. Excessive cast padding, resolution of swelling, or a poorly applied cast may permit progressive malposition within the cast. Fractures should be followed with frequent radiographs until union is secure, to avoid displacement. Unstable fractures should be imaged before consolidation to evaluate for loss of alignment. This allows for easy repeat reduction. In children, the thick periosteum tears on the tension side of a fracture but often remains intact on the compression side. The intact periosteum can then function as a hinge, increasing the success of closed reduction of displaced fractures by three-point molding (see Fig. 19-3). Reduction must be performed gently. Forceful and repeated manipulation of physeal fractures can produce iatrogenic damage and growth disturbances. Entrapment of soft tissue occasionally prevents reduction of an otherwise stable fracture (Fig. 19-8) and requires open reduction and immobilization in a cast. In some cases, internal fixation with crossed pins, plates and screws, intramedullary nails, or external fixation with pins in metal outriggers or rods may be useful (Fig. 19-9). The benefits of each of these devices must be weighed against the future need for operative removal and the possible disturbance to the growth plate. Specific indications for internal and external fixation may include fractures with significant soft tissue injury, fractures in
Radial nerve
Definitive Fracture Management Adequate stabilization of fracture fragments prevents further soft tissue injury, frequently decreases pain, and facilitates wound care and patient mobilization. Techniques of definitive stabilization in children include splinting, casting, skeletal traction, external fixation, pinning, flexible intramedullary nailing, and plating.
, .
. - Supracondylar elbow fracture. Soft tissue may become
entrapped between bone fragments in these types of fractures.
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,
.
..
Anteroposterior radiographs of right femur
fractures fixed with a variety of fixation methods. A, SalterHarris type 2 fracture with crossed pins in a 9-year-old girl. B, Intertrochanteric fracture with screws and side plate in a 7-year-old boy. C,Transverse shaft fracture with elastic intramedullary nails in a 13-year-old boy. D, Subtrochanteric fracture with external fixator in an 8-year-old boy.
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children with closed head injury, those associated with neurovascular injury, and fractures that fail nonoperative treatment. Comminuted and oblique fractures and those with complete tears of the periosteum may be too unstable for cast immobilization. In cases of intra-articular fractures, such as Salter-Harris types 3 and 4, open reduction and internal fixation are frequently necessary to avoid incongruity of the joint or growth disturbances. Fractures associated with neurovascular injury requiring repair should be stabilized first.
HIGH-PRIORITY MUSCULOSKELETAL INJURIES Although many musculoskeletal injuries in children can be treated on an urgent rather than an emergent basis, the discussion of some high-priority musculoskeletal injuries in children is warranted. Even in nonurgent cases, it is important to remember that injuries to growing bones can have lifelong consequences.
Open Fractures and Traumatic Arthrotomies Open fractures are true orthopedic emergencies because a delay in treatment can lessen the chance of saving the limb. These injuries frequently result from high-energy trauma. The fractures communicate with the outside environment and are at increased risk for infection. The cornerstones of management include recognition, administration of appropriate antibiotics, stabilization of the fracture, and prompt irrigation and adequate debridement of wounds. Open fractures may require multiple surgical procedures to achieve adequate soft tissue coverage and fracture healing. When a laceration or abrasion is noted in proximity to a fracture, an open fracture must be suspected. Radiographic evidence of air shadows around the fracture may confirm the diagnosis. A sharp fragment of bone can tear through the skin, and the elastic properties of a child's bone can readily straighten the fracture fragments after the force is discontinued. The protruding point of bone can then draw back under the skin, taking debris and bacteria with it into the deep tissues. Minimal signs of injury do not necessarily mean a minimal chance of infection. Wounds should not be probed in the emergency department, where the risk of iatrogenic contamination is high and the likelihood of adequate debridement is low; if necessary, such procedures should be done in the operating room. The Gustilo system classifies open fractures according to the size and extent of soft tissue damage." Type I is an open fracture with a clean wound smaller than 1 cm. Type I1 is an open fracture with a laceration longer than 1 cm without extensive soft tissue damage, flaps, or avulsion~.Type I11 is an open fracture with extensive soft tissue injury and is further divided into three subtypes; type IIIA has adequate soft tissue coverage of a fractured bone despite extensive laceration of soft tissue, type IIIB involves extensive soft tissue injury with periosteal stripping that requires grafting or a flap for coverage, and type IIIC is an open fracture associated with arterial
injury that requires repair. The risk of infection is related to the severity of the injury: 2% in type I open fractures, 2% to 10% in type I1 open fractures, and up to 50% in type I11 open fractures.'7 Wounds should initially be dressed with sterile gauze soaked with antiseptic. Hemorrhage should be controlled by direct pressure. Patients should receive tetanus prophylaxis and antibiotics at recognition of the injury. Firstgeneration cephalosporins cover the gram-positive organisms found in type I and type I1 injuries. An aminoglycoside is added for type I11 injuries, and ampicillin or penicillin is added for farm injuries to fight potential anaerobic infection. Each wound must be adequately debrided and copiously irrigated with the patient under general anesthesia. Wounds may need to be re-evaluated after 2 or more days for additional debridement. Primary closure or delayed primary closure may be appropriate for some open fractures, whereas grafting or flap coverage is needed for larger soft tissue defects. The goal of debridement is removal of devitalized tissue to avoid the catastrophic consequences of an infection, which may include limb loss or chronic osteomyelitis. Adequate immobilization is necessary for soft tissue healing. For small lacerations, immobilization in a cast that has been windowed for wound inspection may suffice. For larger lacerations, external fixation is often necessary to provide stable fixation with access to the wound. Joint penetration by a foreign body can cause a diagnostic dilemma. Radiographs can be helpful if they reveal an "air arthrogram." Injection of sterile normal saline into the joint can also be diagnostic. If the liquid exits the wound or laceration, joint penetration has occurred and requires imgation and debridement in the operating room.
Compartment Syndrome Compartment syndrome occurs when pressure is elevated within a confined fascia1 space. This causes circulatory compromise and can progress to tissue necrosis. Closed fractures and crush injuries with associated edema may cause compartment syndrome. Forearm and leg compartments are most often involved. Ischemic injury starts when tissue pressure is 30 mm Hg below mean arterial pressure.Z0 The pressure within the compartments surrounding a fracture should be measured if compartment syndrome is suspected. Commercially available tissue pressure monitors or other measuring devices, including electronic arterial pressure monitoring devices, can be used. The diagnosis of compartment syndrome in children can be difficult. Adults with compartment syndrome verbalize extreme pain and demonstrate pain with passive stretch of the muscles within the affected compartments, whereas children often have difficulty communicating their discomfort. The classic signs of compartment syndrome are the five Ps-pain, pallor, paresthesia, paralysis, and pulselessness. These signs are rather unreliable in children and may manifest late in the process. An increasing analgesia requirement is an important sign of compartment syndrome in children.'
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With early recognition and timely management, full recovery can be achieved. All external compression is removed from the limb, compartment pressures are measured, and, if elevated, the compartments are surgically decompressed. In the forearm, volar and dorsal fasciotomies are required. In the leg, all four compartments (anterior, lateral, deep posterior, and superficial posterior) must be released. This can be accomplished with two incisions. Without prompt intervention, the result is irreversible damage to soft tissues with loss of function, subsequent contractures, and d e f ~ r r n i t y . ~ ~
Femoral Neck Fracture Although rare in children, fractures of the femoral neck and intertrochanteric regon require attention (Fig. 19-10). These fractures frequently result from high-energy impact, including traffic accidents and falls from a height,6 and are associated with a high complication rate from avascular necrosis, coxa vara, nonunion, delayed union, . ~ ~upper ~ end of the and premature physeal c l o s ~ r eThe femur lies within the joint capsule. After roughly 4 years of age, blood is supplied primarily by retinacular vessels that course from distal in the neck to proximal in the head. Delay in treatment of a fracture at the neck is associated with increased risk of avascular necrosis of the head and destruction of the joint and can cause lifelong disability. Early decompression of the hip joint, reduction of the fracture, and internal fixation can minimize the complication^.^
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neurovascular structures. Some limbs may be unsalvageable owing to extensive damage, some can be reconstructed with a resulting dysfunctional limb, and others can be salvaged with a good outcome. The Mangled Extremity Severity Score rates injuries based on objective criteria at initial presentation, including skeletal and soft tissue injury, limb ischemia, shock, and patient age. Although it originally developed in a primarily adult pop~lation,~s can be a useful adjunct to managing lower extremity trauma in children.12 Segmental bone loss is rare in children and does not necessitate amputation. If periosteum can be preserved, the potential to reform bone is extensive. P r o ~ e rtechniquis of debridement and stabilization, along k t h adequate time, may produce good results in children. External fixation techniques can allow for bone transport and osteogenesis to replace lost bone and axial deformity. Power lawn mower injuries are uncommon, preventable injuries that cause significant morbidity in children.lOJ3.23 Direct contact with the blade leads to laceration of tissue, amputation, or devitalizing shredding of the extremity. Such injury can result in damage to the vasculature and growth plate, joint stiffness, infection, or amputation. If salvage is undertaken, treatment follows that of open fractures. In the case of amputation, preservation of bony length and retention of all viable soft tissue are important for the ultimate functional outcome. Amputation through the diaphysis of a child's bone frequently results in overgrowth of the bony stump through the skin. This is especially true of the fibula, tibia, and humerus and can necessitate cutting back the bone every few years.
Mangled Extremities Severely traumatized or mangled extremities in children must be assessed and treated through a multidisciplinary approach on a case-bycase basis. They may involve extensive injury to or segmental loss of skin, muscle, bone, and
, - Anteroposterior pelvis radiograph of a l4year-old boy shows a left femoral neck fracture that required internal fixation.
Spine Trauma Injuries of the spine in children can be divided into those affecting the cervical spine and those in the thoracic and lumbar spine (see also Chapter 21).Just as in other parts
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A pediatric backboard should have a torso mattress or an occiput recess to accommodate the child's relatively large head and avoid potentially dangerous cervical spine flexion. of the body, patterns of injury to the spine in children differ from those in adults. Radiographic imaging can be challenging. Principles of immobilization are different for children as well. Cervical spine injuries in children differ from those in adults.' Children have greater ligamentous laxity and weaker neck musculature. In addition, they have large heads relative to body size; this effect is more pronounced in younger children. Cervical spine injuries in children tend to occur higher in the neck and can be primarily ligamentous or apophyseal without bony fracture.lg When immobilizing a child on a backboard, the relatively large head should be considered; a child's backboard splint should have a recess for the occiput or a mattress for the torso to maintain the alignment of the cervical spine, avoiding flexion of the neck (Fig. 19-11).zl Radiographic evaluation of the pediatric cervical spine can be challenging. Pseudosubluxation, or the apparent forward displacement of C2 on C3 and, less commonly, C3 on C4, is a welldescribed plain radiographic finding in normal children younger than 8 years.Wther sources
A
of difficulty in interpreting radiographs include incomplete ossification, epiphyseal variation, and elasticity of the disks and vertebral bodies relative to the neural structures, which allows extensive injury to the soft tissues without evidence of abnormality on plain radiographs or SCIWORA (spinal cord injury without radiographic abnormality). MRI is helpful in evaluating soft tissues in cases of possible cervical spine ligamentous injury in children.14 Injuries to the thoracic and lumbar spine are rare in children. The growth of vertebral bodies occurs through the apophyses or growth centers on the cranial and caudal ends of the bodies. With compression injury, adolescents are at risk for traumatic displacement of the vertebral apophysis and the attached disk into the spinal canal, especially in the lumbar region." Symptoms are similar to those seen in central disk herniation, including muscle weakness and absent reflexes. This injury requires recognition and emergent surgical decompression. Lap-belt injuries occur in children when they violently flex over the seat belt and the posterior spine is distracted." A fracture propagates from the posterior portions of the vertebra to the disks or vertebral body in the front (Fig. 19-12). In addition to the vertebral injury, children can sustain abdominal and aortic injuries. Such injuries should be suspected when an abdominal contusion, or the telltale seat-belt sign, is evident in a trauma patient. These injuries require immobilization and possible internal fixation if the injury is ligamentous.
B
Lap-belt injury of L4 in a 15-year-old girl without neurologic injury. A, Lateral lumbar spine radiograph shows fra L4 body and the I~osteriorspine. B, Sagittal magnetic resonance image of the 11umbar spine shows the extensive bony and soft tissue
both the
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Child Abuse The maltreatment of children is a complex medical and social problem, and its recognition is key to management (see also Chapter 24). Fractures before walking age in the absence of metabolic disease or child abuse are rare. Fractures are the second most common manifestation of child abuse after skin lesi0ns.2~Suspicion of abuse must be raised when there is a discrepancy between history and injury, when multiple fractures are present in different stages of healing, or when bruising, metaphyseal fractures, or long bone fractures appear in children younger than 1 year.3.26 No social stratum is free of this problem.
REFERENCES 1. Akbarnia B, Torg JS, Kirkpatrick J: Manifestations of the battered child syndrome. J Bone Joint Surg Am 1974; 56:1159. 2. Bae DS, Kadiyala RK, Waters PM: Acute compartment syndrome in children: Contemporary diagnosis, treatment, and outcome. J Pediatr Orthop 2001;21:680. 3. Blakemore LC, Loder RT, Hensinger RN: Role of intentional abuse in children 1 to 5 years old with isolated femoral shaft fractures. J Pediatr Orthop 1996;16:585. 4. Canale ST, Bourland WL: Fracture of the neck and intertrochanteric region of the femur in children. J Bone Joint Surg Am 197'7;59:431. 5. Cattell HS, Filtzer DL: Pseudosubluxation and other normal variations in the cervical spine in children. J Bone Joint Surg Am 1965;47:1295. 6. Cheng JCY, Tang N: Decompression and stable internal fixation of femoral neck fractures in children can affect the outcome. J Pediatr Orthop 1999;19:338. 7. Copley LA, Dormans JP: Cervical spine disorders in infants and children. J Am Acad Orthop Surg 1998;6:204. 8. Davidson RS, Markowitz RI, Dormans JP, et al: Ultrasonographic evaluation of the elbow in infants and young children after suspected trauma. J Bone Joint Surg Am 1994;76:1804. 9. Davison BL, Weinstein SL: Hip fractures in children: A long-term follow-up study. J Pediatr Orthop 1992;12:355. 10. Dormans JP, Azzoni M, Davidson RS, et al: Major lower extremity lawn mower injuries in children. J Pediatr Orthop 1995;15:78. 11. Edvardsen P, Syversen SM: Overgrowth of the femur after fracture of the shaft in childhood. J Bone Joint Surg Br 1976;58:339. 12. Fagelman MF, Epps HR, Rang M: Mangled extremity severity score in children. J Pediatr Orthop 2002;22:182. 13. Farley FA, Senunas L, Freenfield ML, et al: Lower extremity lawn-mower injuries in children. J Pediatr Orthop 1996;19:669. 14. Flynn JM, Closkey RF, Mahboubi S, et al: Role of magnetic resonance imaging in the assessment of pediatric cervical spine injuries. J Pediatr Orthop 2002;22:573.
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15. Frankel VH, Nordin M: Basic Biomechanics of the Skeletal System. Philadelphia, Lea & Febiger, 1980. 16. Green NE, Swiontkowski MF: Skeletal Trauma in Children, 3rd ed. Philadelphia, WB Saunders, 2003. 17. Gustilo RB, Anderson JT: Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones. J Bone Joint Surg Am 1976;58:453. 18. Helfet DL, Howey T, Sanders R, et al: Limb salvage versus amputation: Preliminary results of the mangled extremity severity score. Clin Orthop 1990;256:80. 19. Henrys P, Lyne ED, Lifton C, et al: Clinical review of cervical spine injuries in children. Clin Orthop 1977; 129:172. 20. Heppenstall RB, Sapega AA, Scott R, et al: The compartment syndrome: An experimental and clinical study of muscular energy metabolism using phosphorus nuclear magnetic resonance spectroscopy. Clin Orthop 1988; 226:138. 21. Herzenberg JE, Hensinger RN, Dedrick DK, et al: Emergency transport and positioning of young children who have an injury of the cervical spine: The standard backboard may be hazardous. J Bone Joint Surg Am 1989;71:15. 22. Karrholm J, Jansson LI, Laurin S: Computed tomography of intraarticular supination-eversion fractures of the ankle in adolescents. J Pediatr Orthop 1981;1:181. 23. Loder RT, Brown KL, Zaleske DJ, et al: Extremity lawnmower injuries in children: Report by the Research Committee of the Pediatric Orthopaedic Society of North America. J Pediatr Orthop 1997;17:360. 24. McMahon P, Grossman W, Gaffney M, et al: Soft tissue injury as an indication of child abuse. J Bone Joint Surg Am 1995;77:1179. 25. Ogden JA: Skeletal Injury in the Child, 3rd ed. New York, Springer, 2000. 26. Rex C, Kay PR: Features of femoral fractures in nonaccidental injury. J Pediatr Orthop 2000;20:411. 27. Rockwood CA Jr, Wilkins KD, Beaty JH, et al: Fractures in Children, 5th ed. Philadelphia, Lippincott Williams & Wilkins, 2001. 28. Salter RB, Harris WR: Injuries involving the epiphyseal plate. J Bone Joint Surg Am 1963;45:587. 29. Shapiro F: Fractures of the femoral shaft in children: The overgrowth phenomenon. Acta Orthop Scand 1981; 52:649. 30. Skaggs DL, Mirzayan R: The posterior fat pad sign in association with occult fracture of the elbow in children. J Bone Joint Surg Am 1999;81:1429. 31. Smith WS, Kauffer H: Patterns and mechanisms of lumbar injuries associated with lap seat belts. J Bone Joint Surg Am 1969:51:239. 32. Stephens MM, Hsu LC, Leong JC: Leg length discrepancy after femoral shaft fractures in children: Review after skeletal maturity. J Bone Joint Surg Br 1989;71:615. 33. Techakapuch S: Rupture of the lumbar cartilage plate into the spinal canal in an adolescent: A case report. J Bone Joint Surg Am 1981;45:481. 34. Whitesides TE, Heckman MM: Acute compartment syndrome: Update on diagnosis and treatment. J Am Acad Orthop Surg 1996;4:209.
Hand, Soft Tissue, and knvenomation lnjuries Michael L. Bentz and Delora Mount
Evaluation of pediatric hand and soft tissue injuries requires a systematic approach that includes all relevant organ systems at the site of trauma.' A high index of suspicion is necessary to make an accurate diagnosis and exclude subtle problems, particularly in toddlers and infants who are unable to cooperate with a detailed examination. Injuries are triaged according to their threat to life. After such triage has taken place, the more peripheral and often more dramatic and distracting injuries can be better defined.Vhe history is important to define baseline function, previous injuries, right- or left-hand dominance, and the mechanism and timing of injury. The initial physical examination must define vascularity and perfusion because an ischemic or poorly perfused extremity necessitates emergent surgical intervention. Other findings can be handled in a less urgent fashion, after an orderly assessment is complete. The patient should be examined in a well-lighted area with the parents present to exert a calming influence over a frightened child and thus increase the reliability of findings. This chapter focuses on the acute evaluation and management of hand, soft tissue, and envenomation injuries to provide a foundation for the accurate triage of injured children.5.14
HAND AND SOFTTISSUE INJURIES Evaluation Vascularity The goal of the initial examination is to determine the presence or extent of vascular injury, hypoperfusion, or ischemia. Symptoms of ischemia include pallor, paresthesia, paralysis, pain, and lack of pulse. The digits should be pink and warm if the patient has not had hypothermic exposure or proximal tourniquet application. Normal capillary refill time is 3 seconds and is most accurately tested by compressing the lateral aspect of the distal phalanx adjacent to the nail plate. A delayed refill time indicates impaired arterial inflow, whereas a rapid refill
time suggests venous hypertension or insufficiency. The pulse should be palpated bilaterally at the radial, ulnar, and brachial arteries. Percutaneous Doppler ultrasonography can be used to qualitatively and quantitatively define inflow if the pulse cannot be detected or if it is asymmetrical. Allen's test is important to define the relative contributions of the radial and ulnar arteries to the palmar arches of the hand. The ulnar artery is the dominant source of inflow to the hand and continues into a patent palmar arch in 85% of uninjured hands.' Significant bleeding noted during the initial evaluation is managed by firm manual compression or, if the time until definitive intervention is expected to be prolonged, by proximal tourniquet application. A hemostat or clamp should not be placed blindly into the wound, because lack of blood flow may injure adjacent neural structures. Impaled or retained foreign objects should be left in situ until definitive management is possible because they may staunch the flow of blood from a vascular injury.
Peripheral Nerves Peripheral nerves should be evaluated after vascular inflow has been assessed. Isolated nerve injuries cause predictable neurologic deficits that manifest as abnormalities in sensation or motor function, depending on the location of injury.18 Vascular injuries can also cause neurologic deficits, particularly in subacute wounds; therefore, the evaluation of nerve and vascular injuries should generally occur in tandem. A clear concept of cross-sectional anatomy is helpful in visualizing potential at-risk structures. Evaluating the nerve function at the distal aspect of the hand can be used to screen for a more proximal nerve injury. The median nerve is responsible for sensation to the three and a half volar radial digits. The function of this nerve can be tested by a pinprick or, more objectively, by two-point tactile discrimination. Median nerve motor function can be tested by palpating the contraction of the abductor pollicis brevis and opponens pollicis muscles as the patient forms an "0"with the index finger
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The ability to form an "0'' with the index finger and thumb, Mnth palpable contraction of the thenar muscles , indicates an! intac median nerve.
and thumb (Fig. 20-1). The ulnar nerve supplies sensation to the one and a half ulnar digits. Motor function of this nerve is most accurately tested by palpating the contraction against the force of the first dorsal interosseous muscle while the fingers are spread (Fig. 20-2). There is no radial nerve motor innervation of the intrinsic hand muscles, so the motor function of the radial nerve is best screened by wrist and digit extension (Fig. 20-3). The radial nerves provide sensation to the three and a half dorsal radial digits of the hand to the level of the distal phalanges, although overlap is common. Serial examination can be quite helpful, and cooperation and a focused effort are essential for a reliable evaluation. Further, neurologic findings associated with compartment syndrome evolve over time and may not be obvious during the initial examination.l3
Digit spread with palp; traction of the first dorsal interosseous consistent with an intact ulnar nerve.
conscle is
Skeleton, Tendons, and Ligaments Although some skeletal injuries are obvious on routine examination, most require radiographic evaluation. Physical examination findings of fracture include deformity, crepitus, ecchymosis, pain, instability, and swelling. Anteroposterior, lateral, and oblique radiographs should be obtained for all but the most minor injuries to evaluate for fractures, dislocations, and foreign objects. Familiarity with the Salter-Harris classification of pediatric fractures is important because the specific fracture patterns offer prognostic information relevant to subsequent growth (see Chapter 19).'6,23 The presentation of frache tures has been well d o ~ u m e n t e d . ~ 2 . * Texamination and radiographic appearance are combined to accurately describe the fracture. Open fractures have an associated
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full-thickness soft tissue injury, whereas closed fractures do not. Simple fractures result in two bone fragments, whereas comminuted fractures involve several fragments. Greenstick fractures involve one cortex and are particularly relevant in children because of their malleable bones. The description of a fracture should also include information regarding length (shortened, elongated, normal), angulation (volar, dorsal, radial, ulnar), rotation (present or absent), and displacement as a percentage of normal alignment. Tendon injuries can be very difficult to diagnose, particularly in young or uncooperative children. In such cases, surgical exploration is necessary to definitely confirm certain injuries. The posture of the hand at rest gives information regarding tendon integrity. In a relaxed position, the hand should form a gentle cascade; this position results from passive tension of the tendons. With compression of the distal forearm, all digits should adopt flexion posturing as a result of the tenodesis effect. A digit that remains extended out of the cascade suggests
disruption of the flexor mechanism (Fig. 20-4). The flexor digitorum superficialis tendon to each of the four fingers is tested by holding the adjacent digits in a fixed position and allowing metacarpophalangealjoint flexion (Fig. 20-5). The flexor digitorum profundus and flexor pollicis longus tendons are evaluated by holding the middle phalanx and observing distal interphalangeal joint flexion. Ligament injuries can be difficult to diagnose, particularly in the presence of associated soft tissue or skeletal injuries.Z4 Abnormal joint stability is an indicator of disruption of the 1igaments.lZ If the opposite side is uninjured, joint stability should be compared with that side as an indicator of preinjury status. Plain and stress radiographs of an avulsion fracture at the site of ligament insertion can confirm clinical findings.
Soft Tissue A thorough determination of soft tissue injuries is important for a knowledgeable evaluation of wound healing,25 Forearm compression has failed to cause flexion of the index finger in this patient; this suggests flexor mechanism discontinuity to the index finger.
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Function of the flexor digitorum superficialis tendon is tested by demonstrating isolated metacarpophalangeal and proximal interphalangeal joint flexion. Flexor digitorum profundus tendon function is tested by holding the middle phalanx fixed and observing distal interphalangeal joint flexion.
but even more so for the evaluation of long-term function and outcome of primary or secondary reconstructive surgery. The amount of soft tissue present in the area of a wound determines the feasibility of primary repair of vascular, neural, and osteoligamentous injuries, and an adequate amount is required for proper healing. The size (measured objectively),shape, location, and general configuration of each wound is recorded, and the mechanism of injury and preinjury status of the patient are established. Obvious foreign objects are removed, although projectiles impaled through an extremity are left in situ until they can be managed definitively. Exposed vital structures as well as associated fractures and tendon injuries are noted.
Early Treatment Vascular Ischemia is one of the few surgical emergencies associated with upper limb trauma. Revascularization is a top priority after the correction of life-threatening injuries. Because irreversible changes start to occur after 4 hours of ischemia, expeditious surgical intervention is mandatory, especially if the ischemic tissue involves muscle. Primary vascular repair is the most effective procedure and is ideally accomplished by debridement, mobilization, and primary anastomosis of injured segments. Reversed vein grafts, which are frequently done with foot, forearm, saphenous, or cephalic veins, should be used liberally if tension or lack of tissue prevents easy approximation of adjacent segments. In general, all arteries and veins proximal to the elbow should be repaired. Repair of arterial injuries below the elbow should also be considered to prevent cold intolerance; however, only about half of these repairs remain patent.10 If necessary, the radial artery can be ligated primarily. Once repairs are complete, fasciotomy should be considered if ischemia has been prolonged,
soft tissue damage is significant, or adequate postoperative monitoring is not available.l~eria1examination should then be pursued in an effort to make an early diagnosis of recurrent ischemia or postsurgical thrombosis or bleeding. The role of anticoagulation therapy in this setting is controversial and is based on the surgeon's preference and experience.
Peripheral Nerves Injury to the peripheral nerves is not an emergency and can frequently be addressed when an adjacent vascular injury is being repaired. When a wound is clean, uninfected, and well vascularized, primary nerves should be repaired in an end-to-end fashion. Such repair can be facilitated through the mobilization of proximal and distal injured segments, which can reduce tension and augment blood flow. If mobilization of the injured segments cannot adequately repair the defect, interpositional nerve grafts can be used for definitive reconstruction. In such cases, early secondary repair in the first 10 days after injury is optimal. To ensure that the injured area remains intact, the involved limb should be splinted to minimize further proximal migration of the transected nerve before surgery and to relieve anastomotic tension.
Skeleton, Tendons, and Ligaments When injuries to the skeleton, tendons, or ligaments are diagnosed, restoration of normal or acceptable anatomy followed by appropriate immobilization is indicated. In children, an injury that is suspected but not objectively defined is particularly common. Hand fractures may not be evident on radiographs for several weeks. In this situation, presumptive treatment should be carried out, which usually involves immobilization of the potentially injured area, despite equivocal physical examination or radiographic findings. Immobilization is rarely contraindicated in children because it allows protection from further
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injury, improves pain control, and maintains local anatomy. Use of a splint (instead of a cast) is ideal because it allows swelling into a nonfixed space and limits the possibility of vascular compromise during the acute injury and postreduction periods. Anatomic reduction of fractures and dislocations can be done at the time of injury or in the following week, with good functional results.29 In the acute setting, excellent anesthesia can be obtained by performing a hematoma block. This is accomplished by injecting 2 to 3 mL of lidocaine 1% without epinephrine into the fracture site. Reduction in the subacute setting most commonly requires a traditional digital block. Particularly in smaller children, it must be kept in mind that the limiting dose of plain lidocaine is 4 mg/kg of body weight. A description of the reduction maneuvers for specific types of fractures is beyond the scope of this chapter, but in general, gentle manual traction or finger-trap distraction with simultaneous rotation or derotation allows improvement in many types of fractures and dislocation^.^ Postreduction radiographs should be obtained in most if not all patients before or after immobilization. The specific position of immobilization is less critical for children than adults because children are less prone to stiffening and tightening of the ligaments. The "position of safety" can always be used at least initially for splinting: the wrist is placed in 30 to 45 degrees of extension, the metacarpophalangeal joints are placed in 70 degrees of flexion, and the interphalangeal joints are left straight. Serial physical and radiographic examinations are tailored to the specific injury and clinical course.
Soft Tissue After soft tissue and associated vital structure injuries are documented, irrigation of all significant wounds should be performed with normal saline solution, after which foreign objects are removed and tissue that is clearly devitalized is debrided. These procedures may require a local anesthetic, which should be given only after a thorough neurologic examination has been completed. Simple lacerations and small surface-area avulsions can be closed primarily using the same layered closure method used for deep or gaping wounds under tension, Suture choice depends on the location, size, and cause of the wound, as well as the patient's age. A smaller child who requires sedation for the primary wound repair will be hypersensitive to suture removal, when sedation is usually not available. In such cases, absorbable sutures reinforced with Steri-strips and an adhesive are ideal. Permanent sutures should be used in older or cooperative patients to minimize the inflammatory response and avoid early scarring. The potential for scarring depends on the location of the wound and the mechanism of injury. Scarring can be minimized through judicious wound closure. Open wounds that cannot be closed primarily require more elaborate intervention. To bridge the gap between injury and wound closure, the wound must be managed and protected. Normal saline wet-to-wet dressings are a simple and effective way to provide limited debridement, allow the initiation of granulation, and prevent desiccation.
Povidone-iodine dressings should be reserved for shortterm use in infected wounds. Acetic acid solution (0.25%) is appropriate for wounds that have culture documentation of infection with Pseudomonas species. Quantitative wound biopsies should be reserved for nonthermal burns. If the skin defect is only partial thickness and no vital structures are exposed, split-thickness skin grafting or skin distraction is appropriate. Split-thickness skin grafts are used for larger wounds, less cosmetically significant wounds, or those in which the wound bed may not be optimal because of infection, inflammation, or ischemia. Full-thickness skin grafts contract less after revascularization and thus are ideal for cosmetically significant areas or those where wound contraction is undesirable. Local skin flaps can also be used in such settings, offering a cosmetically favorable replacement of like tissue. These skin flaps can be random if they have no specific blood supply or axial if the blood is supplied by a specific vessel." Regional muscle flaps can be used almost anywhere in the body, especially when highly vascularized tissue of significant bulk is required to cover exposed critical structures and fill dead space. Similar to axial pattern skin flaps, these muscle flaps are used on the basis of a known blood supply, which makes their dissection reliable and safe. Finally, when local tissue is not available or is inadequate to provide wound closure, microvascular free tissue transfer is indicated using specific donor "free flaps" to accomplish specific tasks.
Amputations Traumatic amputations in children should be considered for replantation by a qualified microsurgical team, given the excellent results obtained when compared with adult series.15 To optimize the chance of success, the amputated part should be wrapped in saline-moistened gauze, sealed in a plastic bag, and placed in a bag of ice and saline solution; the part must not contact the ice directly.
ENVENOMATION INJURIES Snakebites More than 2700 species of snakes exist; 115 of these species are indigenous to the United States, and only 19 of the 115 species are p o i ~ o n o u s .Pit ~ vipers, which are named for the pit located between their eyes and nostrils, account for most bites. Pit vipers include rattlesnakes, copperheads, and cottonmouth^.*^ Coral snakes represent the other poisonous family. Most bites occur during the summer months in the morning, late afternoon, or evening. Not all bites are associated with envenomation. Signs of envenomation include pain, edema, ecchymosis, nausea, vomiting, hypotension, disseminated intravascular coagulopathy, hemolysis, mental status changes, seizures, and death." The severity of signs is proportional to the degree of envenomation. Early intervention includes reassurance and support, immobilization, limb elevation, venous tourniquet application, and rapid transfer to the nearest medical facility. Cryotherapy and wound incision
CHAPTER
and suction are no longer recommended. Mild pit viper envenomations (characterized by mild pain, local edema, lack of systemic signs, and normal laboratory values) require up to 5 vials of antivenin; moderate envenomations (severe pain, extending edema, nausea, vomiting, neurologic signs, and abnormal laboratory values) require 10 to 15 initial vials of antivenin, with retreatment as necessary; and severe envenomations (rapid progression of local, systemic, and laboratory abnormalities) require an initial Antivenin is admindose of 15 to 20 vials of anti~enin.2~ istered intravenously only after a skin test has been done to rule out the possibility of an anaphylactic reaction. The initial dose for children is one and a half to two times that of adults because of the smaller circulating blood ~ . ~ ~ dosvolume and relative venom c o n ~ e n t r a t i o n .Initial ing should be followed by aggressive intravenous hydration. Fasciotomy should be considered but is seldom required.?"nitial management of bites from snakes from other countries is similar, although antivenin use requires adjustment, depending on the type of snake.2' In addition to its use for pit vipers from North America, antivenin is effective for bites from fer-de-lance, bushmaster, and cantil snakes, which are found in Central and South America. Australian species frequently known to cause envenomations include the common brown snake, mainland tiger snake, lowland copperhead, and red-bellied black snake.
Other Bite Injuries Gila monsters, which are found in the southwestern United States, and their relative the Mexican beaded lizard are active in late spring. These lizards inject venom as long as they cling to the victim. Wounds show edema, but tissue loss is less pronounced than that associated with envenomation by pit vipers; however, systemic signs can ultimately be similar. These injuries are managed by removing the animal from its victim, followed by local and systemic supportive care. Antivenin is not available. Radiographs should be obtained to exclude retained teeth." Black widow spiders are venomous New World spiders; the females are black with an hourglass-shaped red mark on the abdomen.%ocal signs of a bite can be limited, followed by systemic neuromuscular symptoms of diffuse rigidity and spasm that potentially lead to respiratory arrest approximately 1 hour later. Envenomations by black widow spiders are managed by local care, fluid and cardiovascular support, parenteral calcium gluconate, muscle relaxation, and antivenin.2,"11,z Scorpion stings in children have serious sequelae. Bark scorpions are the only toxic species in the United States; however, others are common in Mexico and equatorial countries. Local signs of envenomation are minimal, whereas systemic neuromuscular findings are present in the sympathetic and parasympathetic systems. Children are particularly susceptible to the severe cardiorespiratory and neuromuscular dysfunction associated with envenomation. Therapy of scorpion stings includes local wound care, topical ice, specific antivenin, and systemic support, including ventilation, control of
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tachyarrhythmias, and sedation. Treatment is similar to that for spider bites, although scorpion stings are generally less seri0us.2~ Finally, human bite wounds can pose some of the most challenging definitive management problems among .~ on the quantitative and all bite-induced i n j u r i e ~Based qualitative characteristics of oral flora, including the principal pathogen Eikenella corrodens, aggressive primary intervention is mandatory to achieve a satisfactory outcome in all these injuries. Thorough irrigation of penetrating bite wounds is mandatory, as well as broadspectrum antibiotic coverage, followed by frequent wound checks.
REFERENCES 1. Ablove RH, Moy OJ, Peimer CA: Pediatric hand disease: Diagnosis and treatment. Pediatr Clin North Am 1998;45: 1507-1524. 2. Allen C: Arachnid envenomations. Emerg Clin North Am 1992;10:269-298. 3. Banner W: Bites and stings in the pediatric patient. Curr Probl Pediatr 1988;18:1-69. 4. Bhende MS, Dandrea LA, Davis, HW: Hand injuries in children presenting to a pediatric emergency department. Ann Emerg Med 1993;22:1519-1523. 5. Binder LS: Acute arthropod envenomation: Incidence, clinical features and management. Med Toxic01 Adverse Drug Exp 1989;4:163-173. 6. Buncke GM, Buntic RF, Romeo 0: Pediatric mutilating hand injuries. Hand Clin 2003;19:121-131. 7. Coleman SS, Anson BJ: Arterial patterns in the hand based on a study of 650 specimens, Surg Gynecol Obstet 1961; 113:409424. 8. Eaton RG, LittlerJW: Joint injuries and their sequelae. Clin Plast Surg 1976;3:85-98. 9. Forks TP: Evaluation and treatment of poisonous snakebites. Am Fam Physician 1994;50:123-130. 10. Gelberman RH, et al: The results of radial and ulnar arterial repair in the forearm: Experience in three medical centers. J Bone Joint Surg Am 1982;64:383-387. 11. Hassen LB: Reptile and arthropod envenomations. Occup Med 1991;6:447-461. 12. Hastings H, Simmons BP: Hand fractures in children: A statistical analysis. Clin Orthop 1984;188:120-130. 13. Holden CEA: Compartmental syndromes following trauma. Clin Orthop 1975;113:95-102. 14. Innis PC: Office evaluation and treatment of finger and wrist injuries in children. Curr Opin Pediatr 1995; 7:83-87. 15. Jaeger SH, Tsai TM, Kleinert HE: Upper extremity replantation in children. Orthop Clin North Am 1981;12: 897-907. 16. Leclercq C, Korn W: Articular fractures of the finger in children. Hand Clin 2000;16:523-534. 17. McGregor IA, Morgan G: Axial and random pattern flaps. Br J Plast Surg 1973;16:202-213. 18. Moberg E: Evaluation of sensibility in the hand. Surg Clin North Am 1960;40:357-362. 19. Nofsinger CC, Wolfe SW: Common pediatric hand fractures. Curr Opin Pediatr 2002;14:42-45. 20. Rimsza ME, Zimmerman DR, Bergeson PS: Scorpion envenomation. Pediatrics 1980;66:298-302. 21. Rudolph R, et al: Snakebite treatment at a southeastern regional referral center. Am Surg 1995;61:767-772.
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22. Russell FE: Venomous arthropods. In Schacter LA, Hansen R (eds): Pediatric Dermatology. New York, Churchill Livingstone, 1988. 23. Salter RB, Harris WR: Injuries involving the epiphyseal plate. J Bone Joint Surg Am 1963;45:587-622. 24. Simmons BP, Lovallo JL: Hand and wrist injuries in children. Clin Sports Med 1988;7:495-512. 25. Stewart GM, Quan L, Horton MA: Laceration management. Pediatr Emerg Care 1993;9:247-250. 26. Stewart RM, et al: Antivenin and fasciotomy/debridement in the treatment of the severe rattlesnake bite. Am J Surg 1989;158:543-547.
27. Tibballs J: Diagnosis and treatment of confirmed and suspected snake bite: Implications from an analysis of 46 paediatric cases. Med J Aust 1992;156:270-274. 28. Weber RA, White RR: Crotalidae envenomation in children. Ann Plast Surg 1993;31:141-145. 29. Wood VE: Fractures of the hand in children. Orthop Clin North Am 1976;7:527-542.
Central Nervous System Injuries Thomas G . Luerssen
Injuries to the brain and spinal cord continue to be the major cause of mortality and morbidity from childhood trauma. Despite 25 years of intensive clinical research, no specific medical therapy for any traumatic neurologic injury has yet been defined. Nevertheless, there has been a steady and substantial advance in our understanding of the natural history of brain and spinal cord injuries; moreover, there have been changes in management that have clearly resulted in improved outcomes. We have now entered the era of "evidence-based medicine" whereby recommendations for disease and injury management are supposed to be derived from critical analysis of available scientific research. In the past decade, management strategies for central nervous system (CNS) injuries have been subjected to this type of analysis. These efforts have resulted in the publication ~ ~ , ~ ~ of of practice management g u i d e l i n e ~ . 2 , 2 l ,Analysis the clinical evidence and development of these recommendations represent a substantial amount of work by many of the leading experts in the field. Unfortunately, these reviews also uncovered a remarkable lack of strong scientific evidence on which to develop recommendations, especially in the pediatric age group, so most of the available recommendations regarding the diagnosis and treatment of neurologic injuries can be supported only by the lowest degree of medical certainty. Nevertheless, these published practice parameters are useful summaries of the current understanding of the various treatments of brain and spinal cord injury. These publications are referenced frequently in this chapter, and interested readers are encouraged to review these practice parameters and the citations of the analyzed literature that serve as the basis for the recommendations.
BASIC STRATEGY FOR TREATMENT OF CENTRAL NERVOUS SYSTEM INJURY One of the most enduring concepts underlying the management of brain and spinal cord injury is that of primary and secondary injury.IZ4The primary neurologic injury involves the immediate disruption of neuronal, axonal, and supportive structures and vascular tissues.
The magnitude and location of the primary injury, along with the variety of irreversible cellular processes that immediately ensue, something that has been referred to as "delayed primary injury," are directly related to the mechanism of injury. These immediate tissue disruptions are also considered to be self-limited and are, by definition, essentially untreatable. Given all of this, one can easily see that the primary brain injury is the major determinant of injury outcome. Obviously, the primary injury can be devastating and, in many high-energy mechanisms, immediately lethal. In persons not immediately killed by an injury, the primary injury triggers a cascade of intracellular and extracellular biochemical changes, both in the region of the injury and systemically, many of which are deleterious and cause acceleration and augmentation of the initial injury. These reactive processes represent the onset of what has been termed the "secondary injury." These secondary reactive processes can begin at almost any time after the injury and can persist for some time. The secondary injury not only results in new damage, both in the region of the primary injury and in areas of previously uninjured brain or spinal cord, but also causes deleterious effects in other organs and body systems. Systemic reactions commonly seen after brain or spinal cord injury include hypotension and hypoxia. It has clearly been shown that even brief and mild episodes of either hypoxia or hypotension can have profoundly deleterious effects on the outcome of both brain and spinal cord injury.28,123,141 Although it is well known that spinally injured patients can be rendered hypotensive by an isolated injury, it is now also clear that isolated brain injury can cause systemic hypotension. Multiple injuries, occult organ injuries, or other causes of exsanguination that result in hypovolemia are not required for this hypotensive response to occur. Of the early systemic complications, it appears that hypotension is much more deleterious to an acutely injured brain than hypoxia is. This is probably also true for an acutely injured spinal cord. Finally, it is clear that these complications can occur very early, frequently, and in many cases so briefly that they are either undetected or unreported, even in modern intensive care ~ n i t s . I 2 , ~ ~
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There are also other common systemic responses, many of which occur shortly after an injury but can also cause further injury even days after the institution of therapy. Hyperthermia, either from fever or as a result of overly aggressive warming, is harmful to an injured brain.'" Hyperglycemia, which is commonly seen in the stress response and can be aggravated by fluid administration or attempted nutrition, is also believed to be deleterious to acutely injured neurons.18.*7J4Y Tissue disruptions, commonly referred to as cerebral or spinal cord contusions, cause reactive changes in the tissues immediately surrounding the area of injury. A variety of tissue factors are released, such as those in the kallikrein-kinin system, and these factors can cause disturbances in microcirculation and the blood-brain or blood-spinal cord barrier that ultimately result in the complex entity that has generally been referred to as post-traumatic edema.l13 There are hypermetabolic responses related to neural tissue injury that may outstrip the local or regional substrate supply.13 Excitotoxic amino acids such as glutamate and aspartate are released from injured neurons." Post-traumatic seizures, especially prolonged subclinical seizures, may contribute to this response in the injured brain.172 Along with the reactive biochemical changes, expanding local hemorrhages caused by direct vascular injury can lead to further compression of adjacent vessels and result in an ischemic penumbra around the acute injury. Although the systemic and biochemical processes of secondary injury are complex, it appears that the pathophysiologic end point of all of them is ischemic damage. Ischemic neuronal damage is almost universally seen in the neuropathologic examination of patients who have suffered traumatic brain and spinal cord injUry.70,164 Even though numerous biochemical cascades have been identified and physiologically characterized, and many have been the target of pharmaceutical intervention, no drug has yet been shown to be specifically effective for the treatment of CNS injury. Trials of high-dose steroids, calcium channel blockers, free radical scavengers, and glutamate antagonists have been generally negative, although small and specific subgroups of patients were identified in post hoc analyses that may have benefited from one or another of these therapies. More concerning is that some groups of patients were apparently harmed by the administration of some of these agents." Despite this lack of development of a specific therapy, 20 years of clinical trials involved in the assessment of these agents have shown steady improvement in neurologic outcomes, more so in the arena of brain injury than in spinal cord injury. This trend toward improved outcome is almost certainly due to the realization that many of the ischemic processes can be prevented by aggressive application of systemic manipulation, beginning with the resuscitation phase of the injury and continuing through the period of acute therapy. The essential therapeutic strategies for brain and spinal cord injury are based on preventing ischemic injury by the aggressive support of intravascular volume and blood pressure at all times. The historical idea of restricting fluids in head-injured patients is no
longer accepted. The early use of vasopressors is encouraged. Reduction of focal vascular compression by removal of mass lesions and aggressive prevention and management of reactive brain or cord swelling to protect perfusion are procedures that are aimed at minimizing local and general ischemic injury. These three relatively simplistic concepts--support of systemic blood pressure, reduction of intracranial pressure to ensure cerebral perfusion, and removal of compressive lesions plus prevention of deleterious complications-are now the mainstay of management of brain and spinal cord injuries.
IMMEDIATE ISSUES: RESUSCITATION AND TRANSPORT OF INJURED CHILDREN Effective supportive and preventive therapy should begin as quickly after the injury as possible. Goals of the initial resuscitation are twofold: prevention of as much secondary injury as possible and prevention of any new primary injury before undertaking neurodiagnostic studies. One can accomplish the first goal by ensuring oxygenated perfusion of the brain and spinal cord by restoring and maintaining age-appropriate normal blood pressure and volume as early as possible. This action, coupled with restoring and maintaining normal ventilation, is, at least at this time, more important than the administration of any drug. The exact means of accomplishing this goal, that is, the type of resuscitation fluid or the means of ensuring ventilation, is probably less important than accomplishing the goal itself. Most current studies indicate that isotonic or slightly hypertonic saline solution is an appropriate fluid for resuscitating and maintaining blood pressure in neurologically injured patients,2*,2gx181 although the use of colloids and more highly concentrated hypertonic solutions is also being investigated. Tissue oxygenation is important, and therefore adequate airway and ventilation support is required. Early intubation by experienced personnel with appropriate analgesia and sedation will certainly accomplish this goal. However, the role of intubation of injured children (and adults) in the field is still controversial.77 It appears that this maneuver is associated with a relatively high complication rate and may not be warranted in many s i t u a t i 0 n s . 2 ~ ~ ~ ~ 2 7 ~ 1 ~ ~ For patients with possible spinal injuries, prevention of further injury begins with stabilization of the spine. This maneuver involves much more than the application of a collar or securing a child to a rigid board. It is important that normal anatomic alignment be maintained. Very young children have proportionately larger heads and therefore have a tendency toward cervical flexion when lying supine." A cervical collar alone does not completely immobilize an injured spine in a child.83 Specific attention should be directed to immobilizing the spine in an anatomic position, including ensuring a normal relative position of the head to the body. Young children require some additional elevation of the body so that the head falls back to a truly neutral position. Once these parameters have been achieved, that is, stabilization of the spine in an anatomic position and establishment of systemic blood pressure and respiration
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support, an injured child may be transported for definitive diagnosis and treatment of the injury.
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focal or diffuse. Accepting the caveat that many traumatic injuries are "mixtures" of focal and diffuse injury, one can still base individual management strategies on the initial appearance of the type of brain injury.
TRAUMATIC BRAIN INJURY Focal or Diffuse Brain Injury?
Epidemiology Despite the frequency of head injury in children, epidemiologic data in this area are relatively limited. A study in the United Kingdom indicated that 40% of all patients seen in emergency departments for the treatment of head injuries were children." It is important, however, to distinguish between "head injury" and "brain injury" in discussing outcomes and therapy, although it is probably equally important to group these entities in discussing mechanisms and prevention. Accordingly, population-based studies indicate an average incidence of clinically important head injury in children of about 185 per 100,000, with the incidence generally dropping with increasing age.I9zg6Boys are injured at a rate approximately twice that of girls. Overall, 85% of the brain injuries sustained in childAlthough hood are mild and not life threatening.97,111 severe brain injuries are rare, they still constitute a major concern in pediatric trauma management. Reports from pediatric trauma centers have indicated that well over half of all deaths resulting from blunt trauma in children are caused by a brain injury.l*lJ71 The severity and mechanism of brain injury seem to be linked to outcomes. The mechanism of injury is also age dependent. The most common mechanism resulting in head injury in children is a fall, but the usual falls in childhood are not associated with severe injuries. The major cause of severe brain injury in young children seems to be abuse. In older children, severe brain injury is most commonly seen in relation to motor vehicle accidents. Many accidental brain injuries that occur in children are preventable. Proper use of occupant restraints in motor vehicles can prevent up to 90% of the serious injuries to young children.'47 The implementation of a mandatory child restraint law in Michigan reduced the number of motor vehicle-related injuries in children by 25%.llWearing helmets for bicycle riding, as well as for other recreational activities such as skateboarding, skating, skiing, and horseback riding, should decrease the risk for brain injury,l2"148,167 although educational programs regarding helmet use have had only limited success thus far." Many falls are preventable. Vigilance regarding open windows and stairways, including the use of gates or bars, substantially reduces the occurrence of these injuries.
The Spectrum of Traumatic Brain Injury There are many ways to undertake an overview of the major types of traumatic brain injury. The author has come to prefer one that includes a relationship of injury types, mechanism, and natural history. The simplest way to do this is by categorizing major injury types as either
Focal injuries include contusions, lacerations, traumatic hematomas, and localized damage caused by expanding masses and shifts and distortions of the brain. Diffuse injuries include the spectrum of diffuse axonal injury (DAI), which encompasses what is commonly called cerebral concussion, as well as other diffuse insults such as global ischemia, systemic hypoxia, diffuse brain swelling, and diffuse vascular injury. Focal injuries are usually immediately apparent on admitting computed tomography (CT) scans. Nonetheless, they may be clinically asymptomatic. In contrast, diffuse injuries may show much less striking changes on early neuroimaging studies, even though the patient may exhibit profound alterations in consciousness and neurologic function. Focal injuries are more likely to require therapeutic surgical procedures, whereas diffuse injuries may require extensive diagnostic studies to determine the type and magnitude of the injury. Diffuse injuries are also more likely to require prolonged monitoring of intracranial pressure (ICP) to guide therapy. It is useful to discuss the characteristics of these types of injuries individually, but it is important to remember that in many cases, especially with more severe injuries, both injury types may be present.
Focal Brain Injury Most focal brain injuries are associated with impactrelated mechanisms. Because short falls are the most common cause of accidental head injury in childhood, cranial impacts and their resulting focal injuries are also common. Furthermore, impact mechanisms are associated with skull fractures, which are also commonly seen in the pediatric age group. In fact, about 20% of head-injured children who are admitted to the hospital have skull fractures.105 Despite the frequency of skull fracture in childhood, the majority of children with this injury will not require any intervention or suffer any complication directly related to the fracture. Therefore, the clinical importance of most skull fractures is that the fracture serves as an indicator of both the mechanism and severity of the head injury. Most studies of the importance of skull fractures have determined that the finding of a skull fracture in a head-injured patient is statistically associated with a higher likelihood that an expanding intracranial hematoma or a significant brain injuly is also present.'"8',101~1~)5~166 Furthermore, complex skull fractures, or the occurrence of multiple fractures, is generally associated with higher-energy mechanisms and therefore more severe injuries to the brain. As indicated earlier, most focal brain injuries are immediately apparent on initial neuroimaging studies and, depending on the size and location, result in focal neurologic dysfunction. The most common focal injury resulting from nonpenetrating mechanisms is a cerebral contusion (Fig. 21-1). It is generally a surface lesion
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This cerebral contusion underlying a linear skull
fracture (not demonstrated) was the result of a cranial impact, as demonstrated by the overlying soft tissue swelling and hemorrhage. The patient had no neurologic deficit.
related to cranial impact or brain movement over irregular intracranial surfaces or along the edges of dura. The clinical manifestation of cerebral contusions depends mostly on the extent of the initial injury, the amount of associated hemorrhage resulting in a mass effect, and the location of the contusion in the brain. Even though cerebral contusions may result in localized swelling, isolated lesions are not generally life-threatening. Many cerebral contusions are neurologically silent, only to be discovered on the initial CT scan underlying a skull fracture or along the anterior cranial base. When these injuries are symptomatic, they usually cause a focal neurologic deficit or seizures. The latter are thought to occur commonly in adults with acute cerebral contusion^.^^ However, the incidence of seizures in children with cerebral contusions appears to be no greater than that in children with either normal CT scans or epidural he ma to ma^.'^ Traumatic intracerebral hematomas are unusual lesions in the pediatric age group. The pathogenesis of these hemorrhages is unclear, but it seems likely to be related to disruption of central arterial blood vessels. Accordingly, these lesions are associated with more severe mechanisms of injury and with more profound neurologic dysfunction. In many cases these lesions are part of a larger picture of DAI, which is discussed later. Traumatic intracerebral hematomas are distinguished from hemorrhagic contusions by their lack of contact with the surface of the brain.67 They can be quite large and, because of the location, can leave a child with a profound neurologic deficit. Surgical evacuation can be considered if ICP is high, but in the author's experience,
neurologic outcomes are not improved by evacuation of these hematomas. Children seem to be uniquely prone to nonmissile-associated penetrating injuries of the skull and brain. These injuries are usually the result of a fall onto or being struck by sharp objects such as nails, pencils, sharp sticks, or lawn toys (Fig. 21-2). One of the major dangers of these injuries is that unless the offending object remains embedded, the entry wound may be hidden or seem trivia1.22,44,'26 Anterior penetration of the skull base can be transorbital, via the orbital roof, or through the nose or mouth. Thus, direct evidence of cranial penetration may not be visible or may be masked by local swelling. Penetrating injuries can result in focal contusions, intracerebral hemorrhages, and cerebral lacerations, but these lesions are usually silent because of their locations and small size. Deeper penetrations are more likely to be symptomatic, not only because the tissue injury is more extensive but also because of the potential for injuring major vessels. Many penetrating injuries become symptomatic in delayed fashion because of expansion of intracerebral hemorrhage, recognition of a cerebrospinal fluid (CSF) fistula, or the development of symptoms indicating infection. Therefore, a very high index of suspicion is required, and careful radiologic studies are called for whenever there is a possibility of subtle cranial penetration. Wood, glass, and residual bits of debris may be difficult to detect on routine imaging studies, including CT.76 Cranial penetrating injury is also strongly associated with direct cerebrovascular injury." Magnetic resonance imaging (MRI) with the addition of magnetic resonance angiography (MRA) or the increasingly useful modality of CT angiography (CTA) should be considered whenever there is evidence of deep cranial penetration or if substantial subarachnoid or focal intracerebral hemorrhage is present.
Diffuse Brain Injuries The majority of brain injuries occurring in childhood are diffuse injuries. Diffuse brain injuries are characterized by general disturbances in neuronal function that begin immediately at the time of injury. Despite this, brain structure is generally preserved on admitting CT scans. Diffuse injuries occur as a direct result of energy dissipation within the substance of the brain or as a result of systemic insults. All these injuries exist on a continuum from extremely mild, and apparently completely reversible, to lethal. Frequently, the different types of diffuse brain injury occur together or in sequence and can act synergistically to affect neurologic status and the outcome. Diffuse primary brain injuries are generally the result of angular or translational acceleration (or deceleration), with the amount of tissue disruption being roughly proportional to the amount of energy dissipated in the brain substance.'j8 As the amount of neuronal disruption increases, the depth and duration of neurologic dysfunction increase and the neurologic outcome worsens. There is a strong association with the appearance of certain hemorrhages on CT scan, specifically, subarachnoid hemorrhage, small but widespread
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A
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B
The occult injury frequently seen with low-velocity cranial penetration in young children is demonstrated. The patient was struck in the left parietal region by a lawn dart, and loss of consciousness did not occur. The lawn dart fell out immediately. The injury was misinterpreted as a minor scalp laceration and was closed with butterfly bandages. Three days later, fever and headache developed. A, Appearance of the entry wound before surgical exploration. B, Computed tomography shows a compound fracture and intracerebral hematoma. During surgery, hair, dirt, and bone fragments were removed from the cerebral cortex. I
intracerebral hemorrhages, and intraventricular hemorrhage (Fig. 21-3).l Finally, although the occurrence of traumatic, surgically accessible masses is not characteristic of diffuse brain injury, subdural hematomas are seen commonly along with DAI, and some of these subdural hematomas are large enough that surgical evacuation may be a necessary component of initial therapy. However, these subdural hemorrhages are better viewed as another marker of the diffuse brain injury rather than as a mass that should be treated in isolation, such as an epidural hematoma or hemorrhagic contusion. Like all brain injuries, diffuse primary brain injuries occur within a spectrum of severity. At one end of the spectrum is a very mild, transient physiologic disturbance in neurologic function that includes the syndromes commonly associated with "cerebral concussion," whereas at the other end is the progressively more damaging and ultimately lethal entity that is now called "diffuse axonal injury." The modern view of cerebral concussion is based on the pioneering work of Ommaya and Gennarelli,130J31 which defines concussive brain injuries as a graded set of clinical syndromes showing increasing disturbances in the level and content of consciousness. This definition
allows the inclusion of specific post-traumatic disturbances that are commonly seen in children after so-called mild head injuries, including confusion without amnesia, confusion associated with amnesia of varying depth and duration, and the classic loss of consciousness with and without transient sensorimotor paralysis or disturbances in respiration or circulation. As the amount of energy in the injury mechanism increases, tissue disruption occurs and results in DAI. It is now clear that the most common cause of prolonged coma from mechanical brain injury is DAI. Patients who have suffered DAI are unconscious from the time of injury and remain so for a prolonged period.66 It is not uncommon to note pupillary changes, skewed gaze, and decerebration. This constellation of symptoms had been called "brainstem contusion" in the era before MRI, and although isolated brainstem contusion can certainly occur, it is extremely rare. Instead, most patients in coma who appear to have brainstem dysfunction after closed head injury have suffered DAI. The findings on initial CT scanning depend on the severity of the injury and the degree of associated hemorrhage. In some cases the initial CT scan may be normal. Subsequently, the characteristic lesions may be discovered
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The "classic" appearance of diffuse axonal injury on an admitting computed tomographic scan includes subarachnoid and intraventricular hemorrhage, brain swelling, and small petechial hemorrhages throughout the brain.
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on MRI and can vary from some transient signal changes in the deep white structures to widespread hemorrhagic and nonhemorrhagic shearing injury. The characteristic CT scan appearance of DAI is multiple petechial hemorrhages in the deep white matter and central structures. However, the finding of intraventricular hemorrhage or focal subarachnoid hemorrhage specifically located in the prepontine cistern is also strongly suggestive of DAI.
Gunshot Wounds Injuries from firearms are a major public health problem in children. Because of the way these injuries are reported, it is difficult to determine the overall incidence of this injury in children. However, recent reports indicate that 10% of all childhood injury deaths are related to firearms, a number exceeded only by deaths from motor From vehicle accidents, drowning, and house fi~-es."J~~ the standpoint of management and outcome, there is little to differentiate gunshot injuries in children from those in adults. Poor outcome is related to the depth of coma, bilateral or transventricular injury, elevated ICP, and large intracerebral hemorrhages.~3Vonetheless, most authorities recommend aggressive treatment of all patients except those with clearly nonsurvivable inj~ries,"~ although substantial neurologic and cognitive deficits can be e~pected:""l2~ Injuries caused by nonpowder firearms, such as BB and pellet guns, are three times more frequent than true gunshot wounds in children,176 with adolescent males having the highest risk for injury.122 These injuries are generally less severe and therefore associated with lower mortality rates. Surgical treatment is not usually required for BB gun injuries. Pellet rifle injuries, because they are higher-velocity and larger-caliber missile injuries, are more
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severe and are probably best treated as true gunshot wounds.
Crush Injuries Young children are susceptible to the unusual static loading-type crushing injury to the skull. These injuries occur as a result of a heavy object's falling on a child or being run over by a vehicle. Crush injuries are dramatic in both clinical and radiographic findings (Fig. 21-4), but neurologic outcomes can be quite g ~ o d . ~ W u l t i p l e skull fractures are typical and include complex basilar skull fractures and facial fractures. CSF leaks and cranial nerve palsies are commonly seen. The mechanism of injury and the clinical findings would suggest overwhelming injury and a poor outcome. However, despite the initial appearance of the injury, many times major cortical structures are preserved. Therefore, if the child has survived the initial injury, aggressive multidisciplinary management can result in satisfactory long-term functional outcomes.
Inflicted Injuries By far, the most common cause of severe and lifethreatening brain injury in infants is inflicted injury (also see Chapter 24). All physicians involved in the care of injured children should be familiar with the clinical manifestations and characteristic radiographic findings of inflicted injuries. This entity has recently been reviewed in detai1.37~47Infants with an alteration in consciousness, with or without a new onset of seizures, retinal hemorrhages, and acute intracranial hemorrhages on CT scan, are likely to have suffered nonaccidental injuries, especially if the history of the injury is unknown or reported
B
A -
90 mm Hg Transient hypotension Persistent hypotension Age (yr) 50 *Score doubled for ischemia >6 hr. MESS >7 = 100%prediction for amputation.
Devitalized tissue must be debrided, and fasciotomy should be considered. Nerve function must be evaluated and documented before debating amputation. Although . it is true that children recover amazing-lv well from what ", may initially appear to be devastating injuries, being permanently crippled by an insensate, immobile extremitv is a Door alternative to an active life with a functional and properly fitted prosthesis. The decision to amputate is therefore based on an assessment of limb viability and a prediction of limb functionality. The MESS serves as a Eeasonable guideline, but the ultimate decision rests with the surgeon, the child's parents, and, when possible, the child. Upper extremity vascular injury is usually associated with supracondylar fractures. Axillary stretch injuries, especially when associated with high-energy forces, such as vehicular ejection, may disrupt arterial or venous structures, producing a hematoma that is not as precisely definable as those seen with more distal injuries. In addition to signs of obvious blood loss, diffuse edema of the axilla or shoulder region and diminution of peripheral pulses should prompt angiographic confirkation of both the existence and the anatomic configuration of the injury. Supracondylar fractures may disrupt brachial arterial flow by direct injury or by compression, with or without prolonged spasm. As with the lower extremity, definitive management begins with an assessment of the adequacy of perfusion and confirmation of the vessel's integrity. Of interest is a recent report that describes use of the ipsilateral basilic vein as an ideal interposition graft for the reconstruction of vessels in which segmental loss has 0ccurred.2~Salvage from damage of upper extremity injuries is generally good, with return of functionality related to the nature of the associated musculoskeletal and neurologic disruption. The incidence of compartment syndrome as a result of prolonged ischemia in
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the upper extremity is reported to be significantly lower than that for lower extremity injuries; however, careful follow-up for adequate perfusion and avoidance of postischemia muscle contracture must be part of longterm management.
IATROGENIC INJURY Despite the evolution of increasingly sophisticated methods of imaging for infants and children, the potential for damage to the vascular integrity of a small child or tiny infant remains ever present. There have been numerous reports over the past decade describing this ~ . ~ ~ have been case reports particular p r 0 b l e m . ' . l 2 , ~Many of complications from some usually innocuous maneuver of routine care. Demircin et al.,3 for example, reported an infant with brachial artery pseudoaneurysm resulting from inadvertent puncture during antecubital venipuncture. The lesion was repaired by direct suture under proximal compression. Gamba et al.19 reviewed their experience with iatrogenic vascular lesions in lowbirth-weight neonates. Of 335 infants encountered between 1987 and 1994, 9 (2.6%) were diagnosed with vascular injury. Mean birth weight was 880 g (range, 590 to 1450 g ) , although the mean weight at diagnosis was 1825 g (range, 1230 to 2730 g). Injuries were associated with venipuncture in seven of the nine cases and included six femoral arteriovenous fistulas, two of which were bilateral. One carotid lesion and five femoral arteriovenous fistulas were repaired using microvascular technique. Outcome as determined by follow-up clinical examination and D o ~ ~ l flow e r studies was excellent. leading the authors to emphasize the role of aggressive medical and microsurgical management of these injuries. In 1981 O'Neill et al."? reviewed their experience with the surgical management of 41 infants with-major thromboembolic problems associated with umbilical artery catheters. Although most complications were related to emboli distal to the femoral artery, eight infants required emergency operative intervention for acute aortic obstruction. Four infants underwent transverse aortic thrombectomies, three of whom recovered completely. As principles of umbilical artery catheter management have become better established, these problems appear to have become less frequent. The increasing use of extracorporeal membrane oxygenation has raised the question of the potential need to reconstruct cervical vessels, especially when the process of oxygenation support involves the use of both the carotid artery and the jugular vein. LaQuaglia et a1.2Vescribed their experience in nine children with iatrogenic arterial injuries repaired with microsurgery. An operating microscope was routinely used, and repair was performed using 9-0 to 11-0 nylon suture. Spasm was controlled with topical 2% lidocaine or papaverine. As microsurgical technique continues to evolve and better suture materials become available, this approach will become an increasingly valuable adjunc; ko the management of major injuries to tiny vessels. The femoral artery remains the most common site of iatrogenic injury. As noted earlier in the discussion of
.
L
traumatic injury, efficient collateralization of the pelvis and gluteal region may result in these lesions remaining clinically silent throughout most of childhood. Lin et a1.28 analyzed 1674 diagnostic or therapeutic catheterizations performed in 1431 infants between 1986 and 2001. Thirty-six procedures were required in 34 children. The authors stratified complications into nonischemic, acute femoral ischemia, and chronic femoral ischemia. Nonischemic lesions included pseudoaneurysms ( n = 4), arteriovenous fistulas ( n = 5), and groin hematomas ( n = 5 ) . All were repaired directly, using interrupted polydioxanone (PDS) or polypropylene (Prolene) sutures. Acute femoral ischemic lesions were the most common and required a variety of procedures from thrombectomy to patch repair. Chronic femoral ischemia was defined as evidence of flow disruption noted after 30 days post procedure. Seven children presented with clinical signs an average of 193 days (range, 31 to 842) after the index procedure. All seven were symptomatic with claudication, leg length discrepancy, or gait disturbance. Operative repair consisted of revascularization using reversed saphenous vein for ileofemoral bypass in five children and femorofemoral bypass in one child. Only one child required patch angioplasty. The authors' analysis of potential contributory factors identified a statistically significant predictive relationship for patient age younger than 3 years, more than three previous catheterizations, performance of a therapeutic versus simple diagnostic maneuver, and use of guiding catheters larger than 6 French. The value of this study lies both in the identification of potentially predictive factors and in the documentation of the relatively short time required for chronic ischemia to become symptomatic. Children at risk of vascular injury with any abnormal clinical finding must be followed for at least 5 years, and preferably through the start of adolescence. Limb length discrepancy as a result of disruption of a major vascular structure may not become manifest until years after the precipitating event.48 Recent reports have suggested that operative revascularization of iatrogenic injury before adolescence corrects some limb length discrepancy; however, these have been relatively small series and do not represent a consensus. As is the case with the management of traumatic injury, the high proclivity for spasm and the need to differentiate prolonged spasm from arterial disruption are challenging components of the initial assessment. Prolonged spasm is thought to be the result of intimal injury, which causes derangement of nitric oxide production and disrupts the control of arterial wall tensi0n.'~,~3 When endothelial-medial contact is lost, as can be caused by shearing friction from an oversized or overzealously placed catheter, underlying vascular smooth muscle is incapable of relaxation.2" Angiographic confirmation of spasm requires the additional risk of the very mechanism suspected of causing the problem. Computed tomography-angiography or magnetic resonance arteriography may be the solution to this clinical conundrum, although the dose and concentration of contrast must be carefully considered when comparing risk and benefit. The role of spasm in causing gangrene is controversial, despite case reports suggesting cause and effe~t.~2
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From a clinical perspective, once spasm has been confirmed to be the sole cause of diminished peripheral perfusion, management must focus on the confirmation of evidence of tissue viability and absence of signs of evolving compartment syndrome or peripheral ischemia. Assuming that the basic cause of acute spasm is at least partly related to intimal injury, the risk of thrombosis must be a primary consideration. Over the past few years, routine anticoagulation therapy has been supplemented by thrombolytic agents, especially urokinase.Z0 Recommended doses of urokinase vary and tend to be empirical. Up to 6000 U/kg per hour have been used in infants, with good success and no complications. Most recently, a report by Zenz et a1.49on the use of tissue plasminogen activator suggested that more rapid restoration of flow could be achieved with this drug.
Digital Ischemia Syndrome Intravenous catheter-related, ipsilateral digital ischemia may suddenly develop in infants or small children with an acute infectious disease, usually associated with dehydration and hypovolemia. In a review of 104 cases, Villavicencio et a1.47reported primary involvement of the hand in 68.2% of patients and of the foot in the remainder. The age of the patients ranged from 29 days to 36 months (mean age, 14 months). The infectious process was of respiratory origin in 27.8% of cases, localized to the gastrointestinal tract in 60.5%, and localized to other areas in 11.5%. The most frequently cultured microorganisms were Escherichia coli, Salmonella, Shigella, Streptococcus, Staphylococcus, Klebsiella, and Pseudomonas. Digital cyanosis usually occurs shortly after venous cannulation and is probably the result of venospasm provoked by the presence of an indwelling catheter. As described earlier, damaged endothelium may stimulate vasoconstriction. Immobilization causes constriction of the limbs and impairs the muscle action that is necessary to assist venous return. Persistence of these conditions increases extravascular pressure and gradually produces microcirculatory failure, leading to necrosis, which begins at the most distal areas of the digits. Treatment begins with the prompt recognition of persistent cyanosis, correction of the underlying systemic disorder, and immediate removal of the catheter. Anticoagulation should be initiated immediately. Lesions should be gently washed daily in warm water, and the involved limb should be actively and passively exercised through the full range of motion. Direct heating should be avoided because ischemic tissue burns at lower temperatures than normal. Small pieces of cotton should be placed between fingers or toes, and all lesions should be covered with sterile, dry dressings. Areas of dry gangrene do not require surgical removal. If some question of infection trapped under an eschar exists, the area can be gently elevated at its corners to allow adequate drainage. As is the case with arterial lesions, amputation should not be considered until clear demarcation has occurred.
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SUMMARY Vascular injury in the pediatric population is considerably different from that encountered in adults. Traumatic injury presents a unique set of characteristics that reflect the epidemiology of pediatric trauma and, if carefully managed, can exploit the intrinsically healthy status of the child's vascular system. Iatrogenic injury is the price of miniaturization. It is a recognized trade-off for the dramatic advances that have made many lifesaving procedures possible. Attention to detail in those most at risk may not eliminate the problem but will at least reduce the incidence and raise awareness. Accurate diagnosis, timely revascularization, and aggressive management of reperfusion are essential for complete recovery and normal long-term growth. The key to success is a high index of suspicion, recognition of the unique characteristics discussed ealier, and aggressive operative intervention using the high level of precision that is the cornerstone of success in the surgical care of children.
REFERENCES 1. Chaikof EL, Dodson TF, Salam AA, et al: Acute arterial thrombosis in the very young. J Vasc Surg 1992;16: 428-435. 2. Cox CS Jr, Black CT, Duke JH, et al: Operative treatment of truncal vascular injuries in children and adolescents. J Pediatr Surg 1998;33:462-467. 3. Demircin M, Peker 0 , Tok M, et al: False aneurysm of the brachial artery in an infant following attempted venipuncture. Turk J Pediatr 1996;38:389-391. 4. Dennis JW, Frykberg ER, Crump JM, et al: New perspectives on the management of penetrating trauma in proximity to major limb arteries. J Vasc Surg 1990;11:8492. 5. Dennis JW, Frykberg ER, Veldenz HC, et al: Validation of nonoperative management of occult vascular injuries and accuracy of physical examination alone in penetrating extremity trauma: 5- to 10-year follow-up. J Trauma 1998; 44:242 (discussion). 6. Dennis JW, Jagger C, Butcher JL, et al: Reassessing the role of arteriogram in the management of posterior knee dislocations. J Trauma 1993;35:692-695. 7. de Virgilio C, Mercado PD, Arnell T, et al: Noniatrogenic pediatric vascular trauma: A ten-year experience at a level I trauma center. Am Surg 1997;63:781-784. 8. Eddy AC, Rusch VW, Marchioro T, et al: Treatment of traumatic rupture of the thoracic aorta: A 15-year experience. Arch Surg 1990;125:1351 (discussion 1355). 9. Eren N, Ozgen G, Ener BK, et al: Peripheral vascular injuries in children. J Pediatr Surg 1991;26:11641168. 10. Fagelman MF, Epps HR, Rang M: Mangled extremity severity score in children. J Pediatr Orthop 2002;22:182-184. 11. Fayiga YJ, Valentine RJ, Myers SI, et al: Blunt pediatric vascular trauma: Analysis of forty-one consecutive patients undergoing operative intervention. J Vasc Surg 1994; 20:419 (discussion 424). 12. Flanigan DP, Keifer TJ, Schuler JJ, et al: Experience with iatrogenic pediatric vascular injuries: Incidence, etiology, management, results. Ann Surg 1983;198:430-442. 13. Francis H, Thal ER, Weigelt JA, et al: Vascular proximity: Is it a valid indication for arteriography in asymptomatic patients? J Trauma 1991;31:512-514.
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14. Friedman RJ, Jupiter JB: Vascular injuries and closed extremity fractures in children. Clin Orthop 1984;188: 112-119. 15. Frykberg ER: Advances in diagnosis and treatment of extremity vascular trauma. Surg Clin North Am 1995; 75:207-223. 16. Frykberg ER, Crump JM, Dennis JW,et al: Nonoperative observation of clinically occult arterial injuries: A prospective evaluation. Surgery 1991;109:85-96. 17. Frykberg ER, DennisJW, Bishop K, et al: The reliability of physical examination in the evaluation of penetrating extremity trauma for vascular injury: Results at one year. J Trauma 1991;31:502-511. 18. Furchgott RF, ZawadzkiJV: The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373-376. 19. Gamba P, Tchaprassian Z, Verlato F, et al: Iatrogenic vascular lesions in extremely low birth weight and low birth weight neonates. Vasc Surg 1997;26:643-646. 20. Giacoia GP: High-dose urokinase therapy in newborn infants with major vessel thrombosis. Clin Pediatr 1993; 32:231-237. 21. Harris LM, Hordines J: Major vascular injuries in the pediatric population. Ann Vasc Surg 2003;17:266269. 22. Hoover JD, Almond PS: Isolated pediatric peripheral vascular injury caused by blunt trauma: A new occurrence. J Trauma 2004;56:198-200. 23. Itani KM, Rothenberg SS, Brandt ML, et al: Emergency center arteriography in the evaluation of suspected peripheral vascular injuries in children. J Pediatr Surg 1993;28:677-680. 24. Klein MD, Coran AG, Whitehouse WM Jr, e t al: Management of iatrogenic arterial injuries in infants and children. J Pediatr Surg 1982;17:933-939. 25. Kuo PC, Schroeder RA: The emerging multifaceted roles of nitric oxide. Ann Surg 1995;221:220-235. 26. LaQuaglia MP, Upton J, May JW Jr: Microvascular reconstruction of major arteries in neonates and small children. J Pediatr Surg 1991;26:1136-1140. 27. Lewis HG, Morrison CM, Kennedy PT, et al: Arterial reconstruction using the basilic vein from the zone of injury in pediatric supracondylar humeral fractures: A clinical and radiological series. Plast Reconstr Surg 2003;111:1159 (discussion 1 164). 28. Lin Ph, Dodson TF, Bush RL, et al: Surgical intervention for complications caused by femoral artery catheterization in pediatric patients. J Vasc Surg 2001;34:1071-1078. 29. McCorkell SJ, Harley JD, Morishima MS, et al: Indications for angiography in extremity trauma. AJR Am J Roentgenol 1985;145:1245-1247. 30. Meagher DP Jr, Defore WW, Mattox KL, et al: Vascular trauma in infants and children. J Trauma 1979;19:532-536. 31. Milas ZL, Dodson TF, Ricketts RR: Pediatric blunt trauma resulting in major arterial injuries. Am Surg 2004;70:443447.
32. Mills RP, Robbs JV: Paediatric arterial injury: Management options at the time of injury. J R Coll Surg Edinb 1991; 36:13-17. 33. Moncada S, Higgs A: The L-arginine:nitric oxide pathway. N Engl J Med 1993;329:2002-2012. 34. Nehler MR, Taylor LM Jr, Porter JM: Iatrogenic vascular trauma. Semin Vasc Surg 1998;11:283-293. 35. O'Neill JA, Neblett WW, Born ML: Management of major thromboembolic complications of umbilical artery catheters. J Pediatr Surg 1981;16:972-978. 36. Pigula FA, Buenaventura P, Ettedgui JA, et al: Management of retroperitoneal arterial injury after heart catheterization in children. Ann Thorac Surg 2000;69:1582-1584. 37. Reed MK, Lowry PA, Myers SI: Successful repair of pediatric politeal artery trauma. Am J Surg 1990;160:287-290. 38. Reichard KW, Hall JR, Meller JL, et al: Arteriography in the evaluation of penetrating pediatric extremity injuries. J Pediatr Surg 1994;29:19-22. 39. Reichard KW, Reyes HM: Vascular trauma and reconstructive approaches. Semin Pediatr Surg 1994;3:124132. 40. Reid.JD,WeigeltJA, Thal ER, et al: Assessment of proximity of a wound to major vascular structures as an indication for arteriography. Arch Surg 1998;123:942-946. 41. Rozycki GS, Tremhlay L, Feliciano DV, et al: A prospective study for the detection of vascular injury in adult and pediatric patients with cervicothoracic seat belt signs.J Trauma 2002;52:618 (discussion 623). 42. Russo VJ: Ti-aumatic arterial spasm resulting in gangrene. J Pediatr Orthop 1985;5:486488. 43. SeibertJ, Northington FJ, Miers JF, et al: Aortic thrombosis after umbilical artery catheterization in neonates: Prevalence of complications of long-term follow-up. AJRAm J Roentgenol 1991;156:567-569. 44. Soares G, Ibarra R, Ferral H: Abnominal aortic injury in a child: intravenous digital substraction angiogram (rVDSA) for the diagnosis of pediatric vascular trauma. Pediatr Radio1 2003;33:563-566. 45. Uslu MM, Altun NS, Gila E, at al: Relevance of mangled extremity severity score to compartment syndromes. Arch Orthop Trauma Surg 1995;114:229-232. 46. Victoroff BN, Robertson WW Jr, Eichelberger MR, et al: Extremity gunshot injuries treated in an urban children's hospital. Pediatr Emerg Care 1994;lO:l-5. 47. Villavicencio JL, Gonzalez-Carna JL: Acute vascular problems of children. Curr Probl Surg 1985;22:1-85. 48. Whitehouse WM, Coran AG, Stanley IC, et al: Pediatric vascular trauma: Manifestations, management, and sequelae of extremity arterial injury in patients undergoing surgical treatment. Arch Surg 1976;111:1269-1275. 49. Zenz W, Muntean W, Beitzke A, et al: Tissue plasminogen activator (Alteplase) treatment for femoral artery thrombosis after cardiac catheterisation in infants and children. Br Heart J 1993;70:382-385.
Burns Dai H. Chung, Arthur I? Sanford, and David N. Herndon
In 1944 Lund and BrowderGg developed a diagram that allowed a quantifiable assessment of the percentage of total body surface area (TBSA) burned. While treating victims of the Coconut Grove fire in Boston in 1946, Cope and Moore18 were able to quantify the amount of fluid required to maintain the central electrolyte composition after "burn shock." In the 1960s the discovery of efficacious topical antimicrobial agents, such as 0.5% silver nitrate,75 mafenide acetate (Sulfamylon),68 and silver sulfadiazine ( S i l ~ a d e n e )had , ~ ~ a significant impact on reducing the incidence of burn wound sepsis. These and other advances in burn care during the past several decades have resulted in an overall i m ~ r & e d survival rate for major burn patients. In recent years, continued progress has been made in several areas of burn care. Early surgical excision of eschar and grafting have significantly minimized the incidence of burn wound sepsis and shortened the total length of hospital stay. Treatment with anabolic agents restores net positive nitrogen balance during the prolonged postburn hypermetabolic period. Acute recognition of inhalation injury and effective treatment have also improved the overall outcome for burn patients. These are but a few of the significant advances that have led to a further decline in burn-related deaths.Voday, the overall increased survival rate among major burn victims is most evident in the pediatric population, where the mortality rate is 50% in children 14 years and younger with 98% TBSA burns; in other age groups it is 50% for those with 75% TBSA burns."' Although the overall incidence of burn injuries has declined as a result of preventive measures and legislation, more than 1 million burn injuries still occur each year in the United States. Fortunately, most of these burn injuries are minor, but approximately 45,000 patients suffer moderate to severe burns that require hospitalization. Of these cases, 67% are young males, and 40% are children younger than 15 years3 As the second leading cause of accidental death in children younger than 5 years, burns resulted in 532 pediatric deaths in 2001. In 2002 an estimated 92,500 children younger than 14 years were treated in hospital emergency rooms for burn-related injuries (58,100 with thermal burns and 22,600 with scald burns)." Of the children aged 4
and younger who are hospitalized for burn-related injuries, 65% have scald burns, 20% have contact burns, and the remainder have flame burns. The majority of scald burns in infants and toddlers are from hot foods and liquids. Hot grease spills are notorious for causing deep burns to the involved areas. Hot tap-water burns, which can easily be prevented by installing special faucet valves so that water does not leave the tap at a temperature above 120°F (48.8"C), frequently result in large burned areas in children.' Children also suffer productrelated contact burns from curling irons, ovens, steam irons, and fireworks. Contact with the electrical current in wall outlets also causes a significant percentage of injuries, as does contact with electrical cords. Child abuse also represents a significant cause of burns in children (Fig. 23-1). Burns with bilateral symmetry or a stockingdistribution, particularly t; the dorsum of hands, along with a delay in seeking medical attention, should raise the suspicion of child abuse. In the adolescent age group, flame burns are more common, frequently occurring as a result of experimenting with fire and volatile agents.
, . Scald burn of lower extremities in an infant. Bilateral stocking distribution with well-demarcated margins is consistent with a burn injury resulting from child abuse.
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PATHOPHYSIOLOGY As the largest organ in the body, the skin maintains fluid and electrolyte homeostasis, guards against harmful environmental insults, and acts as a barrier to infection. Other important functions include thermoregulation, metabolism of vitamin D production, and processing of neurosensory inputs. The total surface area of skin ranges from 0.2 to 0.3 m2 in a typical newborn and 1.5 to 2.0 m2 in an adult, making up nearly 15% of total body weight. Anatomically, the epidermis is composed primarily of epithelial cells, specifically keratinocytes. The process of epidermal maturation from the basal layer of keratinocytes to desquamation generally takes about 2 to 4 weeks. The dermis is made up of fibroblasts, which produce collagen and elastin, and is subdivided into a superficial papillary dermis and a deep reticular dermis. The papillary dermis and reticular dermis are separated by a plexus of nerves and blood vessels. The reticular dermis and fatty layer contain skin appendages, such as hair follicles, sweat glands, and sebaceous glands. Therefore, burns involving the deep dermis are generally insensate to touch and painful stimuli. Thermal injury results in coagulation necrosis of the epidermis and varying degrees of injury to the underlying tissue. The extent of burn injury depends on the temperature, duration of exposure, skin thickness, ability of the skin to dissipate heat, and specific heat of the causative agent. For example, the specific heat of fat is higher than that of water; therefore, grease burns often result in much deeper burns than do scald burns from water with the same temperature and duration of exposure. Thermal energy is easily transferred from high-energy molecules to those of lower energy during contact, through the process of heat conduction. The skin generally provides a barrier to the transfer of energy to deeper tissues; therefore, much of the burn injury is confined to this layer. However, local tissue response to the zone of initial burn injury can lead to progressive destruction of surrounding tissue. The area of cutaneous burn injury is divided into three zones: coagulation, stasis, and hyperemia (Fig. 23-2). The zone of coagulation comprises the initial burn eschar, where cells become irreversibly damaged and necrotic at the time of injury. The area immediately surrounding the necrotic area is a zone of stasis, where most cells are initially viable but tissue perfusion becomes progressively
impaired from the local release of inflammatory mediators such as thromboxane A2,arachidonic acid, oxidants, and cytokines.95 Their influence on the microcirculation results in the formation of platelet thrombus, neutrophil adherence, fibrin deposition, and vasoconstriction, which lead to cell necrosis. However, adequate wound care and resuscitation may reverse this process and prevent extensive cell necrosis. Thromboxarie A2 inhibitors can significantly improve dermal blood flow to decrease the zone of stasis.19 Antioxidants as well as bradykinin antag~ ~ , ~ ~of onists also improve local blood f l o ~ . Inhibition neutrophil adherence to endothelium with anti-CD18 or anti-intercellular adhesion molecule monoclonal antibodies improves tissue perfusion in animal models.H,% Peripheral to the zone of stasis lies the zone of hyperemia, which is characterized by vasodilatation and increased blood flow as part of the inflammatory response. The burn-induced inflammatory response is not limited to the local wound in burns involving greater than 40% TBSA. A massive systemic release of thromboxane A2, along with other inflammatory mediators (bradykinin, leukotrienes, catecholamines, activated complement, vasoactive amines), imposes a major physiologic burden on the cardiopulmonary, renal, and gastrointestinal (GI) systems.97 Decreased plasma volume due to increased capillary permeability and subsequent plasma leak into the interstitial space can lead to depressed cardiac function. As a result of low cardiac output, renal blood flow can decrease, leading to a diminished glomerular filtration rate. Activation of other stress-induced hormones and mediators, such as angiotensin, aldosterone, and vasopressin, can further compromise renal blood flow, resulting in 0liguria.7~If not properly treated, this condition can progress to acute tubular necrosis and renal failure, which is associated with a poor outcome for burn patients.61 Atrophy of small bowel mucosa occurs as a result of increased epithelial apoptosis and decreased epithelial proliferation.l~l7JO0Intestinal permeability to macromolecules, which are normally repelled by an intact mucosal barrier, increases after a burn i n j ~ 1 r y . 1 ~ ~ ~ ~ ~ Transient mesenteric ischemia is thought to be an important contributing factor to increased intestinal permeability, which can result in a more frequent incidence of bacterial translocation and subsequent endotoxemia. Burn injury also causes a global depression of immune function. Macrophage production is decreased; neutrophils are impaired in terms of their functions such
.
-
Three zones of
burn injury: coagulation, stasis, and hyperemia.
Subcutaneous
Superficial 2" burn
Deep 2" burn
CHAPTER
23
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385
as diapedesis, chemotaxis, and phagocytosis; cytotoxic ~ - 1 ~ m p h o c ~activity te is decreased: These impaired functions of neutrophils, macrophages, and T lymphocytes contribute to an increased risk for infectious complications after burns.j,6,"',7sfi4J01
First Aid A burn patient must immediately be removed from the source of burn injury, and potential life-threatening injuries must be quickly assessed and addressed independent of the cutaneous burns, as in the case of a multiple trauma victim. Burned clothing and metal jewelry are removed. Immediate cooling by pouring cold water onto the surface of burn wounds must be used with caution to avoid hypothermia. After the removal of clothing, the patient should be kept warm in blankets. With chemical burns, wounds should be irrigated with copious amounts of water, taking care not to spread the chemical to adjacent uninvolved areas. Attempts to neutralize chemicals are contraindicated, as this process may produce additional heat and increase the burn injury. As with any trauma patient, burn patients are quickly assessed through primary and secondary surveys. In the primary survey, airway, breathing, and circulation are assessed, and any potential life-threatening conditions are identified and treated quickly. Symptoms such as wheezing, tachypnea, and hoarseness indicate impending major airway problems; the airway must be rapidly secured with intubation and 100% oxygen support. Oxygen saturation is monitored using a pulse oximeter, and chest expansion is observed to ensure equal air movement. However, adequate oxygen saturation does not mean that the airway is protected, because children have the ability to compensate until just before catastrophic airway collapse occurs. Circumferential full-thickness burns to the chest can significantly impair respiratory function by constricting the trunk and preventing adequate chest expansion. If necessary, escharotomy should be performed to allow better chest expansion and subsequent ventilation. Blood pressure may be difficult to obtain in burned patients with charred extremities. Pulse rate can be used as an indirect measure of intravascular volume; the presence of tachycardia is an indication of the continued need for aggressive fluid resuscitation. Burn depth is categorized according to the involved layers of skin: epidermis, papillary dermis, reticular dermis, subcutaneous fat, and underlying structures (Fig. 23-3). First-degree burns are confined to the epidermis, which is intact, erythematous, and painful to touch. The application of topical ointment containing aloe Vera and the administration of oral nonsteroidal anti-inflammatory agents constitute standard treatment. First-degree burns (e.g., sunburn) heal spontaneously without scarring in 7 to 10 days. Second-degree burns are divided into superficial and deep, based on the depth of dermal involvement. Superficial second-degree burns are limited to the papillary dermis and are typically erythematous and painful with blisters. These burns spontaneously
Reticular
Deep
I
-2"-Burn - - -I
I I I I
Subcutaneous fat
3" Burn I ------I , Bum depth. Firstdegree burns are confined to the epidermis. Superficial seconddegree burns involve the papillary dermis, and deep seconddegree burns involve reticular dermis. Thirddegree burns are full-thickness injuries through the epidermis and dermis. (Adapted from Wolf S, Hemdon DN: Burns. In Townsend CM J r [ed]: Textbook of Surgery, 17th ed. Philadelphia, WB Saunders, 2004, p 571.)
re-epithelialize in 10 to 14 days from retained epidermal structures and may leave only slight skin discoloration. Deep second-degree burns extend into the reticular layer of the dermis. The deep epidermal appendages allow some of these wounds to heal slowly over several weeks, usually with significant scarring. Third-degree burns are full-thickness injuries resulting in complete destruction of the epidermis, dermis, and dermal appendages and are characterized by a dry, leathery eschar that is insensate to any stimuli. Without any residual epidermal or dermal appendages, such burn wounds heal by re-epithelialization from the edges. Fourthdegree burns, typically resulting from profound thermal or electrical injury, involve organs beneath the layers of the skin, such as muscle and bone. An accurate and rapid determination of burn depth is vital to the proper management of burn injuries. In particular, the distinction between superficial and deep dermal burns is critical, as this dictates whether the burn can be managed without surgical procedures. Unfortunately, the determination of whether an apparent deep dermal burn will heal in 3 weeks is only about 50% accurate, even when made by an experienced surgeon. Early excision and grafting provide better results than nonoperative therapy for such indeterminate burns. More precise, objective methods to determine burn depth include techniques such as laser Doppler flowmetry and fluorescein to determine blood flow; ultrasonography to detect denatured collagen; and light reflectance of the Ultimately, burn wound biopsy is the most precise diagnostic too1j3; however, it is not clinically useful because it is invasive and indicates only the static condition of the wound. It also requires an experienced pathologist to interpret histologic findings. Despite these modern technologies, clinical observation is still the most reliable method of determining burn depth.
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Full-thickness circumferential burns to the extremities produce a constricting eschar, which may result in vascular compromise to the distal tissues, including nerves. Accumulation of tissue edema beneath the nonelastic eschar impedes venous outflow, resulting in a compartment syndrome and eventually affecting arterial flow. When distal pulses are absent on palpation or Doppler examination, escharotomies of the extremities are performed to avoid vascular compromise of the limb tissues, after confirmation of the absence of a central circulation problem. Using either a scalpel or electrocautery, escharotomies are performed at the bedside along the lateral and medial aspects of the involved extremities (Fig. 23-4). When the hands are involved, incisions are carried down onto the thenar and hypothenar eminences and along the dorsolateral aspects of the digits, taking care to avoid injury to the neurovascular bundle. Because injuries requiring escharotomy are typically full thickness, minimal bleeding is encountered. If vascular compromise has been prolonged, reperfusion after an escharotomy may cause reactive hyperemia and further edema formation in the muscle compartments. Ischemia-reperfusion injury also releases free oxygen radicals, resulting in transient hypotension. If increased compartment pressures are noted, fasciotomy should be performed immediately to avoid permanent ischemic injuries to the nerves and soft tissues. Intravenous (IV) access should be established immediately to infuse lactated Ringer's solution according to resuscitation guidelines. Peripheral IV access is preferred, but femoral venous access is an ideal alternative in patients with massive burns. If the only IV access available is through burned tissue, this route should be chosen for immediate resuscitation and later changed to a more
appropriate site under sterile conditions. When vascular access is problematic in small children with burned extremities, the intraosseous route is an alternative in those younger than 6 years. A nasogastric tube is placed in all patients with major burns to combat the onset of gastric ileus. Almost immediate enteral nutrition can be initiated via a transpyloric feeding tube. A Foley catheter is placed to accurately monitor urine output as a measure of end-organ perfusion. Admission laboratory studies should include complete blood count, type and crossmatch for packed red blood cells, chemistry, urinalysis, coagulation profile, and chest radiograph. If inhalation injury is suspected, arterial blood gas with carboxyhemoglobin level should also be determined to guide respira l o % TBSA in patients aged < I 0 or >50 yr Second- and third-degree burns >20% TBSA in other age groups Third-degree burns >5% TBSA in any age group Burns involving the face, hands, feet, genitalia, perineum, and skin overlying major joints Significant chemical burns Significant electrical burns, including lightning injury Inhalation injury Burns with significant concomitant trauma Burns with significant preexisting medical disorders Burns in patients requiring special social, emotional, and rehabilitative support (including suspected child abuse and neglect) TBSA, total body surface area.
23
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389
Antimicrobial Agent
Characteristics
Silver sulfadiazine (Silvadene)
Broad-spectrum activity and painless; does not penetrate eschar; impairs epithelialization; leukopenia Broad-spectrum activity, including Pseudomonas; penetrates eschar; painful in second-degree burns; may cause metabolic acidosis (inhibits carbonic anhydrase inhibitor) and inhibition of epithelialization Broad-spectrum activity; does not penetrate eschar; discolors contacted areas; may cause hyponatremia, methemoglobinemia Painless, but limited antimicrobial activity Inhibits fungal growth; frequently used in combination with Silvadene Effective against Staphylococcus Broad-spectrum activity, but possible systemic absorption Effective against almost all microbes
Mafenide acetate (Sulfamylon; 10% cream or 5% soaks)
Silver nitrate (0.5%)
Bacitracin/Polysporin Nystatin Mupirocin (Bactroban) Povidone-iodine Dakin solution (0.025%)
Table 23-4 lists topical antimicrobial agents used for the management of burn wounds. None of these agents effectively prevents the colonization of organisms that are commonly harbored in the eschar, but they maintain the bacterial quantity at less than 10' to lo5 colonies per gram of tissue. Routine punch quantitative wound biopsy can indicate impending burn wound sepsis and possible failure of skin graft from infection. Silver sulfadiazine (Silvadene) is the most commonly used topical agent for burn wound dressings. Although it does not penetrate eschar, it has a broad spectrum of efficacy and soothes the pain associated with seconddegree burns. Silver sulfadiazine on fine mesh gauze can be used separately or in combination with other antimicrobial agents, such as nystatin. This combination, providing additional antifungal coverage, has significantly reduced the incidence of Candida infection in burned patients.z.24 The most common side effect is leukopenia; however, this is caused by margination of white blood cells and is only transient." When the leukocyte count falls below 3000 cells/mm" changing to another topical antimicrobial quickly resolves this complication. Mafenide acetate (Sulfamylon) is more effective in penetrating eschar and is therefore frequently used in third-degree burns. Fine mesh gauze impregnated with Sulfamylon (10%water-soluble cream) is applied directly to the burn wound. Compared with silver sulfadiazine, Sulfamylon has a much broader spectrum of efficacy, including coverage against Pseudomonas and Enterococcus. It is also available in a 5% solution to soak burn wounds, eliminating the need to perform frequent dressing changes. Sulfamylon is a potent carbonic anhydrase inhibitor, so it can cause metabolic acidosis. This side effect can usually be avoided by limiting its use to only 20% TBSA at any one time and rotating application sites
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every several hours with another topical agent, such as Silvadene. Additionally, it is painful when applied, limiting its use in an outpatient setting, especially with children. In addition to 5% Sulfamylon solution, 0.5% silver nitrate and 0.025% sodium hypochlorite (Dakin solution) are available. These solutions-are generally poured onto gauze dressings on the wound, avoiding the need for frequent dressing changes and the potential loss of grafts or healing cells. Silver nitrate is painless on application and has broad coverage, but its side effects include electrolyte imbalance (hyponatremia, hypochloremia) and dark gray or black stains. A new commercially available dressing containing biolog~callyactive silver ions' (Acticoat) retains the effectiveness of silver nitrate without the side effects. Dakin solution is effective against most microbes, including Pseudomonas. However, it requires frequent dosing because of the inactivation of hypochlorite when it comes in contact with protein; it can also retard healing - cells.38 Petroleum-based antimicrobial ointments such polymyxin B, bacitracin, and Polysporin are painless and transparent, allowing easier monitoring of burn wounds. These agents are generally effective only against gram-positive organisms, and their use is limited to facial burns, small areas of partial-thickness burns, and healing donor sites. Like Silvadene, these petroleumbased agents can be used in combination with nystatin to suppress skin Candida colonization.
Wound Dressings Superficial second-degree burns can be managed using various methods. Topical antimicrobial dressings using Silvadene are most commonly used, but synthetic dressings such as Biobrane and Opsite offer the unique advantage of eliminating frequent, painful dressing changes and tissue fluid loss. The general principle of these synthetic products is to provide sterile coverage of superficial second-degree burn wounds to allow rapid, spontaneous re-epithelialization of the involved areas. Biobrane is a thin, synthetic material composed of an inner layer of nylon coated with porcine collagen and an outer layer of rubberized silicone. It is pervious to air but not to fluids and is available in simple sheets or preshaped gloves (Fig. 23-7).@jAfter placement on clean, fresh, superficial second-degree burn wounds using Steri-strips and bandages, the Biobrane dressing dries up, becoming adherent to burn wounds within 24 to 48 hours. Once the dressing is adherent, the covered areas are kept open to air and examined closely for the first few days to detect any signs and symptoms of infection. As epithelialization occurs beneath the Biobrane, the sheet is easily peeled off the wound. If serous fluid accumulates beneath the Biobrane, sterile needle aspiration can preserve its use. However, if foul-smelling exudate is detected, the Biobrane should be removed and topical antimicrobial dressings applied. Alternatively, Opsite or Tegaderm can be used to cover superficial second-degree burn wounds. Commonly used as postoperative dressings in surgical patients, both are relatively inexpensive, are easy to apply, and provide
, Biobrane glove. Biobrane is an ideal synthetic wound coverage material for superficial second-degree burns. It promotes rapid re-epithelialization without painful dressing changes.
an impervious barrier to the environment. Their transparent nature allows easy monitoring of covered second-degree burn wounds. Despite lacking any special biologic factors (e.g., collagen and growth factors) to enhance wound healing, they promote a spontaneous re-epithelialization process. Biobrane and Opsite are preferred to topical antimicrobial dressings when dealing with small, superficial second-degree burn wounds, especially in outpatient settings, to avoid the pain associated with dressing changes. TransCyte, composed of human fibroblasts that are then cultured on the nylon mesh of Biobrane, is another option. Synthetic and biologic dressings are also available to provide coverage for full-thicknessburn wounds. Integra, which is made of a collagen matrix with an outer silicone sheet, is a synthetic dermal substitute for the treatment of full-thickness burn wounds. After the collagen matrix engrafts into the wound in approximately 2 weeks, the outer silicone layer is replaced with epidermal autografts. Epidermal donor sites heal rapidly without significant morbidity, and Integra-covered wounds scar less; however, they are susceptible to wound infection and must be monitored carefully. Alloderm is another dermal substitute with decellularized preserved cadaver dermis. These synthetic dermal substitutes have tremendous potential for minimizing scar contractures and improving cosmetic and functional outcome. Temporary wound coverage can be achieved using biologic dressings, such as xenografts from swine and allografts from cadaver donors. Particularly useful when dealing with large TBSA burns, biologic dressings can provide immunologic and barrier functions of normal skin. The areas of xenograft and allograft are eventually rejected by the immune system and sloughed off, leaving healthy recipient beds for subsequent autografts. Although extremely rare, the transmission of viral diseases from allograft is a potential concern.
Excision and Grafting Early excision with skin grafting has been shown to decrease operative blood loss and length of hospital stay
CHAPTER
and ultimately improve the overall survival of burn p a t i e n t ~ . ~ ' ~ ~ V y p i c a tangential lly, excision of a fullthickness burn wound is performed within 3 days of injury, after relative hemodynamic stability has been achieved. The accurate determination of burn depth is vital to proper management. In particular, distinguishing between superficial and deep thermal burns is critical, as this dictates whether the burn wound can be treated with dressing changes alone or requires surgical excision. Eschar is sequentially shaved using a powered dermatome (Zimmer) or knife blades (Watson, Weck) until a viable tissue plane is achieved. Early excision of eschar (usually lo%). Cyanide toxicity as a result of the combustion of common household items may also contribute to unexplained metabolic collapse. Diagnostic tools, such as bronchoscopy and xenon-133 scanning, are more than 90% accurate in determining the presence of inhalation injury. Fiber-optic bronchoscopic examination of the airway at the bedside (avoiding the need to transport critically injured burn patients to the nuclear medicine department) is usually sufficient to identify airway edema and inflammatory changes of the tracheal mucosa such as hyperemia, mucosal ulceration, and sloughing. It remains the gold standard to confirm the presence of scan with xenon 133 can inhalation inj~ry.~Wentilation also identify regions of inhalation injury by assessing respiratory exchange and excretion of xenon by the lungs.'" The treatment of inhalation injury begins at the scene of the burn accident. The administration of 100% oxygen rapidly decreases the half-life of carbon monoxide. The airway must be secured with intubation in patients exhibiting signs and symptoms of imminent respiratory failure. Aggressive pulmonary toilet with physiotherapy and frequent suctioning is vital to prevent any serious respiratory complications. Humidified air is delivered at high flow, and bronchodilators and racemic epinephrine are used to treat bronchospasm. lV heparin has been shown to reduce tracheobronchial cast formation, improve minute ventilation, and lower peak inspiratory
23
Burns
395
pressures after smoke inhalation. Inhalation treatments such as 20% acetylcysteine nebulized solution (3 mL every 4 hours) plus nebulized heparin (5000 to 10,000 units with 3 mL normal saline every 4 hours) are effective in improving the clearance of tracheobronchial secretions and minimizing bronchospasm, thereby significantly decreasing reintubation rates and r n ~ r t a l i t y . ' ~ , ~ ~ The presence of inhalation injury generally requires increased fluid resuscitation, up to 2 mL/kg per percent TBSA burned more than would be required for the same size burn without an inhalation injury. In fact, pulmonary edema that is associated with inhalation injury is not prevented by fluid restriction; rather, inadequate resuscitation may increase the severity of pulmonary injury by the sequestration of polymorphonuclear cells.40 Steroids have not been shown to be of any benefit in inhalation injury. Prophylactic IV antibiotics are not indicated but are started if there is a clinical suspicion of pneumonia. Early pneumonia is usually the result of gram-positive organisms such as methicillin-resistant S. aureus, whereas later infection is caused by gramnegative organisms such as Pseudomonas. Serially monitored sputum cultures and bronchial washings should guide antibiotic therapy.
NONTHERMAL INJURIES
Chemical Burns Children often accidentally come in contact with various household cleaning products. Treatment of chemical burns involves the immediate removal of the causative agent and lavage with copious amounts of water, taking care to avoid hypothermia and to ensure that the effluent does not contact uninjured areas. Fluid resuscitation is also started. Decontamination is not performed in a tub; rather, the wounds are irrigated toward a drain, such as in a shower. After copious irrigation, wounds should be covered with topical antimicrobial dressing, and appropriate surgical plans should be made. Rapid recognition of the offending chemical agent is crucial to proper management.ZYWhen in doubt, the local poison control center should be contacted to identify the chemical composition of the product involved. The common offending chemical agents can be classified as alkali or acid. Alkalis, such as lime, potassium hydroxide, sodium hydroxide, and bleach, are among the most common agents involved in chemical injuries. Mechanisms of alkali-induced burns are saponification of fat, resulting in increased cell damage from heat, extraction of intracellular water, and formation of alkaline proteinates with hydroxyl ions. These ions induce further chemical reaction in the deeper tissues. Attempts to neutralize alkalis are not recommended, because the chemical reaction can generate more heat and add to the injury. Acid burns are not as common. Acids induce protein breakdown by hydrolysis, resulting in the formation of an eschar, and therefore do not penetrate as deeply as alkaline burns. Formic acid injuries are rare but can result in multiple systemic effects, such as metabolic acidosis, renal failure, intravascular
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TRAUMA
hemolysis, and acute respiratory distress syndrome. Hydrofluoric acid burns are managed differently from other acid burns.94 After copious local irrigation with water, fluoride ions must be neutralized with topical application of 2.5% calcium gluconate gel. If not appropriately treated, free fluoride ions can cause liquefaction necrosis of the affected tissues, including bones. Because of potential hypocalcemia, patients should be closely monitored for prolonged QT intervals.
Electrical Burns Electrical burns are rare in children, accounting for only 3% to 5% of all admitted burn patients. Electrical burns are categorized as either high- or low-voltage injuries.50 High-voltage injuries are characterized by varying degrees of local burns and destruction of deep tissues.",84 Electrical current enters a part of the body and travels through tissues with the lowest resistance, such as nerves, blood vessels, and muscles. Heat generated as electrical current passes through deep tissues with relatively high resistance, such as bones, and damages adjacent tissues that may not be readily visible. Skin is mostly spared owing to its high resistance to electrical current. Primary and secondary surveys, including electrocardiograms, should be completed. If the initial electrocardiogram is normal, no further monitoring is necessary; however, any abnormal findings require continued monitoring for 48 hours and appropriate treatment of dysrhythmias when detected.85 The key to the management of electrical burns lies in the early detection and proper treatment of injuries to deep structures. Edema formation and subsequent vascular compromise are common in extremities. Fasciotomies are frequently necessary to avoid potential limb loss. If myoglobin is present in urine, vigorous hydration, with the administration of sodium bicarbonate to alkalinize the urine and mannitol to achieve diuresis and to act as a free radical scavenger, is indicated. Repeated wound exploration and debridement of affected areas are required before ultimate wound closure because there is a component of delayed cell death and thrombosis. The mechanism of electrical burn injury is to overwhelm the cellular systems that operate at millivolt or milliamp levels, so cells that survive the initial injury may slowly die over a week's time as ion gradients deteriorate and thrombosis of the microvasculature proceeds. Electrical injuries may also have a thermal, nonconductive component as the electricity flashes. This is treated as if it were a conventional thermal burn. Low-voltage injury is similar to thermal injury without the transmission of electrical current to deep tissues and usually requires only local wound care.
OUTPATIENT BURNS The majority of pediatric burns are minor, often resulting from scalds involving less than 10% TBSA or contact with hot objects causing small, isolated areas of thermal injury. Such burns are usually partial-thickness
skin injuries and can be treated on an outpatient basis. After an initial assessment, the burn wound is gently washed with water and a mild soap with appropriate pain control. Blisters can be left intact when they are small and unlikely to rupture spontaneously, especially on the palms of the hand, because they provide a natural barrier against the environment and are beneficial to avoid daay dressing changes. Spontaneous resorption of the fluid occurs in approximately 1 week with the re-epithelialization process. Larger areas of blisters should be debrided, and topical antimicrobial dressings applied. Silvadene is most commonly used owing to 2s broad-spectrum antimicrobial properties, as well as its soothing effect on superficial second-degree burns. However, because silver sulfadiazine can imwede ewithelization, its use should be discontinued when healing partial-thicknesswounds are devoid of necrotic tissue and evidence of re-epithelialization is noted. Alternatively, antimicrobial dressings with triple antibiotic ointment (neomycin, bacitracin, and polymyxin B sulfate) or Polysporin, which has no negative effect on epithelialization, are commonly used. For small, superficial partial-thickness burns, nonmedical white Petrolatumimpregnated fine mesh or porous mesh gauze (Adaptic), or fine mesh absorbent gauze impregnated with 3% bismuth tribromophenate in a nonmedicinal petrolatum blend (Xeroform), is usually sufficient, without the need for topical antimicrobials. Superficial burns of the face can be treated with the application of triple antibiotic ointment without any dressings. The frequency of dressing change varies from twice daily to once a week, depending on the size and depth of the burn and the amount of drainage. Those who advocate twice-daily dressing changes base their care on the use of topical antimicrobials whose half-life is about 8 to 12 hours. Others who use petrolatum-based or bismuth-impregnated gauze recommend less frequent dressing changes-once every 3 to 5 days. The use of synthetic wound dressings is ideal for the outpatient treatment of superficial partial-thickness b ~ r n s . ~ % e n applied appropEiately to fresh, partial-thickness wounds, Biobrane adheres to the wound rapidly and is very effective in promoting re-epithelialization in 1 to 2 weeks (see Fig. 23-7). Although daily dressing changes are eliminated, Biobrane-covered wounds should still be monitored closely for signs of infection.
REHABILITATION Acute Therapy Rehabilitation therapy is an essential component of burn care. During the acute phase of burn care, splints are used to prevent joint deformities and contractures. Made of thermoplastic materials, which are amenable to heat manipulation, splints are fitted individually to each patient. Application of splints at all times except during exercise periods can prevent the severe contractures that occur in patients with large burns. Patients are mobilized out of bed immediately after the graft takes, and aggressive physical therapy is provided.
CHAPTER
After t h e acute phase, hypertrophic scar formation is a major concern. Burn d e p t h , patient age, a n d genetic factors all play a n important role i n hypertrophic scar formation. I n general, d e e p second-degree b u r n wounds, requiring 3 weeks o r m o r e to heal, produce hypertrophic scarring. Children a r e m o r e p r o n e t o hypertrophic scar formation than adults are, probably because of t h e high rate of cell mitosis associated with growth. Constant pressure applied 24 hours a day is t h e most effective m e t h o d t o minimize hypertrophic scar formation; pressure garments should b e worn until scars mature. Scar maturation usually occurs 6 t o 18 m o n t h s after injury; in younger patients, scars mature a t a m u c h slower rate. I n addition to splints a n d pressure garments, exercise therapy is a crucial c o m p o n e n t of rehabilitation therapy. Families should receive thorough instruction o n a program of range-of-motion exercises a n d muscle strengthening.
Extended Therapy Burn survivors a n d their families n e e d rehabilitation therapy for extended periods o n both a physical a n d a psychological level. All must deal with feelings ranging from guilt to post-traumatic stress. In o n e study, a g r o u p of surgeons reviewed t h e images of 12 b u r n survivors with 80% o r greater TBSA b u r n e d a n d 70% third-degree burns, a n d predicted their status with respect to scarring a n d future employability. They predicted that all t h e patients would experience difficult psychological adjustments, a n d that many would require multiple operations in t h e reconstructive phase.45-In reality, t h e patients received twice as many operations as predicted, yet three quarters of these children demonstrated normal adjustm e n t a n d emotional growth. W h e n this longitudinal study was followed f o r additional 10 years, t h e children's emotional assessment scores were equal to those of their uninjured peers. T h a t s o few of these survivors developed serious ps~chologicala n d social difficulties is a striking testament to h u m a n resilience.
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31. Gallico GG 3rd, O'Connor NE, Compton CC, et al: Permanent coverage of large burn wounds with autologous cultured human epithelium. N Engl J Med 1984;311:448. 32. Gamelli RL, He LK, Liu H: Macrophage suppression of granulocyte and macrophage growth following burn wound infection. J Trauma 1994;37:888. 33. Gerding RL, Emerman CL, Effron D, et al: Outpatient management of partial-thickness burns: Biobrane versus 1% silver sulfadiazine. Ann Emerg Med 1990;19:121. 34. Gilpin DA, Barrow RE, Rutan RL, et al: Recombinant human growth hormone accelerates wound healing in children with large cutaneous burns. Ann Surg 1994; 220:19. 35. Goran MI, Peters EJ, Herndon DN, et al: Total energy expenditure in burned children using the doubly labeled water technique. Am J Physiol 1990;259(4 Pt 1):E576. 36. Graves TA, Cioffi WG, McManus WF, et al: Fluid resuscitation of infants and children with massive thermal injury. J Trauma 1988;28:1656. 37. Hart DW, Wolf SE, Ramzy PI, et al: Anabolic effects of oxandrolone after severe burn. Ann Surg 2001;233:556. 38. Heggers JP, Sazy JA, Stenberg BD, et al: Bactericidal and wound-healing properties of sodium hypochlorite solutions: The 1991 Lindberg Award. J Burn Care Rehabil 1991; 12:420. 39. Herndon DN, Barrow RE, Kunkel KR, et al: Effects of recombinant human growth hormone on donor-site healing in severely burned children. Ann Surg 1990;212:424. 40. Herndon DN, Barrow RE, Linares HA, et al: Inhalation injury in burned patients: Effects and treatment. Burns Incl Therm Inj 1988;14:349. 41. Herndon DN, Barrow RE, Stein M, et al: Increased mortality with intravenous supplemental feeding in severely burned patients. J Burn Care Rehabil 1989;10:309. 42. Herndon DN, Gore D, Cole M, et al: Determinants of mortality in pediatric patients with greater than 70% fullthickness total body surface area thermal injury treated by early total excision and grafting. J Trauma 1987;27:208. 43. Herndon DN, Hart DW, Wolf SE, et al: Reversal of catabolism by beta-blockade after severe burns. N Engl J Med 2001;345:1223. 44. Herndon DN, Hawkins HK, Nguyen TT, et al: Characterization of growth hormone enhanced donor site healing in patients with large cutaneous burns. Ann Surg 1995;221:649. 45. Herndon DN, LeMaster J, Beard S, et al: The quality of life after major thermal injury in children: An analysis of 12 survivors with greater than or equal to 80% total body, 70% third-degree burns. J Trauma 1986;26:609. 46. Herndon DN, Parks DH: Comparison of serial debridement and autografting and early massive excision with cadaver skin overlay in the treatment of large burns in children. J Trauma 1986;26:149. 47. Herndon DN, Ramzy PI, DebRoy MA, et al: Muscle protein catabolism after severe burn: Effects of IGF-l/IGFBP-3 treatment. Ann Surg 1999;229:713. 48. Herndon DN, Stein MD, Rutan TC, et al: Failure of TPN supplementation to improve liver function, immunity, and mortality in thermally injured patients.J Trauma 1987;27:195. 49. Herndon DN, Thompson PB, Traber DL: Pulmonary injury in burned patients. Crit Care Clin 1985;1:79. 50. Hildreth MA, Herndon DN, Desai MH, et al: Caloric needs of adolescent patients with burns. J Burn Care Rehabil 1989;10:523. 51. Hildreth MA, Herndon DN, Desai MH, et al: Current treatment reduces calories required to maintain weight in pediatric patients with burns. J Burn Care Rehabil 1990;11:405.
52. Hildreth MA, Herndon DN, Desai MH, et al: Caloric requirements of patients with burns under one year of age. J Burn Care Rehabil 1993;14:108. 53. Ho-Asjoe M, Chronnell CM, Frame JD, et al: Immunohistochemical analysis of burn depth. J Burn Care Rehabil 1999;20:207. 54. Honeycutt D, Barrow R, Herndon D: Cold stress response in patients with severe burns after beta-blockade. J Burn Care Rehabil 1992;13(2 Pt 1):181. 55. Huang PP, Stucky FS, Dimick AR, et al: Hypertonic sodium resuscitation is associated with renal failure and death. Ann Surg 1995;221:543. 56. Hunt JL, Agee RN, Pruitt BA Jr: Fiberoptic bronchoscopy in acute inhalation injury. J Trauma 1975;15:641. 57. Hunt JP, Hunter CT, Brownstein MR, et al: The effector component of the cytotoxic T-lymphocyte response has a biphasic pattern after burn injury. J Surg Res 1998;80:243. 58. Jahoor F, Herndon DN, Wolfe RR: Role of insulin and glucagon in the response of glucose and alanine kinetics in burn-injured patients. J Clin Invest 1986;78:807. 59. Jarrett F, Ellerbe S, Demling R: Acute leukopenia during topical burn therapy with silver sulfadiazine. Am J Surg 1978;135:818. 60. Jerath MR, Schomacker KT, Sheridan RL, et al: Burn wound assessment in porcine skin using indocyanine green fluorescence. J Trauma 1999;46:1085. 61. Jeschke MG, Barrow RE, Wolf SE, et al: Mortality in burned children with acute renal failure. Arch Surg 1998;133:752. 62. Kimura R, Traber LD, Herndon DN, et al: Treatment of smoke-induced pulmonary injury with nebulized dimethylsulfoxide. Circ Shock 1988;25:333. 63. Klein GL, Wolf SE, Goodman WG, et al: The management of acute bone loss in severe catabolism due to burn injury. Horm Res 1997;48(Suppl 5) :83. 64. Klimpel GR, Herndon DH, Stein MD: Peripheral blood lymphocytes from thermal injury patients are defective in their ability to generate lymphokine-activated killer (LAK) cell activity. J Clin Immunol 1988;8:14. 65. Laberge LC, Ballard PA, Daniel RK: Experimental electrical burns: Low voltage. Ann Plast Surg 1984;13:185. 66. La1 S, Barrow RE, Wolf SE, et al: Biobrane improves wound healing in burned children without increased risk of infection. Shock 2000;14:314. 67. LeVoyer T, CioE WG Jr, Pratt L, et al: Alterations in intestinal permeability after thermal injury. Arch Surg 1992;127:26. 68. Lindberg RB, Moncrief JA, Switzer WE, et al: The successful control of burn wound sepsis.J Trauma 1965;5:601. 69. Lund CC, Browder NC: The estimation of areas of burns. Surg Gynecol Obstet 1944;79:352. 70. Marano MA, O'Sullivan G, Madden M, et al: Tourniquet technique for reduced blood loss and wound assessment during excisions of burn wounds of the extremity. Surg Gynecol Obstet 1990;171:249. 71. McDonald AJ, Cooper MG: Patient-controlled analgesia: An appropriate method of pain control in children. Paediatr Drugs 2001;3:273. 72. Mileski W, Borgstrom D, Lightfoot E, et al: Inhibition of leukocyte-endothelial adherence following thermal injury. J Surg Res 1992;52:334. 73. Mochizuki H, Trocki 0 , Dominioni L, et al: Mechanism of prevention of postburn hypermetabolism and catabolism by early enteral feeding. Ann Surg 1984;200:297. 74. Monafo WW: The treatment of burn shock by the intravenous and oral administration of hypertonic lactated saline solution. J Trauma 1970;10:575. 75. Moyer CA, Brentano L, Gravens DL, et al: Treatment of large human burns with 0.5 per cent silver nitrate solution. Arch Surg 1965;90:812.
CHAPTER
76. Moylan JA .Jr, Wilmore DW, Mouton DE, et al: Early diagnosis of inhalation injury using 133 xenon lung scan. Ann Surg 1972;176:477. 77. Murphy KD, Lee JO, Herndon DN: Current pharmacotherapy for the treatment of severe burns. Expert Opin Pharmacother 2003;4:369. 78. Myers SI, Minei JP, Casteneda A, et al: Differential effects of acute thernial injury on rat splanchnic and renal blood flow and prostanoid release. Prostaglandins Leukot Essent Fatty Acids 1995;53:439. 79. Nwariaku FE, Sikes PJ, Lightfoot E, et al: Effect of a bradykinin antagonist on the local inflammatory response following thermal injury. Burns 1996;22:324. 80. O'Reilly TJ, Spence RJ, Taylor RM, et al: Laser Doppler flowrnetry evaluation of burn wound depth. J Burn Care Rehabil 1989;10:l. 81. Park DH, Hwang JW, Jang KS, et al: Use of laser Doppler flowmetry for estimation of the depth of burns. Plast Reconstr Surg 1998;101:1516. 82. Pierre EJ, Barrow RE, Hawkins HK, et al: Effects of insulin on wound healing. J Trauma 1998;44:342. 83. Ramirez KJ, Wolf SE, Barrow RE, et al: Growth hormone treatment in pediatric burns: A safe therapeutic approach. Ann Surg 1998;228:439. 84. Robson MC, Murphy RC, Heggers JP: A new explanation for the progressive tissue loss in electrical injuries. Plast Reconstr Surg 1984;73:431. 85. Robson MC, Smith DJ: Care of the thermal injured victim. In Jurkiewicz MJ, Krizek TJ, Mathes SJ, et al (eds): Plastic Surgery: Principles and Practice. St Louis, CV Mosby, 1990. 86. Rue I,W 3rd, Cioffi WG, McManus WF, et al: Wound closure and outcome in extensively burned patients treated with cultured autologous keratinocytes. J Trauma 1993; 34:662. 87. Ryan CM, Yar~nush ML, Burke JF, et al: Increased gut permeability early after burns correlates with the extent of burn irljjury. Crit Care Med 1992;20:1508. 88. Saito H, Trocki 0 , Alexander JW, et al: The effect of route of nutrient administration on the ~lutritionalstate, catabolic hormone secretion, and gut mucosal integrity after burn injury. JPENJ Parenter Enteral Nutr 1987;ll:l.
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89. Shamoon H, Hendler R, Sherwin RS: Synergistic interactions among antiinsulin hormones in the pathogenesis of stress hyperglycemia in humans..J Clin Endocrinol Metab 1981;52:1235. 90. Sheffield-Moore M, Urban RJ, Wolf SE, et al: Short-term oxandrolone administration stin~ulatesnet muscle protein synthesis in young nlen. J Clin Endocrinol ~ e t a b 1999;84:2705. 91. Sheridan RL, Tompkins RG: Cultured autologous epithelium in patients with burns of ninety percent or niore of the body surface. .J Trauma 1995;38:48. 92. Tht~mpsonPB, Herndon DN, Traber DI., et al: Effect on mortality of inhalation in-jnry.J Trauma 1986;26:163. 93. Traber DL, Herndon DN, Stein MD, et al: The pulmonary lesion of smoke inhalation in an twine model. Circ Shock 1986;18:311. 94. Trevino MA, Herrmann GH, Sprout WI,: Treatment of severe hydrofluoric acid exposures. J Occup Med 1983; 252361. 95. Vo IIT, Papworth GD, Delarley PM, et al: A study of vascular response to thermal injury on hairless mice by fibre optic confocal imaging, laser Doppler flowmetry and conventional histolo.gy. Burns 1998;24:319. 96. Warden GD: Burn shock resuscitation. WorldJ Surg 1992; 16:16. 97. Warden GD: Fluid resuscitation and early management. In Herndon DN (ed): Total Burn Care. Philadelphia, WB Saunders, 1996, p 53. 98. Wilmore DW, Moylan JA .Jr, Bristow BF, et al: Anabolic and e high caloric feedeffects of human growth h o r m o ~ ~ ings following thermal injury. Surg Gynecol Obstet 1974; 138:875. 99. Wolf SE, Barrow RE, Herndon 1)N: Growth horrnone and IGF-I therapy in the hypercatabolic patient. Baillieres Clin Endocrinol Metab 1996;10:447. 100. Wolf SE, Ikeda H, Matin S, et al: (;utaneous burn increases apoptosis in the gut epithelium of mice. J Am Coll Surg 1999;188:10. 101. Zedler S, Faist E, Ostermeier B, et al: Postburn constitutional changes in T-cell reactivity occur in CD8+ rather than in CD4+ cells. J Trauma 1997;42:872.
Child Abuse and Birth Injuries -
-
-
Dennis W. Vane
CHILD ABUSE Child abuse encompasses physical abuse, sexual abuse, emotional abuse, and neglect. This maltreatment of children has become a significant focus of attention in our society. The media routinely publish accounts of the alleged traumatic and sometimes fatal abuse of children among all socioecorlomic classes and levels of celebrity. The myth that child abuse and other violence in the home occur only among the poor and the uneducated has been debunked. Child abuse is a worldwide problem that affects all levels of society. Prevention and effective treatment depend on the timely detection of epidemiologic situations that lend themselves to the maltreatment of children. Unfortunately, the "minor" status of children leads to the justifiable issue of the relative rights of parents and guardians. Religious and societal "norms" have created barriers to the identification of victims in many nations. Around the globe, relatively few nations have addressed this problem at all.3 In the United States and Canada, legislation aimed at identifying child abuse and neglect ~* that time, was enacted beginning in the 1 9 6 0 ~ . Since the reporting of child abuse to civil authorities has been mandated for almost all professionals dealing with children. The legislation protects the reporting individual from liability (usually by using the phrase "suspicion of' or "injuries consistent with"), supersedes all professionalclient privilege, and sometimes even imposes penalties for failure to report abuse.45
age groups, maltreatment of children generally increases with age. In teenagers, the incidence of abuse is thought to be twice that in preschool children.54 Patterns of child abuse occur with differing frequencies over the social strata. Sexual and emotional abuse have no socioeconomic associations,whereas physical abuse and neglect are more frequently associated with p o ~ e r t y . ~ ~ Often several types of abuse are perpetrated on the same child or within the same familv. Additionallv. ,, abuse commonly occurs in families with other forms of intrafamilial violence, such as spousal abuse and violence among sibling^.^" Child abuse is a self-perpetuating social and economic problem. Problems with substance abuse and depression are reportedly two to three times more likely in abused children than in the general population, and abused children are likely to be far more physically aggressive with their peers."
, x
Gene Expression
Examining the expression of tyrosine kinase (Trk) receptors in 39 children with Wilms' tumor, Eggert et al.46 noted that children with high levels of full-length TrkB mRNA (TrkBfull) had a significantly greater risk of death than children whose tumors had little or no TrkBfull expression ( P = 0.02). The 5-year relapse-free DNA Content survival was 100% for patients with low tumor expression Increased tumor cell DNA content has been correlated of TrkBfull, compared with 65% for those with high with a more favorable prognosis in children with a variety tumor expression of TrkBfull ( P < 0.003). Conversely, children with tumors that expressed high mRNA levels of tumors, including embryonal rhabdomyo~arcoma,~~~ of a functionally inactive truncated TrkB receptor and acute lymphoblastic 1eukemia.l34 neurobla~torna,"~ (TrkBtrunc) had a greater 5-year relapse-free survival than For Wilms' tumor, however, the data have been mixed; did children with low levels of TrkBtrunc (95% versus aneuploidy was associated with a worse prognosis among 68%; P= 0.005). patients with favorable-histology Wilms' tumors in one Ghamen et al." evaluated the prognostic value of variseries70 but not in another.5 More recently, possible chroous apoptosis-associated regulatory proteins, such as Bcl-2, mosomal prognostic factors have been identified by Bax, and Bcl-X, in a group of 61 Wilms' tumors. An Grundy et al.," who evaluated DNA gain and loss for sevincreased expression of Bcl-2 was observed in the eral chromosomal segments. In a study of 232 children blastemic component of increasing pathologic stages, registered during NWTS-3 and NWTS-4, LOH of 16q while a gradual decline of Bax expression was observed. markers was present in 17.2% of tumor tissue and was Univariate analysis showed that blastemic Bcl-2 expression associated with a statistically significantly worse 2-year and the Bcl-2/Bax ratio were indicative of clinical progresrelapse-free and overall survival. LOH of chromosome sion, and blastemic Bcl-2 expression was a prognostic l p markers, present in tumor tissue from 11% of chilmarker for clinical progression, independent of stage. dren with Wilms' tumor, was associated with poorer relapse-free and overall survival rates, which were of borderline statistical significance ( P = 0.08 and 0.12, respectively). In contrast, LOH for l l p markers or duplication Growth Factors of l q , present in 33% and 25% of cases, respectively, was Previous reports noted that the sera and urine of chilnot associated with any difference in outcome. Study of dren with Wilms' tumor often contain increased concenthe prognostic significance of tumor cell DNA content trations of hyaluronan. Using a mouse heterotransplant was continued in NWTS-5, with the hope that newly conmodel, Loworn et aL9' noted that the sera of mice supportfirmed DNA variables will facilitate the tailoring of treating tumor growth had a median hyaluronan concentration ment to anticipated outcome.
1
460
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III
MAJORTUMORS OF CHILDHOOD
of 9379 pg/L, compared with a median concentration of The 2 416 pg/L in animals not supporting tumor g r o ~ t h . ~ highest serum hyaluronan concentrations were detected in animals harboring blastema-predominant tumors with an unfavorable histology. Complete resection of established tumors also resulted in the return of serum hyaluronan to preheterotransplant concentrations. Lin et a1.88 measured bFGF levels in preoperative and postoperative urine samples from 97 patients with Wilms' tumor. Urinary bFGF was elevated in 42% of preoperative samples, and higher-stage tumors resulted in higher preoperative levels. Patients with relapse or persistent disease had significantly elevated postoperative bFGF levels. Kayton et a1.81 detected VEGF with increasing frequency and quantity in a mouse model of Wilms' tumor. Lung metastases occurred in 8 of 10 animals with VEGF-positive tumors but in only 3 of 11 animals with VEGF-negative tumors, an association that was statistically significant.VEGF was found in 10 of 12 clinical Wilms' tumor specimens tested. Davidoff et a1.M developed adeno-associatedvirus vectors containing the soluble, truncated form of VEGF receptor-2 (Flk-1), a known inhibitor of endothelial cell activation. Significant antitumor efficacy was observed in two murine models of pediatric kidney tumors. Tumor development was prevented in 10 of 15 mice (67%), with significant growth restriction of tumors in the remaining mice.
OUTCOMES NWTSG Results Five therapeutic studies have been completed: NWTS-1 (1969-1974),NWTS-2 (1975-1979),NWTS-3 (1980-1985), NWTS-4 (19861995), and NWTS-5 (1995-2002). Five-year survival percentages for patients enrolled in NWTS protocols were 79.7% for 1969-1974 enrollees, 81.6% for 1975-1979, 86.3% for 1980-1984, 88.6% for 1985-1989, and 90.4% for 1990-1995. These are among the highest for all childhood cancers. The major conclusions of NWTS-1, -2, and -3 were as follows: 1. Postoperative irradiation therapy of the renal bed is not necessary for stage I tumors or for stage 11 tumors with favorable histology. 2. Survival of patients with stage 111, favorable-histology tumors is best when therapy consists of dactinomycin, vincristine, and doxorubicin combined with 1000 cGy radiation therapy to the flank, or dactinomycin and vincristine combined with 2000 cGy radiation therapy. 3. Cyclophosphamide does not improve the prognosis when added to the treatment of stage IV favorablehistology tumors. As a result of these studies, the 2-year survival rate of children diagnosed with Wilms' tumor rose from 20%47 to 90%."-37 NWTS-4 found that pulse-intensive actinomycin D and doxorubicin dosing is as efficacious as and less toxic than the traditional divided-dose method; it is also more
cost-effective, saving an estimated $790,000 a year.60.61 NWTS-4 also revealed that 6 months of treatment for stage I1 to IV favorable-histologytumors is equivalent to 15 months of treatment. Ritchey et a1.'22 examined the incidence of surgical complications among patients enrolled in NWTS-4. In a random sample of 534 patients, 68 patients (12.7%) experienced 76 complications. Intestinal obstruction was the most common complication (5.1% of patients), followed by extensive hemorrhage (1.9%), wound infection ( 1.9%), and vascular injury (1.5%). Intravascular extension into the inferior vena cava, nephrectomy performed through a flank or paramedian incision, and tumor diameter 10 cm or greater were also associated with an increased risk of surgical complications. NWTS-4 also demonstrated that surgical rupture of the tumor must be prevented, because spills produce an increased risk of local relapse.124 NWTS-5 (also know as POG 9440 and CCG 4941) opened in July 1995 and closed in June 2002. It had a variety of objectives, including to (1) evaluate the importance of various biologic prognostic factors; (2) decrease the morbidity of treatment by limiting initial therapy; (3) improve the survival of patients with unfavorablehistology tumors, including Wilms' tumor with diffuse anaplasia, clear cell sarcoma of the kidney, and malignant rhabdoid tumor of the kidney; and (4) study the biology and pathology of patients who present with bilateral Wilms' tumor. The results from NWTS-5 with regard to the genetic implications for clinical outcome are still being analyzed and have not been published. Of particular interest in NWTS-5 was the management of small stage I tumors. Green and Jaffe,"" in a 1979 review, had suggested that nephrectomy might be adequate therapy for patients younger than 24 months with tumors weighing less than 550 g. A subsequent review of children treated during NWTS-1, -2, and -3 supported the hypothesis that NWTS regimens had not improved the excellent prognosis among this group of children."" Thus a "surgery only" arm was developed for investigation in NWTS-5. By March 31, 1998,69 patients had been entered in the surgery-only treatment arm. Nine patients relavsed: three in the tumor bed or abdomen. one in the pleural space, four in bilateral lungs, and one in the contralateral kidney. The relapse-free survival percentage at 2 years was 82.1%, far below the established relapse-free su-rvivalpercentage cutoff of 95%. Thus the surgery-only trial was suspended.
European Results Results from Europe have been similar to NWTS results. For instance, the results of the UKCCSG Second Wilms' Tumor Study were reported in 2OOO.gg Four-year eventfree survival was as follows: stage 1 with favorable histology, 94%; stage I1 with favorable histology, 91%; and stage 111 with favorable histology, 84%. The outlook for patients with anaplastic or rhabdoid variants was poor. A recent Italian review of 98 nephroblastoma patients treated in three consecutive SIOP trials resulted in a 5-year cure rate of 90%.7Wlinicalcourse was influenced mainly by diffuse anaplasia and, to a minor extent,
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be more vulnerable to the delayed adverse sequelae of cancer therapy, such as effects on growth, fertility, and neuropsychological function. Wilms' tumor patients have known risk factors for cardiac, renal, and pulmonary toxicity. NWTS-1 demonstrated that the risk of congestive heart failure persisted for 8 to 12 years or more from the time of anthracycline treatment. Patients treated in NWTS-1 to -4 were reviewed to determine the frequency of congestive heart failure and the risk factors for it following Wilms' tumor treatment with doxorubicin.62 The cumulative frequency of congestive heart failure was 4.4% at 20 years among patients treated initially and 17.4% at 20 years among Specialized Tumors those treated for relapsed Wilms' tumor. The relative risk of congestive heart failure was increased in females A review of 4669 patients treated with NWTS-3 and and by cumulative doxorubicin dose, lung irradiation, NWTS-4 protocols yielded 53 children with BWS.lI1 BWS and left abdominal irradiation. A more recent report patients were more likely to present with lower-stage noted that the most important predictor of worsening tumors (P= 0.0001). The overall survival rate at 4 years cardiac performance was total anthracycline dose: for BWS patients was nearly identical to that of patients patients receiving less than 240 mg/mZ showed no carwithout BWS (89% versus 90%). Twenty-one percent of diac deterioration more than 10 years after the end of patients with BWS had bilateral disease. BWS patients treatment.lZg enrolled in NWTS4 had smaller tumors than those Children with Wilms' tumor are also at risk for renal enrolled in NWTS3 (P=0.02), suggesting that US screendysfunction from a variety of factors, including radiation ing may be efficacious. therapy, use of nephrotoxic chemotherapy agents, a Argani et a1.l reviewed 351 cases of clear cell sarcoma theoretical risk due to hyperfiltration,43 and the possible of the kidney, including 182 cases entered in NWTS-1 to involvement of a genetic component (e.g., patients with -4. Overall survival was 69%, and multivariate analysis Denys-Drash syndrome). In 1996 Ritchey et al.l18 revealed four independent prognostic factors for surreported the spectrum of renal failure in 55 of 5823 vival: treatment with doxorubicin, stage, age at diagnosis, patients treated in NWTS-1 to -4, noting that the risk of and tumor necrosis. renal failure at 16 years was 0.6% for all unilateral-disease The results for children with the WAGR syndrome patients and 13% for bilateral-disease patients. were analyzed and reported by Breslow et al.17 Of the Survivors of childhood cancer are also at increased 8533 patients enrolled between 1969 and 2002 by the risk of developing a second malignant neoplasm, both NWTSG, 64 patients (0.75%) had the WAGR syndrome. leukemias and solid tumors. The cumulative risk at Comparing WAGR and non-WAGR patients, the average 20 years varies between 3% and 10% over several studies birth weights (2.94 and 3.45 kg), median ages at diagnosis and is 5 to 20 times greater than that expected in the (22 and 39 months), percentage with bilateral disease general population.65,*2"he incidence of second malig(17% and 6%),metastatic disease (2% and 13%),favorablenancies following Wilms' tumor in NWTS patients was histology tumors (100% and 92%), and intralobar initially reported in 1988; 15 second malignancies were nephrogenic rests (77% and 22%) all differed. Survival identified among 2438 patients, and the observed-toestimates for WAGR and non-WAGR patients were simiexpected ratio, or standardized incidence ratio, was lar at 4 year (95% versus 92%) but significantly different 8.5.18 These results were updated in 1996, and a similar at 27 years (48% versus 86%). Five late deaths among standardized incidence ratio of 8.4 was observed, with WAGR patients were from end-stage renal disease. 43 second malignant neoplasms occurring. Three breast cancers were found, and the relative risk in multivariate analysis was 12. To help characterize cases of secondary Treatment Morbidity and Mortality acute myelogenous leukemia on NWTSG protocols, Shearer et a1.126 reviewed the 7 patients with that disease An increasing number of children with Wilms' tumor among the 43 identified as having second malignant can expect to be cured, reflecting the undisputed neoplasms. All patients received chemotherapy regimens progress made in the treatment of children with this that included doxorubicin1° or etoposide,' and 6 were renal cancer. However, there is an increasing awareness treated with infradiaphragmatic irradiation. The median standardized of the late effects of cancer therapy.4"he latency period from initial diagnosis of the renal neomortality ratio observed in the' Childhood Cancer plasm to development of secondary acute myelogenous Survivor Study was 9.6 overall and 14.1 for the 5-year surleukemia was 3 years (range, 1.2 to 4 years). vivors of Wilms' tumor. Cumulative mortality was 1.8%, 3.1%, and 5.0% at 10, 15, and 20 years, re~pectively.~~ Radiation therapy has a variety of adverse effects. One study, designed to estimate the reduction in adult stature Some of the effects occur immediately after-treatment induced by radiation therapy of the spine in children (e.g., after the administration of certain chemotherapy) treated for Wilms' tumor, noted that height reductions and are usually transient, but they may become permawere dependent on dose, portal size, and age at treatnent. Although children seem to tolerate acute toxicities children were more often affected. m e n ~ . 7Younger ~ of therapy better than adults do, the growing child may
by lymph node involvement. A total of 2535 cases registered in 34 population-based cancer registries in 16 European countries were included in a recent EUROCARE report.Il0 The overall, 5-year survival of all children diagnosed from 1985 to 1989 was 83%. There was significantly lower survival among patients registered in the formerly socialist countries of Estonia, Poland, and Slovakia; overall European survival was slightly lower compared with results reported from the United States and Australia.
0
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Observed height deficits were 4.1 c m for 5 7 patients who received 15 to 24 Gy a t a mean age of 5 5 months; there was n o height deficit a m o n g 1 6 children who received doses less than 1 5 Gy a t a m e a n age of 83 months. Another retrospective study was undertaken to determine t h e possible effect of radiation therapy, chemotherapy, o r both o n live births, birth weight, a n d frequency of congenital malformations i n pediatric Wilms' tumor survivors." A questionnaire was distributed a m o n g survivors of Wilms' tumor treated in NWTS1 to -4. Respondents reported 427 pregnancies. Women who received flank radiation therapy were a t increased risk of fetal malposition a n d premature labor, a n d t h e offspring of these women were a t risk for low birth weight, premature birth, a n d the occurrence of congenital malformations. Importantly, fertility can b e preserved i n child r e n with Wilms' tumor after upper abdominal radiation therapy (10 to 20 Gy) that does n o t include the entire pelvis.8o
FUTURE DIRECTIONS For the first time since 1969, the NWTS is n o t conducting a clinical trial of treatment protocols. Current a n d future efforts a r e focused o n using the large cohort of former Wilms' t u m o r patients to study the long-term effects of diagnosis a n d treatment in survivors a n d to better understand the pathogenesis a n d cause of Wilms' tumor. T h e NWTS is currently conducting a Late Effects Study (LATE, also known as P O G 9442 a n d CCG 4941L), which o p e n e d i n October 1995, designed to identify treatment-related conditions that may develop in participants who were originally treated in o n e of the five clinical trials. LATE is a federally funded, multi-institutional observational study that follows participants a n d their children throughout their lives t o continue monitoring treatment results a n d possible late effects. T h e specific study objectives include the following:
1. Determine the incidence of life-threatening medical conditions in survivors of Wilms' tumor. 2. Determine mortality rates in former Wilms' tumor
3. Determine the risk of serious pregnancy complications a n d other adverse reproductive events in survivors of Wilms' tumor. 4. Determine the frequency of Wilms' tumor a n d o t h e r cancers i n the children a n d o t h e r family members of Wilms' tumor patients. 5. Identify the most informative subgroups of Wilms' tumor patients for use by molecular biologists a n d epidemiologists. By identifjing the treatment a n d host factors associated with excess mortality, interventions may b e develo p e d to target those a t highest risk. Now that 90% of children with Wilms' tumor a r e being cured, it is most important to focus attention o n t h e duration a n d quality of life in the survivors. Future Wilms' tumor protocols will b e d o n e through the COG. These protocols are still in development a t the time of this writing.
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MAFOR TUMORS OF CHILDHOOD
60. Green DM, Breslow NE, Beckwith JB, et al: Comparison between single-dose and divided-dose administration of dactinomycin and doxorubicin for patients with Wilms' tumor: A report from the National Wilms' Tumor Study Group. J Clin Oncol 1998;16:237-245. 61. Green DM, Breslow NE, Beckwith JB, et al: Effect of duration of treatment on treatment outcome and cost of treatment for Wilms' tumor: A report from the National Wilms' Tumor Study Group. J Clin Oncol 1998;16:37443751. 62. Green DM, Grigoriev YA, Nan B, et al: Congestive heart failure after treatment for Wilms' tumor: A report from the National Wilms' Tumor Study Group. J Clin Oncol 2001;19:1926-1934. 63. Green DM, Jaffe N: The role of chemotherapy in the treatment of Wilms' tunlor. Cancer 1979;44:52-57. 64. Green DM, Peabody EM, Nan B, et al: Pregnancy outcome after treatment for Wilms' tumor: A report from the National Wilms' Tumor Stttdy Group. J Clin Oncol 2002;20: 2506-2513. 65. Green DM, Zevon MA, Reese PA, et al: Second malignant tumors following treatment during childhood and adolescence for cancer. Med Pediatr Oncol 1994;22:1-10. 66. Gronskov K, Olsen JH, Sand A, et al: Population-based risk estimates of Wilms' tumor in sporadic aniridia: A comprehensive mutation screening procedure of PAX6 identifies 80% of mutations in aniridia. Hum Genet 2001;109:11-18. 67. Grundy P, Koufos A, Morgan K, et al: Familial predisposition to Wilms' tumour does not map to the short arm of chron~osome11. Nature 1988;336:374376. 68. Grundy P, Telzerow PE, Paterson MC, et al: Chromosome 11 uniparental isodisomy predisposing to embryonal neoplasms. Lancet 1991;338:1079-1080. 69. Grundy PE, Telzerow PE, Breslow N, et al: Loss of heterozygosity for chromosonles 16q and Ip in Wilms' tumors predicts an adverse outcome. Cancer Res 1994;54:2331-2333. 70. Gururangan S, Dorman A, Ball R, et al: DNA quantitation of Wilms' tumour (nephroblastoma) using flow cytometry and image analysis.J Clin Pathol 1992;45:498-501. 71. Henry I, Bonaiti-Pellie C, Chehensse V, et al: Uniparental paternal disomy in a genetic cancer-predisposing syndrome. Nature 1991;351:665-667. 72. Henry I, Grandjouan S, Couillin P, et al: Tumor-specific loss of 11p15.5 alleles in del 1lp13 Wilms' tumor and in familial adrenocortical carcinoma. Proc Natl Acad Sci U S A 1989;86:3247-3251. 73. Hing S, Lu YJ, Summersgill B, et al: Gain of l q is associated with adverse outcome in favorable histology Wilms' tumors. Am J Pathol 2001;158:393-398. 74. Hogeboom CJ, Grosser SC, Guthrie KA, et al: Stature loss following treatment for Wilms' tumor. Med Pediatr Oncol 2001;36:295-304. 75. Hu M, Zhang GY, Arbuckle S, et al: Prophylactic bilateral nephrectomies in two paediatric patients with missense mutations in the WT1 gene. Nephrol Dial Transplant 2004;19:223-226. 76. Huang EY, Mascarenhas L, Mahour GH: Wilms' tumor and horseshoe kidneys: A case report and review of the literature. J Pediatr Surg 2004;39:207-212. 77. Huff V, Compton DA, Chao LY, et al: Lack of linkage of familial Wilms' tumour to chromosomal band llp13. Nature 1988;336:377-378. 78. Huff V, Reeve AE, Leppert M, et al: Nonlinkage of 16q markers to familial predisposition to Wilms' tumor. Cancer Res 1992;52:6117-6120. 79. Jenkner A, Camassei FD, Boldrini R, et al: 111 Renal neoplasms of childhood: A clinicopathologic study. J Pediatr Surg 2001;36:1522-1527.
80. Kalapurakal JA, Peterson S, Peabody EM, et al: Pregnancy outcomes after abdominal irradiation that included or excluded the pelvis in childhood Wilms' tumor survivors: A report from the National Wilms' Tumor Study. IntJ Radiat Oncol Biol Phys 2004;58:13641368. 81. Kayton ML, Rowe DH, O'Toole KM, et al: Metastasis correlates with production of vascular endothelial growth factor in a murine model of human Wilms' tumor. J Pediatr Surg 1999;34:743-747. 82. Knudson AG, Strong LC: Mutation and cancer: A model for Wilms' tumor of the kidney. .J Natl Cancer Inst. 1972;48:313-324. 83. Ladd WE, White RR: Emb~yomaof the kidney (Wilms' tumor). JAMA 1941;117:1859-1863. 84. Leape LL, Breslow NE: The surgical treatment of Wilms' tumor: Results of the National Wilms' Tumor Study. Ann Surg 1978;187:351-356. 85. Lee MP, DeBaun MR, Mitsuya K, et al: Loss of imprinting of a paternally expressed transcript, with antisense orientation to KVLZT1, occurs frequently in Beckwith-Wiedemann syndrome and is independent of insulin-like growth factor I1 imprinting. Proc Natl Acad Sci U S A 1999;96: 5203-5208. 86. Lee SB, Haber DA: Wilms' tumor and the WT1 gene. Exp Cell Res 2001;264:7499. 87. Li CM, Guo M, Borczuk A, et al: Gene expression in Wilms' tumor mimics the earliest committed stage in the metanephric mesenchynalepithelial transition. Am J Pathol 2002;160:2181-2190. 88. Lin RY, Argenta PA, Sullivan KM, et al: Diagnostic and prognostic role of basic fibroblast growth factor in Wilms' tumor patients. Clin Cancer Res 1995;1:327-331. 89. Little MH, Williamson KA, Mannens M, et al: Evidence that WTl mutations in Denys-Drash syndrome patients may act in a dominant-negative fashion. Hum Mol Genet 1993; 2:259-264. 90. Lodge AJ, Jaggers J, Adams D, et al: Vascular control for resection of suprahepatic intracaval Wilms' tumor: Technical considerations. .J Pediatr Surg 2000;35: 1836-1837. 91. Look AT, Hayes FA, ShusterJ, et al: Clinical relevance of tumor cell ploidy and N-myc gene amplification in childhood neuroblastorna. A Pediatric Oncology Group Study. J Clin Oncol 1991;9:581-591. 92. Loworn HN Srd, Savani RC, Ruchelli E, et al: Serum hyaluronan and its association with unfavorable histology and aggressiveness of heterotransplanted Wilms' tumor. J Pediatr Surg 2000;35:1070-1078. 93. Lu YJ, Hing S, Williams R, et al: Chromosome l q expression profiling and relapse in Wilms' tumour. Lancet 2002;360:385-386. 94. Marsden HB, Lawler W: Bone-metastasizing renal tumor of childhood. Br J Cancer 1978;38:437-441. 95. Maw MA, Grundy P, Millow LJ, et al: A third Wilms' tumor locus on chromosome 16q. Cancer Res 1992;52: 30943098. 96. McNeil DE, Brown M, Ching A, et al: Screening for Wilms' tumor and hepatoblastoma in children with BeckwithWiedemann syndrome: A cost-effective model. Med Pediatr Oncol 2001;37:349-356. 97. Mertens A, Neglia J, Yasui Y, et al: Mortality rates and causes of death among 5-year survivors of childhood and adolescent cancer. Proc Am Soc Clin Oncol 1999;19:569a. 98. Miller RW, Fraumeni JG, Manning MD: Association of Wilms' tumor with aniridia, hemihypertrophy and other congenital abnormalities. N Engl J Med 1964;270: 922-930.
CHAPTER
99. Mitchell C, Jones PM, Kelsey A, et al: The treatment of Wilms' tumour: Results of the United Kingdom Children's Cancer Study Group (UKCCSG) second Wilms' tumour study. Br J Cancer 2000;83:602-608. 100. Montgomery BT, Kelalis PP, BLute ML, et al: Extended followup of bilateral Wilms' tumor: Results of the National Wilms' Tumor Study. J Urol 1991;146:514518. 101. Narahara K, Kikkawa K, Kimira S, et al: Regional mapping of catalase and Wilms' tumor-aniridia, genitourinary abnormalities, and mental retardation triad loci to the chronlosome segment llp1305-p1306. Hum Genet 1984;66:181-185. 10'2. Neville H, Ritchey ML, Shamberger RC, et al: The occurrence of Wilms' tumor in horseshoe kidneys: A report from the National Wilms' Tumor Study Group (NWTSG). J Pediatr Surg 2002;37:11341137. 103. Okutsu T, Kuroiwa Y, Kagitani F, et al: Expression and imprinting status of human PEG8/IGF2AS, a paternally expressed antisense transcript from the IGF2 locus, in Wilms' tumors. J Biochem 2000;127:475-483. 104. Osler W: Two cases of striated myo-sarcoma of the kidney. J Anat Physiol 1879;14. 105. Owens CM, Veys PA, Pritchard J, et al: Role of chest computed tomography at diagnosis in the management of Wilms' tumor: A study by the United Kingdom Children's Cancer Study Group. J Clin Oncol 2002;20: 2768-2773. 106. Pappo AS, Crist WM, Kuttesch J, et al: Tumor-cell DNA content predicts outcome in children and adolescents with clinical group 111 embryonal rhabdomyosarcoma. J Clin Oncol 1993;11:1901-1905. 107. Park S, Bernard A, Bove KE, et al: Inactivation of WTl in nephrogenic rests, genetic precursors to Wilms' tumour. Nat Genet 1993;5:363-367. 108. PelletierJ, Bruening W, Kashtan CE, et al: Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell 1991;67:437-447. 109. Pelletier J, Bruening W, Li FP, et al: WTl mutations contribute to abnormal genital system development and hereditary Wilms' tumour. Nature 1991;353:431-434. 110. Plesko I, Kramarova E, Stiller CA, et al: Survival of children with Wilms' tumour in Europe. Eur J Cancer 2001; 37:736-743. 111. Porteus MH, Nark001 P, Neuberg D, et al: Characteristicsand outcome of children with Beckwith-Wiedemann syndrome and Wilms' tumor: A report from the National Wilms' Tumor Study Group. J Clin Oncol2000;18:2026-2031. 112. Rahman N, Arbour L, Houlston R, et al: Penetrance of mutations in familial Wilms' tumor gene FW1. J Natl Cancer Inst 2000;96:650-652. 113. Re GG, Hazen-Martin DJ, Sens DA, et al: Nephroblastoma (Wilms' tumor): A model system of aberrant renal development. Semin Diagn Patho11994;11:126-135. 114. Reeve AE, Sih SA, Raizis AM, et al: Loss of allelic heterozygosity at a second locus on chromosome 11 in sporadic Wilms' tumor cells. Mol Cell Biol 1989;9:1799-1803. 115. Renaud EJ, Liu D, Pipe SW, et al: Inferior vena cavectomy for nonexcisable Wilms' tumor thrombus. J Pediatr Surg 2001;36:526-529. 116. Riccardi VM, Sujansky E, Smith AC, et al: Chromosomal imbalance in the aniridia-Wilms' tumor association: 1l p interstitial deletion. Pediatrics 1978;61:604610. 117. Ritchey ML: The role of preoperative chemotherapy for Wilms' tumor: The NWTSG perspective. National Wilms' Tumor Study Group. Semin Urol Oncol 1999;17: 21-27.
27
Wilms' Tumor
465
118. Ritchey ML, Green DM, Thomas PR, et al: Renal failure in Wilms' tumor patients: A report from the National Wilms' Tumor Study Group. Med Pediatr Oncol 1996;26:75-80. 119. Ritchey ML, Kelalis PP, Breslow N, et al: Surgical complications after nephrectomy for Wilms' tumor. Surg Gynecol Obstet 1992;1992:507-514. 120. Ritchey ML, Kelalis PP, Haase GM, et al: Preoperative therapy for intracaval and atrial extension of Wilms' tumor. Cancer 1993;71:41044110. 121. Ritchey ML, Pringle K, Breslow N, et al: Management and outcome of inoperable Wilms' tumor: A report of National Wilms' Tumor Study-3. Ann Surg 1994;220:683-690. 122. Ritchey ML, Shamberger RC, Haase G, et al: Surgical complications after primary nephrectomy for Wilms' tumor: Report from the National Wilms' Tumor Study Group. J Am Coll Surg 2001;192:63-68. 123. Ross JH, Kay R: Surgical considerations for patients with Wilms' tumor. Semin Urol Oncol 1999;17:33-39. 124. Shamberger RC, Guthrie KA, Ritchey ML, et al: Surgeryrelated factors and local recurrence of Wilms' tumor in National Wilms' Tumor Study 4. Ann Surg 1999;229: 292-297. 125. Shamberger RC, Ritchey ML, Haase GM, et al: Intravascular extension of Wilms' tumor. Ann Surg 2001;234:116-121. 126. Shearer P, Kapoor G, Beckwith JB, et al: Secondary acute myelogenous leukemia in patients previously treated for childhood renal tumors: A report from the National Wilms' Tumor Study Group. J Pediatr Hematol Oncol 2001;23:109-111. 127. Shurin SB, Gauderer MW, Dahms BB, et al: Fatal intraoperative pulmonary embolization of Wilms' tumor. J Pediatr 1982;101:559-562. 128. Smith MB, Xue H, Strong LC, et al: Forty-year experience with second malisznancies after treatment of childhood cancer: Analysis of outcome following the development of the second malignancy. J Pediatr Surg 1993;28:1342-1348. 129. Sorensen K, Levitt GA, Bull C, et al: Late anthracycline cardiotoxicity after childhood cancer: A prospective longitudinal study. Cancer 2003;97:1991-1998. 130. Sredni ST, de Camargct B, Lopes LF, et al: Immunohistochemical detection of p53 protein expression as a prognostic indicator in Wilms' tumor. Med Pediatr Oncol 2001;37:455-458. 131. Tagge EP, Hanson P, Re GG, et al: Paired box gene expression in Wilms' tumor. J Pediatr Surg 1994;29:134141. 132. Toretsky JA, Zitomersky NL, Eskenazi AE, et al: Glypican-3 expression in Wilms' tumor and hepatoblastoma. J Pediatr Hematol Oncol 2001;23:496-499. 133. Tournade MF, Com-Nougue C, de KrakerJ, et al: Optimal duration of preoperative therapy in unilateral and nonmetastatic Wilms' tumor in children older than 6 months: Results of the Ninth International Society of Pediatric Oncology Wilms' Tumor Trial and Study. J Clin Oncol 2001;19:488-500. 134. Trueworthy R, Shuster J,Look T, et al: Ploidy of lymphoblasts is the strongest predictor of treatment outcome in B-progenitor cell acute lymphoblastic leukemia of childhood: A Pediatric Oncology Group Study. J Clin Oncol 1992;10:606-613. 135. Vujanic GM, Kelsey A, Mitchell C, et al: The role of biopsy in the diagnosis of renal tumors of childhood: Results of the UKCCSG Wilms' tumor study 3:Med Pediatr Oncol 2003;40:18-22. 136. Vujanic GM, Sandstedt B, Harms D, et al: Revised International Society of Paediatric Oncology (SIOP) working classification of renal tumors of childhood. Med Pediatr Oncol 2002;38:79-82. 0
I
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M q l o ~TUMORS OF CHII.DHOOD
137. Weeks DA, Beckwith JB, Mierau GW, et al: Rhabdoid tunlor of kidney: A report of 111 cases from the National Wilms' Tumor Study Pathology Center. Am J Surg Pathol 1989;13:439-458. 138. White GR,Kelsey AM, Varley JM, et al: Somatic glypican 3 (GPC3) mutations in Wilms' tumour. Br J Cancer 2002; 86:1920-1922. 139. Wilms M: Die Mischgeschwuelste der Niere. In Leipzig, 1899, Arthur Georgi.
140. Zoeller G. Pekrun A. Lakomek M. et al: Wilms' tumor: The problem of diagnostic accuracy in children undergoing preoperative chemotherapy without histological tumor verification. J Urol 1994;151:169-171. 141. Zuppan CW, Beckwith JB, Luckey DW: Anaplasia in unilateral Wilms' tumor: A report from the National Wilms' Tumor Study Pathology Center. Hum Pathol 1988;19: 1199-1209.
Neuroblastoma Jay L. Grosfeld
Neuroblastoma is one of the most common solid tumors in infancy and childhood. This neoplasm, of neural crest origin, may arise in the adrenal medulla and along the sympathetic ganglion chain from the neck to the pelvis. The clinical course is quite variable, as this highly malignant tumor demonstrates unusual behavior. Although instances of spontaneous regression and tumor maturation from a malignant to a benign histologic form have been the disease is progressive in many cases. Survival in children with other malignancies, such as Wilms' tumor, rhabdomyosarcoma, acute lymphocytic leukemia, germ cell tumors, Hodgkin's disease, and non-Hodgkin's lymphoma, has been significantly improved by the aggressive use of combined treatment modalities, but the outlook for many children with advanced neuroblastoma remains dismal.'j,27,67,74,77,83,116 This neoplasm exhibits great heterogeneity in its behavior and represents a significant challenge to practitioners caring for affected children. Primitive neuroblasts can be identified in the fetal adrenal gland in the 10th to 12th intrauterine week. The nodules increase in number by 20 weeks' gestation but gradually diminish in number toward the end of gestation. Neuroblastoma in situ in the adrenal gland is seen in 1 of every 260 neonates who die of congenital heart disease and in as many as 1 in 39 infants in the first 3 months of life who die from other causes. The clinical incidence of the tumor is approximately 1 in 7500 to % 2 ~ , ~ ~ , ~ ~is responsible 10,000 ~ h i l d r e n . ~ ~Neuroblastorna for 10% of all childhood tumors and 15% of all cancer deaths. The exact cause remains unknown. There are 700 cases diagnosed annually in the United States. Approximately 40% of cases are diagnosed by age 1 year, 75% by 7 years, and 98% by 10 years.Z7 More than half the patients are younger than 2 years at the time of diagnosis.7Weuroblastoma is slightly more common in boys than in girls, with a ratio of 1.2:1.0.27~74It is the most common intra-abdominal malignancy in newborns. Although a decrease in cancer incidence and mortality has been observed in adults, the incidence of cancer in infants in the United States increased from 189 cases per million to 220 cases per million from 1980 to 1990.1'5 Male infants have an increased rate of central nervous system tumors, neuroblastoma, and retinoblastoma, while girls have an
increased rate of teratoma and hepatoblastoma.nj The embryonal nature of neuroblastoma has been well documented by its identification on prenatal ultrasonography, and the tumor has been known to rarely invade the placenta during the antenatal period.X.'2.~6,~0~,1()9,146,17II226 More than 55 cases of antenatally discovered neuroblastoma have been reported in the literature since the original description by Fenart et al. in 1983." The masses are usually identified during ultrasound examinations performed after 32 weeks' gestation. The earliest reported instance was observed at 18 weeks.10" Mothers of infants with congenital neuroblastoma occasionally experience flushing and hypertension during pregnancy as a result of catecholamine released from the fetal tumor in utero. The neo~lasmhas been described in twins on many occasions, and familial occurrences in both mother and child and father and son have been reported.37.70.171 Concordance for neuroblastoma in twins-during infancy indicates that hereditary factors may be predominant, whereas discordance in older twins suggests that a random mutation may be more important. The median age for the occurrence of familial neuroblastoma is 9 months, in contrast to 18 months in the general population. Maris et al.I4j observed that 20% of patients with familial neuroblastoma have bilateral or multifocal tumors and reported evidence for a hereditary neuroblastoma predisposition locus on chromosome 16~12-13.Neuroblastoma has been observed in infants with Beckwith-Wiedemann syndrome (BWS), neurofibromatosis (von ~ecklin~hausen's disease), Hirschsprung's disease, central hypoventilation syndrome (Ondine's curse), fetal alcohol syndrome, and in offspring of mothers taking phenytoin (fetal hydantoin syndrome) for seizure d i s 0 r d e r s . ~ ~ ~ ~ ~ ~ ~ ~ , ~ ~it~is2unlikely 0 W t h o uthat g h environmental factors play an important role in causing this tumor, neuroblastoma has been noted among infants of mothers receiving medical therapy for vaginal infection during pregnancy and with paternal occupational exposure to electromagnetic fields.27 Neuroblastoma may occur at any site where neural crest tissues are found in the embryo. The neuroblast is derived from primordial neural crest cells that migrate from the mantle layer of the developing spinal cord. Tumors may arise in the neck, posterior mediastinum,
468
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MAJORTUMORSOF CHILDHOOD
Mediastinal 20%
I Neck 208 Shimada histology was associated with an 85% survival entiated neural crest cells and have a high mitotic karyorrhexis index (MKI). The MKI refers to nuclear rate, compared with 41 % for unfavorable histologic types. fragmentations and is determined by the sum of the All ganglioneuroblastoma nodular (GNBn) cases were number of necrotic tumor cells, the number of cells with initially classified as unfavorable tumors. Umehara et al.230 were the first to define subsets of these specific neoplasms mitosis, and the number of cells with malformed, lobulated, that exhibit different behavior. Peuchmaur et al.l73 or pyknotic nuclei per 5000 cells examined. The MKI varies with age; a high MKI value in infants younger than recently revised the INPC by dividing GNBn cases into two prognostic subsets-favdrable and unfavorable. The 18 months is greater than 200/5000 cells, and for those older than 18 months it is greater than 100/5000 cells. All favorable type was associated with an 86% event-free surpatients older than 5 years have unfavorable histology. vival, whereas the unfavorable type (two thirds of cases) Stroma-poor tumors often have N-myc amplification, had only a 32% event-free survival. Children with the favorable subset of GNBn have an overall survival of greater than 90%, compared with 33.2% for the unfavorable GNBn subset (Fig. 28-'7).17' Large cell neuroblastoma has been identified as a distinct phenotype with aggressive clinical behavior.22Vhese tumors have unfavorable histologic features, including monomorphous undifferentiated neuroblasts, a low incidence of calcification, and a high " MKI. Immunohistochemical studies Favorable Unfavorable showed that large cell neuroblastoma cells stained posiAppearance Histology Histology tive for neuron-specific enolase, prodrug gene products, Stroma rich Well differentiated Ganglioneuroblastoma, and tyrosine hydroxylase and were negative for CD99.229 (ganglioneuroma) nodular On gross examination, neuroblastoma usually appears Ganglioneuroblastoma, as a highly vascular purple-gray mass that is often solid intermixed but occasionally cystic. The tumor has an easily ruptured, Stroma poor friable pseudocapsule that may lead to significant hemor(i.e., neurorhage during operative manipulation. The tumor is often blastoma) necrotic, especially the undifferentiated form. Mature MKI 4%or Age < I 8 mo tumors (ganglioneuromas) have a more solid consistency undifferentiated and frequently have a fleshy white color. The histologic MKI >2% or Age 18-60 mo MKI 5 yr small, blue round dell tumors such as Ewing's tumor, rhabdomyosarcoma, or primitive neuroectodermal tumors. The neuroblast is a small round cell consisting MKI, mitotic karyorrhexis index. predominantly of the nucleus without much cytoplasm. From Shimada H, Chatten J, Newton WA Jr, et al: Histopathologic prognostic factors in neuroblastoma: Definition of subtypes of ganglioneuroblastoma and an age-linked Immature, undifferentiated tumors are characterized bv classification of neuroblastoma.J Natl Cancer lnst 1984;73:405-416;Shirnada H, closely packed small spheroid cells without any special Stram DO, Chatten J, et al: Identification of subsets of neuroblastomas by combined arrangement or differentiation.I42 Nuclei may appear histopathologic and N-myc analysis. J Natl Cancer lnst 1995;87:1470-1476. cone shaped and are hyperchromic. Rosette formation Study and Rhabdomyosarcoma Study Group to form the Children's Oncology Group (COG), which now employs the INSS for all cases of neuroblastoma. At my institution, 266 cases of neuroblastoma were staged as follows: 14 (5.2%) stage I, 52 (19.6%) stage II,62 (23.4%) stage 111,117 (44%) stage IV, and 21 (7.8%) stage IV-S.
-"
CHAPTER
International Neuroblastoma Pathology Classification. FH, favorable histology; GNBn, ganaglioneuroblastoma nodular; MKI, mitotic karyorrhexis index; %MKC, mitotic and karyorrhectic cells; UH, unfavorable histology; * classic GNBn (single, macroscopically visible, usually hemorrhagic nodule in stroma-rich, stroma-dominant tissue background; ** MKC 2%, 100 of .5000 cells; MKC 4%, 200 of 5000 cells. (From Peuchmaur M, d ' h o r e ES, Joshi W, et al: Revision of the International Neuroblastoma Pathology Classification: Confirmation of favorable and unfavorable prognostic subsets in ganglioneuroblastoma, nodular. Cancer 2003;98:22742281.)
r >50%
t
Neuroblastoma
Absent+Ganglioneuroma maturing subtype
I
Ganglioneuroblastorna nodular classic*
Schwannian development
L
GNBn variant (with or without macroscopic b visible nodule(s)*
0 or >50%
Undifferentiated
+-
Differentiated
I -
Differentiating
. k
may be observed and is considered a sign of early tumor differentiation (Fig. 28-8). The center of each rosette is formed by a tangle of fine nerve fibers. More matureappearing, stroma-rich tumors may contain cells that resemble normal ganglion cells, with an admixture of
. - Hlstolog~cappearance of rosettes of neuroblastoma
FH
b~resentq~an~lioneuroblastoma intermixed
visible nodules
cells from a bone m a r m aspirate, an early sign of tumor dlfferennanon
473
Absent-+Microscopic neuroblastic foci
Neuroblastoma
, .
28
FH
UHIFH
UHIFH
%MKC'*
Age
Any MKI
Any age
UH
>4%
Any age
UH
Any MKI
>1.5 yr
UH
1.5 yr
UH
2%
1.5-5.0 yr
UH
Any MKI
Histology
histologic components characterized by abundant nerve filaments, neuroblastic rosettes, and ganglion cells all seen in a single microscopic field.70."7 On electron microscopy, neurofibrils and electrondense, membranebound neurosecretory granules may be observed. The neurosecretory granusles may be the site of conversion of dopamine to norepinephrine. These ultrastructural findings and genetic identification of the tumor tissue can usually separate neuroblastoma from other small cell tumors. Instances of spontaneous maturation from a highly malignant, undifferentiated neuroblastoma to a ganglioneuroblastoma and subsequently a benign ganglioneuroma have been observed. Ambros et al.11 reported that maturing neuroblastomas consist of both Schwann cells and neuronal cells, including ganglion cells. Schwann cells have normal numbers of chromosomes and triploid flow cytometry, in contrast to other neuronal cells, including ganglion cells.11These observations suggest that Schwann cells may be a reactive population of normal cells that invade a neuroblastoma recruited or attracted by trophic factors and may be responsible for tumor maturation and serve as an antineuroblastoma agent.10J~~2~chwann cells also produce angiogenesis inhibitors that induce endothelial cell apoptosis and may limit tumor growth by restricting angiogene~is.~~.~~
474
PART
III
M ~ ~ oTUMORS R OF CHILDHOOD
BIOLOGIC AND G E N n I C ALTERATIONS Unique oncogenes are observed in tumors, such as N-myc and ras 0ncogenes.'"2~ Amplification of N-myc (>lo copies) is associated with advanced disease, tumor progression, and a poor outcome, especially in children older than 1 year.'5x7.'!).1.5'2-15X:212 Overexpression of N-myc probably impairs differentiation and promotes the proliferation of N-myc immature neural crest-derived cells.2"z"he proto-oncogene is located on the short arm of chromosome 2p24. Double minutes and long, nonbanding staining regions have been observed at this site and may represent amplified cellular genes. Approximately 30% of patients with neuroblastoma have tumors with N-myc amplification. More than 90% of patients with N-myc amplification have rapidly progressive disease and are reistant to therapy. DNA flow cytometry studies evaluating tumor ploidy indicate that children with diploid tumors have a worse outcome than those with aneuploid (hyperdiploidy or triploidy) turn or^.^^^^^ N-myc amplification is commonly associated with chromosome l p deletion and diploidy.30,89 Diploid tumors are commonly associated with an unbalanced gain of chromosome 17q, even in the absence of N-myc.11~27~"~144 Allelic loss of l l q and 14q and gains of 4q, 6q, l l q , and 18q have also been observed (Table 28-3).27 High expression of the neurotropin Trk-A (a highaffinity nerve growth factor receptor) is associated with a good prognosis and is inversely related to N-myc.lS7Jj8 Trk-A is observed in young infants and in those with stage I and stage IV-S tumors and indicates a very favorable o ~ t c o m e . l "Trk-A ~ ~ ~ is ~ associated with neural cell
Genetic Feature
Associated Factors
Risk Group
N-myc amplification (2p24 locus)
Diploidy or tetraploidy Allelic loss of l p , high Trk-B, advanced disease (stage Ill, IV)
High
More aggressive tumor associated with N-myc amplification Occurs concurrently with N-myc amplification
High Risk related to N-myc
Often associated with N-myc 70%-80%are near diploid tumors associated with disease progression
High
Few associated with N-myc amplification
Intermediate; decreased survival in patients without N-myc amplification
Allelic gain 17q gain Gain at 4q, 6p, 7q, l l q , 18q observed Allelic loss lp36
I
differentiation and tumor regression and may play a role in angiogenic inhibition. The low-affinity nerve growth factor receptor gene is another proto-oncogene that has a prognostic effect similar to Trk-A and probably influences cellular maturation.'"z7Jz() In contrast, high expression of Trk-B with its ligand BDNF may provide an autocrine survival pathway in unfavorable tumors, particularly those ~ ~ ~ ' ~patients ~ have with N-myc a m p l i f i ~ a t i o n . 2 7 ~These more advanced disease, are usually older than 1 year, and have a dismal 0utcome.27J00.~~"rk-C expression has also been identified in neuroblastoma and is usually observed in lower-stage tumors that do not express N-myc.z7,"0 Another gene has been cloned, the multidrug resistance (MDR)-associated protein gene, that is associated with chemotherapy resistance, overexpression of N-myc, and a poor outcome.lm Similarly, elevated P-glycoprotein levels are associated with progressive disease and a poor outcome.""2" Telomerase is increased in tumor cells and maintains cell viability by preserving the telomeres that . ~ ~ ~is~an ~ ~inverse protect the end of c h r o m ~ s o m e sThere relationship between telomerase levels and outcome in neuroblastoma and a direct correlation between telomerase levels and N-myc amplifi~ation.2~ CD44 is a glycoprotein found on the cell surface of a number of tumors, including neuroblastoma. High expression of CD44 is associated with a favorable outcome. In contrast, nm23 overexpression is observed in instances of advanced and The ganglioside GD2 is aggressive ne~roblastoma.14~ found on human neuroblastoma cell membranes, and increased levels are associated with active disease and tumor progression. Gangliosides inhibit the tumorspecific immune response.15'
llq
Correlates with LOH 14q Correlates with LOH l l q , inverse relationship with l p and N-myc Predisposition 16~12-13 Association Chromosome 1 0 (Ret-oncogene) 11~15.5
Intermediate
Familial neuroblastoma Multifocal and bilateral neuroblastoma
Low
Hirschsprung's disease Beckwith-Wiedemannsyndrome
Variable Low
LOH, loss of heterozygosity. Note: This table does not include changes in the genetic expression of Trk-A, -B, and -C; the multidrug-resistant protein gene; telomerase; or others that are covered elsewhere in this chapter.
1
CHAPTER
28
Neuroblastoma
475
Evaluation of the relationship between tumor angiogendisease had operative resection, but many had microesis and outcome in infants with neuroblastoma demonscopic residual disease or tumor that extended into an strates that increased tumor vascularitv characterized bv intervertebral foramen, making complete resection microvessel density correlates with advanced dissemiimpossible. Some of these patients received localized nated disease and the likelihood of metastase~.~~,~9~",ls3 radiotherapy. Others received only operation, despite Angiogenesis is controlled by the balance of humoral the presence of residual tumor; these patients had only a stimulators, inhibitors, and signal transduction pathways.40 75% to 80% cure rate.74,124,164 Angiogenesis is associated with N-myc amplification, unfaBecause of the wide variabilitv in tumor behavior in vorable histology, and poor outcome. Neuroblastoma stage I1 patients with residual disease and the poor surproduces angiogenic factors that induce blood vessel vival of those with more advanced tumors (stages I11 and IV), it became apparent that additional information was growth, including vascular endothelial growth factor required to determine the appropriate treatment. (VEFG), platelet-derived growth factor (PDGF-A), stem cell factor, and their respective receptors Flk-1, PDGFR, During the past 2 decades, a number of biologic and and C-kit.l5 Komuro et a1.'22 demonstrated that high genetic factors have been identified that are important VEGF-A expression correlated with stage IV disease and prognostic indicators and currently influence therapy. suggested that it could be a target for antiangiogenic therBased on the impact of the new INSS, the use of the apy. Kaicker et a1.H' noted that VEGF antagonists inhibit INPC, and the identification of numerous biologic and nkoangiogenesis and tumor growth in e ~ p ~ r i m e n tneual genetic characteristics as risk factors and predictors of roblastoma in athymic mice with xenograft neuroblasoutcome, a risk-based management system has been develNewer treattoma cell line NGP. They also found that thalidomide oped to determine treatment.27~74.208-210~213 suppressed angiogenesis 'and reduced microvessel denment protocols individualize treatment using risk factors sity but not tumor growth. Kim et al."' and Rowe et al.Ig3 as medictors of outcome in an effort to maximize survival. also demonstrated inhibition of tumor growth in experiminimize long-term morbidity, and improve the quality of mental neuroblastoma models using antiangiogenic life. Current protocols are now based on low-, intermedistrategies. Imatinib mesylate, a compound used to treat ate-, and high-risk tumor categorization (Table 28-4). patients with gastrointestinal stromal tumors, has been Good outcomes are associated with stage I, 11, and IV-S shown to decrease the growth of neuroblastoma in vivo patients who are younger than 1 year and have hyperand in vitro, decrease cell viability, and increase apoptosis diploid DNA flow cytometry, favorable histology, less (by ligand-stimulated phosphorylation of C-kit and than one copy of N-myc, high Trk-A expression, and PDGFR) in a severe combined immunodeficiency (SCID) absence of chromosome l p abnormalities. In contrast, a mouse model.15 Davidoff et a1.4Wemonstrated that gene poor prognosis is likely in children older than 1 year with therapy using in situ tumor cell transduction with retroadvanced tumors (stages I11 and IV), more than 10 viral vectors can deliver angiogenesis inhibitors for the copies of N-myc, low Trk-A expression, diploid DNA Flk-1 receptor and restrict tumor-induced angiogenesis ploidy, allelic loss of lp36, and unfavorable histology. and tumor growth. For low-risk patients, surgical excision of the tumor is The Bcl-2 family of proteins is responsible for relaying usually curative and avoids the risks associated with apoptotic signals that influence tumor cell regression chemotherapy. Intermediate-risk patients are usually and is expressed in most neuroblastomas. The Bcl-2 gene treated with surgery and standard chemotherapy. The a protein that prevents neuronal cell death poor prognosis in high-risk patients justifies a much (apoptosis). The level of Bcl-2 expression is high in more intense treatment regimen, including combination advanced cases associated with a poor outcome and low chemotherapy followed by complete surgical excision (if in cases demonstrating tumor apoptosis (regression) and possible), radiation therapy to achieve local control, expression may aiso play a role differentiation. High ~ c l - 2 myeloablative treatments, and bone marrow rescue. .~~ of in acquired resistance to c h e m ~ t h e r a p y Subgroups the Bcl-family include Bcl-xL, which inhibits apoptosis, and Bcl-xS, which induces natural cell death. VEGF upOPERATIVE MANAGEMENT regulates Bcl-2 expression and promotes neuroblastoma cell survival by altering apoptosis and its regulation Complete surgical removal of the primary tumor proteins.14 Elevated caspase levels (enzymes responsible remains an essential component of treatment in the vast for apoptotic signaling) are associated with an improved majority of cases. Operative procedures are performed outcome in neuroblastomas that demonstrate favorable using endotracheal general anesthesia and careful monbiologic features.Y7 itoring. Appropriate large-bore intravenous catheters are placed in the upper limbs. Adequate intravenous access is important because these tumors are quite vascular, and blood loss may be excessive. Body temperature, oxygen satRISK-BASED MANAGEMENT uration, electrocardiogram, and pulse rate are monitored. For many years, the choice of therapy in neuroblastoma The blood pressure must also be carefully monitored intravaried with the extent of disease at the time of diagnosis, operatively to detect sudden hypertension caused by Total excision or the patient's age, and the ~tage.2"~,~~2" excessive catecholamine release from the tumor. excision of as much tumor as possible in localized cases In patients with primary tumors located in the I lesions were resulted in the best outcome~.6~,~"~tage retroperitoneum, the operation is performed through a t i e nstage ts I1 managed by operation a l ~ n e . ~ ~ ~ ~ W a with long, transverse transperitoneal-supraumbilical incision.
476
PART
III
MAJORTUMORS OF CHILDHOOD
INSS Stage
Age
N-myc Status*
I IIA/IIB
0-21 yr >365 days 365 days-21 yr 365 days-21 yr 365 days-21 yr 365 days-21 yr >365 days-21 yr 10 copies of N-myc, chromosome l p deletion, diploid flow cytometry, unfavorable histology).j4Thirteen percent of stage I1 cases have high-risk prognostic factors and require aggressive chemotherapy. Patients with more advanced disease (stage 111) often require more aggressive treatment, including operative resection (if possible), multiagent chemotherapy, and initial local irradiation. Stage I11 tumors in the pelvis or near the celiac axis are often unresectable initially. After chemotherapy, however, the tumor frequently becomes small enough to be excised at a second-look operation.74-83Patients with stage I11 disease have an improved ~ , ~ type ~ of adjuncoutlook after complete r e s e ~ t i o n . jThe tive therapy depends on tumor resectability, histology, and biologic and genetic characteristics affecting risk for that specific neoplasm. Completely resected tumors with favorable prognostic factors may require less intensive chemotherapy. In contrast, patients with incomplete tumor resection are usually treated with local irradiation to the tumor bed and more dose-intensive chemotherapy regimens. Those with high-risk unresponsive tumors may benefit from intensive cytoablative chemotherapy followed by autologous bone marrow transplantation (BMT).31,84,14"14Wigh-risk stage 111 cases can usually be
480
PART
III
MAJORTUMORS OF CHILDHOOD
patients with a complete response to chemotherapy and tumor resection,78,84,218data concerning the biologic characteristics of the surviving patients were often lacking, and an independent effect of gross tumor resection could not be demonstrated.134 More recently, LaQuaglia et a1.135 reviewed 141 INSS stage IV patients and reaffirmed that the rate of gross tumor resection improved with more intense chemotherapy. The probability of local tumor progression was 50% in unresected patients, compared with 10% in those with gross total resection. The overall survival rate was 50% in resected patients, versus 11% in patients with unresected tumors.'" Aggressive surgical management is occasionally associated with late complications in survivors, including ipsilateral atrophy of the kidney following adrenal resection and ejaculatory problems following pelvic tumor excision.l26 Of interest is the very favorable outlook noted in patients with stage 111 and IV tumors arising in the pelvis following complete tumor r e s e c t i ~ n . ~ ~ , ~ ~
predicted by the presence of adverse biologic features, such as age older than 1 year, unfavorable tumor histology, and more than 10 copies of N-rnyc.148J49 The marrow is purged for tumor cells with multiple monoclonal antibodies before BMT.151 Emwlovment of BMT earlv in the management of unresponsive tumors with high-risk biologic factors results in a better outcome than if BMT is attempted as a lastditch effort in patients with progressive disease.149,151,178In recent years, the use of autologous stem cell transplantation has replaced traditional BMT in many childhood cancer facilities. The CCG compared initial resection at diagnosis with delayed primary resection and second-look procedures for initially inoperable stage IV tumors. Complete resection was possible in 62% of the initial group, 77% of delayed primary operations, and 66% of second-look procedures.84 The risk of concomitant nephrectomy and the incidence of postoperative complications were lower in children in the delayed primary resection Because there was no difference in survival among the three groups (40% among complete responders at 3 years), delayed primary resection after chemotherapy was considered the wrocedure of choice in children with stage IV tumors. The role of primary tumor resection in patients with stage IV disease is unsettled. In patients who respond completely or partially to chemotherapy, it has been my practice to perform a delayed primary or second-look operation to remove all possible residual tumor. There are conflicting reports concerning the efficacy of complete resection i n itage IV disease.-~aaseet al.,84 reporting for the CCG, described a survival advantage for stage IV patients with complete resection following delayed primary excision after chemotherapy. In contrast, reports by Kiely1I6and Shorter et al.215 suggest that there is no survival advantage for stage IV patients with complete resection. However, LaQuaglia et a1.,134in a report of 70 stage IV patients, noted that gross tumor resection and a higher-intensity chemotherapy protocol resulted in improved overall survival. Although some studies have shown an improved survival in stage IV 1
,
NEUROBLASTOMA IN INFANCY Infants younger than 1 year at diagnosis have a significantly improved outcome. At the Riley Hospital for Children, the survival rate was 76% for infants younger than 1 year and only 32% for older patients (Fig. 28-12).7Vhisfavorable outlook for patients younger than 1 year extends across all stages, including infants with stage IV metastatic disease. The incidence of stage IV lesions in infants younger than 1 year is 30%, compared with 60% to 70% in older patients.76 ~1tho;gh resection of the primary tumor in stage IV disease is controversial, in my personal experience, the only infant survivors had excision of the primary tumor.76 Similarly, a CCG report described 7 of 11 infants with stage fi disease who had complete delayed primary tumor resection and remained disease free for more than 5 year^.^^,^^ Infants with stage IV disease respond better to chemotherapy than older children do; 50% of Bar graph d e m o n strates t h e improved survival i n infants with neuroblastoma w h o are younger t h a n 1 year.
Percent survival
I
I*
2
Under 1 yr
0
10
20
30
40 Percent
50
60
70
80
CHAPTER
infants have a complete response to treatment, compared with 22% of older children.85 This observation suggests that resolution of metastases may have a greater impact on length of survival than the surgical excision does. Further, this implies that surgical resection is beneficial in some infants and should be a t t e m ~ t e dwhen disseminated disease is controlled by chemotherapy. Paul et al.170 documented a 75% 5-year survival rate in 24 stage IV patients younger than 1 year, compared with a 10% survival rate for older patients with stage TV tumors. Patients were treated with nitrogen mustard, vincristine, dacarbazine, doxorubicin, cyclophosphamide, and cislat tin without BMT. Schmidt et al.204observed a 93% surviva1 rate in infants younger than 1 year with stage IV disease without N-myc amplification; however, those with more than 10 copies of the N-myc oncogene had rapidly progressive disease and often succumbed despite chemotherapy.204 Therefore, more intensive chemotherapy regimens and BMT may be necessary to attain a cure, especially in highly selected infants presenting with adverse biologic markers. 1
STAGE IV-S The most unusual group of patients with neuroblastoma are those infants younger than 1 year with stage IVS disease, characterized by hepatomegaly, subcutaneous nodules, and positive bone marrow, that would otherwise be classified as stage I or 11 primary tumor. Stage IV-S cases account for approximately 30% of patients with neuroblastoma
A
28
Neuroblastoma
481
of these recognized in the first year of life.7"reatment patients is somewhat controversial. Some infants may die as a result of complications of stage IV-S disease rather than tumor progression. Complications of severe hepatomegaly include respiratory insufficiency, caused by significant elevation of the diaphragm by the large, tumor-filled liver; coagulopathy; and renal compromise due to compression by the mass (Fig. 28-13).",45,50,76,236Vomiting may occur because of a change in the gastroesophageal angle related to the diaphragmatic elevation, resulting in gastroesophageal reflux, protein-calorie malnutrition, and aspiration pneumonia. Total parenteral nutrition may be a useful Most fatalities in stage IV-S therapeutic adjunct.l"J",2" cases occur in infants younger than 2 months with severe symptoms related to hepatomegaly, who do not tolerate ~2 therapy as well as older infants d 0 . ~ " ~ Symptomatic hepatomegaly caused by tumor infiltration may benefit from low-dose irradiation to the liver in the range of 600 to 1200 Gy, administered in doses of 100 to 150 Gy/day.21,76s83 Although some early reduction in the size of the liver is seen, and peripheral edema may resolve in a few weeks, complete resolution may take 6 to 15 months.76Resolution of the liver mass is probably related more to the natural course of stage IV-S disease than to radiotherapy. Administration of low-dose cyclophosphamide 5 mg/kg per day is a reasonable treatment alternative. Although some investigators advocate the insertion of a Dacronreinforced Silastic sheet to create a temporary ventral abdominal wall hernia to accommodate the enlarged liver and reduce intra-abdominal pressure, I have not
B
A, Six-week-old infant presented with abdominal dister tio on and hepatomegaly. B, Appearance of the liver at laparotomy. There were multiple metastatic nodules, and the biopsy confirmed the diagnosis of stage IV-S neuroblastoma.
482
PART
III
MAJORTUMORS OF CHILDHOOD
found this technique to be effective.205Mortality due to septic complications after insertion of an external Silastic sheet has been observed.".76 To reduce the risk of infec~~ the use of an tion, Lee and A p p l e b a ~ m lrecommend internal polytetrafluorethylene patch to create a temporary ventral hernia. The graft can be removed in stages as the bulk of the hepatic mass regresses over time. Survival of these unusual infants with remote metastases is greater than 80%, often without specific treatment. Table 82-5 summarizes the results reported in 12 studies of stage IV-S neuroblastoma, with an overall 86% survival rate. Most patients with stage IV-S disease (>go%) have favorable genetic and biologic factors, including high Trk-A expression, no N-myc amplification, favorable histology, and no evidence of allelic loss of chromosome 1p.This suggests that the majority of stage IV-S tumors undergo spontaneous regression. Although most patients with stage IV-S disease do well, Wilson et a1.S6 reported 18 cases with a heterogeneous tumor presentation and a survival rate of only 50%, including three patients with N-myc amplification. The presence of adverse genetic and biologic prognostic factors suggests that this subset of patients ( 4 0 % ) requires more aggressive therapy. Of interest is that infants with multiple subcutaneous nodules seem to have the most favorable outlook. This may be due to increased immunologic activity as a result of tumor being present in multiple ~ i t e s . 7Increased ~ uptake of major histocompatibility complex (MHC) class I antigen by neuroblastoma cells in vitro and in vivo may influence the outcome favorably.22O Infants with stage IV-S disease have normal levels of MHC class I surface antigen expression, whereas those with stages I to IV have low levels.220 Sugio et al.224 reported that down-modulation of MHC class I antigen expression is associated with increased amplification of the N-myc oncogene in patients with advanced disease. In 2002 ~ickversonei a1.'62 described 80 infants with stage IV-S disease from the CCG. Fifty-eight cases were managed without specific therapy. All 44 asymptomatic patients survived without treatment. Symptomatic patients were treated with cyclophosphamide 5 mg/kg
Author (Year) D'Angio et al (1971)45 Breslow et al (1971)23 Nitschke et al (1980)l65 Nickerson et al (1985)163 Blatt et al (1987)21 Wilson et al (1991)236 Suarez et al (1991)223 DeBernardi et al (1992)50 Grosfeld et al (1993)76 Hatchitanda et al (1996)ss Nickerson et al (2000)162 Schleiermacher et al (2003)203 Total
No. of Patients
94 460
per day for 5 days and hepatic radiation at a dose of 4.5 Gy over 3 days. Five of six deaths occurred in symptomatic infants younger than 2 months. Event-free 5-year survival was 86%, and overall survival was 92%. Early intervention is indicated in stage IV-S patients with lifethreatening complications (e.g+, hepatosplenomegaly, coagulopathy, renal failure).76Ja Surgical resection did not alter outcome. More aggressive chemotherapy is also required in those cases in which the tumor demonstrates more than 10 copies of N-myc, chromosome l p deletion, ~2,2~~ of or other adverse biologic m a r k e r ~ . ~ ~ JAmplification N-myc may be observed in 1 of 12 patients with stage IV-S tumors who develop progressive disease and succumb, despite having a favorable prognostic stage. In 2003 Schleiermacher et al.,203in a report concerning 94 babies with stage IV-S neuroblastoma in France, observed an 88% overall survival and recommended a more intensive regimen using cisplatin and etoposide for those who require therapy. Some infants with stage IV-S have survived without resection of the primary tumor (in some, the primary tumor may not be identified). Knowing that resection of the primary tunlor may have some benefit in infants with stage IV tumors, resection of the primary neoplasm should be accomplished when feasible, especially in high-risk stage IV-S cases with any unfavorable characteristics.76
CYSTIC NEUROBLASTOMA Cystic neuroblastomas are relatively rare and are often identified on prenatal ultrasound examinations.227 They characteristically occur in the adrenal gland, and almost all are diagnosed in early infancy (Fig. 28-14). Few are calcified, and only 10% are associated with elevation of
No. of Survivors (%) 14 (88) 18 (95) 11(100) 31 (89) 8 (73) 9 (50) 28 (75) 63 (83) 17 (81) 36 (80) 74 (92) 83 (88) 392 (85)
Photograph of a cystic neuroblastoma of the adrenal gland in a 5-month-old baby that required complete excision. The patient was managed by surgery alone and is a long-term survivor.
CHAPTER
28
Neuroblastoma
483
urinary VMA and HVA levels.187 They are associated with children with resectable localized neuroblastoma with a benign behavior and a favorable outcome. There is favorable biologic and genetic characteristics. For stage I and most stage I1 patients, surgery alone is all that is necsome evidence that these lesions have a tendency to es~ary.6~,7~28Vtage I1 patients with poor prognostic biologic e regress and undergo spontaneous i n v ~ l u t i o n . ~ ~ ~ o m investigators have recommended observation alone, with and genetic factors, however, are at higher risk and should close serial sonogram monitoring of the mass during the be treated more aggressively with multiagent chemotherfirst few months of life to be sure that the tumor mass apy, including cisplatin, doxorubicin (Adriamycin) , cyclophosphamide, and etoposide (W-16). For advanced shrinks, indicating tumor regression. Operative reseccases (stages I11 and IV), the mainstay agents throughout tion should be reserved for those tumors that fail to the 1970s and early 1980s included cyclophosphamide, regress or that increase in size. When resection is indivincristine, and dacarbazine.6lfj4.67 Treatment failures cated, surgery is the only therapy recommended. The received doxorubicin and teniposide (VM-26). COG has initiated a prospective study of observation only Although these chemotherapy protocols did not effecfor cases of cystic neuroblastoma. It uses strict criteria in tively increase the cure rate of stage IV patients, such treatterms of tumor volume (5 yr Hepatitis B virus Cirrhosis Liver disease
18%to 28%11.26
1
Hepatoblastoma is associated with Beckwith-Wiedemann syndrome, familial adenomatous polyposis, hemihypertrophy, and low birth weight.l",'",44360,66The most common genetic aberrations involve chromosomes lp, lq, 2q, 4q, 7q, 8q, 12p, 17q, 20, 22q, Xp, and Xq.6"71,7Wepatoblastoma has also been associated with stabilizing mutations of p-catenin and activation of Wnt/p-catenin signaling.6 Up-regulation of insulin-like growth factor 2 has also been observed in hepatoblastomas and may be mediated by the overexpression of PLGAl oncogene, a transcrip~~ tional activator on the 8q c h r o m o ~ o m e .Cytogenetic abnormalities have not led to the identification of a causal factor nor been shown to influence prognosis. The cause of hepatoblastoma remains unclear, but recent theories suggest that hepatoblastoma is derived from a pluripotent hepatic stem cell or oval stem cell that can differentiate into both hepatocytes and biliary epithelial cells. Both hepatoblastoma cells and oval stem cells express markers for these two lineages. Further, the structural features of hepatoblastoma resemble those found in distinct phases of h e p a t ~ g e n e s i s . ~ ' , ~ ~ The association between very low birth weight (VLBW) and hepatoblastoma may be explained by a higher likelihood of genetic abnormalities or the susceptibility of the immature liver to the effects of intensive perinatal therapy (e.g., oxygen, diuretics, radiation). In one study, hepatoblastoma patients had a longer duration of and more aggressive perinatal therapy than did birth weightmatched controls.54VLBW infants may also be at higher risk of developing advanced h e p a t ~ b l a s t o m a . ~ ~ o m e reports have suggested that infants with VLBW or other conditions associated with hepatoblastoma might benefit from screening with serial ultrasound examinations and serum alpha fetaprotein (AFP) monitoring to increase the likelihood of early detection." However, a cost-benefit analysis of screening for hepatoblastoma in high-risk patients must be performed before it is applied routinely. Hepatocellular carcinoma occurs predominantly in the setting of underying liver disease and cirrhosis. In young children, hepatocellular carcinoma has been associated with tyrosinemia and other inherited metabolic disorders.76 The incidence of hepatocellular carcinoma in the United States is higher in Asians and foreign-born children.10.14 In Taiwan, hepatocellular carcinoma occurs
CHAPTER
503
Liver Tumors
elevated serum transaminase levels are occasionally observed.57 Diagnosis is ultimately made with biopsy. An algorithm for the diagnosis and treatment of malignant liver neoplasms is presented in Figure 30-1. The most sensitive laboratory test for hepatoblastoma and hepatocellular carcinoma is serum AFP level. AFP is produced in the fetal liver and yolk sac, and levels decline to adult values during the first 6 months after birth. Although AFP can be used effectively as a tumor marker, it is nonspecific. Serum AFP levels are elevated in over 90% of hepatoblastomas and in approximately 70% of hepatocellular carcinomas.13~" Falsely elevated serum AFP levels can be noted in hepatitis, cirrhosis, hemangioendothelioma, germ cell tumor, testicular tumor and gallbladder carcinoma. Normal AFP levels have been observed with both well-differentiated and immature hepatoblastomas and frequently occur with the fibrolamellar variants of hepatocellular c a r c i n o m a . l ~ JSerum 3 ~ ~ AFP levels can be used to monitor chemotherapeutic efficacy and to detect disease recurrence. Rarely, hepatoblastoma may secrete Phuman chorionic gonadotropin, associated with sexual precocity.
predominantly in hepatitis B viral carriers.14 Hepatitis B vaccinations led to a significant decrease in the rate of hepatocellular carcin0ma.~,"~46A Taiwanese study comparing hepatocellular carcinoma in children and adults demonstrated that hepatitis B viral infection was always present in children (100% versus 80%), the frequency of liver cirrhosis was similar (70%), and the rate of resectability was lower in children (18% versus 56%).1°
CLINICAL FEATURES AND LABORATORY DATA Most patients with liver tumors present with an abdominal mass, and more than two thirds of liver tumors are malignant." Although most patients are asymptomatic, some note abdominal distention, anorexia, weight loss, pain, nausea, and fatigue. An abdominal computed tomography (CT) or ultrasound scan is obtained, which usually reveals a solid liver mass. Laboratory studies should include complete blood cell count, chemistry panel, liver function tests, coagulation profile, and serum AFP levels. Thrombocytosis is present in 60% of cases.7Unemia and
Algorithm for the diagnosis and treatment of a liver mass. AFP, alpha fetoprotein; CBC, complete blood count; CT, computed totnography; CXR, chest radiograph; LFT, liver function tests; MRI, magnetic rcsonance imaging; PT/PTT, prothrombin time/partial thromboplastin time; US, ultrasound.
30
Liver Mass
.
Diagnostic lmaging (US andlor CT)
-w
Solid
Vascular or Cystic
&
J. Staaina Workaroup: Labs (AFP, CBC, LFTs, PTIPTT, Chemistry) CXR Chest CT MRI
*
J. Surgery for Exploration
Resectable
Angiography IResection vs. Obsewation
(+) Metastasis
I
7
Not Resectable
Biopsy
J.
Neoadjuvant Chemotherapy
lmaging Resection
4
I
Not Resectable
3. Chemotherapy (* Chemotherapy for Stage I - Pure Fetal Histology)
Follow-UP
Original AFP
Serial AFP
t
Original AFP Normal
Serial Imaging
1
504
PART
III
M A ~ TUMORS R OF CHII.DHOOD
IMAGING Imaging is helpful both for diagnostic purposes and to assess tumor resectability. Ultrasonography or CT of the abdomen is performed initially to assess the tumor.Z3 A chest radiograph or CT scan of the chest should also be obtained to rule out metastatic disease. Ultimately, imaging should delineate the size and location of tumors, evaluate for metastastic disease, and determine whether vascular invasion of the portal vein, hepatic veins, or inferior vena cava is present. Although advances in imaging have improved the ability to predict resectability, the ultimate assessment is made in the operating room by the surgeon. Ultrasonography is helpful for the initial evaluation and to assess vascular involvement. Liver lesions can be categorized sonographically as solid, cystic, or vascular. Malignant liver neoplasms are usually well-defined hyperechoic (solid) lesions on ultrasonography.15 Color Doppler ultrasonography is helpful in diagnosing venous thrombosis and vascular shunts within the tumor." It has also been used intraoperatively to aid in determining vascular involvement and tumor resectability. CT with intravenous and gastrointestinal contrast enhancement is useful to delineate tumor type, size, and location and to detect regional lymphadenopathy. Abdominal CT usually reveals a mass with low attenuation. Helical CT with three-dimensional reconstruction can be performed in complex cases that require nonstandard resections.
A
Magnetic resonance imaging (MRI) and magnetic resonance angiography are especially helpful in determining the tumor's relationship to the hepatic vasculature and biliary anatomy. Liver tumors have homogeneous hypointensity on T1-weighted images and hyperintensity on T2-weighted images." Three-dimensional reconstruction can significantly enhance the surgeon's ability to predict resectability (Fig. 30-2). Angiography was used in the past to delineate the anatomy of the hepatic vasculature, but with the availability of MRI and contrast-enhanced CT, it is rarely required for the diagnostic evaluation of malignant liver neoplasms. Angiography is used in some cases to perform selective chemoembolization as a therapeutic intervention.
DIFFERENTIAL DIAGNOSIS AND HISTOLOGY Diagnosis is ultimately made with biopsy using percutaneous, laparoscopic, or open approaches. Fine-needle aspiration can be sufficient for diagnosis. Some groups permit the initiation of neoadjuvant chemotherapy based on clinical criteria when those clinical features are highly suggestive of hepatoblastoma or hepatocellular carcinoma.13 However, given the significant error rate in clinical diagnosis, we strongly advocate biopsy in all cases.'" The distribution of malignant and benign primary hepatic tumors of children is shown in Table 30-2. Hepatoblastoma and hepatocellular carcinoma are of
B
A, Magnetic resonance imaging o f a &month-old cklild demonstrates a 10-cm right hepatic mass. B, Magnetic resonance angiography with three-dimensional reconstruction allows image roctation and delineation o f vascular anatomy. Compression o f the intrahepatic vena cava demonstrates unresectability.
CHAPTER
Tumor Malignant Hepatoblastoma Hepatocellular carcinoma Sarcoma Benign Benign vascular tumor Mesenchymal hamartoma Adenoma Focal nodular hyperplasia Other
30
Liver Tumors
505
% of Patients 43 23 6
13 6 2 2 5
Adapted from Weinberg AG, Finegold MJ: Primary hepatic tumors of childhood. Hum Pathol 1983;14:512-537.
epithelial origin and account for more than 90% of malignant liver neoplasms.76Primary liver neoplasms can also be of mesenchymal origin; of these, sarcomas are the most common. Undifferentiated embryonal sarcomas and rhabdomyosarcoma usually occur in children aged 5 to 10 years. They are associated with a normal serum AFP level and are vimentin positive on staining.74Other reported malignancies include the malignant transformation of mesenchymal hamartoma,58 angiosarcoma, cholangiocarcinoma, rhabdoid tumor,"g immature teratoma, and c h o r i o c a r ~ i n o m aMetastatic .~~ disease to the liver is relatively uncommon in children. Histologic classification of hepatoblastomas has minimal predictive value in determining prognosis. Uniform criteria have not been established, but most pediatric pathologists have simplified the classification into epithelial and mixed (epithelial and mesenchymal) types. The epithelial type is subdivided into fetal, embryonal, macrotrabecular, and small cell undifferentiated types.60 Small cell undifferentiated histology may confer an unfavorable outcome.22 Conversely, pure fetal histology (PFH) with minimal mitotic activity (5 cm) be the first to be considered for this type of treatment.40 Radiotherapy for synovial sarcoma is often used for microscopic residual disease or histologic evidence of tumor close to the resected margin. As with other NRSTSs, its efficacy has not been proved, and radiation's negative effects on growth in children and the risk of secondary cancers and other late effects make its use in small, totally resected tumors questionable.89 Genetic evaluation of synovial sarcoma tumor tissue shows a poorer outcome for tumors associated with the SYT-SSX fusion type.@This fusion type is more common in patients presenting with metastases than is SYT-SSX2; in patients with localized disease, SYT-SSXl is associated with a shorter overall survival time. Certain primary sites, such as synovial sarcoma of the hand, are rare. No clear guidelines exist with regard to their management. A functional limb-saving approach, without compromising the principles of cancer management, should be individualized in each case.51 Primary renal synovial sarcomas are now an accepted entity and are likely a subset of what was previously considered an adult variant of Wilms' tumor."
~~ results can be expected with be c ~ r a t i v e .Similar fibrosarcoma of the trachea.93
Hemangiopericytoma Only 5% to 10% of hemangiopericytomas occur in children and and many of these are infantile hemangiopericytoma, an entity with a more benign course than that seen in older patients. The infantile form is more likely to occur in the head and neck and has a low metastatic potential. Infants with incomplete removal of hemangiopericytoma often do well with no further therapy.6 Responses to chemotherapy have been reported.4xWongenital hemangiopericytoma generally does not metastasize and has a good prognosis, although some instances of metastases and death have been reported."pontaneous resolution has been reported after biopsy alone." This lesion can present in odd locations, such as a thyroglossal duct remnant," on rare occasions. This tumor can mimic a benign arteriovenous malformation that is sometimes still referred to as an "angioma."7Vt has also been reported to occur in association with trisomy 15 as a sole anomaly."'
Neurogenic Sarcoma Infantile Fibrosarcoma Infantile fibrosarcoma is the most common soft tissue sarcoma of infants, accounting for about half of fibrosarcomas in the pediatric population. These tumors usually present as a slowly enlarging mass that may have been present for months to years. Most occur on the extremities, but head and neck tumors are also common. The name infantile fibrosarcoma is a misnomer, because the improved prognosis it implies and the chromosomal changes associated with this tumor are also seen in children up to about 5 years of age. Younger children with fibrosarcoma also have a good prognosis, with a better than 90% long-term survival rate. Although childhood fibrosarcoma has a recurrence rate of about 50%, the metastatic potential is less than 10%.24,113 Infantile fibrosarcoma grows rapidly, infiltrates locally, but rarely metastasizes. Although complete surgical resection is curative, it is not always possible. Neoadjuvant chemotherapy causes many tumors to shrink sufficiently to allow resection. There does not seem to be a role for adjuvant chemotherapy or radiation after complete resection. Although recurrence is frequent, most cases can be managed with additional surgical excision. Overall survival is greater than 90%.37 Because of the typically benign course of infantile fibrosarcoma in children younger than 5 years, conservative surgical procedures are recommended to preserve function. Infantile fibrosarcoma is generally responsive to chemotherapy and in some instances can be successful as initial therapy.",H0 Spontaneous regression has also been .~~ fibrosarreported in infantile f i b r o ~ a r c o m aPulmonary coma is a rare malignant tumor in childhood. In the absence of metastasis, complete resection appears to
Neurogenic tumors (malignant peripheral nerve sheath tumors, neurofibrosarcomas, neurosarcomas, and malignant schwannomas) often present with pain or neurologic symptoms that have been present for prolonged periods before diagnosis. Neurogenic sarcomas may arise de novo or from a preexisting fibroma. In pediatric series, NF-1 was Less than 5% of present in 21% to 62% of patients.17~3'r~~ patients with NF-1 develop a sarcoma, however."2 Primary sarcomas of the central nervous system are rare in children. Their cell of origin is controversial, but the most widely accepted theory names the pluripotential primitive mesenchymal cells in the dura mater, the leptomeninges or their pial extensions into the brain and the spinal cord along the periadventitial spaces, the choroidea, and the stroma of the choroid plexus. The reported incidence of sarcomas at this site varies from 0.1% to 4.3%,owing to the inconsistent definitions from study to study. These tumors frequently arise in the supratentorial compartment in children. Dural attachment and central nervous system dissemination are often found. Metastasis outside the central nervous system is associated with a poor prognosis, although aggressive resection with postoperative radiation may offer a chance for long-term survival. Repeat craniotomy should be offered for recurrent local disease. Newer chemotherapy protocols may hold promise in the future.' These are very aggressive tumors, and radical surgery is the primary treatment. In patients with NF-1, the tumors present at an earlier age and recur and metastasize more quickly and more f r e q ~ e n t l y . ~ - ~ ~ . " W a l i g n a n t peripheral nerve sheath tumors are rare and usually fatal, with a high risk of local recurrence and distant metastasis.115
CHAPTER
Complete excision is the most important prognostic factor, with a 5-year disease-free survival rate of 67%. With microscopic residual tumor, the 5-year disease-free survival rate is 43%; this falls to 22% when the tumor is not completely resected because recurrence is inevitable, with most tumors metastasizing to the lungs.126 External beam radiation does not appear to impact survival, but brachytherapy (BRT) and intraoperative radiation are beneficial.lz6
Liposarcoma Although liposarcoma is one of the more common soft tissue sarcomas in adults, it is rare in children.19,"fi4J11 Gross total resection is the indicated treatment. Tumor shrinkage to allow for complete excision has been chemotherapy.39 Adjuvant achieved with radiation1"nd chemotherapy or radiation has been used in children with microscopic residual tumor, but its effectiveness has not been do~umented."f'~The 5-year survival rates in extremity liposarcoma in adults is dependent on histologic subtype and are as follows: for well-differentiated tumors, 100%; for myxoid tumors, 88%; for fibroblastic tumors, 58%; for pleomorphic tumors, 56%; and for lipoblastic tumors, 40%.20 The better prognosis in children with liposarcoma compared with adults may be related to the higher incidence of myxoid and welldifferentiated subtypes (70% to 85% of pediatric liposarcomas).
Desmoplastic Small Round Cell Tumor Desmoplastic small round cell tumor occurs primarily in young men who present with pain, ascites, abdominal distention or mass, nausea and vomiting, or signs of bowel or bladder obstruction. Presentation with widely disseminated metastases to liver, lungs, and lymph nodes is common.45 Although the precise tumor type may be difficult to determine, the RT-PCR method for formalin-fixed material has a 94% to 100% specificity for tumor type.43 Because of widespread dissemination at presentation, complete surgical resection is rarely possible. Response to chemotherapy, including high-dose chemotherapy and autologous stem cell rescue, has been docuLong-term survival remains dependent mented.1023624~"J~4 on the ability to resect all gross disease after neoadjuvant chemotherapy. Radiation therapy may be of benefit in treating microscopic residual disease. The use of radiofrequency for the ablation of unresectable hepatic metastasis in desmoplastic small round cell tumor may be e f f e ~ t i v e . ~ ~
Malignant Melanoma of Soft Parts Approximately 25% of these tumors occur in patients younger than 20 years. Most patients present with an enlarging mass in the extremities that has been present for a long time.25J0fi Local recurrence is common. Metastases occur to lung (59%), lymph nodes (53%), and bone (22%).
33
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547
Treatment is surgical excision. The median overall survival duration is 49 months,l06 but patients with metastases at diagnosis generally survive less than 1 year. Local relapses and metastases can occur years after diagnosis and treatment. The role of adjuvant chemotherapy or radiation is uncertain for these tumors.44
Alveolar Soft Part Sarcoma Approximately 25% of alveolar soft part sarcomas are seen in patients younger than 20 years. This tumor is predominant in women (61%), especially in younger patients." Presentation consists of a painless enlarging mass of the extremity, with head and neck tumors also common in ~hildren.~6,~"toccurs in 0.8% to 1.8% of children. Mean length of survival is 20 years in patients age 0 to 9 years at diagnosis and 14 years in those age 10 to 19 years. Tumors greater than 5 cm in diameter have an increased risk of metastasis, which usually occurs early in the disease. Excision of metastasis can influence survival.83 Approximately 20% of patients have metastases at diagnosis. Metastases can sometimes occur many years after the initial diagnosis and affect the lung, bone, and brain. Treatment is primarily surgical, with complete excision being the best treatment. There is a low risk of local recurrence if adequate margins are obtained. In patients presenting with metastatic disease at diagnosis, the median survival duration is 3 years.66Younger patients have a longer survival time, but this is related primarily to a lower incidence of metastases at diagto the Soft-Tissue Sarcoma Italian nosis.66~*~ccording Cooperative Group, pediatric alveolar soft part sarcoma has a more favorable prognosis than its adult counterpart.16
SPECIAL DIAGNOSTIC AND SURGICAL CONSIDERATIONS New Imaging Modalities Magnetic resonance spectroscopy appears to be effective in assessing tumor response in childhood cancer and could potentially be used to tailor chemotherapy to the individual child's needs."* The prognostic significance of magnetic resonance spectroscopy has been studied in sarcomas of the extremity, where the aim was to determine whether pretreatment spectra might be useful in defining good- versus poor-risk tumors and to determine whether changes that occur early during the course of therapy can be useful to predict tumor response.sg Fluorodeoxyglucose positron emission tomography scans have been assessed for their diagnostic and therapeutic role in childhood sarcomas through a systematic review of the relevant literature and a meta-analysis. There is no apparent indication for the use of this modality in the standard treatment of sarcomas at present, although it may be used for the detection, grading, treatment, and evaluation of locally advanced sarcomas.'
548
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in certain situations, especially in the vicinity of major nerves or vessels, the margns may be only a few millimeters. The value of fine-needle aspiration is primarily to differIn this case, it is advisable to remove the adventitial sheath entiate a solid mass from a fluid-containing mass or an along with the specimen.55J02Although resection is the primary concern, dissection is often tailored to the individual abscess that may require drainage. In all other instances, patient, based on preoperative diagnostic imaging. at a minimum, a Tru-Cut needle biopsy is warranted.12,52,65~94,99~100 Although needle tract recurrences The skin from the previous biopsy site is completely ellipsed, and the flaps are raised. The deeper extent of the have been documented, these are extremely rare events and are more common among patients with carcinoma.lo8 dissection is usually initiated on one side 2 to 3 cm from the When the tissue obtained is insufficient to obtain a spetumor. Often the deep margins overlie the vessels or nerve. cific diagnosis or a discrepancy exists, an open biopsy is In this case, the adventitial sheath or ~erineuralsheath indicated. For extremity lesions, the incision should be adjacent to the tumor should be resected. to acquire a little placed longitudinally or parallel to the neurovascular more margin. If the vessel is grossly involved, resection of bundle. A transverse biopsy incision would contaminate the vessel with interposition of a vascular prosthesis can be multiple tissue compartments and thus preclude limb considered. If the Gmor abuts the bone; stripping of the An excisional biopsy of a lesion is periosteum, marginal resection of the bone, or resection of salvage ~urgery.~~99~10l undertaken only if the tumor is small (< 2.5 cm) or situa segment of the bone can be performed. In these ated such that an eventual wide local resection could be instances, the bony defect may be bridged by a vascularized done without risk of functional deformity.119 In all other fibula graft or allograft plus intramedullary nails. instances, an incisional biopsy is obtained and should be In the popliteal fossa and the elbow, compartmental carefully planned and placed, so that the tract can be resection of a tumor with satisfactory margins is almost completeiy excised at the time of definitive surgery. impossible because of the complex 'eurovascular anatomy, the loose connective tissue, and the close conIt has been shown repeatedly that when resection is 0 5 ~ ~tumors ~ are not fines of adjacent s t r ~ c t u r e s . g 0 ~ ~These planned for a benign tumor or when resection of a maligconfined by fascia1 boundaries and are considered extranant lesion is not carefully planned, the quality and compartmental. It is my policy to maintain limb function amount of tumor resection are inadequate. In these whenever feasible with resection of these lesions, albeit instances, residual tumor can be identified following priwith tenuous margins. Radiation therapy is added for mary re-excision in 30% to 49%of patients.12,14,47,gg,102,122,124 If primary radical resection is -not performed, local local control in the form of interstitial brachytherapy, recurrence rates of 50% to 90% have been external beam radiation, or a combination of both. observed.'"1"47~5ji~99~10'L~128 Therefore, whenever diagnostic Major ablative procedures such as amputation should be imaging, the operative notes, or pathologic examination considered when there is neurovascular involvement, for local recurrence, and in a skeletally immature child. suggests that there is residual tumor or that the tumor is A similar situation arises in lesions of the hand or foot, close to the specimen margin, it is recommended that which are relatively uncommon primary sites. The tight the patient undergo primary re-excision of the operative site whenever possib~e.12,~4,58,99,101,~~99~25 compartments interspersed with tendons and neurovasculai- bundles make resection with adequate margins difficult. Surgical procedures may include ray amputation of one or more digits, wide local excision of the EXTREMITY TUMORS al or use of a neurovascuarea, and s u ~ ~ l e m e n tradiation lar free transfer technique, especially in the case of Two major factors have contributed to reduced amputa, ~ the 8s~ lower ~ , ~extremity, ~ resection of the t h ~ m b . ~ ~ In tion rates in children with soft tissue sarcoma. First, amputation still has a role in the management of large, although amputation results in a high rate of local con124~125 invasive tumors or when combination thertrol, it fails to improve overall s ~ r v i v a l . 1 4 ~ 5 5 ~ 9 9 ~ ~ ~ 2 ~ ~ 2 2 ~ high-grade apy could result in a poor functional outcome. Second, limb salvage procedures with or without adjuvant radiation therapy have effectively decreased local recurAmputation may also be appropriate for pain control, rence rates to less than 10%.22,*1-42,77,9","2,124 Although especially in a weight-bearing limb, and for recurrent local disease. amputation may be logical in an elderly patient, it is not This combined-modality management has led to 90% the best choice for a growing child. Amputation in adult to 95% limb salvage in NRSTS, with local recurrence patients obviates the musculoskeletal deformity or the In recent vears. rates in the vicinity of 10%.12,99,101,122J24 risk of a second malignan~y.~~,94,"~~~~,~~2 , , The surgical principle is to obtain a wide local resecbetter understanding of tumor biology and improved tion with adequate margins, generally considered to be techniques for the delivery of radiation have emerged. e nthe d i size n g and site of the about 2 ~ m . l ~ ~ ~ ~ ~ W e pon Radiation therapy may be administered preoperatively, tumor, wide local resection may be obtained by means of intraoperatively, or postoperati~ely.'2~'".42~R1~122-123 a radical compartmental resection, resection of a muscle from insertion to origin, or radical wide local resection." Although wide margins are obtained in most directions, MANAGEMENT OF EXTREMITY LYMPH
Biopsy and Surgery
x x
NODE DRAINAGE The role of regional node dissection in soft tissue sarcoma has become clearer in recent years. In a collective
CHAPTER
33
Other Soft Tissue Tumors
549
involvement survived. The need for nodal assessment in review of more than 2500 cases of NRSTS, the incidence all patients with extremity rhabdomyosarcoma was conof nodal involvement was around 3.9%. In the same firmed in an analysis of Intergroup Rhabdomyosarcoma series, the authors detected a slightly increasing inciStudy-111.2 dence of lymph node metastasis with increasing tumor grade, ranging from 0% for grade 1 lesions to 12% for grade 3 lesions.69 In a review of NRSTS at St. Jude Children's Hospital, a similar range was noted.ll* In FUNCTIONAL OUTCOME FOLLOWING LIMB another review, 76 of 204 patients underwent either SALVAGE SURGERY lymph node dissection or biopsy of suspicious lesions; it Over the past two and a half decades, limb salvage surgery was positive for tumor in nine, and in seven of the nine with adjuvant irradiation has emerged as the optimal treatIt children the tumors were high-grade le~ions.~8~99J~lJ(Q ment and has been performed on a substantial number of is my practice to biopsy only suspicious nodes of highpatients. Although the outcome of this combined modalgrade lesions that are more than 5 cm in size, or if the ity addresses primarily cosmetic concerns, in young lymph nodes are present in the field of dissection of the children and particularly the skeletally immature, attenprimary tumor. tion should be given not only to quality of life but also to When lymph node involvement is suspected in associated local complications, including a stiff, painful, extremity tumors, it can be assessed by injection with isoshortened, or disfigured extremity or fractures associated sulfan blue dye into the lesion at the time of surgery. Children should with demineralization of bone.9.'14~56J2~ Uptake of the dye into the nodes draining the lesion can have active physical therapy to minimize contracture. be determined in this fashion (Fig. 33-1). Use of the Musculoskeletal Tumor Society functional Mandell et a1.68 evaluated 34 patients with extremity outcome evaluation has been detailed mostly in the adult rhabdomyosarcoma, 27 of whom underwent evaluation literature. Excellent to good results were obtained in of regional lymph node drainage. Thirteen patients 75% to 80% of patients, with more than 75% returning to (48%) demonstrated evidence of nodal involvement, full employment. A similar detailed study in the pediatric only one of whom survived. In contrast, there were literature is lacking. Complications noted in my experience 12 survivors among the 14 patients without nodal among long-term survivors after combined treatment involvement. Even when patients with distant metastasis include limb shortening requiring epiphysiodesis, flexion were excluded, 11 of the 12 patients with no nodal
550
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by means of absorbable mesh and to deliver at least a portion of the radiation therapy dose as brachytherapy. Brachytherapy increases local control and reduces the probability of late complications (especially altered bone and organ growth) in comparison to external beam radiation (Fig. 33-2). Low-energy radionuclides and remote afterloading technology allow the treatment of infants and very young children while reducing radiation exposure to patients, family, and medical personnel.'8
REFERENCES a
.
Afterloading catheters are placed for brachytherapy
in the patient with epithelioid sarcoma depicted in Figure 33-1. (Courtesy of Dr. Bhaskar Rao, St.Jude Children's Research Hospital,
Memphis, Tenn.)
deformity, fibrosis, chronic edema, fracture, and secondary osteosarcoma in 7 of 50 long-term survivors with extremity sarcoma. These patients have been followed for 12 to 104 months (median, 36 months).
SOFT TISSUE SARCOMA OF THE TRUNK When a chest wall resection is indicated, a standard thoracotomy incision is appropriate. The investing layer of the serratus anterior or pectoralis is incised at an appropriate distance from the tumor. Careful palpation should be used to gauge the extent of resection, which may include resection of the periosteum with placement of afterloading catheters for brachytherapy. However, if imaging studies or visualization at the time of surgery indicates infiltration of the intercostal muscles or intrathoracic extension, a formal chest wall resection is indicated. The intercostal muscles are divided at an appropriate point, after ligation of the intercostal vessels. Careful palpation of the intrathoracic extension determines the extent of resection and the number of ribs to be removed. The anterior and posterior extent of resection should be 2.5 to 5 cm. The superior and posterior extent is generally a rib above or below the primary lesion. Any adhesions between the pulmonary parenchyma and tumor are excised using an endoscopic linear stapler, so that the specimen can be removed en bloc. The resultant defect is closed by a double layer of mesh and neighboring muscle flaps or myocutaneous flaps. The abdominal wall is a rare primary tumor site. Accurate preoperative imaging can determine tumor resectability. The entire extent of the tumor is resected to obtain satisfactory margins. The deep margins should include resection of the peritoneum whenever possible. The peritoneal defect may be closed by an omental patch or absorbable mesh. Direct contact between the nonabsorbable mesh and the bowel should be avoided to reduce the risk of bowel fistula. It is my policy, especially in the case of lower abdominal wall lesions, to place the bowel loops away from the postoperative radiation field
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62.
63. 64. 65. 66. 67. 68.
69. 70. 71. 72. 73.
74. 75.
76. 77.
78. 79. 80.
81.
82.
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MAJOR TUMORS OF CHILDHOOD
survival with aggressive multimodal therapy. J Clin Oncol 1996;14:1526-1531. Ladanyi M, Antonescu CR, Leung DH, et al: Impact of mTSSX fusion type on the clinical behavior of synovial sarcoma: A multi-institutional retrospective study of 243 patients. Cancer Res 2002;62:135-140. Ladenstein R, Treuner J, Koscielniak E, et al: Synovial sarcoma in childhood and adolescents: Report of the German CWS-81 study. Cancer 1993;71:3647-3655. LaQuaglia MP, Spiro SA, Ghavimi F, et al: Liposarcoma in patients younger than or equal to 22 years of age. Cancer 1999;72:31143119. Lawrence W, Neifield JP: Soft tissue sarcomas. Curr Probl Surg 1989;2:753-827. Lieberman PH, Brennan MF, Kimmel M, et al: Alveolar soft-part sarcoma: A clinico-pathologic study of half a century. Cancer 1989;63:1-13. Madden NP, Spicer RD, Allibone EB, et al: Spontaneous regression of neonatal fibrosarcoma. Br J Cancer Suppl 1992;18:S72-S75. Mandell L, Ghavimi F, LaQuaglia M, et al: Prognostic significance of regional lymph node involvement in childhood extremity rhabdomyosarcoma. Med Pediatr Oncol 1990;18:46&471. Mazeron JJ, Suit HD: Lymph nodes as sites of metastasis from sarcomas of soft tissue. Cancer 1987;60:1800-1808. McClain KL, Leach CT, Jenson HB, et al: Association of Epstein-Barr virus with leiomyosarcomas in children with AIDS. N Engl J Med 1995;332:12. Meis JM, Enzinger FM, Martz KL, et al: Malignant peripheral nerve sheath tumors (malignant schwannoma) in children. Am J Surg Pathol 1992;16:694707. Merens WC, Bramwell VH: Adjuvant chemotherapy for soft tissue sarcomas. Hematol Oncol Clin North Am 1995; 9:801-815. Meterissian SH, Reilly JA, Murphy A, et al: Soft-tissue sarcomas of the shoulder girdle: Factors influencing local recurrence, distant metastases, and survival. Ann Surg Oncol 1995;2:530-536. Miller RW, Young JL, Novakovic B: Childhood cancer. Cancer 1995;75:395-405. Miser JS, Triche TJ, Kinsella TJ, et al: Other soft tissue sarcomas of childhood. In Pizzo PA, Poplack DG (eds): Principles and Practice of Pediatric Oncology. Philadelphia, Lippincott-Raven, 1997, pp 865-888. Mounayer C, Benndorf G, Bisdorff A, et al: Facial infantile hemangiopericytoma resembling an arteriovenous malformation. J Neuroradiol 2004;31:227-230. Nag S, Olson T, Ruymann F, e t al: High-dose-rate brachytherapy in childhood sarcomas: A local control strategy preserving bone growth and function. Med Pediatr Oncol 1995;25:463-469. Nag S, Tippin DB: Brachytherapy for pediatric tumors. Brachytherapy 2003;2:131-138. Neifeld J, Maurer H, Dillon P, et al: Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) in children. Society of Surgical Oncology, 1994. Newton WA Jr, Soule EH, Hamoudi AB, et al: Histopathology of childhood sarcomas, Intergroup Rhabdomyosarcoma Studies I and 11: Clinicopathologic correlation. J Clin Oncol 1988;6:67-75. Nielsen OS, Cummings B, O'Sullivan B, et al: Preoperative and postoperative irradiation of soft tissue sarcomas: Effect of radiation field size. Int J Radiat Oncol Biol Phys 1991;21:1595-1599. Okeu MF, Despa S, Choroszy M, et al: Synovial sarcoma in children and adolescents: Thirty three years of experience with multimodal therapy. Med Pediatr Oncol 2001;37:90-96.
83. Ordonez NG: Alveolor soft part sarcoma: A review and update. Adv Academ Pathol 1999;6:125-139. 84. Pappo AS, Fontanesi J, Luo X, et al: Synovial sarcoma in children and adolescents: The St Jude Children's Research Hospital experience. J Clin Oncol 1994;12: 2360-2366. 85. Pappo AS, Parham D, Cain A, et al: Alveolar soft part sarcoma in children and adolescents: Clinical features and outcomes in 11 patients. Med Pediatr Oncol 1996;2681-84. 86. Pappo AS, Parham D, Lobe TE: Soft tissue sarcomas in children. Semin Surg Oncol 1999;16:121-143. 87. Pappo AS, Shapiro DN, Crist WM, et al: Biology and therapy of pediatric rhabdomyosarcoma. J Clin Oncol 1995;13:2123-2139. 88. Parham DM, Webber BL, Jenkins JJ 111, et al: Nonrhabdomyosarcomatous soft tissue sarcomas of childhood: Formulation of a simplified system for grading. Mod Pathol 1995;8:705-710. 89. Paulino AC: Late effects of radiotherapy for pediatric extremity sarcomas. Int J Radiat Oncol Biol Phys 2004;60:265-274. 90. Philippe PG, Rao BN, Rogers DA, et al: Sarcomas of the flexor fossae in children: Is amputation necessary? J Pediatr Surg 1992;27:964967. 91. Picard E, Udassin R, Ramu N, et al: Pulmonary fibrosarcoma in childhood: Fiber-optic bronchoscopic diagnosis and review of the literature. Pediatr Pulmonol 1999;27:347-350. 92. Pitcher ME, Thomas JM: Functional compartmental resection for soft tissue sarcomas. Eur J Surg Oncol 1994; 20:441-445. 93. Postovsky S, Peleg H, Ben-Itzhak 0 , et al: Fibrosarcoma of the trachea in a child: Case report and review of the literature. Am J Otolaryngol 1999;20:332-335. 94. Pratt CB, Kun LE: Soft Tissue Sarcomas of Children. Boston, Kluwer, 1993. 95. Pratt CB, Maurer HM, Salzberg A, et al: Treatment of unresectable or metastatic pediatric soft tissue sarcomas with surgery, irradiation and chemotherapy: A Pediatric Oncology Group study. Med Pediatr Oncol 1998;4: 201-209. 96. Pratt CB, Pappo AS, Gieser P: Role of adjuvant chemotherapy in the treatment of surgically resected pediatric nonrhabdomyosarcomatous soft tissue sarcomas: A Pediatric Oncology Group Study. J Clin Oncol 1999; 17:1219-1226. 97. Raney RB, Kollath J, Anderson.J, et al: Late effects of therapy for patients with primary orbital rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Study (IRS-III), 19841991. Med Pediatr Oncol 1997;29:425. 98. Rao BN: Malignant lesions of the chest and chest wall in childhood. Chest Surg Clin North Am 1993;3:461-475. 99. Rao BN: Nonrhabdomyosarcoma in children: Prognostic factors influencing survival. Semin Surg Oncol 1993;9: 524531. 100. Rao BN: Present day concepts of thoracoscopy as a modality in pediatric cancer management. Int Surg 1997;82: 123-126. 101. Rao BN, Etcubanas EE, Green AA: Present-day concepts in the management of sarcomas in children. Cancer Invest 1989;7:349-356. 102. Rao BN, Santana VM, Parham D, et al: Pediatric nonrhabdomyosarcomas of the extremities: Influence of size, invasiveness, and grade on outcome. Arch Surg 1991;126: 1490-1495. 103. Rosen G, Forscher C, Lowenbraun S, et al: Synovial sarcoma: Uniform response of metastasis to high dose ifosfamide. Cancer 1994;73:2506-2511.
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104. Rosoff PM, Bayliff S: Successful clinical response to irinotecan in desmoplastic round blue cell tumor. Med Pediatr Oncol 1999;33:500-503. 105. Rydholm A, Gustafson P, Rooser B: Limb-sparing surgery without radiotherapy based on anatomic location of soft tissue sarcoma. J Clin Oncol 1991;9:1757-1765. 106. Sara AS, Evans HL, Benjamin RS: Malignant melanoma of soft parts (clear cell sarcoma): A study of 17 cases, with emphasis on prognostic factors. Cancer 1990;65:367-374. 107. Schmidt D, Thum P, Harms D, et al: Synovial sarcoma in children and adolescents: A report from the Gel Pediatric Tumor Registry. Cancer 1991;67:1667-1672. 108. Schwartz HS, Spengler DM: Needle tract recurrences after closed biopsy for sarcoma: Three cases and review of the literature. Ann Surg Oncol 1997;4:228-236. 109. Serpell JW, Ball AB, Robinson MH, et al: Factors influencing local recurrence and survival in patients with soft tissue sarcoma of the upper limb. Br J Surg 1991;78:1368-1372. 110. Shetty AK, YLILC, Gardner RV, et al: Role of chemotherapy in the treatment of infantile fibrosarcoma. Med Pediatr Oncol 1999;33:425-427. 111. Shmookler BM, Enzinger FM: Liposarcoma occurring in children: An analysis of 17 cases and review of the literature. Cancer 1983;52:567-574. 112. Sorensen SA, MulvihillJ, Nielsen A: Long-term follow-up of von Recklinghausen neurofibromatosis: Survival and malignant neoplasms. N Engl J Med 1986;314:1010-1015. 113. Soule EH, Pritchard DJ: Fibrosarcoma in infants and children. Cancer 1977;40:1711-1721. 114. Spunt SL, Poquette CA, Hurt YS, et al: Prognostic factors for children and adolescents with surgically resected nonrhabdomyosarcomatous soft-tissue sarcoma: An analysis of 121 patients treated at St Jude Children's Research Hospital. J Clin Oncol 1999;17:3697-3707. 115. Stark AM, Buhl R, Hugo HH, et al: Malignant peripheral nerve sheath tumors: Report of 8 cases and review of the literature. Acta Neurochir 2001;143:357-364. 116. Taylor SR, Nunez C: Fine-needle aspiration biopsy in a pediatric population: Report of 64 consecutive cases. Cancer 1984;54:1449-1453.
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117. Vadlamani I, Ma E, Brink DS, et al: Trisomy 15 in a case of pediatric hemangiopericytoma and review of the literature. Cancer Genet Cytogenet 2002;138:116-119. 118. Vaiday SJ, Payne GS, Leach MO, et al: Potential role of magnetic resonance spectroscopy in assessment of tumour response in childhood cancer. Eur J Cancer 2003;39:728-735. 119. Valle AA, Kraybill WG: Management of soft tissue sarcomas of the extremity in adults. J Surg Oncol 1996;63: 271-279. 120. Wall JE, Kaste SC, Greenwald CA, et al: Fractures in children treated with radiotherapy for soft tissue sarcoma. Orthopedics 1996;19:657-664. 121. Wexler LH, Helman LJ: Rhabdomyosarcoma and the undifferentiated sarcomas. In Pizzo PA, Poplack DG (eds): Principles and Practice of Pediatric Oncology. Philadelphia, Lippincott-Raven, 1997, pp 799-829. 122. Wiklund T, Huuhtanen R, Blomqvist C, et al: The importance of a multidisciplinary group in the treatment of soft tissue sarcomas. Eur J Cancer 1996;32A:269-273. 123. Willett CG, Suit HD, Tepper JE, et al: Intraoperative electron beam radiation therapy for retroperitoneal soft tissue sarcoma. Cancer 1991;68:278-283. 124. Williard WC, Collin C, Casper ES, et al: The changing role of amputation for soft tissue sarcoma of the extremity in adults. Surg Gynecol Obstet 1992;175:389-396. 125. Wilson AN, Davis A, Bell RS, et al: Local control of soft tissue sarcoma of the extremity: The experience of a multidisciplinary sarcoma group with definitive surgery and radiotherapy. Eur J Cancer 1994;30A:746-751. 126. Wong WW, Hirose T, Scheithauer BW, et al: Malignant peripheral nerve sheath tumor: Analysis of treatment outcome. Int J Radiat Oncol Biol Phys 1998;42:351-360. 127. Zalupski MM, Baker LH: Systemic adjuvant chemotherapy for soft tissue sarcomas. Hematol Oncol Clin North Am 1995;9:787-800. 128. Zornig C, Peiper M, Schroder S: Re-excision of soft tissue sarcoma after inadequate initial operation. Br J Surg 1995;82:278-279.
Teratomas and Other Germ Cell Tumors -
Richard G . Azizkhan
Pediatric germ cell tumors (GCTs) are a heterogeneous group of rare neoplasms. They occur at a rate of 2.4 cases per million children and account for approximately 1% of cancers diagnosed in children younger than 15 years.195 These neoplasms occur in both gonadal and extragonadal sites, with extragonadal and testicular tumors predominating in children younger than 3 years and gonadal tumors predominating during and after puberty. GCTs exhibit a broad spectrum of clinical presentation and histopathologic features and carry varying risks for malignancy, depending on the type of lesion. Irrespective of such differences, lesions are presumed to originate from the primordial germ cell. Clinical and pathologic variations stem from differences in the stage of germ cell development at tumorigenesis, gender, and oncogenic influences.36 Early in embryogenesis, germ cells begin to undergo a directed migration along the midline dorsal mesentery of the hindgut and are eventually incorporated into embryonic gonadal tissue. When this migratory process is perturbed, nests of germ cells may be deposited in abnormal locations. Thus, GCTs are found in the sacrococcygeal area, the mediastinum, the retroperitoneum, the pineal area of the brain, and the ovary and testis. Malignant transformation can occur at any of these sites. The broad spectrum of GCTs and tissue types in different anatomic locations reflects the totipotential nature of germ cells, with specific tumor types associated with the degree of cell differentiation. Most GCTs are associated with a number of biologic markers that are useful in identifying and managing these tumors and assessing their recurrence. Treatment depends on multiple factors, including specific pathology, anatomic location, tumor stage, histology, and resectability. Optimal outcomes are achieved with complete surgical resection, accurate histologic examination, and the selective use of chemotherapy. Of particular importance, the introduction of cisplatinum chemotherapy in the late 1970s led to a dramatic improvement in both survival and salvage rates for recurrent and metastatic disease.46 Current survival rates for low-stage extragonadal sites and for both low- and high-stage gonadal sites vary from
90% to loo%, depending on location. Survival for higherstage extragonadal lesions approximates 75%.'48 This chapter focuses on the most common extragonadal GCT, the teratoma, and on the malignant extragonadal GCTs typically seen by pediatric surgeons. Tumors of the ovaries and testes and intracranial tumors are discussed here only briefly but are covered in more detail in Chapters 36, 37, and 41, respectively.
EMBRYOLOGY Primordial germ cells originate near the allantois of the embryonic yolk sac endoderm and become evident by the fourth week of gestation. By the fifth week, these cells migrate through the mesentery to the gonadal ridgew and eventually become the gonads. This migration appears to be mediated by the c-kit receptor and stem cell factor. The latter is expressed in an increasing gradient from the yolk sac to the gonadal ridge, along which germ cells appear to migrate.'08J71Migration of cells cephalad to the gonadal ridges is complete by 6 weeks' gestation. At this stage, the ridges extend from the cervical to the lower lumbar levels on either side of the developing vertebral column.'j7 In animal models, the absence of c-kit receptor expression in primordial germ cells is associated with failure of migration and proliferation into the gonad.36 The prevailing hypothesis is that extragonadal GCTs arise from aberrant migration or the deposition of germ cells l l s migrate into along the path of m i g r a t i ~ n . ~ ~ emay areas that are not within the normal pathway (e.g., pineal and sacrococcygeal regions) or may remain outside the coalescence of gonadal tissue.
HISTOPATHOLOGIC CLASSIFICATION AND STAGING Although there is slight variation among the published classifications, GCTs are generally considered to consist of seven main histologic types: dysgerminorna (or seminoma),
CHAPTER
Stage I: Localized disease, with complete resection at any site (coccygectomy for sacrococcygeal site); negative tumor margins; tumor markers positive or negative Stage II: Microscopic residual disease; capsular invasion; negative lymph nodes or microscopic lymph node involvement; tumor markers positive or negative Stage Ill: Gross residual disease; gross lymph node involvement; cytologic evidence of tumor cells in ascites or pleural fluid; tumor markers positive or negative Stage IV: Distant metastases involving lungs, liver, brain, bone, distant nodes, or other sites. Adapted from staging systems of the Children's Oncology Group and the National Cancer Institute.
yolk sac (endodermal sinus) tumor, embryonal carcinoma, polyembryoma, choriocarcinoma, teratoma, and mixed GCT. Most malignant GCTs occur in pure form, but in 10% of cases, two or more tumor types are combined.'6l In order of frequency, the most common are teratoma, endodermal sinus tumor, germinoma, and mixed GCT. Choriocarcinoma, embryonal carcinoma, and polyembryoma are rarely seen. The existence of multiple tumor types and sites of origin precludes the development of a homogeneous staging system comparable to that for other organ-specific malignancies. The Children's Oncology Group and the National Cancer Institute have, however, adopted a general staging system for malignant extragonadal GCTs (Table 341). (For staging systems for female and male gonadal tumors, see Chapters 36 and 37.)
MAJOR BIOLOGIC MARKERS Alpha Fetoprotein Over the past several decades, a number of biologic markers used in the diagnosis and management of GCTs
I!
Mean
SD
34
555
Teratomas a n d O t h e r Germ Cell Tumors
have been the subject of intensive investigation,'5 and the clinical importance of these markers has become well established. Most GCTs secrete either alpha fetoprotein (AFP) or P-human chorionic gonadotropin (P-HCG); optimally, both markers should be measured before surgical excision of a suspected tumor to establish a baseline so that the impact oftherapy can be determined. AFP, which was first identified as a serum marker of liver tumors, is the predominant serum-binding fetal protein. The fetal and neonatal liver secretes AFP in large quantities, with newborn levels of 50,000 ng/mL being normal; higher levels are noted in premature infants. AFP reaches its peak concentration at 12 to 14 weeks' gestation and gradually drops to a normal adult level of 10 ng/dL by 8 months to 1 year of age."' Interpretation of AFP levels must thus be viewed within the context of the wide variability in normal levels during the first year of life. These levels become clinicallv relevant when thev are significantly elevated over the normal range for any particular age (Fig. 341). Elevated serum AFP levels or positive immunohistochemical staining of GCTs for AFP indicates the presence of malignant c&mponents, specifically yolk sac or embryonal carcinoma. Operative excision alone usually returns serum AFP levels to normal: its serum half-life is 5 to 7 davs.109 In most cases, treatment regimens are closely linked to the behavior of AFP, and postoperative monitoring is useful to detect tumor recurrence before it is clinically. apparent. If metastasis or residual tumor is susuected because AFP levels do not fall as expected, an extensive search should be undertaken using diagnostic imaging and possibly surgery. Elevations of AFP are not, however, always indicative of tumor progression. Chemotherapy-induced tumor lysis can cause abrupt though transient AFP elevation.187 Disorders associated with abnormal hepatic function, such as benign liver conditions, hepatic and gastrointestinal malignancies, viral hepatitis, cholestasis secondary to anesthesia, or drug-induced hepatic cholestasis, can also conditions ther lead to persistently high AFP l e v e l ~ . ~ " ~ " ~ ~ W associated with AFP elevation include hypothyroidism, ataxia telangiectasia, and hereditary tyrosinemia.194 Although these disorders are readily distinguishable from -
A
7
Premature Newborn Newborn -2 wks
134,734 541,444
48,406 %34,718
2 wks -1 mo
33,113 532,503
2 mos
9,452 i12,610
3 rnos 323 +278
4 mos 88 587
74 +56
5 mos 46.5 i19.0
6 mos 12.5 +9.8
7 moss
8 rnos
9.7 i7.1
+5.5
1
1 Declining serum alpha fetoprotein levels in normal infants. (Adapted from Wu JT, Sudar K: Serum alpha fetoprotein (AFP) levels in normal infants. Pediatr Res 1981;15:50.)
556
PART
III
MAJORTUMORS OF CHILDHOOD
GCTs, they should be considered when interpreting an elevated AFP level.
P-Human Chorionic Gonadotropin 0-HCG is a glycoprotein presumed to be produced by placental syncytiotrophoblasts. It is composed of a and p subunits, and the latter can be reliably assayed. P-HCG elevation suggests the presence of syncytiotrophoblasts as seen in choriocarcinoma, seminoma or dysgerminoma, . ~contrast ~ to the and occasionally embryonal c a r ~ i n o m aIn long half-life of AFP, the P subunit of HCG has a half-life ranging from only 24 to 36 hours.106 Its decline is rapid, and its sustained disappearance indicates complete tumor removal. Monitoring P-HCG levels helps assess the progress of patients with P-HCGsecreting tumors. As with AFP, a sudden elevation of serum P-HCG can occur after cell lysis secondary to chemotherapy.187 Also, rising levels of this marker may be associated with an increase in luteinizing hormone after bilateral orchiectomy or oophorectomy; this occurs because of immunologic cross-reactivity between the a subunit of luteinizing hormone and that of HCG.GOAlthough a number of other neoplasms (e.g., multiple myeloma and malignancies of the pancreas, gastrointestinal tract, breast, lung, and bladder) are associated with modest serum P-HCG elevation, these disorders are seen primarily in adults.
not require additional chemotherapy. Although it appears that tumor marker levels and the rate of half-life marker clearance are of prognostic importance, mild to moderate elevations during the later phases of chemotherapy may be less reliable indicators of persistent disease.
OTHER MARKERS
Elevated levels of serum lactate dehydrogenase (LDH), a glycolytic liver enzyme, have been observed in patients with GCTs and may be a prognostic indicator.90 LDH is a nonspecific marker thought to correlate with tumor growth and regression, although it shows no particular association with any GCT In patients with dysgerminoma, increased serum LDH isoenzyme 1 does, however, correlate with tumor burden and is useful in surgical management.I60 Spurious increases in LDH are seen with viral illnesses, liver diseases, and during and after chemotherapy."' Placental alkaline phosphatase (PLAP) is a reliable marker of GCT differentia ti or^,^^ and immunohistochemical staining for PLAP is useful for determining the origin of histologically undifferentiated GCTs.106 PLAP is elevated in the sera of virtually all patients with advanced seminoma and in 30% of patients with stage I semin0ma.103.l~~ It may also be useful in the analysis of other tumors of uncertain histogenesis, particularly if the differential diagnosis lies between seminoma and lymphoma.2" Two recent studies indicate that the concentration of Observations and Caveats s-kit (the soluble isoform of c-kit) in cerebrospinal fluid Over the past decade, investigators have made important may be a useful clinical marker for central nervous system observations that have stimulated debate regarding the germinomas, particularly for detecting recurrence 01-subAnother study indicates interpretation of AFP and HCG serum levels. Of particuarachnoid dis~emination.'2gJ~~ that combined CD117 (c-kit) and CD30 (Ki-1 antigen) lar relevance, a study conducted by Trigo et al.lsOindicated that the lack of elevated tumor markers is not always a reliimmunohistochemistrv, mav, be a valuable tool for d&tinguishing seminoma from embryonal carcinoma.l13 able indicator of the absence of recurrent disease. The authors suggested that although tumor marker assessment Vascular endothelial growth factor protein expression should be included in treatment follow-up, early detection is higher in testicular GCTs than in normal testes and correlates with microvessel count and svstemic metastases.58 of recurrence should not rely on this assessment alone. The prognostic significance of the prolonged half-life The epidermal growth factor receptor is a useful marker clearance of AFP or HCG has been the focus of a number to identify the syncytiotrophoblastic cells in testicular GCTs.81 of studies, with findings reflecting a lack of consensus or, at Investigators continue to look for biologic and the very least, a degree of confusion. Christensen et al.S4 questioned the concept of a fixed half-life for HCG, sugimmunohistochemical markers that will help differentiate gesting that a half-life delay following the later stages of GCT types and stratify patient^.^^",^"^^^,'?^,^^ Although chemotherapy may not always indicate persistent disease. many interesting observations have been made, further This delay has been attributed to a biphasic pattern of study in larger patient populations is required to validate the findings. Moreover, it is important to keep in mind half-life clearance, with a slower component occurring later in chemotherapy. Findings of other clinicians~?5J~~that most studies have been conducted in adult populasuggest that the rate of marker decline early in chemothertions rather than in children. apy is of prognostic value across risk groups. Bosl and Head26 reported that pretreatment risk status and posttreatment marker clearance are independent and equal prognostic variables, with prolonged half-life clearance being an important variable in both previously untreated New cytogenetic technologies have improved our underand treated patients. In contrast, Morris and Bosll30 standing of the genetics and molecular mechanisms reported six cases in which stable, modest elevations in involved in the development of GCTs. Genetic alterserum markers were present after treatment, even though ations may be associated with clinical outcome and are there were no radiographic or clinical indications of perthe subject of intense study. Flow cytometry has detersistent disease. Patients were closely monitored but did mined that pediatric GCTs have varied DNA ploidy and
APTER
34
Teratomas and Other Germ Cell Tumors
557
are thus unlike adult GCTs, which tend to have aneuploid DNA.168 Most teratomas in children younger than 4 years are diploid, have normal karyotypes, and behave in a benign fashion regardless of site of Malignant GCTs in this age group are almost always yolk sac tumors and are generally diploid or tetraploid.14jJ70 The most common cytogenetic abnormalities involve chromosomes 1, 3, and 6. Studies have demonstrated deletion of lp36 in 80% to 100% of infantile malignant GCTs arising from testicular and extragonadal sites.145J70 A small minority of these tumors show evidence of c-myc or n-myc amplification, proto-oncogenes that may have prognostic s i g n i f i ~ a n c e . ' ~ ~ In older children and adolescents, cytogenetic analysis of central nervous system teratomas has shown a high frequency of sex chromosome abnormalities, most commonly increased copies of the X c h r o m o ~ o m e . ~ * J ~ ~ Although isochromosome 12p or i(12p) is quite common in all types of adult GCTs, it is infrequently seen in childhood GCTs. Having three or more copies of this isochromosome has been associated with treatment failure and is considered to be of prognostic i m p ~ r t a n c e . ~ ~ This abnormality has been described in pineal germinomas but has not been seen in pineal t e r a t ~ m a s . ~ ~ J ~ ~ J ~ ~ Sacrococcygeal teratoma in an infant at 30 weeks' Isochromosome 12p has also been identified in ovarian gestation. The tumor was successfully resected, and the patient is now tumors in both adolescents and a d ~ l t s . ~ a young adult. -
TERATOMAS
1
Disfiguring cleft palate defects are found in newborns with massive cranial and nasopharyngeal t e r a t o m a ~ . ~ ~ , ~ ~ Teratomas are the most frequently occurring GCT. These Teratomas can present as solid, cystic, or mixed solid neoplasms arise in both gonadal and extragonadal locaand cystic lesions. By definition, these lesions are comtions, and location is thought to correspond to the posed of representative tissues from each of the three embryonic resting sites of primordial totipotential germ germ layers of the embryonic disk (ectoderm, endoderm, cells. Teratoma presentation correlates with both age and mesoderm) and usually contain tissues foreign to the and anatomic site. Teratomas occurring in infancy and anatomic site of origin.40 One germ cell layer may preearly childhood are generally extragonadal, whereas dominate, and occasionally a teratoma can be monoderthose presenting in older children more commonly mal. Most teratomas that are present at birth consist of occur in the ovary or testis.164 More than half of terectodermal and mesodermal components. Epidermal atomas are observed at birth; they present in many locaand dermal structures such as hair and sebaceous and tions but are most common in the sacrococcygeal area sweat glands are frequently present, as are fairly well(Fig. 342). In prepubertal children, approximately 75% developed teeth. Pancreatic, adrenal, and thyroid tissue of teratomas occur in the sacrococcygeal area, and the diagnosis is generally made during the first year of life. Although more than one third of teratomas of the testis are recognized in the first year of life, these lesions are rarely diagnosed in the neonatal period?gJ76 The sacrococcyx is also the most common extragonadal location irrespective of age (45% to 65%) (Table 342). Cervicofacial Incidence (%) Site tumors and tumors of the intracranial cavity are seen less 45-65 Sacrococcygeal region frequently. Teratomas presenting in the mediastinum, 10-12 Anterior mediastinum heart, retroperitoneum, and liver are rare. Excluding 10-35 Gonadal (ovary and testis) testicular teratomas, 75% to 80% of teratomas occur in 3-5 Retroperitoneum females. Approximately 20% of tumors contain malig3-6 Cervical area nant components, the most common being endodermal 3-5 Presacral area 2-4 sinus tumor. Central nervous system go%) in cases of cervical teratomas that are not diagnosed or treated until late adolescence or adulthood.2' To minimize operative morbidity, dissection of the teratoma should begin in areas distant to important regional nerves. Cervical teratomas often have a pseudocapsule, facilitating gentle elevation of the tumor out of the neck. If the tumor arises from the thyroid gland, the involved thyroid lobe is excised in continuity with the teratoma. Any enlarged lymph nodes should be excised with the tumor, because glial metastases may be present. After excision, a drain is left in place for 24 to 48 hours. Because these tumors are often large, envelopment of vital anatomic structures in the neck is common. In some cases, complete tumor excision with acceptable functional and cosmetic results may be achieved only by staged procedures.8 In contrast to the high incidence of malignancy (>60%) in adults, malignant cervicofacial teratomas with metastases are comparatively uncommon in neonates, with a 20% incidence reported by Azizkhan et a1.8 Despite the existence of poorly differentiated or undifferentiated tissue in the primary tumor, many infants remain free from recurrence following complete resection of a cervical teratoma. Such cases suggest that malignant biologc behavior is uncommon in this population.l6~45,~ Reported findings show a number of consistent histologic patterns.8 Neuroectodermal elements and immature neural tissue are the most commonly observed tissues in metastatic foci. In approximately one third of cases, the metastases are more differentiated but are confined to
CHAPTER
regional nodes. Patients with isolated regional node metastases who are treated with excision of the primary tumor generally survive free of disease. This supports the concept that the presence of metastases containing only differentiated tumor usually correlates with a good prognosis. There are currently no chemotherapy guidelines for neonates with malignant cervical teratomas. Based on results of their series, however, Azizkhan et a1.8 recommended that this modality be reserved for infants with disseminated disease (that has not differentiated) and those who have invasive tumors and residual disease after resection. Although cervical teratoma is generally a benign tumor, the possibility of malignant transformation mandates close surveillance for tumor recurrence. Serum AFP levels should be monitored at 3-month intervals in infancy and annually thereafter, with a rising level alerting the clinician to the possibility of tumor recurrence. As discussed earlier in this chapter, serum AFP levels must be interpreted with caution and viewed within the framework of their natural half-life. Imagng studies twice a year for the first 3 years of life are also recommended for surveillance. Because the thyroid and parathyroid glands may be removed or affected by tumor excision, the risk of temporary or permanent hypothyroidism must be con~idered.~ If encountered, these complications must be monitored and managed appropriately.
Mediastinal Teratoma Mediastinal teratomas account for approximately 20% of all mediastinal pediatric neoplasms. They are the second most common extragonadal site of teratomas and affect boys and girls equally. Though uncommon, other malignant mediastinal GCTs with various histologic patterns also arise. Mediastinal teratomas more frequently arise in the anterior mediastinum but are also observed within the pericardium or heart and, rarely, in the posterior mediastinum. Less than 50% of childhood mediastinal teratomas occur in neonates. Although adolescents and young adults are frequently asymptomatic, infants and children usually have symptoms that are related to compression of the lung or bronchi; they may range from acute respiratory distress to a chronic cough, chest pain, or wheezing. Anterior mediastinal and pericardial tumors are associated with superior vena cava syndrome. Some boys with mediastinal teratomas may present with precocious puberty associated with a benign or malignant P-HCGsecreting neoplasm. Because such neoplasms are associated with Klinefelter's syndrome, chromosomal karyotyping should be performed. More than 30 cases have been diagnosed prenatally. Accompanying polyhydramnios, fetal hydrops, and a number of other serious conditions have resulted in fatal outcomes. It is thought that open fetal surgery may have a role in a select subset of patients, although the two attempts to date have been unsuccessful. A postnatal chest radiograph may reveal a mediastinal mass; in approximately one third of cases, this mass is calcified. US of the chest shows a mass with cystic and solid components and
34
Teratomas and Other Germ Cell Tumors
565
may be useful in distinguishing the mass from the pericardium and heart. CT often clarifies the extent of the tumor and its relationship to surrounding anatomic structures. The differential diagnosis includes thymoma, thymic cyst, lymphatic malformation, mediastinal nonHodgkin's lymphoma, esophageal duplication, and bronchogenic cyst. When there is an index of suspicion, bone scintigraphy may be performed to detect osseous metastases. Serum levels of AFP, P-HCG, LDH, and PLAP may be ele~ated.~2 An overall malignancy rate of 15% has been reported in the pediatric age g r o ~ p . ~AOnumber of studies have shown that both mature and immature mediastinal teratomas occurring in newborns and infants behave in a in these age benign fashion if resected.3~J~7~~7Wutcomes groups have been shown to be more favorable than those in adolescents and adults. Complete surgical removal is the treatment of choice for both benign and malignant lesions. Because anterior mediastinal masses frequently compress the airway, anesthesia management is critical. Once spontaneous respiration has been eliminated by intravenous paralytic agents, patients may lose their ability to be ventilated, even with a properly positioned endotracheal tube. A sternotomy or thoracotomy provides excellent operative exposure. Care should be taken to avoid injury to the phrenic nerves. Histologic study reveals immature cellular elements in approximately 20% of mediastinal tumors in young children. Although this carries almost no increased risk of maliznancv in these children, the presence of immature " tissue is asiociated with high'mor(a1ity from progressive tumor in older teenagers and young adults. Thus, they should be treated with adjuvant chemotherapy. In cases in which malignant tumor has infiltrated into vital structures, resection may not be possible, and chemotherapy may be required to make the teratoma amenable to subsequent resection. Because cure of malignancy is unusual with resection alone, all patients undergo adjuvant postoperative chemotherapy to prevent disease recurrence and progression. Although results from cooperative multiagent chemotherapy trials have not been as impressive as those with sacrococcygeal lesions, they have been quite favorable. In a recent series,22 18 of 36 patients underwent biopsy followed by chemotherapy and then tumor resection. Tumor size remained stable or increased in 6 patients and decreased a mean of 57% in 12. The overall 4year survival rate for children treated with a regimen of etoposide, bleomycin, and cisplatin was 71%; the eventfree survival rate was 69%. The authors suggested that boys aged 15 years or older may be a high-risk subgroup for mortality from tumor progression.
Cardiac Teratoma Although a teratoma may arise in the heart, this occurs only rarely and almost exclusively in girls. Cardiac teratomas typically present with signs and symptoms of congestive heart failure, confined to the right side of the heart. The diagnosis is suspected on echocardiography, which reveals the presence of a multicystic intracardiac mass.
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Arrhythmias and an intraventricular block may be observed on an electrocardiogram. Associated congenital heart defects such as atrial septal defect and ventricular septal defect are frequently seen. To avoid the occurrence of complete outflow obstruction or a fatal arrhythmia, prompt resection is essential. Malignant teratomas (25%) require treatment with chemotherapy. For patients with benign, resectable cardiac teratomas, cardiac transplantation offers a reasonable therapeutic alternative.
RetroperitonealTeratoma The retroperitoneum is the third most common extragonadal site, accounting for 5% of all teratomas.us Most tumors are observed in early infancy, with 50% identified in the first year of life and 75% occurring by age 5. Girls are more dommonlv affected (21) . , than bovi. Patients usually present with a large palpable abdominal mass that may cause symptoms of alimentary tract compression. The differential diagnosis includes a number of other tumors seen in early childhood (e.g., neuroblastoma and Wilms' tumor), as well as cystic retroperitoneal lymphatic malformations, omental cyst, and fetus in fetu. Plain abdominal radiographs may .reveal displacement of bowel and calcification within the tumor. When calcification is present, the pattern is more distinct and noticeably different from the diffuse stippled calcification seen in neuroblastoma. CT or MRI of the abdomen helm differentiate this neoplasm from more common childhood tumors. Laparotomy for complete tumor resection is the therapy of choice.~ecausemost of these tumors are benign, this approach is usually successful. Approximately 20% of retroperitoneal teratomas are malignant at diagnosis, and 30% to 40% may have immature tissues. Benign glial implants have occasionally been observed, in&caiing a maturation process of these metastatic foci. Because malignant recurrence has been reported in patients with benign teratomas containing immature components, both malignant lesions and those containing high-grade immature elements should be treated with postoperative chemotherapy. '"5
Other Rare Extragonadal Teratomas Gastric Teratoma Gastric teratomas are exceedingly rare. These lesions may present as a palpable epigastric mass, with symptoms of gastric outlet obstruction or upper gastrointestinal bleeding occurring in infancy. These neoplasms are usually large and are often multicystic. Plain radiographs of the abdomen often show calcification. An upper gastrointestinal contrast study defines the stomach and tumor relationship. Upper endoscopy may reveal an extrinsic mass that compresses the gastric lumen or evidence of erosion by the tumor. Histologic examination reveals that these lesions are composed of mature tissues, frequently containing immature neuroglial elements. Resection of the tumor is the treatment of choice. The prognosis for this teratoma is generally fa~orable.47.Y1.~~2
Vaginal Teratoma These rare lesions present in the first year of life, often in the neonatal period. Examination may reveal minor bleeding from an easily visible vagnal mass. Most lesions are yolk sac tumors. A chest radiograph is performed to rule out lung metastases, and CT delineates the extent of the lesion. If the tumor is localized, management entails local resection of the tumor by partial vagmectomy and lowdose multiagent chemotherapy. Involvement of the uterus requires a hysterectomy. Preliminary adjuvant chemotherapy may limit the extent of the required resection.164
Gonadal Teratomas Ovarian Teratoma Teratomas are the most common pediatric ovarian tumor, accounting for more than 50% of all ovarian neoplasms and 25% of all childhood teratomas. Most ovarian teratomas present between 5 and 16 years of age and are unusual in the first 2 to 3 years of life. Pain is the most common presenting symptom, observed in more than 50% of patients. Acute abdominal pain from torsion of the tumor is reported in 25% of patients. Because most tumors are large (10 to 15 cm), the identification of an asymptomatic abdominal mass is another common presentation. Intra-abdominal and pelvic calcifications resembling teeth are seen in approximately half of abdominal radiographs. Tumors occur equally on the right and left ovaries and are bilateral in 5% to 10% of cases. Although abdominopelvic US shows a mass composed of cystic and solid components as well as the structure of the contralateral ovary, CT is the optimal imaging study for preoperative staging. Serum AFP and HCG levels should be obtained. If elevated, they may be indicative of malignant potential. Simple or salpingo-oophorectomy is the treatment of choice for benign tumors with an intact capsule and mature elements on histologic examination. At the time of surgery, any ascitic fluid is collected for cytologic analysis. If ascitic fluid is absent, peritoneal washings are obtained and evaluated for the presence of tumor cells. All peritoneal surfaces, including the underside of the diaphragm, are inspected for peritoneal implants. If they are observed, biopsy specimens are obtained. An infracolic omentectomy should be performed if the omentum has gross tumor. Gonad-sparing resection of benign cystic ovarian teratomas has been advocated by some surgeons. However, long-term follow-up is limited, and this approach remains controversial.l~s The management of immature ovarian teratomas with extraovarian peritoneal involvement is complex. Fortunately, most patients have mature glial implants. They do not require chemotherapy and hive an excellent prognosis.155 Tumors with a higher histologic grade (grades I1 and 111) have a risk of malignancy and require adjuvant multiagent chemotherapy. Treatment with current chemotherapeutic regimens has resulted in a survival rate approaching 90%.Y7 (For a more detailed discussion, refer to Chapter 36.)
CHAPTER
Testicular Teratoma Testicular teratomas are the most common testicular neoplasms in childhood. They present bimodally in terms of age, with infants younger than 2 years and teenagers and young adults most commonly affected. Infants usually present with a nontender scrota1 mass. In 15% of patients, a hydrocele may also be present. Preoperative serum AFP and HCG levels are obtained. A chest radiograph and an abdominal CT scan are obtained to evaluate for nodal and visceral metastases. Tumors are staged by virtue of their resectability and the presence of nodal and distant metastases. In stage I disease (80% of cases), treatment consists of a transinguinal radical orchiectomy and includes excision of the spermatic cord at the internal ring. Radical orchiectomy alone in stage I disease in infants is associated with greater than 90% 5-year survival. Most malignant tumors in infants are yolk sac tumors that rarely metastasize to retroperitoneal lymph nodes. . ~ e t r o ~ e r i t o n e alymph l node -dissection is thus not required for infants with stage I disease who are younger than 2 years and have a normal preoperative abdominal CT scan. If elevated serum tumor markers do not return to normal after resection (20% of cases), the teratoma is restaged, ., retroperitoneal lymph node dissection is subsequently perfdrmed, and adjuvant chemotherapy is administered. Retro~eritonealnode dissection is usuallv performed unilaterally, using nerve-sparing techniques to prevent retrograde ejaculation. Suspicious contralatera1 lymph nodes should be biopsied. The frequency of relapse following lymphadenectomy is 10% to 15%, with disease usually recurring in the lungs or mediastinum. Most patients with metastatic disease benefit from multiagent chemotherapy. (For a more detailed discussion, refer to Chapter 3'7.) A
YOLK SAC TUMOR Yolk sac tumors are the most common malignant GCT affecting children from infancy to adolescence. In neonates and young children, these neoplasms are found primarily in extragonadal sites, particularly the sacrococcygeal area. However, they are also common in the testes of infants and young boys,'" with yolk sac tumor being the predominant pediatric malignant GCT involving the testis. In older children and adolescents, the ovary is the most common location. Less common primary sites include the mediastinum, retroperitoneuk, pineal area, and vagina. In adolescents, these tumors rarely occur in pure form in extragonadal sites but are seen as a component of mixed malignant G C T S . ~Pediatric ~ , ~ ~ yolk sac tumor is cytogeneticdly and biologically distinctfrom its adult counterpart. Examination of pediatric tumor tissue has shown deletions in chromosomes 1 ( l p ) and 6 (6q), but no evidence of the i(12p) deletion observed in adult GCTs. 43 Grossly, yolk sac tumors appear as pale gray to yellow friable, mucoid tissue with foci of cystic areas and necrosis."J7 One relatively recent and credible theory suggests that these neoplasms originate from the primary yolk
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sac,l36 a structure that develops early in embryogenesis. The yolk sac consists of multipotential primitive endoderm tissue capable of differentiating into the primitive gut and its derivatives, including the liver, thus leading to variable histologic patterns. The pseudopapillary (festoon) and microcystic (reticular) patterns are the most common and widely recognized. Both usually display perivascular sheaths of cells referred to as endodermal sinus structures or Schiller-Duval bodies. Most welldifferentiated yolk sac tumors also contain intra- and extracellular hyaline deposits that are resistant to periodic acid-~chiffdiastase staining and positive for AFP. However, in that the microcystic pattern is less differentiated, it is often associated with eosinophilic globules and strands that infrequently stain positively for AFP. Occasionally, endodermal sinus tumors are more solid and can be difficult to distinguish from embryonal carcinoma. Some tumors may have a hepatoid- pattern that resembles fetal liver 'cells.7" Variations in histologic pattern do not appear to correlate with outcome, which has improved considerably with multiagent chemotherapy. ~ e v ~ r t h e l e sass ,evidenced by the Pediatric Oncology Study (19'71-1984), 7 h e o n a t a l SCTs may recur as yolk sac tumors, which are associated with a worse -prognosis owing to their invasive nature. -
EMBRYONAL CARCINOMA Though far less common than yolk sac tumors, embryonal carcinoma also presents in the first year of life. It rarely occurs in pure form in children; more often, it is a component of a mixed malignant GCT. The major histologic pattern is epithelial, comprising large nests of cells with varying amounts of central necrosis. However, pseudotubular and papillary patterns, which may be confused with those of volk sac tumors. are also common. Cells are AFP negative, and tumors generally lack the eosinophilic hyaline globules characteristic of some yolk sac tumors. In contrast to other GCTs, embryonal carcinoma is positive for cytokeratin by immunohistochemical staining.36
GERMINOMA The term germinoma is currently used to refer to a group of neoplasms with common histologic characteristics. Formerly, a lesion was termed a seminoma if found in the testis, a dysgemzinoma in the ovary, and a germinoma in an extragonadal site. These tumors are thought to arise f r ~ m t o t i ~ o t e n t igerm a l cells present at the indifferentiated stage of gonadal development. They are commonly seen in the ovary, anterior mediastinum, and pineal region and are the most common pure malignant GCT occurring in the ovary and central ;ervous system in children.49J7"In children, germinomas account for 10% of all ovarian tumors and approximately !5% of GCTs in all locations. These tumors are rarely seen in infants and small children and occur most often in prepubertal girls and young women, with 44% of cases presenting before age 20 years.73 Germinoma is the predominant malignancy found in dysgenetic gonads and undescended testes.
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On gross examination, germinomas appear solid, encapsulated, gray-pink or tan in color, with occasional small foci of hemorrhage and necrosis and a rubbery consistency. Tumor cells are arranged in nests separated by bands of fibrous tissue associated with variable degrees of lymphocytic infiltration. The cells are large, with clear to slightly eosinophilic cytoplasm, distinct cell membranes, and large round nuclei having one or two h with giant prominent n u ~ l e o l i . ~ W t h o u ggranulomas cells as well as syncytiotrophoblasts may be present, they alter tumor prognosis only when associated with cytotrophoblasts in foci of choriocarcinoma. Germinoma cells strongly stain for PLAP, whereas syncytiotrophoblasts stain for P-HCG. As noted by Scully et al.,lMgerminomas are also immunoreactive for vimentin and, in some cases, LDH, neuron-specific enolase, Leu-'7, cytokeratin, desmin, and glial fibrillary acidic protein. In one study,183c-kit localization was found in 92% of germinomas.
to extraovarian spread of tumor at presentation.lV2 The histologic tumor appearance is characterized by a preponderance of embryoid structures that resemble normal early embryos in various stages of development. These structures are composed of yolk sac, embryonal, and hepatic elements, as well as chorionic elements such as syncytiotrophoblastic giant cells. Mature and immature teratomatous elements, predominantly of endodermal derivation, are usually present as well.1" In many cases, elevated serum levels of AFP and P-HCG have been noted. Histologically, both the yolk sac and the hepatic elements are immunoreactive for AFP and alphal-antitrypsin. Syncytiotrophoblastic elements are immunoreactive for HCG.l02,133",47,173
GONADOBLASTOMA Gonadoblastoma is a relatively rare tumor composed of aerm cells intermixed with stromal c e l l s . ~ ~ " .is~con~~8~t sidered a precursor to the development of a malignant GCT. Gonadoblastoma is most commonly found in dysgenetic gonads of phenotypic females wh&have at least a .~~ are generally fragment of the Y c h r o m ~ s o m ePatients older adolescents or in the third decade of life and have a history of primary amenorrhea. They may exhibit a lack of secondary sexual characteristics and the presence of elevated gonadotropin levels and streak gonad~:~(),l"-lg0 These tumors are often quite small, soft to firm, gray-tan to brown, and slightly Ibbulated. Microscopic Features include the proliferation of both germ cells and gonadal sex cord cells. Germ cells show positivity for PLM.36 Most gonadoblastomas behave in a benign fashion, although there is a 30% risk of overgrowth of a malignant germ cell elernent.18Warying malignant elements may be present; germinoma is the most common, occurring in ~ ~malignant ~~!) potential approximately 50%of c a s e ~ . I ~The of this tumor is determined by the underlying malignant component. Gonadectomy is recommended for young patients with mixed gonadal dysgenesis because of the increased frequency of gonadoblastoma arid germinoma and the virilizing effects of residual testicular tissue.1"'
-
Choriocarcinoma is a rare, highly malignant tumor seen primarily in females. This tumor typically occurs as a component of a malignant mixed GCT. As with yolk sac tumors and embryonal carcinoma, this lesion can occur during the first year of life, either as a metastasis secondary or as a primary tumor to a placental chorio~arcinoma",~~ arising from locations such as the liver, lung, brain, kidney, or maxilla."".l" The most common site is the pineal region.5(i,~(i(i I~ presents in both prepubertal children and young adolescents, occurring primarily in the gonads and less frequently in the mediastinum. Pure choriocarcinoma in young infants almost always represents disseminated metastasis from maternal or placental gestational trophoblastic tumor.i"55 On gross examination, pure choriocarcinoma is characteristically solid, hemorrhagic, and friable. Microscopically, both cytotrophoblasts and syncytiotrophoblasts are present. Cytotrophoblasts typically appear as closely packed nests of relatively uniform, medium-sized cells with clear cytoplasm, distinct cell margins, and vesicular nuclei, whereas syncytiotrophoblasts represent giant multinucleated syncytial trophoblastic cells." Both cell types are typically immunoreactive for cytokeratin. The syncytiotrophoblastic cells are also immunoreactive for HCG, human placental lactogen, and pregnancy-specific Dl-glycoprotein. In addition, immunoreactivity for PLAP, epithelial membrane antigen, neuron-specific enolase, alphal-antitrypsin, and carcinoembryonic antigen is seen in some tumors.161
POLYEMBRYOMA Polyembryomas are exceedingly rare malignant tumors of the ovary, with fewer than 10 cases reported during the last 4 decades.'" They are often reported in combination with other neoplastic components.l8.l02Patients are typically children or young women who present with clinical symptoms and signs indicative of the presence of a large pelvic mass. Rarely, patients have symptoms related
MIXED GERM CELL TUMORS GCTs often comprise two or more pure histologic types. .Benign throughhossibly malignan; GCTs such as immature teratomas may coexist with frankly malignant GCTs, and 10% to 40% of patients with malignant tumors have Of these patients, 40% are diagmixed hi~tology.l~",~"~12~ nosed before-puberty.~" The most common histolog~c component of mixed GCTs is dysgerminoma (germinoma), although immature teratoma, endodermal sinus tumor, and embryonal carcinoma may be detected in varying proportions.36 Also, mixed GCTs account for 8% to 10% of malignant primitive GCTs of the o ~ a r y . l ~ ) ~ - l ~ ~ The occurrence of these tumors underscores the importance of careful gross examination and judicious tumor tissue sampling.- he prognosis of patiknts with mixed GCTs is generally thought to depend on the tumor's most malignant element, but some investigators have > .
CHAPTER
reported that a minor component of a highly malignant element affects the prognosis less adversely than does a major component.IO5
TREATMENT OVERVIEW AND FUTURE PERSPECTIVES Advances in surgical treatment, together with the use of platinum-containing multiagent chemotherapy regimens, have resulted in a dramatic improvement in the outcome for children with malignant GCTs. International studies using integrated multimodal treatment strategies are reporting impressive survival rates, ranging from 75% to 90%.1".fi5121,149,178,193Although chemotherapy protocols in these studies differ somewhat, the standard chemotherapy regimen in the United States for children with malignant extragonadal GCTs includes a combination of cisplatin, etoposide, and bleomycin (PEB). This protocol has, however, been associated with a high risk of late effects, particularly the nephrotoxicity and ototoxicity Growing concern about these effects has of ci~platin.".~~ spurred investigations into alternative protocols with less deleterious long-term effects. In the United Kingdom, the combination of carboplatin, etoposide, and bleomycin UEB) has undergone clinical investigation in children younger than 16 years. Authors have reported comparable event-free survival with less ototoxicity and renal impairment than PEB.HgCorroborating these findings, a recent prospective study conducted in the United States concluded that carboplatin could be substituted for cisplatin without sacrificing response or survival; overall survival and In event-free survival were 91% and 87%, respe~tive1y.l~~ contrast, adult studies that substituted standarddose carboplatin for cisplatin in combination with etoposide alonegor with etoposide and lowdose bleomycinx8 demonstrated inferior event-free and overall survival in patients with malignant GCTs. To date, no randomized comparison of PEB versusJEB has been conducted in children. Because pediatric extragonadal GCTs are rare and treatment is effective, the number of relapsed patients is small, ranging from 20% to 30%. Children with recurrent malignancy following resection may be salvageable with the standard PEB regimen. For patients with cisplatinrefractory or poorly responding tumors, a further dose escalation of cisplatin under protection with amifostine is being evaluated in the United States, with results regarding toxicity still pending. Results from German protocols suggest that locoregional hyperthermia offers an attractive alternative, in that cisplatin is a good thermosensitizer and hyperthermia may thus overcome cisplatinum resistance.l* Additionally, authors anticipate that locoregional hyperthermia will result in fewer systemic side effects than cisplatin dose escalation. Although ifosfamide is not used as a first-line therapy, it has been incorporated into various treatment strategies and, in for adults with relapsed or refractory disease115~l2.fi combination with cisplatin and etoposide (ICE), has been There used in a small number of pediatric patient~.l22J2~ is, however, increasing concern about the nephrotoxicity of this drug combination in children. Another area of ongoing research, particularly for high-risk GCTs in
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older adolescents and young adults, is high-dose chemotherapy with peripheral blood stem cell transplant.23 Outcomes of this approach have not yet been clearly established. In a further effort to minimize the late toxic effects of treatment, the Pediatric Oncology Group and the Children's Cancer Group cooperatively developed a classification scheme that allows for less intense and more individualized treatment approaches. Based on the results of their studies, patients are stratified into three distinct risk groups: Low risk-patients with stage I malignant gonadal and extragonadal GCTs, including stage I immature teratomas Intermediate risk-patients with stage I1 to IV gonadal and stage I1 extragonadal GCTs High risk-patients with stage I11 and IV extragonadal GCTs The Children's Oncology Group is currently developing risk-specific treatment strategies based on this new scheme. Under consideration is observation without adjuvant chemotherapy after surgical resection for all patients with stage I tumors."J1g To ensure that recurrent disease is detected early, strict guidelines for the evaluation and follow-up of these patients will be mandated. For patients with intermediate-risk tumors, consideration is being given to a modified standard PEB treatment that decreases the length of therapy. For children with high-risk extragonadal GCTs, the previously cited investigation using high-dose PEB in combination with amifostine is ongoing.
REFERENCES 1. Ablin A, Krailo M, Ramsey N, et al: Results of treatment of malignant germ cell tumors in 93 children: A report from the Children's Cancer Study Group. J Clin Oncol 1991;9:1782. 2. Alpers CE, Harrison MR: Fetus in fetu associated with an undescended testis. Pediatr Path01 1985;4:37. 3. Altman RP, Randolph JG, Lilly JR: Sacrococcygeal teratoma: American Academy of Pediatrics Surgical Section Survey-1973. J Pediatr Surg 1974;9:389. 4. Atkin NB, Baker MC: Abnormal chromosomes including small metacentrics in 14 ovarian cancers. Cancer Genet Cytogenet 1987;26:355. 5. Aubry F, Satie AP, Rioux-Leclercq N, et al: MACE-A4, a germ cell specific marker, is expressed differentially in testicular tumors. Cancer 2001;92:2778. 6. Azizkhan RG: Neonatal tumors. In Carachi R, Azmy A, Grosfeld JL (eds): The Surgery of Childhood Tumors. New York, Oxford University Press, 1999, ch 8. 7. Azizkhan RG, Caty MG: Teratomas in childhood. Curr Opin Pediatr 1996;8:287. 8. Azizkhan RG, Haase GM, Applebaum H, et al: Diagnosis, management, and outcome of cervicofacial teratomas in neonates: A Children's Cancer Group study. J Pediatr Surg 1995;30:312. 9. Bajorin DF, Sarosdy MF, Pfister DG, et al: Randomized trial of etoposide and cisplatin versus etoposide and carboplatin in patients with good-risk germ cell tumors: A multiinstitutional study. J Clin Oncol 1993;11:598.
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10. Bale PM: Sacrococcygeal developmental abnormalities and tumors in children. Perspect Pediatr Pathol 1984;8:9. 11. Balmaceda C, Diez B, Villablanca J, et al: Chemotherapy the only strategy in primary central nervous system germ cell tumours: Results of an international study. J Neurooncol 1993;15:S3. 12. Balmaceda C, Heller G, Rosenblum M, et al: Chemotherapy without irradiation: A novel approach for newly diagnosed CNS germ cell tumours: Results of an international cooperative trial. J Clin Oncol 1996;14:2908. 13. Balnlaceda C, Modak S, Finlay J: Central nervous system germ cell tumours. Semin Oncol 1998;25:243. 14. Baranzelli MC, Patte C: The French experience in paediatric malignant germ cell tumours. In Jones WG, Appleyard I, Harnden T, et a1 (eds): Germ Cell Tumours, 4th ed. London, John Libbey & Co, 1998, p 219. 15. Bartlett NL, Freiha FS, Torti FM: Serum markers in germ cell neoplasms. Hematol Oncol Clin North Am 1991;5:1245. 16. Batsakis JG, Littler ER, Oberman HA: Teratomas of the neck. A clinicopathologic appraisal. Arch Otolaryngol 1964; 79:619. 17. Baumann FR, Nerlich A: Metastasizing cervical teratoma of the fetus. Pediatr Pathol 1993;13:21. 18. Beck JS, Fulmer HF, Lee ST: Solid malignant ovarian teratoma with "embryoid bodies" and trophoblastic differentiation. J Pathol 1969;99:67. 19. Belchis DA, Mowry J, Davis JH: Infantile choriocarcinoma: Re-examination of a potentially curable entity. Cancer 1993;72:2028. 20. Berry CL, Keeling J, Hilton C: Teratomata in infancy and childhood: A review of 91 cases. J Pathol 1969;98:241. 21. Bianchi DW, Crombleholme TM, D'Alton ME: Fetology: Diagnosis and Management of the Fetal Patient. New York, McGraw-Hill, 2000, chs 111, 116. 22. Billmire D, Vinocur C, Rescorla F, et al: Malignant mediastinal germ cell tumors: An intergroup study. J Pediatr Surg 2001;36:18. 23. Bokemeyer C, Kollmannsberger C, Meisner C, et al: Firstline high-dose chemotherapy compared with standard-dose PEB/VIP chemotherapy in patients with advanced germ cell tumors: A multivariate and matched-pair analysis. J Clin Oncol 1999;17:3450. 24. Bond SJ, Harrison MR, Schmidt KG, et al: Death due to high-output cardiac failure in fetal sacrococcygeal teratoma. J Pediatr Surg 1990;25:1287. 25. Bosl GJ, Chaganti RS: The use of tumor markers in germ cell malignancies. Hematol Oncol Clin North Am 1994;8:573. 26. Bosl GJ, Head MD: Serum tumor marker half-life during chemotherapy in patients with germ cell tumors. Int J Biol Markers 1994;9:25. 27. Buckley NJ, Burch WM, Leight GS: Malignant teratoma in the thyroid gland of an adult: A case report and a review of the literature. Surgery 1986;100:932. 28. Bussey KJ, Lawce HJ, Olson SB, et al: Chromosome abnormalities of eighty-one pediatric germ cell tumors: Sex-, age-, site-, and histopathology-related differences-a Children's Cancer Group study. Genes Chromosomes Cancer 1999; 25:134. 29. Calaminus G, Schneider DT, Bokkerink JP, et al: Prognostic value of tumor size, metastases, extension into bone, and increased tumor marker in children with malignant sacrococcygeal germ cell tumors: A prospective evaluation of 71 patients treated in the German cooperative protocols Maligne Keimzelltumoren (MAKEI) 83/86 and MAKEI 89. J Clin Oncol 2003;21:781. 30. Carney JA, Thompson DP, Johnson CL, et al: Teratomas in children: Clinical and pathologic aspects. J Pediatr Surg 1972;7:271.
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CHAPTER
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Hodgkin's Disease and ~ o n r ~ o d ~ l uLymphoma n's Michael t? La Ouaglia and WendyT. Su
HODGKIN'S DISEASE
Incidence and Epidemiology
Hodgkin's disease was first described by Hodgkin in 1832, based on anatomic observation. The original paper was entitled "On Some Morbid Appearance of the Absorbent Glands and Spleen."44~ f t e r t h edevelopment of microscopic histology, Sternberg in 1898 and Reed in 1902 were the first to characterize the histopathology.l"JJ21 They emphasized the unique appearance of a multinucleated giant cell with prominent nucleoli, which distinguished it from tuberculosis. The first reports of radiotherapy for Hodgkin's disease were published in 1902 and 1903.98The radiotherapeutic principles required for curative treatment of Hodgkin's disease were reported by Gilbert.33Petersg4in Toronto subsequently published a series of patients who survived disease-free 20 years after treatment. Staging laparotomy was developed in the late 1960s to map out patterns of metastatic spread and for research.34Kaplan et al.1"51J0htStanford University laid the foundation for modern supervoltage treatment of Hodgkin's disease. Use of a derivative of nitrogen mustard to treat patients with lymphosarcoma and Hodgkin's disease was published in 1946,Shnd the results of multiagent treatment with MOPP (Mustargen [mechlorethamine], Oncovin [vincristine], procarbazine, prednisone) were reported in 1967.22As survival improved, it was noted that more patients developed adverse side effects, such as secondary malignancy and infertility. The non-cross-resistant ABVD regimen (Adriamycin [doxorubicin] , bleomycin, vinblastine, dacarbazine) was developed in the 1970s, with less risk of secondary acute myelo~enousleukemia and infertility. In the 1980s more investigators began to recognize the long-term sequelae of standard-dose radiotherapy and chemotherapy, especially in the pediatric population. A combined-modality regimen was applied to a subset of patients initially selected with staging laparotomy and later by diagnostic imaging in the 1990s. Risk-adaptive trials and tailored therapy were the main investigational efforts of that decade, with the aim of finding the optimal combination therapy with maximal efficacy and minimal toxicity.
Hodgkin's disease (HD) is characterized by a bimodal age distribution. The first peak is from 15 years to the late 20s, and the second peak occurs in those older than 50 years. Three forms of HD have been recognized by epidemiologic studies. The childhood form occurs in those younger than 14 years, the young adult form occurs in those 15 to 34 years old, and the older adult form occurs in those between 55 and 74 years. Children and adolescents account for 15% of all HD patients, and HD is twice as common in teenagers as it is in those younger than 10 years. HD accounts for 5% of all pediatric malignancies, with an incidence of about 6 cases per 1 million. Histologic subtypes also vary with age. Mixed cellularity HD is more common in young children, whereas nodular sclerosing HD is more frequently observed in adolescents. The cause of HD is multifactorial, but there is an association with Epstein-Barr virus (EBV) exposure that is most frequently seen in children younger than 10 years. The viral infection appears to precede tumor cell expansion, and EBV may act alone or in conjunction with other carcinogens. Until recently, the origin of Reed-Sternberg cells was elusive. Advances in immunohistology and molecular biology have revealed the clonal nature of these cells. Reed-Sternberg, lymphocytic, and histiocytic cells seen in HD appear to derive from a single transformed B cell that has undergone monoclonal expansion. Immunophenotyping of HD cells has demonstrated B-cell antigens. HD is also characterized by many cytokineproducing and -responding cells, which are responsible for the nonspecific signs and symptoms seen with this tumor.
Clinical Presentation Painless cervical or supraclavicular lymphadenopathy is the most common presenting symptom of HD (80%). Enlarged nodes primary to the axilla or groin are relatively 575
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than 38°C (100.4OF). Pruritus is also commonly observed among HD patients but does not carry as much prognostic value. The immune profiles of HD patients are altered, and the disease is characterized by generalized immune deficiency, ineffective host autoimmune response, and cutaneous anergy.123
.
Thoracic computed tomography scan showing tumor in the mediastinum (avow) in a patient with stage IIB Hodgkin's disease. These studies should be obtained before surgery to identify tracheobronchial obstruction. uncommon (30%), and primary inguinal involvement is encountered in less than 5% of cases. The lyrnphadenopathy is usually firm, rubbery, and nontender. More than two thirds of patients have mediastinal involvement at presentation, and good posteroanterior chest radiographs are essential to evaluate the mediastinum and to rule out airway obstruction before any invasive procedures. When a mediastinal mass is identified by plain radiographs, it is also advisable to obtain a thoracic computed tomography (CT) scan with intravenous contrast material to evaluate the airway and obtain further anatomic information (Figs. 35-1 and 35-2). Clinicians should always assume that airway compression by tumor is a possibility before the institution of general anesthesia. The superior vena caval syndrome, with facial swelling, distended neck veins, and plethoric complexion above the neck, is highly suggestive of superior vena cava obstruction by mediastinal tumor. Approximately one third of patients present with systemic symptoms (substage B symptoms; see later), which may include loss of more than 10% of body weight in the past 6 months, drenching night sweats, or fever greater
The workup of patients with suspected HD should begin with a careful history and physical examination. All nodal groups should be evaluated, and enlarged lymph nodes measured. The lymphatic tissue composing Waldeyer's ring (adenoids and tonsils) should also be examined. The diagnosis of HD requires lymph node biopsy for histologic evaluation. The presence of Reed-Sternberg cells is pathognomonic of HD (Fig. 35-3). There are four histologic subtypes defined by the Rye classificationlymphocyte predominance, nodular sclerosing, mixed cellularity, and lymphocyte depletion-each with a unique immunophenotypic profile.40Nodular sclerosing is the most common subtype seen in children (>65%), followed by mixed cellularity and lymphocyte predominance. The lymphocyte-predominance subtype carries the best prognosis historically. However, since the develop ment of highly effective multiagent and multidisciplinary treatment regimens, all histologic subtypes have become responsive to therapy. Laboratory studies should include a complete blood cell count with differential, erythrocyte sedimentation rate, baseline hepatic and renal function tests, and electrolytes. The serum copper and lactate dehydrogenase (LDH) levels at diagnosis have been correlated with tumor burden, but there are no specific tumor markers.
Staging Staging of HD can be either clinical or pathologic. Clinical staging is based on the well-established Ann Arbor
.
The same patient in Figure 35-1 after chemotherapy. The nodular mediastinal mass has resolved (avow), but there is homogeneous thymic enlargement. This rebound thymic hyperplasia can be confused with disease persistence or recurrence.
.
.
A histopathologic section from a patient with nodular
sclerosing Hodgkin's disease. The arrow identifies a Reed-Sternbergcell.
CHAPTER
1 Stage
111
IV
Criteria lnvolvement of a single lymph node region (I) or a single extralymphatic organ or site (IE) lnvolvement of two or more lymph node regions on the same side of the diaphragm (11) or localized involvement of an extralymphatic organ or site and one or more lymph node regions on the same side of the diaphragm (IIE) Involvement of lymph node regions on both sides of the diaphragm (Ill); this may include splenic involvement (IIIS) or localized involvement of an extralymphatic organ (IIIE) or site (IIIES) Disseminated involvement of one or more organs or sites with or without associated lymph node involvement
I
staging system (Table 35-1) and requires information obtained from the history, physical examination, and diagnostic imaging studies. The substage classifications A, B, and E are based on defined clinical features. Substage A indicates asymptomatic disease. Substage B symptoms are strictly defined as more than 10% weight loss over 6 months, drenching night sweats, and fever greater than 38°C for 3 days. Substage E denotes minimal extralymphatic disease. Radiographic imaging is an integral component of clinical staging. Chest radiographs often reveal the presence of a mediastinal mass, and the ratio of its maximal diameter to that of the thoracic cavity on a posteroanterior view is prognostically important. A ratio greater than 1:3 places the patient in the subcategory of bulky mediastinal disease, which is associated with a worse prognosis and requires systemic chemotherapy for adequate treatment. CT of the chest and abdomen permits a more accurate assessment of disease extent. If high cervical nodes are involved, CT of the neck is also obtained to evalute Waldeyer's ring. CT of the chest provides the best information regarding the extent of mediastinal disease and also evaluates the pulmonary parenchyma, pleura, pericardium, and chest wall. Both intravenous and oral contrast agents should be administered for CT evaluation of infradiaphragmatic disease, to better distinguish lymphadenopathy from other structures. CT scanning is of limited usefulness in children because of the small quantity of retroperitoneal fat and the frequency of benign lymphadenopathy in this age group. Under these circumstances, CT scanning is inaccurate in detecting splenic or periaortic nodal involvementl4 and has a reported accuracy of 71% to 74% when compared with laparotomy. Magnetic resonance imaging (MRI) provides a more accurate evaluation of infradiaphragmatic disease compared with CT, with better visualization of fat-encased retroperitoneal nodes. Lymphangiography is technically difficult and is rarely performed in children. Gallium 67 scans are less specific and do not differentiate inflammatory changes from malignancy, but persistent activity may indicate residual disease. Positron emission tomography has recently been shown to detect disease
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Hodgkin's Disease and Non-Hodgkin's Lymphoma
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not identified on CT scans in adults, although data are limited in children.30 Pathologic staging theoretically requires surgical staging, including splenectomy, unless metastatic disease is found in bone, marrow, liver, or lung biopsies. However, modern HD therapy almost always includes systemic chemotherapy, so the results of pathologic staging do not affect treatment. Therefore, surgical staging with splenectomy is almost never done today. The only exception, which is very rare, is the treatment of localized HD in an adolescent male with radiotherapy alone.
Surgery All patients with HD require a biopsy, usually of involved lymph nodes, to establish the diagnosis and histologic subtype. Frozen sections are inadequate for diagnostic purposes, and permanent hematoxylin-eosin sections must always be obtained. In addition, it is important to procure tissue for more detailed studies, such as immunohistochemistry, immunophenotyping, and cytogenetics. Biopsies should be taken from the most easily accessible site. In patients with only mediastinal involvement, biopsy samples can be obtained via mediastinoscopy, Chamberlain procedure, or thoraco~copy.~~ Retroperitoneal lymphadenopathy is often accessible through laparoscopic biopsy. Fine-needle aspiration cytology is inadequate to detect sparse Reed-Sternberg cells, and 20% of interventional radiologic procedures for HD diagnosis were falsely negative in one study.% Excisional lymph node biopsy or incisional biopsy of massively enlarged or matted nodes is essential to make an accurate diagnosis. Every attempt should be made to provide a specimen that preserves cytoarchitecture without crush or cautery artifact. The role of surgical staging has changed with the paradigm shifts in the treatment of HD. Staging laparotomy was initially devised by radiation oncologists to define the pathologic extent of disease and direct accurate supervoltage radiation fields, because all involved nodal sites required irradiation if cure was to be achieved. Low-stage HD presenting in the neck often followed a predictable route of progression that could be defined by sampling retroperitoneal lymph nodes and removing the spleen. If the disease had extended beyond reasonable radiation portals, chemotherapy would be necessary. The historical purpose of laparotomy-splenectomy in HD was to document the anatomic distribution of disease and thus determine nodal echelons requiring radiotherapy. It was not designed as a therapeutic maneuver. With the wide application of chemotherapy in all stages of HD,2"62 surgical staging has become irrelevant because the additional information it provides does not alter treatment. As noted earlier, the exception is the rare male adolescent with localized disease who might be treated by radiation alone. Traditionally, surgical staging requires laparotomy, splenectomy, bilobar liver needle and wedge biopsies, and thorough sampling of multiple lymph node sites
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(splenic hilum, porta hepatis, suprapancreatic, bilateral effectiveness of both MOPP and ABVD and the fact that para-aortic, and mesenteric) . Bilateral oophoropexies their toxicities do not overlap, trials combining the two are also performed in girls. Staging performed laparoregimens were done, with good preliminary results.10 7 , ~ 2 9regimens are given in an outpatient setting and have scopically may reduce postoperative m 0 r b i d i t y , ~ ~ 0 ~ ~ ~ 6 ~ ~ ~These including the risk of postoperative bowel 0bstruction.2~ easily manageable acute toxicities. However, their sigHowever, the susceptibility to infection caused by nificant long-term toxicity prompted the design of splenectomy is not altered. alternating regimens of MOPP-ABVD to avoid reaching cumulative doses associated with toxicitv. The current trend is the application of "tailored therChemotherapy apy" based on disease response. This approach aims to Effective chemotherapy regimens for HD contain drugs limit the cumulative dose, thus minimizing toxicity while that are individually effective and that have different maintaining efficacy. Results of response-based therapy mechanisms of action so that multiple homeostatic funcwere recently reported by the Pediatric Oncology Group.114 For advanced-stage HD, early responders received only tions in the tumor cell are attacked and drug resistance is minimized (Table 35-2). The agents should have three cycles of ABVE-PC (Adriamycin, bleomycin, vinnonoverlapping toxicities so that a full dose of each drug cristine, etoposide, prednisone, cydlophospha&ide) vercan be given. The MOPP regimen fulfills these requiresus five cycles, followed by 25 Gy of radiation. The 2-year ments and was the first multidrug regimen found to be event-free survival was 90.8% for early responders and effective against HD. In a long-term study of 188 patients 87.7% for slow responders. Low-stage patients received from the National Cancer Institute treated with MOPP, either two or four cycles of ABVE (for early and slow the complete remission rate was 89%, and 54% of patients responders, respectively), followed by radiotherapy, with remained disease free at 10 years.67The mean age at diagno difference in outcome. New trials are under way to nosis for this group was 32 years and ranged from 12 to evaluate the use of dose- and time-intensive delivery. 69 years. In this study, 95% of patients had stage I11 or IV disease, and 89% had B symptoms. Maintenance therapy Radiation Therapy did not affect the remission rate and does not seem to be necessary in HD. Historically, the application of radiation therapy was ABVD was the second regimen used in the treatment based on the concept of contiguous lymph node basin of HD." It was developed for the treatment of patients involvement. Ideally, a 4 to 8-MeV linear accelerator is failing MOPP therapy and contains individually effective used for treatment. Orthovoltage techniques are condrugs with nonoverlapping toxicities. In view of the traindicated, and cobalt 60 is associated with significant radiation scatter, which should be avoided in children. The risk of recurrence is 10% or less if doses of 3500 to 4400 cGy are used. Thus, clinically involved areas are usually given 4000 to 4400 cGy, whereas prophylactic treatment of subclinical areas can be accomplished with 3000 to 4000 cGv. The combination of chemothera~v 1 Regimen Agents and radiotherapy can be effective, with local control rates Doxorubicin (Adriamycin), bleomycin, vinblastine, of 97%. However, the long-term toxicity prompted trials dacarbazine in the 1980s with protocols incorporating six cycles of ABVE (DBVE) Doxorubicin (Adriamycin), bleomycin, vincristine, chemotherapy and lowerdose (1500 to 2500 cGy), limitedetoposide field radiotherapy. This resulted in excellent disease control Vincristine, doxorubicin (Adriamycin),methotrexate, and decreased musculoskeletal deformity.25.87 prednisone The application of risk-adapted therapy using combinaOPPA f COPP Vincristine (Oncovin), prednisone, procarbazine, tion chemotherapy has achieved excellent disease-free (females)lo7 doxorubicin (Adriamycin), cyclophosphamide, survival and overall survival. Recent studies have shown vincristine (Oncovin), prednisone, procarbazine that the addition of low-dose involved-field radiation OEPA f COPP Vincristine (Oncovin), etoposide, prednisone, (males)lo7 doxorubicin (Adriamycin), cyclophosphamide, im~rovesevent-free survival but does not affect overall vincristine (Oncovin), prednisone, procarbazine survival in patients with a complete response to chemoCyclophosphamide, vincristine (Oncovin), therapy.84Currently, the standard of care for the majority prednisone, procarbazine, doxorubicin of children and adolescents with HD is risk-adapted (Adriamycin), bleomycin, vinblastine combined-modality therapy using lowdose, involved-held BEACOPP Bleomycin, etoposide, doxorubicin radiation in conjunction with multiagent chemotherapy. (advanced (Adriamycin),cyclophosphamide, vincristine /
x ,
stage)S4 COPP CHOP ABVE-PC (DBVE-PC)"
(Oncovin), prednisone, procarbazine Cyclophosphamide, vincristine (Oncovin), prednisone, procarbazine Cyclophosphamide, doxorubicin (Adriamycin), vincristine (Oncovin), prednisone Doxorubicin (Adriamycin), bleomycin, vincristine, etoposide, prednisone, cyclophosphamide
Complications Treatment Toxicity Late effects of treatment include surgical complications, soft tissue and bone growth abnormalities, cardiopulmonary effects, endocrine sequelae, and secondary
CHAPTER
malignancies. An alteration in the proportion of sitting to standing height has been noted in patients receiving radiation to the axial skeleton.97 Boys seem to be more severely affected than girls. There is also shortening of the clavicles, reduced interclavicular distance, fibrosis of the soft tissues in the neck, and thinning of hair in the posterior cervical region. Growth disturbance is not significant in children with bone ages of 14 to 15 years at the time of treatment. Significant radiation-induced pulmonary injury can occur, depending on the volume included in the radiation field, the dose, and the daily fraction size. Symptomatic pulmonary injury occurs in 3.6% of patients receiving high-dose mantle therapy. Bleomycin also may cause severe pulmonary dysfunction. Radiation injury to the myocardium is also related to dose, fraction size, and volume irradiated. Approximately 13% of children receiving high-dose mantle therapy develop cardiac injury. The coronary arteries and great vessels can be affected as well. Doxorubicin is also known to cause cardiac injury, and Raynaud's syndrome has been reported in patients receiving vinblastine and bleomycin. Endocrine effects include hypothyroidism, sterility, and other alterations in fertility. Using thyroid-stimulating hormone as a marker for hypothyroidism, between 4% and 79% of patients develop this complication.19Thyroid abnormalities depend on the dose given to the neck; 17% of patients receiving less than 26 Gy develop thyroid abnormalities, whereas 78% of those receiving 26 Gy or more become hypothyroid. Gonadal dysfunction (both ovarian and testicular) has been documented after HD therapy.lll Pelvic irradiation carries a high likelihood of ablating ovarian function. Ovarian transposition, whereby the ovaries are moved away from the radiation field, can preserve ovarian function and fertility.31 The ovaries can be moved to the midline behind the uterus or to both flanks. A small clip should be placed on the peritoneum in the area where the ovaries were moved for identification by the radiotherapist. Sterility is a much greater problem in males, and gonadal dysfunction may exist at the time of diagnosis in 30% to 40% of patients.l5288J27 Pretreatment storage of sperm in older patients should be considered.
Secondary Malignancies Second malignancies include acute nonlymphocytic leukemia, non-Hodgkin's lymphoma, thyroid cancers (usually differentiated), breast cancer (in irradiated p a t i e n t ~ ) , ~ , l ~ , ~ " 7 " ~ bone % n d or soft tissue sarcomas. Patients who underwent prior splenectomy also have a risk of developing leukemia. The MOPP regimen involves a higher risk of secondary malignancy compared with the ABVD regimen. Children who require retreatment also have higher risk of secondary malignancy as a direct dose effect." The incidence of secondary leukemia in patients primarily treated with MOPP may be 5% to 7%; this increases to 10% if MOPP is given with radiotherapy. The risk of leukemia decreases after 10 years, whereas the risk of non-Hodgkin's lymphoma increases with time, underlying the importance of continual monitoring. Solid tumors may develop in as many as 4% of patients.
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Complications of Laparotomy Complications specific to staging laparotomy can be divided into three groups: (1) early postsurgical complications (6 months after surgery), and (3) septic complications related to splenectomy. Hays et a1.42,4~eviewedthe experience of the Intergroup Hodgkin's Disease in Childhood Study, consisting of 234 staging laparotomies; in the initial report, 55% of children were followed for at least 2 years, and in the updated summary, the median follow-up was 5 years. In the first 6 weeks after laparotomy, three pulmonary and three abdominal complications were noted, for an overall incidence of 2.6%. These included one case of right ureteral obstruction secondary to scar, which required operative lysis; one intestinal obstruction from adhesions, requiring reoperation; one superficial wound infection; and three cases of atelectasispneumonia. There were no postoperative deaths. Five late surgical complications occurred (2.1%) . There were four cases of bowel obstruction requiring adhesiolysis, and in one of these an intestinal perforation secondary to volvulus of a bowel segment around an adhesive band required repair. In the filfth patient, a right oophorectomy was necessary because of torsion and secondary necrosis. This ovary had been moved to the flank during staging laparotomy to avoid the major radiation portals. Thus, the combined incidence of early and late surgical complications specific for laparotomy was 4.7%, including clinically significant atelectasis. Schneeberger and GirvanH2reported on 39 children with HD who underwent staging laparotomy. No operative deaths were reported, and there were no minor complications such as atelectasis. There were five (12.8%) cases of small bowel obstruction, and four were managed nonoperatively with nasogastric suction. One patient required re-exploration 11 years after staging laparotomy because of a small bowel volvulus around adhesions. Donaldson ~ that the rate of significant, nonand K a ~ l a n 2reported lethal complications in the immediate postoperative period after staging laparotomy in children was approximately 1%. Significant complications in this study included wound infection and dehiscence, subphrenic abscess, pulmonary infection, retroperitoneal hematoma, pancreatitis, and significant postoperative bleeding. Complications such as mild postoperative atelectasis were not included. Late complications such as adhesive bowel obstruction have been reported in 3% to 12% of patients in other series and may occur even if abdominal radiation is not given."O
Complications of Splenectomy Increased susceptibility to infection after splenectomy was first noted by King and Shumackefiqn 1952, and multiple confirmatory reports have been published since then.2R119 The incidence of postsplenectomy sepsis is increased in younger children, especially those younger than 10 years. In interpreting data from patients undergoing splenectomy in the setting of HD, it should be remembered that the disease process itself and chemotherapeutic agents are immunosuppressive.
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Serious questions about the use of splenectonly in children with HD were raised following the report of Chilcote et a1.16 in 1976. This was a retrospective study of 200 children aged 19 years or younger treated for HD at collaborating institutions of the Children's Cancer Study Group. In this study, 20 episodes of sepsis were noted in 18 patients, and the interval from splenectomy to infection varied from 8 days to 3 years. The median age of patients developing sepsis was 10 years. All but three of these patients had received or were receiving chemotherapy, and all but two had received radiation therapy. Organisms included pneumococci, Haemophilus influenzae, streptococci, and meningococci. Ten of the children who developed sepsis died; and most of them had a fulminant course. Significantly, only two contributing institutions used prophylactic antibiotics at the time, and neither reported serious infections. The overall follow-up interval was not stated. Subsequent analysis of postsplenectomy sepsis rates by the Intergroup Hodgkin's Disease in Childhood Study showed that this was less of a problem with the use of vaccination and prophylactic antibiotics.42 In the first report from this group, with 55% of patients followed 2 years or more, only two disease-free patients developed documented sepsis. An additional two children developed sepsis in the setting of chemotherapy given for relapse. There were also three cases of possible sepsis, but blood cultures were negative. Most important, no deaths were noted in this group. Significantly, 83% of these children received pneumococcal vaccination before splenectomy, and 74% were given prophylactic antibiotics. In an u ~ d a t eof this series, with a median follow-up of 5.5 years, the total number of documented cases of sepsis had risen to five, but no deaths were reported. In two patients, pneumococcus was isolated from the blood, and in the remaining three, H. injluenzae was found. Of the five children who developed sepsis, four had received pneumococcal vaccine, but only three had been vaccinated preoperatively. Four of the five children had antibiotics discontinued or interrupted before the development of sepsis. Age at diagnosis ranged from 4 to 14 years, with a median of 9 years in the group developing sepsis. An additional five patients became gravely ill and were thought to have sepsis because of a good response to antibiotics; blood cultures in these children were negative, and there was no mortality. With a mean follow-up-of more than 5 years, there were five (2.1%) confirmed cases and five suspected cases of sepsis, and the lethality from this complication was zero. The defect in humoral immunity caused by splenectomy is permanent, however, and additional cases of postsplenectomy infection can be expected in HD surg vivors undergoing staging l a p a r ~ t o m y . ~ ~ W s ai nsepsis incidence of 0.38% per year derived from the Intergroup Hodgkin's Disease in Childhood Study (2.1% incidence in 5.5 years), it was estimated that almost 20% of splenectomized HD patients would develop this complication over a 50-year period." The incidence of sepsis is reduced in adults and falls with age, so this is probably an overestimate. The cumulative risk of sepsis over a lifetime is not known.
Treatment of Metastatic Disease and Relapse The salvage therapy for patients with refractory or recurrent disease depends on the initial therapeutic regimen. Fifty percent to 80% of patients treated initially with radiation alone can be cured with chemotherapy or combined-modality therapy. With the use of combined-modality therapy for early-stage disease and a risk-adapted approach for advanced-stage disease, nearly 90% of patients with Hodgkin's lymphoma are cured with initial therapy. However, in patients who have primary refractory or relapsed disease, highdose therapy and autologous stem cell transplantation constitute the best curative option. The use of peripheral blood progenitor cells has decreased transplant-related mortality to less than 3%, but long-term p r e gression-free survival has shown minimal improvement.77-79
Prognostic Factors The current treatment approach to HD is risk-adapted therapy. Risk features at the time of diagnosis include the presence of B symptoms, age, stage, nodal bulk, and number of involved nodal regions. Patients with localized nodal involvement and the absence of B symptoms have a favorable clinical presentation. Those with B symptoms, bulky mediastinal or peripheral lymphadenopathy, extranodal extension of disease, and advanced disease (stage IIIB to IV) have an unfavorable clinical presentation. Patients with an unfavorable clinical presentation are treated with standard non-cross-resistant chemotherapy on a conventional schedule, followed by consolidation therapy of low-dose, involved-field radiation. Alternatively, abbreviated, dose-intensive multiagent chemotherapy followed by consolidating radiation is being evaluated. Early response to therapy is correlated with better prognosis and reflects tumor bulk and biology.12
Outcome The application of risk-adapted therapy consisting of chemotherapy alone has resulted in 5-year survival of greater than 90% and disease-free survival of greater than 85%. The goal of optimal therapy is to preserve the high survival rate, decrease the relapse rate, and minimize late adverse effects.
NON-HODGKIN'S LYMPHOMA The non-Hodgkin's lymphomas are divided into Burkitt's and Burkitt's-like lymphomas, lymphoblastic lymphomas, diffuse large B-cell lymphomas, and anaplastic large cell lymphomas. The anatomic distribution of these neoplasms can be at least partially understood by reference to normal B-cell and T-cell ontogeny.
Incidence and Epidemiology There are 750 to 800 new cases of non-Hodgkin's lymphoma each year in the United States.93 Burkitt's and
CHAPTER
Burkitt's-like lymphomas have a fivefold higher incidence in males than in females in patients younger than 20 years (3.2 versus 0.7 cases per million). The overall incidence of Burkitt's lymphoma rises after 5 years of age and falls again after age 15. In contrast, the incidence of diffuse large cell lymphoma rises steadily with age and has a male-female ratio of 1.4. Lymphoblastic lymphomas occur at similar frequencies in those younger than 20 years and have a male-female ratio of 2.5.
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small, noncleaved cell lymphomas. Burkitt's lymphoma is a subset of these undifferentiated lymphomas. Because B cells develop in the bone marrow and then migrate to secondary lymphoid organs (lymph nodes, spleen, Peyer's patches, liver), one would expect clinical localization of the developing neoplasm in those anatomic sites. As a corollary, B-cell lymphoma should not occur in the anterior mediastinum in the region of the thymus because normal B cells are not thymic dependent. Usually, but not always, this anatomic distribution is consistent with clinical observations. In the United States, Burkitt's lymphoma has a predilection for the abdomen (in western Biology equatorial Africa, it usually arises in the mandible, but abdominal lymphoma is al& noted in up to 20% of these Lymphocyte Ontogeny and Differentiation patients). Burkitt's lymphoma of the tonsil and testis (as a site of relapse) has also been reported, but Burkitt's lymAlthough a detailed discussion of lymphoid cell developphoma of the anterior mediastinum is extremely rare.53j.57 ment is beyond the scope of this chapter, a short review A simplified schema for the differentiation of T cells of this subject may help in understanding the various is depicted in Figure 35-5. Because thymic residence is a histologic subgroups and their unique clinical behavior. necessary part of T-cell development, most lymphomas Basic to our current understanding of the normal and presenting in the anterior mediastinum originate from pathologic immune system is the idea that there are func~ ~ T-cell ~ J ~ ~lineage. Fifty percent to 70% of patients with tionally separate B-cell and Tcell c o m p a r t m e n t ~ . ~ ~the lymphoblastic lymphoma ( T cell) present with an A second important notion is that mature lymphocytes are intrathoracic tumor, usually an anterior mediastinal not end-stage cells but can undergo transformation to an mass; an abdominal presentation is uncommon. There is effector cell type in the presence of antigen. Lymphoid for T-cell-dependent or B-cella general development can be conceptualized as progressing dependent anatomic areas of the lymphoid system to be through a differentiation path from a stem cell to an actiinvolved by lymphomas that also express surface markers vated cell. This is followed by transformation to an effector specific for their respective T or B lymphocytes. Of interest phenotype when the proper stimulus is provided. A simis the observation that removal of the thymus prevents plified scheme for B-cell differentiation is illustrated in T lymphomas in mice, whereas removal of the bursa of Figure 35-4. B cells originate in the bone marrow from Fabricius prevents B lymphomas in ~ h i c k e n s . Y ' ~ l ~ ~ totipotential stem cells that differentiate through many intermediate cell types to eventually become antibodyproducing plasma 'cells. Malignant .transformation can Cytogenetic and Molecular Biologic Findings occur at any point along the differentiation path, thus In 1976, a characteristic chromosomal translocation involvproducing some readily recognizable clinical syndromes ing chromosomes 8 and 14 was discovered in Burkitt's or histopathologic subtypes. Of interest to the pediatric lymphoma.lg"t was subsequently shown that the c-myc surgeon is that B cells, at the developmental stage when proto-oncogene was translocated from chromosome 8 to immunoglobulin M (IgM) surface immunoglobulin is the immunoglobulin heavy-chain locus on chromosome detectable (see Fig. 35-4), can undergo malignant trans14.124 Finally, it was determined that in a minority of formation into undifferentiated lymphoma. Because of Burkitt's lymphomas, the 8;14 translocation was replaced their light microscopic appearance, these are also called by an 8;22 or 2;8 translocation.YThis still involved the c-myc gene on chromosome 8. The difference in this minority of cases was that instead of an immunoglobulin heavy-chain locus, the K light-chain locus on chromosome 2 or the h light-chain locus on chromosome 22 was involved. Thus, ahroto-oncogene was always juxtaposed to an immunoglobulin constant region coding sequence. Because Burkitt's lymphomas are of B-cell origin, it was thought that these cytogenetic abnormalities involving known proto-oncogene and immunoglobulin coding sequences were not coincidental and had pathophysiologc significance. It was subsequently shown that the translocated c-myc allele becomes activated by its proximity to the may result in an immunoglobulin coding region."his inappropriate expression of c-myc RNA and protein in Pre-B Cells Mature 13Cell B lymphocytes at this stage of differentiation.% Act~vatedmature B Cell In contrast to the extensive cytogenetic data in small, S~mpl~fied d~agramof the B-cell d~fferentiat~on pathnoncleaved cell tumors, most lymphoblastic lymphomas do not manifest specific, nonrandom r n u t a t i ~ n sA. ~small ~ way Und~fferent~ated lymphoma developsjust after cells express surface percentage of lymphoblastic tumors of T-cell origin have ~mmunoglobuhnM
.
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CD2, CD7, CD38, CD71
Stage I
.
CD1, CD2, CD4, CD7, CD8, CD38
1
Stage I1
1
1
CD2, CD3, TCR, CD418, CD5, CD38
Stage Ill
Simplified diagram of T-cell differentiation. Lymphoblastic lymphomas usually express the enzyme terminal deoxynucleotide transferase. T cells must traverse the thymus during differentiation.
translocations, most often involving chromosome 14 (14qll) in a region occupied by the T cc and 8 receptor gene (T-cell receptor) or chromosome 7 near TP.Z1 This is analogous to the involvement of immunoglobulin gene coding regions in &cell lymphomas. Information from cytogenetic and molecular biologic analysis has provided important insights into the molecular mechanisms of malignant degeneration of lymphoid cells.
Lymphoma Subtypes and Histopathology This brief description of immune system ontogeny serves as a basis for understanding the three major subcategories of childhood non-~odgkin'slymph om^: (1) undifferentiated, which are also called small, noncleaved cell lymphomas; (2) lymphoblastic; and (3) large cell (diffuse large B-cell and anaplastic large cell). All three are considered high grade in contrast to other subtypes observed in adult patients. The exceptions to this rule are certain large cell lymphomas with a follicular-center cell type, which are considered intermediate in grade but are rare in childhood and adolescence. The undifferentiated lymphomas are primarily abdominal in origin and develop from B-cell precursors. Malignant degeneration occurs before cleavage of the nucleus during differentiation. They can be divided into Burkitt's and non-Burkitt's categories based on their appearance under light microscopy. Burkitt's lymphoma is characterized by medium-sized nuclei that are approximately the same size as interspersed benign histiocytes, which provides a convenient method of measurement and confers a "starry-sky" L
L
appearance (Fig. 35-6). There are usually two to five prominent basophilic nucleoli. A high nuclear-to-cytoplasmic ratio is observed. Non-Burkitt's varieties often show frequent, single, large nucleoli and more variation in nucleolar size and shape. A later age at presentation and an increased incidence of peripheral lymph node or bone marrow involvement have been associated with non-Burkitt's small, noncleaved cell lymphomas. No cytogenetic, immunohistochemical, or molecular biologic markers distinguish the two. Small, noncleaved cell lymphomas express surface immunoglobulin of the IgM class
.
Histopathologic section from a Burkitt's lymphoma showing multiple prominent nucleoli.
CHAPTER
.
35
Hodgkin's Disease and Non-Hodgkin's Lynlphoma
583
.
Representative section from a lymphoblastic lymphoma. The dark-staining cells are normal lymphocytes.
Representative section from a diffuse large cell lymphoma. Several macrophages (arrow)are seen ingesting tumor cells.
and surface antigens detected by the monoclonal antibodies CD19 and CD2O.logThey do not contain the enzyme terminal deoxynucleotide transferase, which is always found in lymphoblastic lymphomas. Small, noncleaved cell lymphoma must be distinguished from small cell nodular lymphomas that occur in adults and have a more indolent course. Lymphoblastic lymphomas are located predominantly in the anterior mediastinum and are characterized by diffuse effacement of nodal architecture. A lobular appearance may be observed because of extension of tumor cells along normal tissue planes. Cytologically, the nuclei are smaller than those of the interspersed histiocytes, and the nucleoli are inconspicuous (Fig. 35-7). Again, the starry-sky pattern can be appreciated, and the nuclear-to-cytoplasmic ratio is higher than that seen in small, noncleaved cell lymphomas. In about half the cases, the nuclear membrane is convoluted or cleaved. The enzyme terminal deoxynucleotide transferase is invariably found, and most lymphoblastic lymphomas express Tcell markers, including CD7 or CD5.65 Large cell lymphomas (diffuse large cell lymphomas) are usually high grade. As noted previously, the follicularcenter cell type is technically intermediate in grade but shows aggressive biologic behavior. The normal nodal architecture is effaced by cells with large nuclei and scant cytoplasm (Fig. 35-8). The nuclei are larger than those of invading histiocytes. These cells are large and cleaved and have cleaved nuclei, whereas nucleoli are inconspicuous. Another cell type consisting of large, cleaved cells with a narrow rim of cytoplasm and prominent, pyknotic nucleoli may also be present. The two cell types may coexist in the same tumor. A study done by the Pediatric Oncology Group categorized large cell lymphomas into two subtypes.85 The first was a large cell, cleaved or uncleaved lymphoma arising in germinal centers of lymphoid follicles and of B-cell origin. The second type of large cell lymphoma was described as immunoblastic, and most of these originated from T-cell precursors. A plasmacytoid variant of the immunoblastic large cell lymphoma is thought to be of B-cell origin. A variant of large cell lymphoma expresses the Ki-1 antigen, which
is also found on Reed-Sternberg cells and is of T-cell 0rigin.4,104.113 It should be emphasized that all childhood nonHodgkin's lymphomas are diffuse and fast growing. This contrasts with the nodular and often indolent forms of lymphoma observed in adults. Thus, childhood lymphoma should be treated as a systemic disease from the time of diagnosis, with the early institution of multiagent chemotherapy. It is estimated that the growth fraction of childhood lymphoma approaches 100% in some cases and that uncorrected doubling times that do not take into account spontaneous cell death (apoptosis) are as low as 12 hours to several days. Measured doubling times that account for cell death have been reported to average approximately 3 days for small, noncleaved cell tumors injected subcutaneously into mice. It is estimated that the cell death rate for African Burkitt's lymphoma is 70% of all progeny cells. Undifferentiated B-cell tumors of childhood have the highest growth fractions, with up to 27% of cells in S phase by flow c y t ~ m e t r y . ~ ~ , ~ ~
Clinical Presentation Undifferentiated Lymphoma In the United States, children with non-Hodgkin's lymphoma present with a small number of defined syndromes that generally correlate with cell type. More than 90% of patients with small, noncleaved cell lymphoma present with a palpable abdominal tum0r.7.1~'The tumor can cause abdominal pain, distention, change in bowel habits, nausea, vomiting, intestinal obstruction, intussusception, intestinal bleeding, ascites, or bowel perforation. Commonly, the lymphoma presents as a right iliac fossa mass and can be confused with appendicitis or an appendiceal abscess. These patients may have enlarged inguinal or iliac lymph nodes. Patients with extensive intra-abdominal involvement may have fatigue, malaise, and weight loss. An example of an extensive abdominal Burkitt's lymphoma almost totally replacing the liver is illustrated in Figure 35-9. Interestingly, Burkitt's lymphoma in equatorial Africa,
584
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M q l o ~TUMORS OF CHILDHOOD
Abdominal computed tomography scan of a patient
Thoracic computed tomography scan of a patient with lymphoblastic lymphoma and a large anterior mediastinal mass (arrow).The airway is displaced but not compressed.
with Burkitt's lymphoma showing almost total hepatic replacement with tumor. The diagnosis was made by bone marrow aspiration.
although usually presenting as a diffuse jaw tumor, also involves the abdomen in more than 50% of patients. In the United States, other sites of involvement at presentation include bone marrow, pleural effusions, cerebrospinal fluid, central nervous system, peripheral nodes, kidneys, and pharynx.j7J" The ovary is a common site of presentation in both the United States and Africa.80 For practical purposes, patients with abdominal nonHodgkin's lymphomas can be divided into two groups. In the first group, the disease process is localized anatomically within the abdomen. In this case, the tumor often involves the bowel wall, and many of these children present with acute abdominal symptoms suggesting appendicitis or intussusception. The majority can undergo complete gross tumor resection, often with a simple bowel resection and reanastomosis, with little consequent morbidity. In the second group, there is extensive intraabdominal tumor, and presentation with an abdominal mass without acute symptoms is more likely. The mesenteric root and retroperitoneum are heavily involved, and attempts at complete excision are associated with a higher complication rate.
Lymphoblastic Lymphoma Fifty percent to 70% of patients with lymphoblastic lymphoma present with an anterior mediastinal mass or intrathoracic tumor (or both). Figure 35-10 shows a thoracic CT scan of a patient with mediastinal lymphoblastic lymphoma. These tumors may be distinguishable from the middle mediastinal mass associated with HD, but this is often not feasible, especially with extensive mediastinal masses. Fifty percent to 80% of patients have supradiaphragmatic lymphadenopathy, including cervical, supraclavicular, and axillary regions. Abdominal involvement is uncommon and, when observed, usually includes hepatosplenomegaly. Bone marrow infiltration is common in this situation, making the distinction from acute
lymphoblastic leukemia difficult. In these cases, survival may be better after treatment with a lymphoblastic leukemia-type regimen. Pleural effusions are often observed, and patients may complain of dyspnea, chest pain, or dysphagia. Vena caval syndrome with facial, chest, and upper extremity edema and dilated cutaneous veins over the upper torso and shoulders, or airway compression with severe dyspnea or orthopnea (or both), may require the urgent institution of chemotherapy or radiation.','" The central nervous system is rarely involved at diagnosis.
Large Cell Lymphoma The anatomic distribution of primary sites in large cell lymphoma is similar to that observed for small, noncleaved cell tumors. Unusual sites of presentation are possible, however, such as B-cell large cell lymphomas that arise in the anterior mediastinum. Ki-1-positive (anaplastic, usually derived from T cells) large cell lymphomas often involve the skin, central nervous system, lymph nodes, lung, testis, and muscle in addition to the gastrointestinal tract. Lung, facial, and intracerebral primary tumors are more likely to be large cell lymphomas.R6s106J08 A progressively enlarging mass is the most common mode of presentation.
Post-Transplant Lymphoproliferative Disease Post-transplant lymphoproliferative disease (PTLD) occurs as a complication of allogeneic transplantation and can be progrkssive, with a fatal outcome. 1tcan occur after both solid organ and bone marrow transplants. The probability of PTLD is increased after T-cell-depleted bone marrow grafts, after transplants from unrelated donors, in who develop @aft-versus-hostdisease, and particularly in patients treated with aggressive immunosuppressive regimens, including those that contain antithymocyte globulin. PTLD that occurs after bone marrow transplantation arises from transformation
CHAPTER
35
Hodgkin's Disease a n d Non-Hodgkin's Lymphoma
585
chemotherapy. Many patients also require surgical interof the donor B cells by EBV. These patients often present vention because of abdominal com~licationssuch as with gastrointestinal disturbance such as nausea and intussusception or bleeding or to obtain diagnostic tissue. vomiting or derangement in hepatic function. For tumors The pediatric surgeon must be aware that childhood arising in the gastrointestinal tract, endoscopic biopsy lymphoma is a systemic disease, and the operative procemay establish the diagnosis. Multiple biopsies are usually dure should not delay the institution of chemothkrapy. required to identifj the transformed cells. Liver lesions can The Ann Arbor staging system for HD is not relevant be biopsied laparoscopically or percutaneo~sly.~,~~~~~~9s,~2~-~2'L Treatment of PTLD consists of stopping immunosupto non-Hodgkin's lymphomas, and a number of groups pression and administering an anti-CD20 monoclonal have attempted to develop more appropriate classifications.k82 Presently, no clinical staging schema is entirely antibody (rituximab). In addition, various targeted cellular satisfactory, and it may be more important to assess the strategies directed against EBV-transformed cells have been tumor volume at presentation rather than trying to fit a developed, including reinfusion of donor lymphocytes at diffuse systemic process into a limited number of staging low dose. There is no role for surgical resection. categories. The most widely used system for non-Hodgkin's lymphoma staging in childhood is that from St. Jude's Children's Research Hospital (Table 35-3). The Children's Diagnosis Oncology Group divides non-Hodgkin's lymphomas into The evaluation of a patient presenting with possible nontwo categories: limited and extensive. Limited disease Hodgkin's lymphoma includes an extensive history and corresponds to stages I and I1 in the St. Jude's system, physical examination. This is followed by a complete and extensive correlates with stages I11 and IV.81 blood count; liver function tests, including LDH, serum electrolytes, blood urea nitrogen, creatinine, and uric acid level; chest radiograph; bone marrow aspirations; Treatment and lumbar puncture with cytospin for cytology. A four-site bone marrow aspiration and two-site bone marrow biopsy Surgery frequently identify marrow involvement, which has Magrath et a1.,70 basing their conclusions on an extensive serious implications for outcome. A gallium-67 scan and experience with patients in Uganda with abdominal CT scan of the chest and abdomen with oral and intraBurkitt's lymphoma, suggested that surgical reduction of venous contrast material can provide valuable informatumor bulk has a favorable impact on survival. In retrotion concerning tumor location and extent. Gallium is spect, there are several problems with this conclusion. taken up by neoplastic lymphoid cells (in particular, small, First, extent of disease at diagnosis was not evaluated for noncleaved cells) and provides a good total-body screen its predictive effect on outcome. Subsequent studies have for disease. Bone scans can identify suspected skeletal shown that the most important predictor of survival is involvement. MRI may play a role, especially in the evalextent of disease. Second, only 9 of the 68 patients (13%) uation of epidural disease, but is probably not absolutely actually underwent total resection (defined as >90% necessary. The role of positron emission tomography resection). The vast majority had biopsy alone (63%) or remains investigational. subtotal resection (24%). This observation strongly suggests a biologic selection for the patients undergoing total resection. In addition, the patients received single-agent Staging chemotherapy (cyclophosphamide), whereas the standard Staging laparotomy is not performed in non-Hodgkin's is currently a multiagent, histopathology-specific protocol. Finally, the reported surgical mortality rate in this lymphoma because all patients require systemic
Stage
Lymphoblastic
Single extra-abdominal tumor Resected intra-abdominal (>go%)tumor Multiple extra-abdominal sites except BM and CNS Unresected intra-abdominal tumor or non-stage IV epidural disease Intra-abdominal and extra-abdominal tumor except BM
I II lllA lllB
Single extrathoracic tumor Multiple extrathoracic tumors except BM and CNS Single thymic tumor Mediastinal tumor with pleural effusion
IVA
IVA
BM without abdominal or CNS involvement
IVB
IVB IVC
BM and abdominal tumor without CNS involvement CNS disease (cells in cerebrospinal fluid, cranial nerve palsy)
IVC IVD
Mediastinal tumor with extrathoracic extension except BM or CNS BM and intrathoracic tumor without CNS or other extrathoracic involvement EM and extrathoracic tumor without CNS involvement Bone marrow and CNS disease
Stage I IR II lllA
--Undifferentiated
*Tumor burden is assessed at diagnosis, which is the main determinant of outcome. BM, bone marrow; CNS, central nervous system.
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series was 10%, which seems excessive under the present circumstances. Kemeny et al." evaluated the role of surgery for treatment of the primary tumor and for treatment of complications in patients with American Burkitt's lymphoma. They suggested that complete resection has an advantage but pointed out that extent of disease was not analyzed as an independent variable. A role for surgical intervention in the supportive therapy of non-~odgkin'slymphoma was also suggested. As noted, small, noncleaved cell tumors in particular have high growth fractions. As a consequence, renal shutdown caused by urate nephropathy is a real danger and could be complicated by mechanical ureteral obstruction by a retroperitoneal mass. In addition, the tumor lysis syndrome may occur, especially during induction chemotherapy of small, noncleaved cell lymp h o m a ~ . I Final13 ~ ~ ~ ~ "multiple gastrointestinal complications, including bleeding, obstruction, or perforation, can occur. The authors pointed out that surgery can provide vascular access for dialysis or hydration, ureteral stenting in the h c e of obstruction, and definitive operations for intestinal complications. Initial surgical management should include incisional biopsy for diagnosis, followed by intense, multiagent chemotherapy, except for small, easily resectable lesions.52 Data regarding the role of surgery in abdominal Burkitt's lymphoma indicate that the extent of disease is a more significant predictive variable than is completeness of surgical resection."? Major surgical procedures in patients with extensive abdominal disease are u~llikelvto result in complete excision and may be associated with an increased complication rate, resulting in a delay in instituting chemotherapy. ' I 5 Similarly, the surgical committee of the Children's Cancer Group (CCG) evaluated the role of surgical therapy in 68 patients with non-Hodgkin's lymphoma in the CCG-551 study.(i0Variables analyzed included (1) extent of disease at diagnosis; (2) completeness of surgical resection (complete gross resection); (3) radiation therapy to the prima~ysite; and (4) sex, age, and race. Laparotomy was performed in 67 children (99%), with complete gross resection accomplished in 28 (42%).Age at diagnosis, sex, and race had no effect on event-free survival. Tumor burden was the most important prognostic factor. Complete resection was also a significant predictor of event-free survival but was not as important as tumor burden. Of the 10 reported surgical complications, 8 occurred in the group with extensive disease and incomplete resection. These data support a role for complete surgical resection in the setting of localized disease, especially when confined to the bowel. Resections performed in these circumstances positively af'fect outcome by reducing tumor cell burden and preventing certain comBecause extensive plications, such as bowel perforati~n.'~ r e t r ~ ~ e r i t o n edissection, al with the possibility of significant hemorrhagic or septic con~plications,is avoided, chemotherapy can be initiated promptly. Attempts at resection of massive retroperitoneal masses or-large hepatic lymphomas are associated with an increased complication rate and serve to postpone essential chemotherapy. This is particularly deleterious because undifferentiated lymphomas grow so rapidly. In patients
presenting with extensive abdominal disease, diagnosis can often be made by bone marrow aspiration because at least 20% of all patients have obvious marrow involvement (symptoms, positive bone scan), and an additional 20% have microscopic involvement that is unsuspected clinically. Additional sources of diagnostic tissue include ascites and pleural effusions, peripheral lymph nodes, or localized bone lesions, which can sometimes be biopsied by needle. Tumor may invade the bowel wall and undergo subsequent necrosis, resulting in free perforation and peritonitis or severe hemorrhage. Often, Burkitt's lymphoma is localized to the right lower quadrant in the region of Peyer's patches, and symptoms may mimic acute appendicitis. I11 this situation, resection of the ileocecal segment and adjacent mesentery often results in complete gross resection. Patients with large mediastinal masses need careful preoperative evaluation; preoperative airway assessment by clinical and radiographic examination is crucial. Plain chest radiographs and CT scans indicate the degree of airway compression. Because cervical, supraclavicular, and axillary lymph node involvement approaches 50%, diagnostic biopsies performed at these sites under local anesthesia avoid the dangers associated with a general anesthetic and airway manipulation. Aspiration of malignant pleural effusions may also provide diagnostic material.
-
Technique of anterior mediastinotomy, or the
Chamberlain procedure. This is a useft11approach when the diagnosis of lymphoma cannot be made using less invasive techniques, such as lymph node biopsy, bone marrow aspiration, or thoracentesis.
CHAPTER
If intrathoracic biopsy is required, the anesthetic technique may be modified so that patients can be safely intubated. Postoperative extubation is usually not feasible, however, until the tumor has been treated, and arrangements should be made for patient transfer to an intensive care environment.ZYFigure 35-11 depicts the technique for mediastinotomy, or the Chamberlain procedure. This approach can be useful in patients with large mediastinal masses but without more accessible nodal involvement. It can be performed on either side, depending on the CT findings, and thoracostomy drainage is almost never necessary. At present, there is no defined role for resection of mediastinal lymphomas, and operative removal is not indicated. Rarely, patients with mediastinal lymphoblastic lymphoma present with a malignant pericardial effusion and incipient tamponade. If clinical signs are apparent, including tachycardia, tachypnea, neck vein distention, pulsus paradoxus, and muffled heart tones, an emergency echocardiogram must be done. A large pericardial effusion can almost always be drained by catheter pericardi~centesis.~~ Minimally invasive techniques that allow much more thorough thoracic or abdominal exploration without the attendant morbidity of large incisions may have a role in the diagnosis, staging, and treatment of childhood non-Hodgkin's lymphomas. This role remains undefined by prospective or randomized studies; however, trials by both the Pediatric Oncology Group and the CCG are under way to determine their eventual role in this disease process. Laparoscopy may be the optimal method for managing lymphoproliferative disease in the following settings: for the differential diagnosis of hepatic or splenic focal lesions; when percutaneous needle biopsy fails or genetic analysis is needed for a therapeutic decision; for the primary diagnosis and abdominal staging of patients with diffuse retroperitoneal lymphadenopathy in the absence of peripheral lymphadenopathy; for cases of abdominal restaging after concurrent chemoradiotherapy, and in cases of suspected relapse when percutaneous biopsy is not technically possible; and for patients with lymphoproliferative disease when splenectomy is req~ired.110,116,~~.'2" Significant bone marrow infiltration can cause severe thrombocytopenia; therefore, a complete blood count with platelet count should be available preoperatively. The production of serum clotting factors may also be affected by hepatic infiltration, and a full coagulation screen should be performed in preparation for surgery. Surgical intervention in non-Hodgkin's lymphoma should obtain sufficient biopsy material when other sources are unavailable. If adequate diagnostic material can be obtained from bone marrow aspirates, a more invasive procedure may not be required. Laparotomy is indicated when acute abdominal symptoms are present or when sufficient diagnostic tissue cannot be obtained from other sources. Similarly, a thoracic or mediastinal procedure such as the Chamberlain procedure should be designed and carried out with minimal surgical trauma and prompt institution of systemic chemotherapy. An adequate workup to rule out life-threatening metabolic or hematologic problems and to establish airway
35
Hodgkin's Disease and Non-Hodgkin's Lymphoma
587
integrity should be done before operation. The surgeon is obligated to verify that tissue samples are sent in an appropriate condition for immunohistochemistry, immunophenotyping, and cytogenetics. Children with localized abdominal disease, especially if it involves an intestinal segment, should undergo complete gross resection if this can be accomplished with speed and minimal morbidity. Patients with extensive infiltration of tumor throughout the small bowel mesentery or retroperitoneum or those with massive parenchymal involvement are best treated by adequate tissue biopsy through the smallest possible incision and prompt initiation of appropriate multiagent chemotherapy. Mediastinal or cervical primary tumors should undergo initial diagnostic biopsy, and complete tumor resection must be avoided. Laparoscopic and thoracoscopic approaches may prove useful in the diagnosis and treatment of non-Hodgkin's lymphomas. These techniques minimize tissue trauma, which may prove useful because systemic treatment can be initiated with little delay. Studies to evaluate the role of minimal-access surgery in patients with solid tumors are being undertaken by cooperative groups.
Chemotherapy Non-Hodgkin's lymphomas in childhood are disseminated at diagnosis. This concept is supported by the finding that patients with completely excised, localized disease almost always relapse in distant sites (e.g., bone marrow, cerebrospinal fluid) .">l3l Effective therapy must therefore be systemic, and chemotherapy is the primary treatment modality. Historically, only 20% to 30% of patients with non-Hodgkin's lymphoma survived for 5 years until in 1975, the pioneering work of Wollner et a1.28,13"1M when the LSA2-L2 regimen, adapted from the treatment of acute lymphoblastic leukemia, resulted in a 73% salvage reported rate. At about the same time, Ziegler et a1.7i~ix successful treatment of these patients using the COMP (cyclophosphamide, Oncovin [vincristine], methotrexate, prednisone) regimen. The Children's Cancer Study Group began a randomized trial comparing these two high-dose chemotherapy regimens for non-Hodgkin's lymphoma in 1977 (CCG551),9 with patients being randomized at diagnosis. The results suggested that therapy for non-Hodgkin's lymphoma in children should be modified to take into account the specific histopathologic subtype. A short summary of this trial is illustrative. Overall disease-free survival was 60% at 2 years for patients in CCG551. Patients with nonlocalized disease and lymphoblastic histopathologic findings had a disease-free survival of 76% at 2 years if treated with LSA2L2, whereas similar patients treated with COMP had only a 26% survival (P=0.00002). Conversely, in patients with nonlocalized, undifferentiated (small, noncleaved cell) tumors, disease-free survival was 57% for COMP, compared to 28% for LSA2-L2 (Y = 0.02). Lymphoblastic tumors did significantly better when treated with LSA2L2, whereas COMP was more effective for undifferentiated lymphomas. Chemotherapy is the primary treatment modality for all stages and histopathologic subtypes of non-Hodgkin's lymphoma. Given the high growth fractions encountered,
588
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MAJORTUMORS OF CHII.DHOOD
Lymphoblastic Lymphoma Stage I, II Vincristine, doxorubicin, cyclophosphamide, prednisone, mercaptopurine, meth~trexate~~
Small Noncleaved Lymphoma
Stage Ill, IV BFM-NHL 90: prednisone, dexamethasone, vincristine, daunorubicin, doxorubicin, L-asparaginase, cyclophosphamide, cytarabine, rnethotrexate, 6-mercaptopurine, 6-thioguanine, CNS irradiation3' CHOP + MTX (NCI-POB-7704): LMTB1: LSA2L2 regimen supplemented cyclophosphamide, doxorubicin, by 1 0 courses of high-dose rnethotrexatego vincristine, and prednisone, alternating with infusional methotrexateG9 COMP: cyclophosphamide, vincristine, rnethotrexate, prednisone3
especially with undifferentiated non-Hodgkin's lymphoma, it is crucial that chemotherapy be initiated as expeditiously as possible. Chemotherapeutic protocols for non-Hodgkin's lymphoma continue to evolve, and some of these regimens are listed in Table 35-4. Many lymphomas with localized gross disease still receive COMP chemotherapy. Mediastinal Tcell tumors are treated with regimens similar or identical to those used for lymphoblastic lymphoma, and LSA2-L2 is no longer widely used. Small, noncleaved cell lymphomas, including Burkitt's, are treated with regimens that are dose intense but shorter in duration. The use of supportive granulocytecolony stimulating factor has been associated with a reduction in hospital readmission for febrile neutr~penia."-~"glAn anti-CD20 monoclonal antibody has been used for refractory or recurrent B-cell lymphomas.118 There are no reported trials in childhood lymphomas.
Radiation Therapy In the treatment of localized non-Hodgkin's lymphoma, radiation therapy has been shown to add toxicity with no therapeutic benefit.26.8Vonversely, external beam radiation cannot be used to treat diffuse involvement at multiple anatomic sites. At present, radiotherapy should be reserved for specific emergent situations, such as mediastinal involvement with airway obstruction or massive testicular involvement. Routine central nervous system prophylaxis is readily accomplished with intrathecal methotrexate and cytosine a r a b i n ~ s i d eA . ~number ~ of recent studies continue to show a favorable outcome for non-Hodgkin's lymphoma patients treated with chemotherapy without radiotherapy.37,63,101
Stage I, II COMP French LMB-89: high-dose cyclophosphamide, vincristine, prednisone, doxor~bicin~~
Stage Ill, IV French LMB-89
CHOP NHL-BFM 90 CHOP + MIX (NCI-POB-7704) NHL-BFM 90: prednisone, NCI-89-C-0041F: dexamethasone, vincristine, cyclophospharnide, doxorubicin, cyclophosphavincristine, doxorubicin, mide, ifosfamide, etoposide, and methotrexate cytarabine, methotrexatelo' (Codox-M),alternating with cytarabine, etoposide, and ifosfamide (IVAC)2
have extremely high growth fractions and rapid cellular turnover rates. This results in a large turnover of tumor cells, either because they outgrow their blood supply or undergo cell death and lysis for other reasons. Depending on the size of the tumor, this places a tremendous metabolic load on the kidneys, composed of phosphates, potassium, purines, and protein. Patients may present with elevated serum uric acid, lactate, and potassium levels. This syndrome may be further aggravated during the initial massive cell lysis caused by chemotherapy. The result is the tumor lysis syndrome, which can result in hyperuricemic nephropathy and renal shutdown.41 Obviously, the metabolic and hematologic status of the patient should be determined before surgery. A full serum electrolyte screen, as well as determinations of serum creatinine and blood urea nitrogen, is mandatory before surgical intervention, and preoperative hemodialysis may be required to control electrolyte disturbances. All patients should be treated with allopurinol and undergo alkaline diuresis before chemotherapy. Ancillary roles for surgery include the establishment of vascular access for chemotherapy and, if necessary, hemodialysis. Decompression of the urinary tract may also be required in cases of ureteral obstruction by a large abdominal tumor. Cystoscopic placement of ureteral catheters (doub1e-J) can result in marked improvement in urine output and renal function. This technique is preferable to percutaneous puncture both for patient comfort and to avoid infectious complications from percutaneous catheters when the granulocyte counts fall after chemotherapy.
Prognostic Factors Complications As previously noted, childhood non-Hodgkin's lymphomas, especially the small, noncleaved cell subtype,
Clinical outcome depends on tumor burden at the time of diagnosis. This is reflected by the clinical stage, but no current staging system correlates linearly ~ . ~ ~ of serum parameters with tumor b ~ r d e n .A~ number
CHAPTER
can be used to estimate tumor amount, as these substances are secreted or shed from malignant cells. These include LDH, interleukin-2 receptor, P2-microglobulin, uric acid, lactic acid, and p0lyamines.2~~~~J2~ Determination of serum LDH levels is readily available and easy to obtain. LDH levels greater than 250 mg/U/L suggest significant tumor burden, whereas levels greater than 500 are associated with a significantly worse prognosis.
Summary Non-Hodgkin's lymphoma is a heterogeneous group of lymphoid malignancies that can be systematized by reference to normal lymphoid ontogeny. Most abdominal tumors are of the undifferentiated histopathologic subtype (also called small, noncleaved cell), with Burkitt's lymphoma included in this group. Present data support complete resection of abdominal lymphomas only when this can be accomplished with minimal morbidity and without delaying the initiation of chemotherapy. Most mediastinal lymphomas are of T-cell orgin, and resection should not be performed. Surgical intervention may also be required to treat complications, such as massive tumor lysis, bowel perforation, gastrointestinal hemorrhage, or urinary tract obstruction.
REFERENCES 1. Abruzzo LV, Jaffe ES, Cotelingam JD, et al: T-cell lymphoblastic lymphoma with eosinophilia associated with subsequent myeloid malignancy. Am J Surg Pathol 1992;16: 236-245. 2. Adde M, Shad A, Venzon D, et al: Additional chemotherapy agents improve treatment outcome for children and adults with advanced B-cell lymphomas. Semin Oncol 1998;25 (Suppl 4) :33-39; discussion 45-48. 3. Anderson JR, Jenkin RD, Wilson JF, et al: Long-term follow-up of patients treated with COMP or LSA212 therapy for childhood non-Hodgkin's lymphoma: A report of CCG551 from the Children's Cancer Group. J Clin Oncol 1993;ll: 10241032 (see comments). 4. Anderson MM, Ross CW, Singleton TP, et al: Ki-1 anaplastic large cell lymphoma with a prominent leukemic phase. Hum Pathol 1996;27:1093-1095. 5. Anderson T, Chabner BA, Young RC, et al: Malignant lymphoma. 1. The histology and staging of 473 patients at the National Cancer Institute: Validity of the Ann Arbor staging classification for the non-Hodgkin's lymphomas. Cancer 1982;50:2699-2707. 6. ar-Rushdi A, Nishikura K, Erikson J, et al: Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma. Science 1983;222:390-393. 7. Arseneau JC, Canellos GP, Banks PM, et al: American Burkitt's lymphoma: A clinicopathologic study of 30 cases. I. Clinical factors relating to prolonged survival. Am J Med 1975;58:314321. 8. Beaty 0 3rd, Hudson MM, Greenwald C, et al: Subsequent malignancies in children and adolescents after treatment for Hodgkin's disease. J Clin Oncol 1995;13:603-609 (see comments). 9. Behrendt H, Brinkhuis M, Van Leeuwen EF: Treatment of childhood Hodgkin's disease with ABVD without radiotherapy. Med Pediatr Oncol 1996;26:244248.
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Ovarian Tumors
621
foci of immature tissue. Int J Gynecol Pathol 1987;6: 203-212. Young JL Jr, Wu XC, Roffers SD, et al: Ovarian cancer in children and young adults in the United States 1992-1997. Cancer 2003;97(10 Suppl):26942700. Young RH: Ovarian tumors other than those of surface epithelial-stromal type. Hum Pathol 1991;22: 763-775. Young RH, Clement PB, Scully RE: Calcified thecomas in young women: A report of fou; cases. IntJ Gynecol Pathol 1988;7:343-350. Young RH, Dickersin GR, Scully RE: Juvenile granulosa cell tumor of the ovary: A clinicopathological analysis of 125 cases. Am J Surg Pathol 1984;8:575-596. Young RH, Eichhorn JH, Dickersin GR, et al: Ovarian involvement by the intraabdominal desmoplastic small round cell tumor with divergent differentiation: A report of three cases. Hum Pathol 1992;23:454464. Young RH, Kozakewich HPW, Scully RE: Metastatic ovarian tumoFs in children: A report of 14 cases and review of the literature. Int J Gynecol Pathol 1993;12:8-19. Zanetta GRS, Rota S, Chiari S, et al: Behaviour of borderline tumors with particular interest to persistence, recurrence, and progression to invasive carcinoma: A prospective study. J Clin Oncol 2001;19:2658-2664.
Testicular Tumors Hsi-Yang Wu and Eugene Wiener
Testicular tumors in prepubertal boys differ from those in postpubertal men in both pathology and tendency for metastasis. This difference allows testis-sparing procedures to be applied more liberally in younger patients but requires careful evaluation of pubertal development in older patients. The peak incidence for testicular tumors is 2 to 4 years of age.13 These tumors represent 1% of all pediatric solid tumors and are rare in the African American and Asian populations. Testis tumors that arise later in life are associated with a history of cryptorchidism and mixed gonadal dysgenesis. The risk of malignancy arising from an undescended testis after puberty is 1% in inguinal testes and 5% in abdominal testes.The most common pathology in a testis that remains undescended is seminoma, whereas a testis that has been surgically placed in the scrotum is more likely to have embryonal or teratocarcinoma pathology. Orchiopexy does not reduce the incidence of testicular cancer.' Because prepubertal testis biopsies rarely detect tumors in undescended testes, the pathologic finding of normal testicular parenchyma does not preclude the later development of tumor.
CLINICAL PRESENTATION A nontender, solid scrotal mass is the usual presenting sign of a testicular tumor. Often a history of trauma is volunteered, but this likely alerted the boy or his parents to a previously unrecognized painless, enlarged testis, rather than being the cause. The differential diagnosis includes testicular torsion and epididymitis, but in the absence of pain, dysuria, and inflammation, tumor is more likely. However, it is not unusual for a patient with a tumor to be mistakenly operated on for suspected torsion. Physical examination should differentiate between epididymal swelling (spermatocele or epididymitis) and testicular swelling (orchitis or tumor). There may be an associated hydrocele. Transillumination does not rule out the presence of a tumor, because a tumor and a hydrocele can coexist. Stromal testicular tumors can present with precocious puberty (Leydig cell) or gynecomastia (Sertoli cell).
DIAGNOSIS Imaging If the testis cannot be palpated owing to a tense hydrocele or if the examination is unclear, scrotal ultrasonography is belpful in determining the architecture and echogenicity of the testis. The normal testis has a homogeneous texture, whereas a tumor has a heterogeneous texture in comparison to the normal testicular parenchyma next to it. If there are cystic areas in the involved testis, a teratoma or epidermoid cyst is the likely diagnosis, and testis-sparing surgery should be considered. The presence of multiple small calcifications (microlithiasis) is of unclear significance. It has been found in association with testis tumor in adult men. If microlithiasis is found in the contralateral (presumably normal) testis, follow-up imaging is warranted owing to the possibility of the later formation of a testis tumor. l 1 A metastatic evaluation is performed after the diagnosis of a malignant tumor is established. A chest computed tomography (CT) scan should be obtained because metastases from yolk sac tumors are more likely to occur in the lung than the retroperitoneum. A CT scan of the abdomen and pelvis to look for retroperitoneal nodal involvement is performed postoperatively.
Tumor Markers Serum alpha fetoprotein (AFP) and P-human chorionic gonadotropin (P-HCG) levels should be obtained preoperatively in all patients with suspected testis tumor. Although elevated levels are occasionally useful in making the diagnosis, they are most beneficial in followup for recurrence. AFP (a marker for yolk sac tumors) is normally elevated in newborns until 8 months of age27 and in patients with liver dysfunction, so serial determinations after orchiectomy are needed. The half-life of AFP is 5 days, so the level should be normal 25 days after orchiectomy if the entire tumor was removed. P-HCG is occasionally elevated in seminoma and more commonly in choriocarcinoma, both of which are rare
CHAPTER
37
Testicular T ~ ~ m o r s
623
entering puberty, teratoma should be treated as it is in adult patients, with radical inguinal orchiectomy, owing to its more malignant behavior. If the AFP level is elevated relative to age-adjusted levels, Percentage Tumor Type --.one should assume that yolk sac elements are present and Yolk sac 62 not perform testis-sparing surgery. Scrota1 ultrasonography 23 Teratoma showing internal calcifications and a heterogeneous 4 Gonadal stromal mass in the testis, in association with a normal AFP level, 3 Epidermoid cyst suggests a teratoma. The testis is approached through an 3 Juvenile granulosa inguinal incision, and after vascular control has been 3 Sertoli cell obtained at the level of the internal inguinal ring, the 1 Leydig cell 1 Gonadoblastoma teratoma can be shelled out from the testis; a frozen section can confirm the patholocgy.ylEven when the teratoma significantly compresses normal testicular parenchyma, postoperative ultrasound studies usually show good in the prepubertal population. Its half-life is 1 day, so it recovery of testicular tissue, with presumably preserved should return to normal by 1 week postoperatively. function.I4 There are two different approaches to the use of frozen sections. The classic approach is to obtain a frozen section STAGING AND CLASSIFICATION to confirm teratoma pathology and that there are no maturation changes in the neighboring parenchyma.Z0 Table 37-1 lists the distribution of pathologies in the Others have suggested that the combination of ultrasound 2002 American Academy of Pediatrics Testis Tumor findings and normal AFP level should be sufficient to Registry.") The predominance of yolk sac tumors may make the diagnosis of teratoma preoperatively. They also reflect a reporting bias; in many single-institution studies teratomas are more common, but they are often not recommend that any patient with pubertal development reported to registries because they are benign.1,14,2"26 should be excluded from testis-sparing surgery.14.':4Most Table 37-2 shows the staging system for testis tumor used prepubertal boys with teratomas have good gonadal preservation after testis-sparing surgery. by the Children's Oncology Group (COG).
TREATMENT BY TUMOR TYPE Germ Cell Tumor Teratoma Teratomas are derived from ectoderm, mesoderm, and endoderm and therefore can have solid and cystic components. Epidermoid cysts can be considered monophasic teratomas, in that they are derived only from ectoderm. Before puberty, teratoma can be managed with a testissparing approach")^"^?^ because it is always benign, even shows immature el em en^.^ In patients when the path~lo~gy
Stage
Description
I
Limited to testis, completely resected by high inguinal orchiectomy; no clinical, radiographic, or histologic evidence of disease beyond the testes; patients with normal or unknown tumor markers at diagnosis must have a negative ipsilateral retroperitoneal node sampling to confirm stage I disease if radiographic studies demonstrate lymph nodes >2 cm Transscrotal biopsy, microscopic disease in scrotum or high in spermatic cord (25 cm from proximal end) Retroperitoneal lymph node involvement, but no visceral or extra-abdominal involvement; lymph nodes >4 cm by computed tomography or >2 cm and 63)
-
645
(36-72) (12-192) 55 (19-101) 69 (59-80)
From LaQuaglia MP: The surgical managementof metastases in pediatric cancer. Semin Pediatr Surg 1993;2:75.
for pulmonary metastasectomy are osteosarcoma, soft tissue sarcoma, and Wilms' tumor.3g
Osteosarcoma Children with osteosarcoma should be considered for resection of pulmonary metastases once the primary lesion is controlled. The overall disease-free survival is approximately 40% in children who develop metachronous pulmonary metastases. Multiple factors, such as number of pulmonary nodules and time of recurrence, play an important role in children with osteosarcoma 2 1 ~ ~et a1.61showed that and pulmonary m e t a s t a s e ~ . ~Roth patients with fewer than four pulmonary nodules had an improved survival over those with more than four lesions. According to Goorin et a1.,26 a complete resection of all pulmonary lesions is an important determinant of outcome, and penetration through the parietal pleura is associated with an adverse outcome. Although somewhat controversial, the outlook seems to be somewhat improved, even in patients presenting with pulmonary metastases, if complete resection of all metastatic lesions can be accomplished.46 Harris et al.30 reported a 68% survival rate in 17 patients with fewer than eight pulmonary nodules at presentation following chemotherapy, resection of the primary tumor, and pulmonary metastasectomy. The data in Table 39-4 suggest that an aggressive attempt at surgical resection of pulmonary metastases is indicated in osteosarcoma, possibly irrespective of the number of lesions or the interval to the development of metastases.
Soft Tissue Sarcoma The usefulness of resecting pulmonary metastases in patients with soft tissue sarcoma depends on the histologic subtype. Rarely is pulmonary resection of metastatic lesions required in rhabdomyosarcoma, and resection of pulmonary metastasis in Ewing's sarcoma has not been found to be efficacious." The remaining
sarcomas should be considered for resection if complete excision is possible and the patient's primary tumor is under control. The time to development of pulmonary metastases, number of lesions, and tumor doubling time are all significant prognostic factors in soft tissue sarcomas. Historically, approximately 10% to 20% of these patients can be salvaged by resection of pulmonary meta~tases.~~
Wilms' Tumor Rarely is pulmonary resection of metastatic disease required in children with Wilms' tumor. In a review of the National Wilms' Tumor Study by Green et a1.,28 no advantage of pulmonary resection was found compared with chemotherapy and radiation therapy alone. In an attempt to avoid pulmonary radiation, deKraker et a1.18 suggested a protocol using primary pulmonary resection after chemotherapy for pulmonary metastases. The overall results were not encouraging, and few patients ultimately required resection of pulmonary metastases following chemotherapy. Because the results of chemotherapy and whole-lung irradiation are excellent for children with Wilms' tumor and pulmonary metastases, pulmonary resection of metastases should be reserved for only selected cases (see Chapter 27).
Comments Operation for pulmonary metastases in children depends on the histology of the primary tumor, the extent of the metastatic disease, and whether the metastatic disease is responsive to chemotherapy. The surgical approach varies, depending on the disease process and the age of the patient. No difference ir. survival has been demonstrated with sequential lateral thoracotomy versus sternotomy, but the latter is preferable in older patients with osteosarcoma. Complete resection of all metastatic disease is an imporiant consideration, and the use of automatic stapling devices can be helpful. Wedge resection is
646
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usually possible in children with osteosarcoma. However, formal lobectomy or segmentectomy may be required to remove all tumor completely, especially when the primary tumor is not responsive to chemotherapy or radiation.6 Muscle-sparing techniques are available in those children requiring posterolateral thoracotomies, and thoracoscopy may be appropriate in certain cases.55 However, port site recurrences have been reported following thoracoscopic resection of pulmonary metastatic disea~e.~z.~~
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CHAPTER
38. Jalal A, Jeyasingham K: Bronchoplasty for malignant and benign conditions: A retrospective study of 44 cases. Eur J Cardiothorac Surg 2000;17:370. 39. Karnak I, Senocak ME, Kutluk T, et al: Pulmonary metastases in children: An analysis of surgical spectrum. Eur J Pediatr Surg 2002;12:15. 40.Kaslovsky RA, Purdy S, Dangman BC, et al: Bronchioalveolar carcinoma in a child with congenital cystic adenomatoid malformation. Chest 1997;112:548. 41. Krous HF, Harper PE, Perlman M: Congenital cystic adenomatoid malformation in bilateral renal agenesis: Its mitigation of Potter's syndrome. Arch Pathol Lab Med 1980;104:368. 42. LaBerge JM, Puligandla P, Flageole H: Asymptomatic congenital lung malformations. Semin Pediatr Surg 2005; 14:16. 43. Lack EE, Harris GBC, Eraklis AT, et al: Primary bronchial tumors in childhood: A clinicopathologic study of six cases. Cancer 1983;51:492. 44. LaQuaglia MP: The surgical management of metastases in pediatric cancer. Semin Pediatr Surg 1993;2:75. 45. MacSweeney F, Papagiannopoulos K, Goldstraw P, et al: Assessment o f the'expanded classification of congenital cystic adenomatoid malformations and their relationship to malignant transformation. Am J Surg Pathol 2003; 27:1139. 46. Marina NM, Pratt CB, Rao BN, et al: Improved prognosis of children with osteosarcoma metastatic to the ling(s) at the time of diagnosis. Cancer 1992;70:2722. 47. Martinez JC, Pecero FC, Gutierrez de la Pena C, et al: Pulmonary blastoma: Report of a case. J Pediatr Surg 1978;13:93. 48. Martini N, Havos AG, Mike V, et al: Multiple pulmonary resections in the treatment of osteogenic sarcoma. Ann Thorac Surg 1971;12:271. 49. McDermott VG. MacKenzie S. Hendrv GM: Case reDort: Primary intrathoracic rhabdokyosarcbma: A rare c'hildhood malignancy. Br J Radio1 1993;66:937. 50. Morales L, Julia V, Tardio E, et al: Pulmonary blastoma at the site of a congenital pulmonary cyst. Chir Pediatr 1986; 27:53. 51. Morresi A, Wockel W, Karg 0 : Adenomatoid cystic lung abnormality in adults with associated bronchioalveolar carcinoma. Pathologe 1995;16:292. 52. MurphyJ, Blair GK, Fraser GC, et al: Rhabdomyosarcoma arising within congenital pulmonary cysts: Report of three cases. J Pediatr Surg 1992;27:1364. 53. Nistal M, Jimenez-Hefferman JA, Hardisson D, et al: Malignant fibrous histiocytoma of the lung in a child. Eur J Pediatr 1997;156:107. 54. Ozcan C, Celik A, Ural Z, et al: Primary pulmonary rhabdomyosarcoma arising within cystic adenomatoid malformation: A case report and review of the literature. J Pediatr Surg 2001;36: 1062. 55. Papagiannopolous KA, Sheppard M, Bush AP, et al: Pleuropulmonary blastoma: Is prophylactic resection of congenital lung cysts effective? Ann Thorac Surg 2001; 72:604. 56. Parsons SK, Fishman SJ, Hoorntje LE, et al: Aggressive multimodal treatment of pleuropulmonary blastoma. Ann Thorac Surg 2001:72:939. 57. Paupe A, Martelli H, Lenclen R, et al: Pneumothorax revealing pneumoblastoma in an infant. Arch Pediatr 1994;1:919. 58. Prichard MG. Brown PI. Sterrett GF: Bronchioalveolar carcinoma arising in longstanding lung cysts. Thorax 1984;39:545. 4 ,
39
Tumors of the Lung
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59. Ribet ME, Copin MC, Soots JG, et al: Bronchalveolar carcinoma and cystic adenomatoid malformation. Ann Thorac Surg 1995;60:1126. 60. Rosenberg SA, Flye MW, Conkle D, et al: Treatment of osteogenic sarcoma. 11. Aggressive resection of pulmonary metastases. Cancer Treat Rep 1979;63:753. 61. Roth JA, Putnam JB, Wesley MN, et al: Differing determinants of prognosis following resection of pulmonary metastases from osteogenic and soft tissue sarcoma patients. Cancer 1985;55:1361. 62. Sartorelli KH, Patrick D, Meagher DP Jr: Port-site recurrence after thoracoscopic resection of pulmonary metastasis owing to osteogenic sarcoma. J Pediatr Surg 1996;31:1443. 63. Schaller RTJr, Haas J, SchallerJ, et al: Improved survival in children with osteosarcoma following resection of pulmonary metastases. J Pediatr Surg 1982;17:546. 64. Seballos RM, Klein RL: Pulmonary blastoma in children: Report of two cases and review of the literature. J Pediatr Surg 1994;29:1553. 65. Senac MO Jr, Wood BP, Isaacs H, et al: Pulmonary blastoma, a rare childhood malignancy. Radiology 1991;179:743. 66. Seo IS, Warren M, Mirkin LD, et al: Mucoepidermoid carcinoma of the bronchus in a four year old child. Cancer 1984;53:1600. 67. Shariff S, Thomas JA, Shetty N, et al: Primary pulmonary rhabdomyosarcoma in a child with a review of the literature. J Surg Oncol 1988;38:261. 68. SogaJ, YakuwaY Bronchopulmonary carcinoids: An analysis of 1875 reported cases with special reference to a comparison between typical carcinoids and atypical varieties. Ann Thorac Cardiovasc Surg 1999;5:211. 69. Spanos PK, Payne WS, Ivins JC, Pritchard DJ: Pulmonary resection for metastatic osteogenic sarcoma. J Bone Joint Surg Am 1976;58:624. 70. Stephanopoulos C, Catsaras H: Myxosarcoma complicating a cystic hamartoma of the lung. Thorax 1963;18:144. 71. StockerJT: Congenital pulmonary ainvay malformationsa new name for and an expanded classification of congenital cystic adenomatoid malformation of the lung. Histopathology 2002;41(Suppl):S424. 72. Su W, KO A, O'Connell TX, et al: Treatment of pseudotumors with nonsteroidal anti-inflammatory drugs: J Pediatr Surg 2000;35:1635. 73. Sudou M, Sugi K, Murakami T: Bronchioalveolar carcinoma arising from a congenital cystic adenomatoid malformation in an adolescent: The first case in the Orient. J Thorac Cardiovasc Surg 2003;126:902. 74. Sumner TE, Phelps CR, Crowe JE, et al: Pulmonary blastoma in a child. AJR Am J Roentgen01 1979; 133:147. 75. Tagge EP, Mulvihill D, Chandler JC, et al: Childhood pleuropulmonary blastoma: Caution against nonoperative management of congenital lung cysts3 Pediatr ~ u r g1996; 31:187. 76. Tagge EP, Yanis E, Chopy KJ, et al: Obstructing endobronchial fibrous histiocytoma: Potential for lung salvage. J Pediatr Surg 1991;26:1067. 77. Telander RL, Pairolero PC, Pritchard DJ, et al: Resection of pulmonary metastatic osteogenic sarcoma in children. Surgery 1978;84:335H. 78. Thompson RC Jr, Cheng EY, Clohisy 'DR, et al: Results of treatment for metastatic osteosarcoma with neoadjuvant chemotherapy and surgery. Clin Orthop 2002;397:240. 79. Ueda K, Gmppo R, Unger F, et al: Rhabdomyosarcoma of lung arising in congenital cystic adenomatoid malformation. Cancer 1977;40:383.
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80. Valderrama E, Salija G, Shende A, et al: Pulmonary blastoma: Report of two cases in children. Am J Surg Pathol 1978;2:415. 81. Verbeke JIML, Verberne AAPH, Den Hollander JC, Robben SGF: Inflammatory myofibroblastic tumor of the lung manifesting as progressive atelectasis. Pediatr Radiol 1999;29:816. 82. Vujanic GM, Dojcinov D: Inflammatory pseudotumor of the lung in children. Pediatr Hematol Oncol 1991;8:121. 83. Weinberg AG, Currarino G, Moore GC, Votteler TP: Mesenchymal neoplasia and congenital pulmonary cysts. Pediatr Radiol 1980;9:179.
84. Weinblatt ME, Siege1 SE, Isaacs H: Pulmonary blastoma associated with cystic lung disease. Cancer 1982; 49:669. 85. Wille GA, Gregory R, Guernsey JM: Tumor implantation at port site of video-assisted thoracoscopic resection of pulmonary metastasis. West J Med 1997;166:65. 86. Williams RA: Embryonal rhabdomysosarcoma occurring in cystic adenomatoid malformation. Pediatr Pathol 1986; 5:118. 87. Zaidi A, Zamvar V, Macbeth F, et al: Pulmonary blastoma: Medium-term results from a regional center. Ann Thorac Surg 2002;73:1572.
Bone Tumors Saminathan S. Nathan and John H. Healey
Bone tumors are rare. In the United States there were GENERAL CONSIDERATIONS 166,487 cases of breast cancer and 164,753 c a ~ e s 2of ~ prostate cancer in 2000. By comparison, there were only Pathophysiology 2,051 of all types of bone sarcomas that year. A large proThe main aim of this section is to illustrate the specific portion of these tumors occur in the pediatric population. issues of the pathophysiology of bone tumors that distinIn one published database 26.8% of all bone sarcomas guish them from tumors of soft tissue. occurred in the pediatric age group. There are no popu" Bone tumors should be approached initially from the lation-based benign bone registries so it would be imposstandpoint of being benign or malignant. Whereas tradisible to guess at the true incidence of benign bone tional approaches regarding the treatment of most tumors. Most databases of this nature derive from tertinonskeletal benign lesions have been one of benign ary referral institutions, and so benign conditions, which neglect if these lesions are not perceived to be causing are often asymptomatic, would be grossly underrepreproblems, the management of benign bone lesions is sented. Nevertheless, one study has shown that up to complicated by a potential c o m p r o m ~ eof skeletal struc43% of children have a bone lesion during skeletal develtural integrity. Cortical deficiency weakens bones and opment.18 This implies that the overwhelming majority can mandate treatment to prevent fracture. The pruof lesions are benign. dent, if rare, consideration is-one of syndromic presentsThe pediatric surgeon will often be called into the mantion and malignant transformation. Many of these agement of the patient with bone tumors for a number of principles are applicable to malignant lesions as well. reasons. The very young child on follow-up for an unreHowever, malignant lesions have at their cornerstone of lated condition may manifest with a bone lesion secondary consideration their im~licationon survival, which will be to osteomyelitis or leukemia. The older child with a elaborated. Metastatic lesions to bone are not common metastatic osteogenic sarcoma may require the expertise in the pediatric age group. Their pathophysiologic impliof the pediatric thoracic surgeon for the resection of pulcations tend to be structural or diagnostic. monary nodules. The teenager with a pathologic fracture In the pediatric age group benign lesions far outnumthrough a unicameral bone cyst or nonossifylng fibroma ber primary malignant lesions, which in turn outnumber may present first to the pediatric surgeon on call in the metastatic lesions. Owing to the protean manner in which pediatric emergency department. benign lesions behave, some are not evident in the physiThe diagnosis of these rare groups of conditions is readcian's office. Conclusions about their natural history and ily attained through a careful clinical evaluation. In that malignant potential are therefore difficult to ascertain.67 regard, the utility of plain radiographs can never be overThis is obviously not the problem with malignant and stated. They facilitate the initial workup of these patients metastatic lesions. In this section we discuss pathologc and allow them to be referred to specialized centers with conditions of the bone that occur most commonly in the multidisciplinary expertise. Although the subsequent pediatric age group. In the pediatric population the imaging modalities are important, the radiographs form a commonly occurring benign lesions are the unicameral key part of surgical planning. bone cyst, aneurysmal bone cyst, enchondroma, osteoIt is with the pediatric surgeon in mind that this chapchondroma, nonossifylng fibroma, and osteoid osteoma. ter is written. Lengthy discourse on the pathology is The common malignant bone tumors are osteogenic saravoided, and several excellent references e~ist.62,~~,~2~,~35 coma and Ewing's family tumor (Table 40-1). Here we Instead, the format adopted is a practical approach to the highlight specifiE features of each tumor. For a more thormanagement of these conditions. Where prudent, insights ough understanding of pathology the reader is directed to and controversies are highlighted to spur interest into any one of a number of fine books on the s~bject.62,6~,"~,~35 specific areas.
650
PART
III
MAJOR TUMORS OF CHILDHOOD
Benign Tumors
Malignant Tumors
Tumor-like Conditions
Birth to 5 years
Eosinophilic granuloma
5 t o 1 5 years
Unicameral bone cyst Osteochondroma Aneurysmal bone cyst Osteoid osteoma Enchondroma Nonossifying fibroma Chondromyxoid fibroma Chondroblastoma Unicameral bone cyst Osteochondroma Osteoid osteoma Aneurysmal bone cyst Nonossifying fibroma Giant cell tumor Enchondroma Chondroblastoma Chondromyxoid fibroma
Leukemia Metastatic neuroblastoma Ewing's sarcoma Osteogenic sarcoma
Osteomyelitis Nonaccidental injury Fibrous dysplasia Osteomyelitis Osteofibrous dysplasia Stress fracture
Osteogenic sarcoma Ewing's sarcoma
Fibrous dysplasia Stress fracture
1 5 to 2 0 years
1
By consideringthefactors age, frequency, and location in the long bones (see Fig. 40-3), a diagnosis can be arilved in the majority of cases. The possibility of trauma should always be borne in mind and in the noncommunicativechild youngerthan 5 years old, nonaccidental injury may be the cause.
Benign Lesions The typical benign lesion in the pediatric age group (Table 40-2) is determined incidentally. These lesions rarely cause any symptoms and are often diagnosed when a parent notices a lump or deformity (e.g., osteochondroma) or a radiograph is obtained for an unrelated
Tumors Benign Osteochondroma Aneurysmal bone cyst Osteoid osteoma Nonossifying fibroma Enchondroma Giant cell tumor Chondroblastoma Chondromyxoid fibroma Unicameral bone cyst Malignant Osteogenic sarcoma Ewing's sarcoma
All Bone Tumors (%)
Bone Tumors in the First Two Decades (%)
7.86 2.60 2.99 1.13 3.02 5.10 1.07 0.41 Unknown
4.69 1.96 1.94 0.99 0.98 0.80 0.66 0.14 Unknown
14.9 4.6
7.53 3.50
In usingthis table a number of caveats need to be remembered. Most benign lesions are often asymptomatic, and only symptomatic ones will present. Of these, most will be managed at the primary care setting. Malignant lesions will, however, usually present to a referral center. Hence in terms of population incidence these figures are unreliable. In relative terms, however, they have some utility in indicatingtheirprevalence. Unicameral bone cysts are left in this list as a reminder of their frequency.
condition (e.g., nonossifying fibroma). In these cases there are two main surgical indications: diagnosis through a biopsy and surgical stabilization of bones that have fractured or are likely to fracture, especially through a precarious location. For example, a bone cyst in the neck of a femur should be seriously considered for surgical stabilization because a fracture through this area may result in avascular necrosis of the femoral head. The biopsy itself cannot be undertaken lightly because it can weaken the bone, mandating surgical or external splinting. This is pertinent because benign lesions are often asymptomatic whereas the biopsy itself incurs morbidity. The challenge is in improving the yield from biopsy in terms of distinguishing malignant from benign disease.
Size of the Tumor Size is an important consideration. For example, cartilaginous tumors larger than 4 cm in a heterogeneous group of patients with cartilaginous rib lesions were found to have increased likelihood of malignant behavior.62 Because of their aggressive malignant potential large cartilaginous tumors should be resected widely despite their relatively bland histologic appearance (Fig. 40-1). Large tumors can also grow into neighboring compartments and cause mechanical compromise to joints. Although this is less critical in joints of the upper limb, it is more important in the spine and in the lower.limbs, where they cause mechanical impingement and pain. The disruption of a tubular bone that results from the growth of a lesion results in weakening of the bone. Thus, lesions that involve more than 50% of the cross-section of a bone should be treated from a mechanical standpoint.45~462.5" These lesions are at increased risk of fracture and, on the
CHAPTER
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Bone Tumors
651
of the growth plate, caused disordered linear growth of the long bone.135 These cases are often familial and rarely compromised by their condition.Joints of the upper limb often have high tolerance for the resultant deformity. In the occasional case, however, especially in the lower limb, degenerative arthritis develops necessitating premature surgery.
Multiplicity of Bone Tumors
B
A
-
A, Chondrosarcoma in the proximal humerus of a 13-year-old boy. This is an exceedingly rare diagnosis in this age group. B, A proximal humeral resection with allograft reconstruction was performed. In children, the available prostheses may be too large and hence bulk allografts may be the only choice. o
1
1
Multiple bone lesions are often syndromic and may confer a higher incidence of malignant degeneration.67-128-135 Multiple osteochondromas occur in multiple hereditary exostoses-an autosomal dominant condition caused by abnormalities of the EXTI, EXT2, and EXT? genes on chromosomes 8, 11 and 19.30,74,142Patients with this condition have an increased incidence of malignant degeneration into chondrosarcomas of 10% to 27.6%. By comparison, isolated osteochondromas have a malignant degeneration rate of about l%.62,67l1z8Because only symptomatic lesions will present to the physician, the true incidence of malignant degeneration in isolated lesions is probably impossible to ascertain with certainty. Multiple enchondromatoses is a sporadic condition that confkrs an increased incidence of malignant transformation of up to 50% in the involved bones.67 Limb-length inequality and malalignment are also common. OllierS dzsease, as this condition is termed, has another counterpart
chance that they may be malignant, could result in a potential limb-sparing operation being deferred for an amputation.
Fracture Through a Benign Lesion The fractured benign lesion is typified by the unicameral bone cyst. These lesions may appear aggressive, but a careful history and physical examination with appropriate imaging modalities will usually establish their benign nature (Fig. 40-2). Unicameral bone cysts that fracture have been known to resolve spontaneously. However, the vast majority of them will continue to fracture through a child's lifetime and prove to be disabling.g8 In general, they should be treated surgically, especially if they are symptomatic. The timing of surgery is critical. An early biopsy would show callus formation that would be difficult to distinguish from a malignant process. Therefore, these lesions should be observed during fracture healing for about a month, following which a biopsy and a definitive procedure are performed.
A I
Location in Relation to the Physis Location in relation to the physes is an important consideration distinguishing tumor assessment and management of children versus adults (Fig. 40-3). The term diaphyseak aclaszs was coined to highlight a condition in which multiple osteochondromas, a condition primarily
- , I
t3 A, Large unicameral bone cyst of the proximal
humerus that had fractured. The aggressive appearance may lead one to suspect a malignant process, but a careful evaluation of the margins of this lesion and absence of periosteal reaction reaffirms the management decision of observation before surgery. B, This cyst was curetted and packed with an allograft 1 month after the fracture. Treatment with an intramedullary fibular graft provided stabilization, and supplemental bone graft healed the lesion.
652
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MAJORTUMORS OF CHILDHOOD
Benian lesions
Malignant lesions
Osteogenic sarcoma
Ewing's sarcoma
osteoblastoma , The location of lesions in relation to the physis gives a clue to the diagnosis. In most cases the diagnosis can be made on radiographs, leaving further imaging to plan for surgery. 1 1
classically affecting one limb anlage. A variant, MafSucci's syndrome, describes widespread enchondromas associated with hemangiomas of the hand. The occurrence of multiple nonossifylng fibromas, associated with mental retardaendocrine disorders. cardiovascular Lon, cafe-au~laits~ots, malformations, 'and ocular abnormaliiies has been termed Jafie-Campanacci syndrome but has no malignant implications.67~94
the outset.73 However, of the truly benign lesions that do metastasize, they tend to be in atypical lesions and have had surgical manipulation that may have embolized tumor cells. When followed, some of these metastatic lesions, primarily in the lung, may remain dormant and not progress. The possibility, therefore, is that they represent a transport phenomenon more akin to a mechanical embolism and not true metastasis, which would require a number of mutations before finally seeding.62~~~
Site of lnvolvement The site of benign cartilaginous lesions has important Malignant Lesions implications on malignant potential. Peripheral lesions in the hand rarely turn malignant, whereas those toward Epidemiology the axial skeleton have important malignant potential even if they appear benign histologi~ally.62,67~86,94,128,135The main histologic types of bone tumors are osteogenic Lesions in bones about weight-bearing joints should be sarcoma, Ewing's family tumor, chondrosarcoma,and other regarded with special care. In the pediatric group these sarcomas. They affect children at a rate of 6:3:2:1.2s,128 lesions are usually chondroblastomas. They grow epiphyOsteogenic sarcomas (also known as osteosarcomas) seally and in so doing can cause weakening of the s u b are malignant bone-forming tumors of the bone. They chondral bone and ultimately an intra-articular extension occur at any age but most frequently present in middle or fracture that may even mimic osteochondral defects. teenage years in the extremity. There are various subIn the case of sarcomas, a relatively conservative resection types with varying implications on survival. In general, in this context would have to be deferred to an extrathe subtypes perform similarly except perhaps for telanarticular resection. giectatic osteogenic sarcomas, which bear special mention. In the pre-chemotherapy era this was regarded as the tumor with the poorest prognosis.91 Presently, howMetastatic Potential The lytic nature of these ever, it has the best progno~is.~S A unique feature of benign bone tumors is that there sarcomas weakens bone, resulting in the highest rate of is a small incidence of metastasis in these lesions. pathologic fracture. Increasingly, rarer forms of osteogenic Accordingly 1.7% of chondroblastomas and 3% of giant sarcoma are described. Two variants of note are the small cell do metastasize. It is controversial cell sarcoma and giant cell rich osteogenic sarcoma. The if some of these lesions were, in fact, malignant from former can be confused with Ewing's family tumor and as
CHAPTER
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Bone Tumors
653
such is often treated by similar chemotherapy protocols.9O,ll6The latter can be confused in the appropriate setting with giant cell tumors of the bone, which is a benipn " condition.l2J3,41 Ewing's sarcoma occurs at a younger age (see Table 40-1) and may affect any bone, particularly the femur, pelvis, and humerus. It is the most common cancer in the pelvis, ribs, foot. and fibula. It was once considered to be distinct from peripheral neuroectodermal tumors but has been shown to be genetically identical to this entity. It is presently considered to be in the same family of neoplasms also known as Ewing's family t ~ m o r s . ~ 2 , l ~ ~ Chondrosarcoma is less prevalent in the pediatric age group. It is more widely distributed in the body compared with its occurrence in adults.
Genetics There have been few consistent " ~ e n e t i cor svndromic associations with osteogenic sarcoma. Patients with the Li-Fraumeni syndrome77 have a TP53 germline mutation78,81on 9p21 and are predisposed to osteogenic sarcoma, breast cancer, and leukemia (Fig. 40-4). Two to 3 percent of patients with osteogenic sarcoma will be the proband for Li-Fraumeni families.lz4 Another germline mutation of 13q14, hereditary retinoblastoma, predisposes to osteogenic sarcomas.ll Children who received radiation therapy for retinoblastoma, Hodgkin's and nonHodgkin's lymphoma, Ewing's family tumor, and other cancers are at 5% to 10% risk of developing osteogenic sarcoma. Patients with an RB gene deletion and a history of alkylating agent exposure from a prior malignancy are predisposed to this complication as well.lZ7 About 5% of all osteogenic sarcomas occur as postradiation sarcomas.65 Ewing's family tumor is a malignancy associated with a number of translocations. The 11 to 22 translocation resulting in an EWSFLIl fusion transcript is the most common variant, and type 1 is associated with the best prognosis.15 Other translocations include type 2 EWSFLI1, EWSERG from a 21,22 translocation, and EWSETVl from a 7,22 translocation. These rarer variants have not been as well studied but appear to confer a poorer prognosis.15 Further additive mutations involving cell-cycle genes reduce the prognosis of these tumors further. Ewing's family tumor is the most common solid tumor to metastasize to the brain.32
A, Osteogenic sarcoma in the left scapula of a female patient with Li-Fraumeni syndrome. This patient had a family history of osteogenic sarcoma in a firstdegree relative. At the time of staging for the osteogenic sarcoma in the scapula a lesion in the breast was discovered on CT of the chest. This was subsequently found to be an adenocarcinoma. B, The patient underwent a scapular replacement. A latissimus dorsi flap was used for skin cover.
Diagnosis and Staging Bone tumors are diagnosed based on the well-recognized triad of history, physical examination, and investigation. After a clinical diagnosis it is imperative that imaging and staging procedures are done before biopsy. Preoperative imaging allows for planning of the definitive procedure and hence placement of the biopsy incision. In addition, changes that would occur in the lesion after biopsy would be difficult to distinguish from changes due to tumor growth on imaging. Furthermore, changes in the lung after general anesthesia (e.g., atelectasis) are difficult to distinguish from metastatic deposits.
Clinical Evaluation Although it is not possible to be comprehensive in this section, the history and physical examination are important parts of the assessment of a patient w~tha bone tumor. Patient demographics and tumor location narrow the differential diagnosis and focus the workup efficiently. The patient's age is important (see Table 40-2). Most malignancies occur in the second decade of life.62,67,128J35 Among children, subtle variation occurs in the prevalence of disease with respect to age (see Table 40-1).
654
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MATORTUMORS OF CHILDHOOD
diaphyseal lesions are typical of Ewing's family tumor, Demographically, it is exceedingly rare for patients of fibrous dysplasia, or enchondromas. African descent to have Ewing's family tumor.135 Pain at rest is an important sign that occurs in tumors and in other organic conditions such as infection and Laboratory Evaluation bone infarction. It distinguishes these conditions from The main blood parameters of importance are lactate mechanical pain, which occurs with activity. Most malignant Lactate dehydrogenase and alkaline pho~phatase.50,7"~23 tumors will present as pain. Pain relieved by nonsteroidal dehydrogenase levels have been used as a surrogate for anti-inflammatory drugs (NSAIDs) is pathognomonic of tumor load and have been correlated with survival in . ~ ~ can occur at any age and is charosteoid o ~ t e o m aThis the case of Ewing's family tumor.jOSerum alkaline phosacterized by painful scoliosis when it occurs in the spine. phatase elevation is characteristic of osteogenic sarcoma A family history of malignancy should be discerned and is correlated with poor survival in this ~ondition.7~J2" especially in possible sentinel cases of the Li-Fraumeni syndrome.77,78181 Such patients should have systemic Glucose intolerance is associated with chondrosarcoma of workups to rule out other sites of involvement in the the bone.48.85Erythrocyte sedimentation rates, C-reactive protein, and white blood cell and differential counts form of radioisotope bone scans or positron emission should be sought to rule out infection. tomographic scans. As described earlier, the surgeon should be alert to any dysmorphism that the patient may have. Cutaneous Preoperative Planning stigmata are evident in patients with neurofibromatosis, Magnetic resonance imaging (MRI) of the lesion offers an fibrous dysplasia, and Jaffe-Campanacci syndrome.94 Limb discrepancies are seen in patients with multiple assessment of compartmentalization of the tumor. A comenchondromatoses and multiple hereditary e x o s t o ~ e s . ~ ~partment is an abstract concept and refers to any plane that Infection should be a differential diagnosis in almost offers a fascia1 or cortical bone bamer to contiguous every case seen. Tumor epidemiology is very telling. For spread. It has implications on the extent of surgery, which example, childhood leukemia is nearly 10 times as comby definition must be outside the compartment to be radimon as Ewing's family tumor and so rare manifestations cal (see later) .37 Also by forming a baseline assessment one is able to make an assessment of response to chemotherapy of leukemia are more common than routine presentain the case of neoadjuvant treatment.6O It has secondary tions of Ewing's family tumor. importance in providing the actual diagnosis. In specific The nature of bony reconstruction also requires that examples it is useful in histologic diagnosis. The aneurysthe method chosen be matched with the demands of the mal bone cyst shows fluid-fluid levels on an MR image. patient. As such, an idea of the patient's expectation should be sought at this time. Pigmented villonodular synovitis is hypointense (dark) on TI- and T2-weighted imagng owing to hemosiderin deposition. Cartilaginous lesions are hyperintense (light) on Radiology T2-weighted imaging. Mineralized and dense fibrous tissue The minimal radiologic assessment at the first visit should are dark on T1- and T2-weighted imagi11g.~,96 be two orthogonal radiographic views of the area in question. Radiographs remain the most specific diagnostic Staging imaging tests and are the only ones that give the "gestalt" Staging studies are meant to assess the degree of spread of overall assessment of skeletal biology and mechanics. of the disease. In the case of bone tumors two systems are By analyzing the location of the tumor (see Fig. 40-3) as used: the Enneking system or Surgical Staging System well as whether it is benign or malignant, the diagnosis (SSS)39as adopted by the Musculoskeletal Tumor Society can be arrived at in the majority of cases.@Jj7J~8,l3j Benign lesions are well circumscribed, with a good scleand the American Joint Committee on Cancer (AJCC) rotic border, and have no soft tissue edema. Malignant system, which at the time of writing is in its sixth revision.j3 In the case of Ewing's family tumor a different classificalesions have lucent or variegated matrices and permeative tion from Enneking is used.36 borders. Edema is often apparent as the presence of In the SSS, tumors are designated GO, G1, and G2 for fat lines. benign, low-grade, and high-grade lesions. Benign The often-quoted eponymous phrases are not specific lesions (GO) are classified as latent, active, or aggressive to specific malignancies. Codman's triangle refers to the lifting and ossification of periosteum at the periphery of designated by Arabic numerals 1, 2, and 3, respectively. Malignant lesions are designated I if low grade and I1 an osteogenic sarcoma. The sunburst appearance is due to if high grade. The further designation A or B denotes the ossification of fibers and vessels subperiosteally as the intracompartmental or extracompartmental disease. tumor expands out of the cortex. Onion skinningrefers to Stage III disease is metastatic disease. Therefore, in this the periodic ossification and expansion of periosteum classification, grade, compartmentalization, and metasfrom the cortex. Any of these conditions can be seen in tases are the fundamental prognostic factors. tumors or infections that are sufficiently fast growing. In the AJCC system, I and I1 similarly designate In the diagram, epiphyseal lesions are typical of chondroblastoma or giant cell tumors; physeal lesions are low- and high-grade lesions. A and B designate tumors typical of osteochondromas; metaphyseal lesions are smaller or larger than 8 cm, respectively. I11 denotes multicentric disease, and l%' denotes metastatic disease. typical of osteogenic sarcomas, unicameral bone cysts, IVA denotes pulmonary metastases, and IVB denotes aneurysmal bone cysts, and nonossifylng fibromas; and
CHAPTER
extrapulmonary metastases. Therefore, this classification considers grade, size, multicentricity, and metastases as prognostic factors. In the Enneking staging system of Ewing's family tumor, stage I tumors are solitary intraosseous lesions, stage I1 are solitary lesions with extraosseous extension, stage I11 are multicentric lesions, and stage N are metastatic. It is unclear how to stage patients who have independent sites of bone marrow involvement versus those who have circulating tumor cells identified by light microscopy (i.e., Enneking stage I11 or N ) . Modern pathology analysis extends these concepts to include immunohistochemistry or reverse transcriptase polymerase chain reaction (RT-PCR) of recombinant gene products. The modalities used for staging are bone scans and computed tomography (CT) of the chest.3g Positron emission tomographic scans are presently being evaluated but have fundamental utility in the management of recurrent or metastatic disease.I6 In the case of Ewing's family tumor, bone marrow biopsies are done in an attempt to capture cases that are multicentric at presentation. The utility of this approach is being evaluated.40
a A and B, An aneurysmal bone cyst of the right proximal fibula in a 17-year-old boy. C, In this instance a primary wide resection was done because the bone was expendable and it prevented contamination of the common peroneal nerve (arrow). -
1
1
40
Bone Tumors
655
Biopsy The biopsy is a critical procedure that can complicate management severely if not performed appropriately. Misplaced incisions continue to be important causes of resectable tumors being rendered nonamenable to limb salvage surg e ~ ~ .A " ,good ~ ~ pathologist comfortable in handling bony tissue is critical to this process. In the appropriate case, extra tissue may be needed for cytogenetic studies. Ewing's family tumors are particularly fragile, and biopsy specimens should be handled carefully to allow for processing.
Presurgical Considerations As a general rule, all imaging and staging should be completed before biopsy. The lesion that warrants biopsy should be given consideration for a primary wide excision. This approach is typically applicable to small lesions less than 3 cm, lesions in expendable bones (e.g., distal phalanx), distal ulna lesions, and proximal fibula lesions, where there is a risk of common peroneal nerve contamination (Fig. 40-5).
656
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M A ~ O TUMORS R OF CHILDHOOD
The lesion should preferably be sampled in the instituin the treatment of benign conditions. Up to 10% risk of tion where the definitive procedure is to be done by the malignant transformation occurs when benign lesions are irradiated.l9,62,~,67,l27,128,135 definitive surgeon. It has been shown repeatedly that when this was not adhered to the results were comprorni~ed.8Y,~~ Both chemotherapy and radiation therapy can be used Consideration should be given to needle biopsies in the in the neoadjuvant (preoperative) or adjuvant (postoperacase of lesions in the pelvis or about the spine where the tive) setting in the treatment of malignant conditions. The exposure necessary for an open biopsy may be extensive neoadjuvant approach has the advantage of "shrinking" and oblige the commitment to a definitive procedure. the tumor and provides a more discernible margin, theoA pathologist familiar with processing bone tissue should retically improving local control of the disease. In the case be on hand to evaluate the biopsy. If tumor tissue can be cut of chemotherapy, before the era of modular prosthesis, with a knife, then it can be cut with a microtome. Frozenthe neoadjuvant route was necessary while the custom section analysis is required primarily to ascertain the adeprostheses were manufactured. This technique has been quacy and representativeness of the specimen and secondshown to be as efficacious as primary surgery. Even so, arily for the definitive diagnosis. the one randomized trial of preoperative and postoperaAntibiotics should be withheld before the biopsy to tive chemotherapy versus only postoperative chemotherimprove the yield of microbiologic assessment. The biopsy apy failed to show any difference in survival. Therefore, may be done with use of a tourniquet to prevent bleeding in selected cases it is reasonable and may be prudent to and dissemination of the tumor locally. When the tourniperform surgery first.92 quet is applied, simple elevation should be used for exsanguination. Compressive exsanguination should be Chemotherapy avoided because this could rupture the tumor. At all times Historically, before the era of chemotherapy, survival the limb should be protected from fracturing because in osteogenic sarcomas was less than 20%. Between 1972 this would cause extensive local dissemination of disease. and 1981 the development of chemotherapy protocols for osteogenic sarcoma revolutionized treatment and Surgical Considerations the present 5-year disease free survival rates are 60% to 76%.6,55,64,87,92,106 The planned incision for the definitive surgery should be marked. This should generally follow extensile expoAt present the standard approach to the treatment of sures and be longitudinal along the line of the definitive osteogenic sarcoma has been neoadjuvant therapy to treat unrecognized microscopic disease, followed by definitive incision. The incision should be placed directly over the lesion. Flaps and dissection should be avoided. resection and then adjuvant chemotherapy. This approach The incision is developed directly into the tumor. If there has been more traditional than empirical. Still the availabilis a soft tissue component of the tumor, then this alone needs ity of comparison tissue at the time of definitive resection be sampled. If a bone biopsy is necessary, then the edges of has been an important tool in prognostication. the biopsy specimen should be rounded to minimize a stress Chemotherapy-associated necrosis in resected speciriser. Frozen section analysis will confirm the adequacy of mens has been graded. Grade I necrosis is necrosis the biopsy. In the meantime, a culture is taken, the tourniamounting to less than 50% of a tumor. Grade I1 necrosis quet is released, and antibiotics are given. Absolute hemoamounts to necrosis of 50% to 90% of a tumor. Grade I11 stasis is needed at the conclusion of the procedure to necrosis is necrosis in more than 90% of a tumor, and minimize spread of tumor cells in the hematoma. grade IV necrosis is necrosis in virtually the entire tumor. This has further been grouped with grades I and I1 necroThe wound is closed in layers. If a drain is necessary, this should be brought out in the line of the incision so sis being referred to as standard response and grades I11 and IV necrosis being designated good response. Good that it can be excised at the time of definitive surgery. response in post-resection specimens is an important indicator of good prognosis in osteogenic sarcoma as Postsurgical Considerations well as Ewing's family tumor patient~.~2J~3 The patient should be limited to protected weight bearIt should be remembered that historically 20% of ing at least until some healing of the biopsy or ossification patients had been cured by surgery alone and even now of the tumor as a response to neoadjuvant chemotherapy up to 24% to 40% are not cured of their disease. This occurs. This typically takes up to 6 weeks. means that 44% to 64% of patients have no change in Fractures through osteogenic sarcomas have traditioncure. Nevertheless, even they benefit from chemotherapy ally precluded limb salvage surgery. Recent studies have by enjoying longer survival, better local disease control, shown that limb salvage may still be possible in selected and higher limb salvage rates.% The typical agents used can be classified as cell cycleSpecial surgical consideration is needed in these cases. specific and cell cycle-nonspecific agents. Cell cyclespecific agents include methotrexate and, doxorubicin. These interfere with cell division and hence affect cells that are actively proliferating. In any cell population there Adjuvant Therapy are quiescent cells. These cells would not be affected by cell This section concentrates on the use of radiation and cycle-specific agents. For this purpose the cell cyclechemotherapy. In general, these modalities are not used nonspecific agents are used. Cisplatin and alkylating
CHAPTER
agents (e.g., cyclophosphamide and ifosfamide) directly damage the DNA of a cell and so even quiescent cells are affected. This Goldie-Coldman model of chemotherapeutic administration is the most commonly used in the treatment of osteogenic sarcomas and Ewing's family tumors.51 Multiple-agent chemotherapy has been adopted by a number of working groups in the treatment of osteogenic sarcoma. In Europe the Cooperative Osteosarcoma Study group (COSS) reports an actuarial 10-year survival of 64%.14The Rizzoli Institute reports an 8-year disease-free survival rate of 59%.43Hence, it appears that in its present form multimodality treatment with multiple-agent chemotherapy and surgical resection appears to have stagnated in the past 20 years. Novel approaches and agents are continually being developed. The traditional agents cisplatin, doxorubicin, and high doses of methotrexate have been combined with ifosfamide in a number of centers. Preliminary results are promising. The Rizzoli Institute, as part of thk Italian Sarcoma Group/Scandinavian Sarcoma Group, reports that the combination is associated with a 5-year overall survival of 87% and a 5-year disease-free survival of 73%, improving on their earlier result^.^,^^ Ifosfamide has been used in this manner at our center with variable results. Chemotherapy-associated necrosis has not been dramatic. nor has this been associated with an increased survival benefit in our patients. Chemotherapy as the sole agent in the treatment of osteogenic sarcoma has been reported to have inferior results.'j8 The complications with this approach include increased local recurrence and metastases. Cure was convincingly achieved in only 10% of patients. Recently, it has been discovered that bisphosphonates may have important anticancer properties and these agents are being investigated clinically in some centers.70 The optimal route of delivery for chemotherapeutic agents continues to be developed. In a recent study, the use of neoadjuvant intra-arterial cisplatin and intravenous doxorubicin, followed by surgical resection of the tumor and completion of chemotherapy, conferred an 84% 10-year event-free survival rate. Necrosis was monitored preoperatively by angiography, and surgery was performed only after 90% or greater reduction in neovascularitv was achieved. After resection and assessment of necrosis, adjuvant chemotherapy was tailored according to the chemotherapeutic response seen in the resection specimen. This state of the art represents a culmination of a number of techniques that h e been developed in the field and represents the necessary multidisciplinary approach in these conditions.137
40
Bone Tumors
657
effective but has been reported to have a higher rate of local recurrence than surgery alone. When used alone, doses up to 6600 cGy may be necessary to produce local control.lZ2 In contrast, 3000 to 4000 cGy in divided doses is given in this condition when surgery is combined with radiation therapy.89 Because of its propensity to cause and 2 ~the ~~ premature physeal closure and bone n e c r o s i ~ ~ additional concern of radiation sarcoma developing in these genetically altered patients in whom alkylating ~ , role " , ~of" ~ radiation ~~ agents have been ~ s e d , ~ ~ , ~the therapy in local control in some institutions has been limited to the treatment of spine and pelvic lesions. In these settings the treatment may be used solely or intraoperatively in conjunction with surgery (Fig. 40-6). In the ireatment of extremity lesions a purely surgical approach may be desirable, reserving irradiation for when margins of resection are compromised or when the response to preoperative chemotherapy has been incompIete.89,108,143 Although not studied specifically in the pediatric age group, radiation therapy has been shown to increase wound complications in the perioperative period, which is another factor to consider if the patient is to have chemotherapy.lo2 Thus, in general this modality is best used judiciously. 1 n - ~ a n ~ e r h ahistiocytosis, ns low-dose radiation therapy amounting to less than 1000 rads effects good local control of disease while avoiding the skeletal side effects of radiation therapy.ll5
Surgery In bone tumors, resection and reconstruction are two aspects of management that have largely complementary but occasionally conflicting goals (e.g., cryotherapy is good for extending the margins of resection of a tumor
Radiation Therapy Radiation therapy has been used in both the neoadjuvant and adjuvant setting in the treatment of Ewing's family tumor. Osteogenic sarcoma does not respond well to radiation therapy, and its use in this tumor has been limited to only very select situations.34.75 Regimens for treatment of Ewing's family tumor differ according to site and center. Radiation is generally
Intraoperative radiation therapy in a 19-month-old girl who underwent a wide resection with nodal clearance for a rhabdomyosarcoma of the pelvis.
658
PART
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MAJORTUMORS OF CHILDHOOD
but results in weakening of the bone). Therefore, while the goals of resection are generally quite clear (i.e., cure), the goals of reconstruction are often compromised, especially in malignant conditions. In benign conditions, reconstruction tends to have to be more restorative of function. In this section we present a general list of considerations that will be elaborated on in the section on specific considerations.
Minimally lnvasive Options The minimally invasive option is reserved for benign conditions. It is born of two management philosophiesthe desire to effect local control and the hesitation to cause more morbidity than the primary lesion. Whichever modality is chosen, it is imperative that a histologic diagnosis be obtained a priori.
Radiofrequency Ablation Radiofrequency ablation employs high-intensity heat in proximity to a lesion to effect thermal necrosis. It has wide utility in the ablation of various solid tumors. In bone tumors it has principally been used in the ablation of osteoid osteomas. This condition is a painful condition marked by increased night pain and is promptly relieved by the use of NSAIDs. Otherwise it is relatively benign. It can be found most commonly in the proximal femur. In these locations, surgical ablation in the form of a resection can incur high morbidity. Hence an option such as radiofrequency ablation is ideal, although it incurs a 10% to 15% recurrence rate"2lo7 compared with surgery, which has a near 0% recurrence rate.2Vt has limited utility in the spine owing to the indiscriminate high heat generated.
Injection This technique is principally used in the treatment of unicameral bone cysts. Clinically apparent bone cysts have a tendency to recurrent fracture and need to be treated." However, they have no malignant potential ~ ,controversial ~~ and have been known to r e g r e s ~ .It~ is if corticosteroid injection is a necessary element of treatment-it has been shown that simple decompression of a cyst is sufficient to induce a regression.126 Cure rates of up to 50% are reported, with a median injection rate of three and a range of one to up to nine injecEach of these sessions requires the child to ti0ns.22,~~ be under anesthesia. Therefore, it has not been widely received. As alluded to earlier, various forms of decompression have been advocated in the literature with varying success. One approach involves the injection of bone marrow.s5.71,79,1°9,144Cure rates of up to 50% to 70% may be achieved. However, with this technique repeated injections may be necessary, incurring multiple inductions of anesthesia and donor site morbidity. Curettage, widely regarded to be the gold standard, has a recurrence rate of 5% to 50%.98Thus there is no clearly superior modality in the treatment of this condition.
NSAlD Treatment Although not a surgical modality, NSAID treatment has been used in the treatment of osteoid osteomas in selected individuals. In patients who have lesions in the spine or in the acetabular area, surgical or radiofrequency ablation could result in disordered growth, necessitating spinal fusions or corrective hip surgery. In these instances, NSAID treatment associated with a predictable amelioration of symptoms may be attempted. This can be continued as long as there are no gastric or renal side effects. Cure rates of up to 45% are possible but require protracted ingestion of NSAIDs for about 30 months.66
Resection Surgical decisions are based on the concept of compartments in relation to a tumor (Fig. 40-7). The compartment is bound by a barrier, which naturally limits the expansion of a tumor. When first described it was useful in teaching the principles of wide resection or a resection with a margin of healthy tissue: if a resection was performed outside a compartment it resulted in a margin that was free of maligThis idea was useful in drawing paralnant inv~lvement.~~ lels to conventional cancer surgery of the time. We realize now that this theory is flawed at many levels. For example, most osteogenic sarcomas present with tumors that have breached the cortex and so their distinction from a "contained osteogenic sarcoma is moot. In the lower limb a tumor that has involved the rectus femoris has involved a compartment extending from the anterior inferior iliac spine of the pelvis to the tibia1 tubercle. Clearly it would not be practical in this setting to perform a hindquarter amputation. Finally, especially in the region of the linea aspera, there are numerous perforating vessels, which go through the lateral intermuscular septum---clearly these do not form a continuous barrier to tumor spread. Still, the concept of compartmentalization is useful when one describes the surgical procedures as intralesional, marginal, wide, and radical." Although not often used in the context of amputations, these principles are applicable as well. Intralesional procedures, as the name implies, are procedures that leave macroscopic residual tissue. A biopsy or injection of a lesion is an intralesional procedure. A marginal procedure stops at the level of the extent of maximal expansion of a tumor. Curettage is a marginal procedure. A wide procedure goes beyond the reactive zone of the tumor. When first described, the "reactive zone" referred to the zone of reaction around the tumor marked by inflammatory change (i.e., hyperemia and This assessment was made predominantly at the time of surgery. With the advent of more sophisticated imaging modalities it can now be demonstrated that this "zone" may extend further than previously appreciated. Therefore, it appears that the description of a reactive zone is rather more abstract than real. As a general rule, resecting a tumor beyond its capsule where vessel tortuosity and edema is seen is a wide resection and hence this appreciation, while strongly influenced by newer imaging, remains largely surgical. Most malignant tumors are resected widely. A radical resection is an excision of the compartment in
CHAPTER
Resections
40
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659
Amputations Radical
Radical
Wide Radical
Wide Marginal Marginal lntralesional lntralesional
Surgical margins in relation to the compartments involved. At left are the resections, and at right are the amputations. These classifications are largely academic because in the strictest terms most of the resections except radical resections and only wide or radical amputations are performed. Radical resections involve the compartment bearing the tumor and hence in this case would amount to removing the tibia (arrows). Marginal amputations may be resorted to in the spine and pelvis whereupon local adjuvants assume significant roles in disease control (see Fig. 40-6). Intralesional amputations are obviously not therapeutic applications in tumor surgery but are included here for completeness. Of interest, intercalary amputations in the pediatric population can be problematic when the remnant stump elongates through appositional growth. To avoid this complication it may be necessary to resort to a through-joint (e.g., through-knee) amputation.
which a tumor resides. An above-knee amputation for a tibia1 lesion is a radical resection. There are a number of surgical adjuvants that may be employed. This can be in the form of heat (e.g., argon beam coagulator) or cold (e.g., liquid nitrogen cryotherapy).80ta8In addition, chemical measures may be employed (e.g., phenol, polymethylmethacrylate ~ e m e n t ) . * In ~ , the l~~ occasional case, specialized forms of radiation (e.g., brachytherapy, intraoperative radiation therapy) may be used especially in the pelvis (see Fig. 40-6). The purpose of these surgical adjuvants is to extend the margins of resection beyond what can be mechanically removed by the surgeon. These improve local control of the tumor.
Benign Lesions It is useful at this juncture to recall the staging system for benign lesions. This is classified as benign, active, and aggressive. It is evident in these entities that even within this group specific nuances of the condition warrant special considerations. In benign bony conditions the procedures available are curettage, high-speed burring of lesional walls, , ~ ~ to adjuvant procedures, and wide r e s e c t i ~ n .It~is~helpful describe these procedures from most to least aggressive. In benign conditions, wide resection may occasionally be resorted to when the involved bone is expendable (e.g., rib or terminal phalanx of the little toe) or at the
end of a bone (e.g., distal ulna or proximal fibula). In these situations, reconstruction provides little value and can, in fact, be the source of considerable morbidity. Additionally, it may be resorted to in the context of a recalcitrant recurrent benign or aggressive lesion. Typical lesions that are resected in this manner are giant cell tumors, aneurysmal bone cysts, or fibrous dysplasia. Marginal excision is typified conceptually by the technique used to excise a soft tissue lipoma. Such a procedure is not technically feasible in most bony lesions. Osteochondromas and periosteal chondromas may be removed in such a fashion. Intralesional procedures are more commonly performed in benign tumors. This typically involves curettage of a lesion with high-speed burring of the wall. By and large this is the typical procedure for most latent or active benign bony conditions (e.g., unicameral bone cyst). The use of heat, cold (Fig. 40-8), or chemical modalities serves to extend this margin of clearance further and is typically used in active or aggressive tumors (e.g., giant cell tumor, chondroblastoma).
Malignant Lesions The sine qua non of the resection of malignant bone lesion is that at minimum a wide resection must be performed. In certain situations, however, this may not be possible
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Cryosurgery in a patient with chondrosarcoma. Liquid nitrogen is poured into a funnel that directs the agent into the lesion while avoiding contact with the surrounding skin. The effect of freezing extends the margins of necrosis beyond that which can be felt by the surgeon, effectively extending the surgical margins from an intralesional or marginal excision to a wide resection.
A
'
(e.g., a tumor that has expanded into the spinal canal or a t;mor that has invaded-into the ~ e l v i ccaGtv). ,, In these instances, the results tend to be suboptimal. With newer imaging modalities it is now often possible to perform a physeal-sparing procedure in growing children (Fig. 40-9). Although it used to be believed that the physis is an effective barrier to tumor spread, it has been shown that up to 80% of tumors abutting the physis have Physeal-sparing procedures in fact breached it.38,69,99,118 must therefore be carefully balanced with the response to chemotherapy to determine if this is feasible. As a variation on this theme it is occasionally possible to save the epiphysis and hence the neighboringjoint by performing a distraction procedure through the growth plate. This effectively increases the margin of normal tissue proximal to a tumor. A resection may then be performed through this now-lengthened segment.z4 Another approach to retaining a joint would be to perform a Van Nes rotationplasty (Fig. 40-10).133This procedure, generally undertaken for high-grade tumors about the kiee, involves wide extra-articular resections whereupon the distal leg and foot are joined to the proximal remaining femur. In the process, the sciatic nerve is resection of the femoral arterv retained and a segmental " with a true femoral-popliteal arterial anastomosis is performed. The foot is rotated with the heel pointing anteriorly. Of practical interest the distal segment is rotated externally, bringing the sciatic nerve and vessels anteromedially. This should be documented in the surgical note to facilitate further surgical procedures as may be necessary. The ankle, therefGre, finctions as a kneejoint. This procedure has poor acceptance among patients owing to their cosmetic abhorrence but is highly functional and durable.Z0 A similar Winkelmann procedure may be performed where the proximal tibia-is brought to.the hip. In children it is remarkable to note the plasticity and remodeling of these disparate bones, which in time will accommodate each other in a stable f a s h i ~ n . l ~ ~ . l ~ ~
B
A, Ewing's sarcoma of the tibia in an 11-year-oldboy. The lesion extended to 1 cm from the growth plate. It responded well to chemotherapy with virtually no remaining soft tissue involvement. A physeal-sparing resection was done along a resection plane (double-headed arrow) carefully performed under image intensifier guidance. B, The use of a pin fixator in this regard is extremely advantageous because it allows stabilization of the small proximal tibial segment that precludes routine pin fixation. The remaining gap was reconstructed with a proximal tibial allograft (thick arrow) and vascularized fibular graft (broken arrow) harvested with a paddle of skin, which provided skin cover of the construct.
Radical procedures and amputations have received poor support because they are regarded as being disfiguring. Studies have shown that patients with limb salvage procedures do better in terms of function and cost savings."J04 Although this appears true at face value, in-depth analysis shows that these studies are too heterogeneous to allow any firm conclusions. With the aid of modern prosthesis, patients with amputations are able to achieve very high levels of activity. Furthermore, complications are three to four times higher in limb salvage compared with limb ablative surgery. Although most series have not shown a significant survival benefit between amputation and limb-sparing surgery, these studies are underpowered or include cases of amputation being salvage procequestion that needs to be d ~ r e s . ~ ~ ,The ~ z , "primary ~ answered is whether there is any survival and functional benefit in two-site and stage-controlled groups with respect to amputation or wide resection. This would require a case-controlled study with amputation and wide resection arms, and it is a safe assumption that this will never be done. There is still a role for amputations, especially when the tumor is in the distal extremity, adjuvant therapies are ineffective, or reconstruction is too problematic because of nerve, vessel, or soft tissue problems.
CHAPTER
40
,)
Bone Tumors
661
\
Tumor
Above knee amputation\
Acetabular remodelling in Winkelrnann procedure
Van Nes rotationplasty\
/
Winkelrnann rotationplasty
A, Osteogenic sarcoma (arrow) with large soft tissue extension in an 8-year-old child. The small size of the child and high level of activity precluded endoprosthetic reconstruction. B, A Van Nes rotationplasty was performed. C, Variants of the rotationplasty are compared with the above-knee amputation. The bottom panel illustrates how the proximal tibia remodels and accommodates the acetabulum in the Winkelmann procedure.
Local recurrence in malignant lesions is a poor prognostic factor and is associated with a 90% fatality rate. It is generally a reflection of compromised local control, although in one study good chemotherapy response was associated with a low local recurrence rate.47Specifically, in this series when intralesional procedures had been performed for osteogenic sarcoma, standard responders were three times as likely to get a local recurrence as good responders. However, even among good responders, local recurrence was 14 times more likely if a intralesional procedure had been done as opposed to a wide resection. This underscores the need both for good surgical margins and effective chemotherapy.
Reconstruction In most instances after the resection of benign lesions, small defects arise. These are easily dealt with through the use of various gap fillers. With malignant lesions, large creative solutions are needed. It becomes difficult to determine which lesions are best treated by which technique because of the relative paucity of cases and the high-risk nature of these procedures. In this section we will highlight the various modalities available and the pertinent qualifiers for each modality.
Benign Lesions Following the resection of these lesions one is usually left with a small defect. In latent and perhaps active
conditions there is a low rate of local recurrence. Thus the aim here is the reconstitution of bone. The modalities that have been tried are bone graft and bone graft s u b stitutes. In general, autografts tend to have better incorporation rates but incur the risk of donor site morbidity or-worse--donor site tumor implantation. Allografts have a low risk of disease transmission and immunologic r e ~ p o n s e . l ~Synthetic J~~ grafts tend not to incorporate as well.aJ32 In the more aggressive lesions the risk of recurrence increases. In these situations bone substitutes could be resorbed by the disease process and increase the delay before subsequent radiologic imaging is able to distinguish between postoperative change and recurrence. In this setting, bone cement becomes a good alternative.a0J03 Furthermore, radiopaque cement acts as a contrast agent. Recurrence at the margin of the cemented defect can readily be identified and treated.
Malignant Lesions The solutions that have been tried to solve the complex bone, joint, and soft tissue defects left after tumor resections form a veritable cornucopia of techniques, spanning all of orthopedic and plastic surgery. It is impossible to reiterate all these solutions here. Instead, we present a list of principal solutions pertinent to the specific reconstructive option. The paramount requirement of all solutions is as a spacefiller and skin closure. Without these two requirements
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chemotherapy cannot resume and the patient will not survive. Most solutions will provide space-filling ability if there is adequate skin for closure. If skin closure is not possible a local flap or vascularized pedicular graft may be necessary. In some instances, especially with intercalary resections, the ability to provide intercalary stability with overlying skin closure can be provided by a vascularized fibular graft with a skin paddle. The skin paddle affords the additional advantage of monitoring the viability of the flap. Rotationplasties and their variants are remarkably functional solutions to the problem but have poor acceptance among patients because of their appearance. Similarly, amputations are often an instant solution to the problem, although even here the occasional exception exists.104 Joint reconstruction is a challenging endeavor. Biologic solutions include the use of bulk allograft (Fig. 40-11). They have the advantage of becoming incorporated by the body. The disadvantages82are high fracture rates of 19%, nonunion rates of 17%, and infection rates of 11%.
Osteoarticular allografts also become arthritic (16%) with time. Theoretically, however, with good incorporation of the allograft one would be able to perform a conventional less constrained joint replacement (Fig. 40-12). The endoprosthetic solution tends to be easier but is less resilient, suffering from wear and loosening with time.flJ"J4With advancements in technology, better designs will allow for longer-lasting implants (Fig. 40-13). The allograft prosthetic composite is another approach that appears to capitalize on the lasting nature of allografts and their soft tissue capsular attachments and the simplicity of prosthetics (Fig. 40-14). In very young children the available endoprostheses may be too large, and this may be a relative indication for the use of bulk allografts instead (see Fig. 40-1). Downsized pediatric implants are incapable of holding up in adults and are destined for failure and revision (Fig. 40-15). Prosthetic reconstruction has the distinct advantage of allowing immediate weight bearing, which is very important in patients who may have a reduced life expectancy. In truth, the various modalities are complementary rather than independent.
C
.
-
A, Ewing's sarcoma of the proximal tibia in an 11-year-old. Band C, This was widely resected and reconstructed with an osteoarticular tibia1 allograft. A gastrocnemius flap was raised to provide soft tissue cover to the construct. A
#
B • A, Resection and reconstruction of Ewing's sarcoma of the pelvis. B, Degenerative changes developed in his hip 2 years later and required hip replacement surgery. d
l
CHAPTER
A
Bone Tumors
A
.
- AI A, Osteogenic sarcoma in a 16-year-old girl. B, An endoprosthetic device was placed in the patient after resection of the lesion. C, With growth of the child, it becomes occasionally necessary to swap implants with devices that can provide further extensibility. prox.imal hum era1 losite was
663
Growth is a complex problem in the management of these patients. In the year that patients receive chemotherapy growth is often stunted. After this, however, the child resumes growth. There are various means to predict this growth.Xg% a rule of thumb, the distal femur grows 1 cm a year and the proximal tibia grows 7 mm a year. Girls generally stop growing at 14 years and boys at 16 years. Therefore, a 10-year-old boy who had an extra-articular resection would have potentially 10 cm of growth to accommodate. In general, a 2-cm length discrepancy is considered compensable and does not require treatment. Thus, in this example an additional 8-cm correction is needed. The modalities available include contralateral epiphysiodeses. This method ablates the growth plate of the contralateral knee. The procedure needs to be timed accurately and tends to be really only practical in the older child approaching the last few centimeters of growth. Bone transport is another option. This yields good results but the child must remain in the apparatus for long periods of time. At an elongation rate of 1 mm/day, the child with an 8-cm defect must remain in the apparatus at minimum for 3 months for the elongation and a further 3 months for consolidation of the regenerate (Fig. 40-16). This duration is commonly doubled when distraction osteogenesis is done during chemotherapy. Even in healthy individuals the risk of pin tract infection during the procedure is greater than 9076." In the patient with malignant disease who is to receive chemotherapy this would be an important consideration.Io5In addition, the regenerate tends to be weak and is prone to fracture (Fig. 40-17). Patients on chemotherapy are prone to osteoporosis and are already at risk for fracture. The extensible prosthesis is a marvel of modern science that is presently ;ndergoing "teething" issues.111.112,1m-134 The manual designs require repeated surgical procedures to periodically lengthen the limb to keep pace with L.
B
r: -
A, 0,steogeiiic s; humerus of a l&year-old boy. B, A resection with allograft and PIrostlused to reconstruct the defect
40
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Ewing's sarcoma of the tibia. The patient underwent wide resection and a planned bone transport procedure. The middle ring ( a m ) is secured to a segment of bone that has been osteotomized. This segment of bone is allowed 5 days for a provisional callus to form. By progressively advancing the ring distally at a rate of 1 mm/day, the segment of bone is transported to fill the defect while at the same time remaining connected to the proximal tibia. This regenerate is weak and requires an equivalent amount of time to consolidate. For example, an 80-mm defect would require 5 days to form provisional callus, 80 days to lengthen, and 80 days to consolidate befire removal of the frame. This ungainly device needs to be tolerated by the patient for the duration of the limblengthening procedure.
As such there are many solutions to the problem but no perfect one. Therefore, it is apparent that the surgeon dealing with this condition must be able to perform or at least facilitate all of these procedures. Any one of these procedures is applicable to the individual case, and they remain complementary to each other.
A
.
B
- A# A, Osteogenic sarcoma of the proximal femur in a 14year-old girl. B, A wide resection and bipolar hemiarthroplasty with proximal femoral replacement was performed. Of note, the femoral head matched the acetabulum so an additional bipolar component was not added.
normal growth (see Fig. 40-13C). The Stanmore implants have been used for nearly 20 years and have a 23% revision rate.'" Survivorship analysis, however, shows a nearzero survivorship at 10 years.lZ9 Self-extending designs work through electromagnetic couplers or heating coils that allow motors or heat release springs to extend the implant. The Phenix device is presently undergoing evaluation in the United States.138 Preliminary results show a complication rate of up to 44%, necessitating revision. The Repiphysis system uses an external electromagnetic field to provide controlled released of a spring held in place by a locking mechanism. This device is associated with a implant revision rate of 44%.49 In general, the stems in these devices are too narrow and mechanically insufficient and fixation techniques remain inadequate. As such, all these designs have poor longevity but reduce immediate surgical complications (e.g., infection). They are well tolerated by patients and families.
SPECIFIC CONSIDERATIONS In this section specific issues are highlighted that pertain to characteristics of the individual case and the way they may affect management. A discussive rather than a didactic style is used to facilitate familiarity with the problems and to unify the concepts as presented in the section on general considerations. Features specific to respective diagnoses are covered in the section on pathophysiology.
Diagnosis In the very young child, below 5 years of age, the patient who presents with a lesion in the bone is likely to have one of only a few diagnoses (see Table 40-1). The main considerations in this group are infection and localized manifestations of systemic malignancies (i.e., leukemias). Consideration should be given to metastatic disease, which in this group is often neuroblastoma. In the group between 5 and 10 years of age, Ewing's family tumor needs to be considered. In the second decade, with increased activity of the child and increased use of radiographs in assessing incidental trauma, many of the benign conditions are diagnosed. In addition, osteogenic sarcoma and Ewing's family tumor become prevalent.
CHAPTER
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Bone Tumors
665
Site The implications of site of disease in relation to pathology and pathophysiology have been alluded to earlier. Here the focus is on the implications of site of involvement to the reconstruction of a defect.
Upper Limbs
A
B
A, A patient presented with osteogenic sarcoma of the proximal humerus that was resected and reconstructed with a vascularized fibular graft shoulder arthrodesis at 6 years of age. He developed a shortened humerus at maturity, which was lengthened. B, Post lengthening, the regenerate was protected with a plate and hypertrophied with time.
Growth Issues of linear growth have been touched on earlier. In the treatment of conditions of the bone adjacent to a physis the potential for future growth should be considered. This is more prudent in the benign case when conceivably nonsurgical management can be offered without dire consequences. Thus in the typical case of the unicameral bone cyst adjacent to the growth plate it may be prudent not to subject the physis to curettage, accepting that this may increase recurrence rates. In the case of a chondroblastoma, which tends to be more aggressive, however, growth plate damage may be unavoidable and a local adjuvant may be indicated (e.g., cryosurgery). By contrast in malignant conditions, sacrificing the growth plate with the aim of achieving good surgical margins is an acceptable concession (see Fig. 40-13).
In general terms, load-bearing requirements in the upper limbs differ considerably from those in the lower limb. In the upper limb the prehensile functions of feeding and personal hygiene are considered fundamental in terms of goals of surgery. In the lower limb, weight bearing is paramount. With that in mind the upper limb tends to be more forgiving in terms of reconstructive durability but more demanding in terms of mobility. The following discussion is more applicable to large segmental bony defects. Cavitary lesions are managed with appropriate bone fillers (see bone graft and bone graft substitutes, earlier). In the shoulder, good function can be achieved by ~~~~~~~~~ periscapular resections and r e c o n s t r ~ c t i o n s . 2The options for reconstruction here involve suspensory arthroplasties or scapular replacements (see Fig. 40-4). Abduction is limited, but otherwise prehensile function remains good. Humeral resections generally perform well but, owing to the indicated pathologic processes, tend to be applicable only to lower grade lesions. Replacements with osteoarticular allografts (see Fig. 40-1) or allograft prosthetic composites (see Fig. 40-13) afford good replacement of function. In lower-grade lesions, in which the deltoid and rotator cuff may be retained, abduction is often acceptable. The elbow has limited options because of the poor soft tissue coverage in this area.l*OJ31J36Osteoarticular allografts and endoprosthesis provide reasonable flexion and extension and pronation and supination. Forearm bone resections are highly specialized affairs involving intercalary bone resections and replacement with vascularized fibular grafts. In the event of wrist disruption, this may have to be fused. Involvement of various nerves in the forearm may necessitate tendon transfers. Cross circulation in the palm is an important sign to document in the event of the need to sacrifice the radial or ulnar artery. Lesions occurring distally in the hand rarely require treatment if benign and often require varying forms of amputation if malignant.
Lower Limbs In the lower limb, pelvic resections are classified into type I resections above the acetabulum, type I1 resections in the periacetabular area, and type 111 resections below the acetabulum.1~21JOOComplications in this type of surgery are very high, mainly because the internal iliac supply to the posterior gluteal flap is often disrupted in the process of resection and because the duration of the procedures is long. In addition, because of the limited bone available afterward, reconstructive options become challenging.
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In type I resections, the need is for a strut to span the remaining hemipelvis to the sacrum. Allografts or autogenous fibular grafts are usually used in this context. This is occasionally not possible and a defect is left. In these cases patients are able to function reasonably well. In type I1 resections, replacement of the joint becomes necessary. This can be achieved through a custom prosthesis, an allograft-prosthetic composite (see Fig. 40-12), or an arthrodesis. Type I11 resections are usually stable and can be left with a defect. Combination defects especially after type 1-11 resections are especially challenging. The options include allograft prosthetic composites and saddle prostheses. Occasionally, hindquarter amputations are still necessary. In proximal femoral lesions, articular involvement may necessitate type 11-like extra-articular pelvic resections and reconstructions. Contained proximal femoral lesions are treated with prostheses or allograft prosthetic composites. Intercalary femoral and tibial resections are generally managed with allografts or vascularized fibular autografts or combinations of these. Bone transport is another viable option but, as mentioned, takes a protracted course and has a high complication rate. Recent work suggests that pin fixators are safe even if the patient is to undergo chemotherapy. Resections about the knee are generally treated with Bulk osteoarticular endoprosthetic re~onstmction.~~~~~3o~~~~~ allografts have been used and provide reasonable function (see Fig. 40-11). These invariably become arthritic with time.8' But at that point a more traditional joint replacement may be performed. Arthrodeses have generally fallen out of favor, although they remain good alternatives with reasonable function in the appropriate setting.lo4 In the ankle, variable resections of the fibula may be performed with reasonable expectation of function. In general, with tibial resections, arthrodesis needs to be performed.27,2"lo4 In the foot, as with the hand, various types of amputations are generally recommended.
and surgical induction of remission by removal of all macroscopic disease. These are multidisciplinary efforts that should be reserved for specialized centers. Patients may have to undergo segmental pulmonary resections together with resections of their tumors and reconstructic& thereof. The patient who develops metastases after a remission has a very variable prognosis, ranging from 0% to 26% in ~ ' these ~ ~ ~ patients, although the princivarious s e r i e ~ . In ples of management are similar, the expectation is different. Surgical induction of remission is still a very effective method in these patients and the main determinant of survival.44This entails bilateral thoracotomies and segmental resections of solitary bony metastases as needed.S12l Ironically, owing to the poor prognosis, limb salvage surgery is relatively indicated. This, however, needs to be balanced with the duration of recuperation from surgery during which the child will not be on chemotherapy. The surgeon should select the operation with the fastest most predictable recovery. For example, this would drive the decision to use a cemented prosthesis rather than the uncemented i m ~ l a n tthat would be used in localized disease in children. Timing of surgery can be complex. Pulmonary metastasis occurring at presentation of the primary lesion should be resected in a staged manner during recovery from the primary resection. A lesion that develops during consolidation chemotherapy should be resected after completion of a round of chemotherapy. Metastasis that develops after chemotherapy should be aggressively resected, with consideration given to staged bilateral thoracotomies if this occurs early. In these patients the issues df management may not necessarily be curative. The surgeon needs to be able to balance the procedures that may be offered with the expected prognosis of the child. Two actual cases illustrate this point.
Case 1 Metastatic Disease The implications of aggressiveness in the case of benign lesions and compartmentalization in the case of malignancies have been touched on previously. Here the discussion is confined to metastatic osteogenic sarcoma and Ewing's family tumor. Patients with metastatic osteogenic sarcoma may present in two settings: the patient with metastasis at the outset and the patient who has developed metastasis despite having had a remission. It has been shown that patients who present with early unilateral pulmonary metastasis within 2 years of diagnosis have a high incidence of contralateral disease and should undergo staged Late unilateral pulmonary bilateral thora~otomies.l2~ metastasis tends not to be associated with contralateral disease. Patients with metastasis at the outset have been shown to have a survival of 11% to 36%.9,93Management of this group requires the aggressive implementation of chemotherapy to treat unrecognized microscopic disease
A patient with advanced osteogenic sarcoma of the tibia fungating through the skin presents for the first time with multiple metastases to the lungs and regional lymph nodes. Note that in the AJCC staging system this patient has stage IVB disease. This patient underwent an amputation before chemotherapy. A few questions arise, the foremost being why a limb salvage procedure was not performed in this case. Limb salvage in this case would have required either an allograft or vascularized fibular graft and hardware to be placed into the defect. This would have incurred a significant risk of skin breakdown and infection, requiring a free muscle flap. In the meantime the metastatic disease would have progressed and the patient might have died. When a thoracotomy for this patient is done to resect.the pulmonary metastases, it should be planned with consideration that a free latissimus flap may be needed and so the muscle should not be compromised. A second question may be posed as to the use of neoadjuvant therapy in this setting. Here, the patient would
CHAPTER
have been immunocompromised in the presence of an infected wound. Hence in this situation the most prudent approach was an amputation.
Case 2 A patient with a history of osteogenic sarcoma of the left distal femur that has been resected and reconstructed and is 2 years out from chemotherapy now presents with metastasis in the right distal femur and proximal tibia. This patient underwent resection and reconstruction with an endoprosthesis. An amputation would not have been curative in this case because it is assumed that other sites of metastases must exist. Yet a surgical induction of remission was necessary because the patient developed metastases soon after chemotherapy and thus may have developed resistance to the chemotherapeutic agents. These two cases illustrate the many levels of complexity that underlie the management of these patients. Only through a careful consideration of all factors can the most appropriate line of management be offered.
REFERENCES 1. Aboulafia AJ, Buch R, Mathews J, et al: Reconstruction using the saddle prosthesis following excision of primary and metastatic periacetabular tumors. Clin Orthop Relat Res 1995;(314):203-213. 2. Abudu A, Sferopoulos NK, Tillman RM, et al: The surgical treatment and outcome of pathological fractures in localised osteosarcoma.J Bone Joint Surg Br 1996;78:694698. 3. Anderson M, Green WT, Messner MB: Growth and predictions of growth in the lower extremities. Am J Orthop 1963; 45A:l-14. 4. Araki Y, Tanaka H, Yamamoto H, et al: MR imaging of pigmented villonodular synovitis of the knee. Radiat Med 1994;12:11-15. 5. Aung L, Gorlick R, Healey JH, et al: Metachronous skeletal osteosarcoma in patients treated with adjuvant and neoadjuvant chemotherapy for nonmetastatic osteosarcoma. J Clin Oncol 2003;21:342-348. 6. Bacci G, Briccoli A, Ferrari S, et al: Neoadjuvant chemotherapy for osteosarcoma of the extremity: Long-term results of the Rizzoli's 4th protocol. Eur J Cancer 2001;37:2030-2039. 7. Bacci G, Ferrari S, Longhi A, et al: Nonmetastatic osteosarcoma of the extremity with pathologic fracture at presentation: Local and systemic control by amputation or limb salvage after preoperative chemotherapy. Acta Orthop Scand 2003;74:449-454. 8. Bacci G, Ferrari S, Longhi A, et al: High dose ifosfamide in combination with high dose methotrexate, Adriamycin and cisplatin in the neoadjuvant treatment of extremity osteosarcoma: Preliminary results of an Italian Sarcoma Group/ Scandinavian Sarcoma Group pilot study. J Chemother 2002;14:198-206. 9. Bacci G, Picci P, Briccoli A, et al: Osteosarcoma of the extremity metastatic at presentation: Results achieved in 26 patients treated with combined therapy (primary chemotherapy followed by simultaneous resection of the primary and metastatic lesions). Tumori 1992;78:200-206. 10. Bauer TW, Muschler GF: Bone graft materials: An overview of the basic science. Clin Orthop Relat Res 2000;(371):10-27.
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Brain Tumors Phillip B. Storm and Leslie N. Sutton
Except for injuries, neoplasms are the most common cause neuroblastomas, melanotic neuroectodermal tumors in of death in children younger than the age of 15 years. infancy, and atypical teratoid/rhabdoid tumors (ATRT). Tumors of the central nervous system arethe most common solid neoplasms found in children, account for 20% of cancer deaths, and are second only to leukemia in CLINICAL FEATURES ,22,~~ 1700 pedioverall cancer f r e q u e n ~ y . ~ ~Approximately atric brain tumors are diagnosed each year, for an inciThe signs and symptoms of brain tumors in children vary dence of 3.1/100,000 children at risk.lo considerably based on tumor type and location and on the Important factors in diagnosing brain tumors are locaage of the child. In the absence of a seizure or a focal tion, age, and cell type. Location is probably the most neurologic deficit, such as a sixth nerve paresis causing important factor radiographically, with age being the double vision, the vast majority of the symptoms are nonsecond most important. The brain is divided into two comspecific and easily attributable to many more common partments by thk tentorium. Above the tentorium (supraand less serious causes. Common symptoms are headache, tentorial) are the cerebral hemispheres, the basal ganglia, nausea, vomiting, lethargy, subtle changes in personality, and the thalamus. Below the tentorium (infratentorial) and worsening school performance. This constellation of are the pineal gland, the tectum, the pons, the medulla, symptoms is often attributed to gastrointestinal problems, and the cerebellum. UnL~keadult tumors,which tend to be depress'\on,school anxiety, mig.raines, sinusitis, or a presupratentorial, pediatric tumors are evenly split between scription for glasses. Even a long-standing seizure disorder supratentorial and infi-atentorial. There is an interesting ultimately may be caused by a supratentorial brain tumor. division of location based on age. In children younger Infants typically present with a failure to thrive, decreased than 2 years of age, the tumors are typically supratentorial, intake, macrocephaly, or lethargy. whereas children between the ages of 3 and 15 predominately have infratentorial tumors (Table 41-1).15,2° The is usually poor in children who present with brain tumors when younger than the age of 1 year,8 with choroid plexus papilloma being the exception. Age Tumor Histology The development of immunohistochemical techniques has allowed pediatric tumors to be classified by 0-2 Teratoma Primitive neuroectodermal tumor histology. Tumors can arise from any of a number of cell Astrocytorna (high grade) types in the brain. The brain is composed of neurons and Choroid plexus papilloma glial cells. The glial cells far outnumber the neurons and 2-15 Supratentorial tumors (50%) provide a nourishing and supportive role. The three main Astrocytoma (low grade) glial cells are astrocytes, oligodendrocytes, and ependymal Craniopharyngioma cells, and the neoplasms they give rise to are gliomas. More Hypothalamic glioma specifically they form astrocytomas, oligodendrogliomas, Primitive neuroectodermal tumor and ependymomas, respectively. Tumors involving both Ependymorna neuronal and glial cells are called ganglion cell tumors and Choroid plexus papilloma consist of gangliogliomas, desmoplastic infantile ganglilnfratentorial tumors (50%) Primitive neuroectodermal tumor: medulloblastoma ogliomas, and gangliocytomas. Another mixed neuronal Cerebellar astrocytorna and glial tumor is a dysembryoplastic neuroepithelial Ependymoma tumor (DNET). Lastly are the embryonal tumors or Brainstem glioma primitive neuroectodermal tumors (PNETs). Embryonal tumors include medulloblastoma, m e d ~ l l o e ~ i t h e ~ o m a ,
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Pediatric patients with brain tumors are typically between the ages of 2 and 14years with a few days to weeks of headache, nausea/vomiting, gait ataxia, and/or diplopia, who have an enhancing midline posterior fossa tumor on magnetic resonance imaging (MRI) with associated hydrocephalus. In fact, it is the resultant hydrocephalus that is responsible for this constellation of symptoms rather than the tumor itself. Headaches are common in children with viral infections, but frequent, daily, morning headaches should raise the clinical suspicion for a mass lesion, especially in the absence of fever or other sequela of a viral infection. Patients with elevated intracranial pressure often have an exacerbation of their symptoms in the morning because lying in the recumbent position overnight raises intracranial pressure compared with being upright. Furthermore, sleeping results in hypoventilation, which results in an increase in Pco~,causing an even greater increase in the intracranial pressure. The elevated intracranial pressure can also cause the cerebellar tonsils to herniate into the foramen of magnum and result in occipital headaches and neck pain. There are two instances in which tumors cause nausea and vomiting. One is the elevation of intracranial pressure, and the other is direct irritation/infiltration of the vomiting center. The vomiting center (area postrema) is located on the floor of the fourth ventricle and is vulnerable from compression from large posterior fossa tumors or from direct invasion of intrinsic brainstem tumors causing vomiting. Because an intrinsic tumor in the medulla can cause vomiting in the absence of other neurologic findings, persistent vomiting should raise the possibility of a posterior fossa tumor and not be attributed to gastrointestinal diseases such as reflux without a detailed history and neurologic examination. Ataxia is often described by the parents as clumsiness, "walking like he is drunk," walking with the head tilted to one side, or falling to one side. The visual complaints resulting from posterior fossa tumors are most frequently diplopia, difficulty looking up (sunsetting eyes-Parinaud's syndrome), and occasionally decreased visual acuity. Again, these findings are a result of the hydrocephalus. Decreased visual acuity can occur because of papilledema. Loss of vision is more common in supratentorial tumors because of optic nerve atrophy from direct compression. Patients with posterior fossa tumors are usually diagnosed by MRI because their other symptoms occur long before they develop visual loss; thus, a lack of visual signs or symptoms does not exclude a tumor. Visual loss is still seen in some patients with posterior fossa tumors because of poor access to medical care. Even though the "typical" pediatric brain tumor is in the posterior fossa there are many supratentorial tumors, especially in patients younger than 2 years old. Children younger than 2 years of age often present with a failure to thrive, hemiparesis, seizures, or a full bulging anterior fontanelle with an enlarged head circumference.l*,35,43 Children who are older than age 2 years with supratentorial tumors present similarly to adult patients with brain tumors, with headaches and/or seizures. Patients who present with sudden onset of severe headache and/or rapidly declining mental status usually have hemorrhaged into their lesion. Occasionally, obstructive hydrocephalus can cause a rapid decline, but because of the
relative slow rate of growth of the tumor they present before the cerebrospinal fluid (CSF) pathways are completely obstructed. Less common signs and symptoms arise from endocrine abnormalities such as weight gain, weight loss, diabetes insipidus, short stature, truncal obesity, and delayed puberty; and galactorrhea is from tumors affecting the hypothalamic-pituitary axis. Because of the proximity of these tumors to the optic nerves and chiasm they often cause decreased vision as well as visual field cuts, most of which are asymptomatic.
RADIOGRAPHIC EVALUATION Patients suspected of having a brain tumor need to be evaluated with MRI with and without gadolinium enhancement. Even though MRI is the gold standard for evaluating tumors, patients presenting to an emergency department with clinical signs and symptoms of a brain tumor need head computed tomography (CT) without instillation of a contrast medium. CT is excellent in evaluating hydrocephalus and hemorrhage, the two main causes of a rapid neurologic decline. Furthermore, CT can be done in minutes and frequently does not require sedation, gives excellent detail and information, and is considerably less expensive. If the patient's condition is rapidly deteriorating, a contrast agent-enhanced head CT needs to be performed to better characterize the lesion for the radiologist and the neurosurgeon if the patient requires emergent surgical intervention. If the patient's condition is stable, the contrast agent can be omitted and MRI with and without gadolinium can be done, the timing of which is dictated by the clinical signs and symptoms. MRI provides much better brain resolution and provides images in the sagittal, axial, and coronal planes and, with newer imaging sequences and spectroscopy, may even point to a specific histologic diagnosis.62 This is far superior to the axial-only images that are obtained with CT. Furthermore, it is difficult to evaluate the lower brainstem with CT because of the bony artifact from the skull base. A limitation of MRI is that it does not show intratumoral calcifications very well and occasionally patients require both studies to aid in the proper diagnosis. The addition of gadolinium provides more information about the tumor. The blood-brain barrier is made up of tight junctions in the endothelial cells lining the brain capillaries, which prevent most blood contents from entering the brain, including gadolinium. Certain brain tumors cause breakdown of the blood-brain barrier and permit the gadolinium to enter the tumor and then appear bright on an enhanced T1-weighted image. In general, especially in the adult population, contrast medium enhancement in an intra-axial lesion means a more aggressive brain tumor and a poorer prognosis. This is not as consistent in pediatric tumors. There are enhancing pediatric brain tumors that are not aggressive and are curable with a total resection. In general, tumors that do not enhance are less aggressive. When looking at MRIs the important factors to consider are (1) the location of the tumor (e.g., supratentorial, infratentorial, pineal region, suprasellar), (2) whether it
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is intra-axial (within the brain tissue) or extra-axial (outside brain tissue), (3) the age of the patient, (4) whether it enhances, and (5) if it is single or multiple. By systematically looking at the scans and considering these factors, the differential diagnosis can be narrowed considerably and can be extremely helpful in preoperative planning. If there are multiple lesions in the brain, or the location and enhancement suggest a tumor type that metastasizes or tends to cause "drop mets" to the spine, then a spinal MRI with and without enhancement is performed. It is preferable to obtain the spinal MRI preoperatively but this is often dictated by the patient's clinical examination. All patients with brain tumors receive a postoperative MRI within 48 hours to evaluate the extent of resection and rule out hydrocephalus, bleeding, or ischemia. The timing is important because after 48 hours expected postoperative changes/"scarringn can enhance and make it difficult to distinguish scarring from residual tumor. If the patient did not get a preoperative MRI evaluation of the spine and the histiologic diagnosis is consistent with tumors that produce "drop mets," then the study should be done 2 weeks after surgery for staging of the tumor.
SURGICAL INTERVENTION The goal of surgical intervention is to safely debulk as much tumor as possible, to obtain a histologic diagnosis, and to reestablish normal CSF pathways or divert CSF. The location of the tumor often determines how aggressively the tumor is debulked. In fact, some tumors because of their location and their ability to be diagnosed with MRI are not sampled. For example, a pontine glioma, which is an intrinsic astrocytoma of the brainstem, cannot be debulked safely and has a characteristic finding on MRI. These patients are referred to the neuro-oncologist for management without needing a tissue diagnosis. Pineal region tumors are another example of a lesion that may be diagnosed without surgical intervention. Patients with a pineal lesion need to have serum beta-human chorionic gonadotropin (FhCG), alpha-fetoprotein (AFP), and placental alkaline phosphate (PLAP) levels obtained. If these are negative, then CSF markers are needed. If the markers are positive, then a diagnosis of pineal germ cell tumor is made. The treatment is stereotactic radiation without the need for a tissue diagnosis, and the cure rate approaches 100%for a germinoma. Most tumors, however, require surgical intervention consisting of either a stereotactic biopsy or an open craniotomy. The most important tool for preoperative planning is MRI. Tumors that are diffuse, intrinsic tumors of the thalamus or basal ganglia typically undergo stereotactic biopsy. This procedure involves rigidly fixing an MRIcompatible frame to the patient's skull. The patient then has an MRI, and the X, Y, and Z coordinates are determined. These coordinates are used to position the frame and arc so that the tip of the needle is exactly where these three points intersect in the brain. The advantages of a stereotactic biopsy are that the surgical procedure is done quickly, diagnosis is possible in areas of the brain that carry an unacceptable morbidity and mortality with an open craniotomy, and the patient is discharged on
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postoperative day 1. The disadvantages are that the pathologist is only given a small amount of tissue; if bleeding is encountered at the time of surgery it may not be recognized until the patient deteriorates neurologically after the procedure; and if the diagnosis requires the neurosurgeon to operate, the patient needs a second operative procedure and the tissue in that area may not be representative of the true grade of the tumor. The majority of pediatric tumors are treated with a craniotomy/craniectomy for open biopsy with an attempt at maximal microsurgical tumor resection, because prognosis of many tumors is strongly influenced by the amount l of postsurgical residual t ~ r n o r . ~ V e r e b r ahemispheric tumors are approached by craniotomy. Preoperative planning consists of an MRI coupled with a frameless stereotactic navigation study. The navigation study allows the neurosurgeon to view the tumor in the operating room in the sagittal, axial, and coronal planes and can be used to plan the incision and find the tumor. The limitation of this technology is that it is not a real time study and as the brain is retracted, cysts or CSF spaces are drained, the brain shifts position, and the accuracy is compromised. Intraoperative ultrasound is extremely helpful in finding lesions when brain shifting has decreased the accuracy of the intraoperative navigation system. Intraoperative MRI aims at correcting the limitation of the navigation systems by providing a real-time image; however, intraoperative MRI is severely limited by the resolution because the magnet is considerably weaker than those used for conventional MRI. This is exciting technology and as the resolution improves it will be used on all tumor cases and be an invaluable tool to the tumor surgeon. Functional MRI techniques can localize speech and motor cortex in relation to the tumor and aid in selecting the safest site to incise the cortex if these areas of eloquent cortex are involved by the tumor.48Functional MRI requires a cooperative, nonsedated patient. which in the pediatric population can be challenging. Electrophysiologc recording and stimulation are sometimes helpful in locating the motor strip. Even though these advances have substantially aided the neurosurgeon there is still no substitute for an outstanding understanding of the three-dimensional anatomy of the brain. When choosing a route, anatomic planes such as the interhemispheric fissure, the Sylvian fissure, and the cranial base are used if possible to avoid resecting normal brain. If there is no plane, the approach is usually through the least amount of brain tissue, with the obvious exception of areas of eloquent cortex such as language and motor. Tumors of the midline (hypothalamus, thalamus, basal ganglia, and brainstem) were once considered inoperable. Microsurgical techniques and innovative instrumentation, however, now make these tumors approachable. At the same time, advances in chemotherapy and singledose and fractionated radiosurgery oEfer alternatives, and it is unclear at this time which strategy or combination of strategies is best for a particular tumor. Pineal region tumors may be approached via a posterior fossa route, retracting the cerebellum from the underside of the tentorium, or by a supratentorial route between the hemispheres and through the posterior corpus callosum,
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or through the tentorium itself. The relationship of the pineal tumor to the tentorium dictates the approach. Tumors of the cerebellum and lower brainstem are approached by a posterior fossa craniotomy or craniectomy. Midline tumors of the fourth ventricle usually present as obstructive hydrocephalus. Although some neurosurgeons prefer to place a shunt before tumor resection, most n o w favor giving the child corticosteroids and placing a ventriculostomy at the time of the craniectomy, which is either removed or converted to a shunt if needed in the postoperative period. Between 20% to 40% of children will ultimately require a shunt." The patient is placed in the prone position, and the bone overlying the cerebellum is removed, occasionally including the posterior ring of C1. After opening the dura, the cerebellar vermis is vertically incised, providing access to the cavity of the fourth ventricle. The tumor is removed with bipolar cautery, suction, or the ultrasonic aspirator. Laterally placed tumors of the cerebellopontine angle are reached by retracting the cerebellum medially, and working around the cranial nerves, using electrophysiologic monitoring of cranial nerves V, VII, VIII, IX, X, XI, and XI1 as required. Tumors of the brainstem may be debulked, if they are dorsally exophytic and have low-grade histology. The dura is closed and covered with DuraGen, a collagen product that augments dura, but replacement of bone is not required. Postoperative problems include acute hydrocephalus and pseudomeningoceles, aseptic meningitis, mutism, pseudobulbar palsy,eg cranial nerve or brainstem dysfunction, gastrointestinal hem~rrhage,"~) and spinal instability.58 Patients with swallowing dysfunction and aspiration may require tracheostomy and feeding gastrostomy.
TUMOR TYPES Cerebellar Astrocytomas These tumors are usually histologically benign and curable with total surgical resection. The average age at presentation is 9 years, and patients present with pernicious vomiting, intermittent morning headache, and disturbances of balance, often over a period of months. The classic CT appearance7] is of a low-intensity cystic cerebellar mass in proximity to the vermis with a brilliantly enhancing "mural nodule." About one fourth will be entirely solid, however. MRI is helpful in defining the surgical anatomy, particularly the relationship of the tumor to the brainstem, and the nature of the cyst wall. Cerebellar astrocytomas are typically of low signal intensity on T1-weighted MRI sequences, are of increased intensity on T2-weighted sequences, and show enhancement of the solid component with intravenous gadolinium (Fig. 41-1). Obstructive hydrocephalus is common. Histologically, the tumors are composed of benignappearing astrocytes. Subtypes are the juvenile pilocytic form (60%) and the fibrillary form (30%).A "diffuse" form has also been described, which may carry a poorer prognosis." Detailed examination may reveal cellular pleomorphism and tumor extension to the subarachnoid space, but these tumors rarely disseminate. Malignant tumors
1 A 2-year-old girl presented after several days of vomiting and lethargy. A sagittal T1-weighted MR image with gadolinium shows a large posterior fossa tumor based in the cerebellum (small arrow). The patient has hydrocephalus (large nrrozu showing a dilated third ventricle). She also has herniation of the cerebellar tonsils through the foramen magnum (arrozuheczd).At surgery a diagnosis of cerebellar astrocytoma was made.
are rare and usually follow radiation therapy given for a previously benign tumor.j7 Treatment is complete surgical excision. This may be accomplished in a high percentage of cases in which there is no brainstem involvement. These tumors rarely recur after radiographically confirmed complete excision, and no adjuvant therapy is indicated.' Therefore, if there is residual tumor on the postoperative scan, reoperation for total excision is recommended. Radiation therapy may be considered for multiply recurrent lesions or in cases in which brainstem involvement precludes complete removal, but even in these cases residual tumor may remain indolent for years without specific therapy. Regular postoperative surveillance scanning is appropriate when there is suspicion for residual tumor. Recurrence is treated with reoperation if this is feasible.
Primitive NeuroectodermalTumor and Medulloblastoma A posterior fossa PNET is termed a medullohlastoma. Medulloblastoma is the most common malignant brain tumor of childhood. Histologically, the classic medulloblastoma is composed of densely packed cells with hyperchromatic nuclei and little cytopla'sm, giving the histologic slides a blue color when stained with hematoxylin and eosin. When the lesion is located in the posterior fossa, the tumor is termed medullohlastoma or posterior fossa PNET Tumors with identical histology can occur in the cerebral hemispheres and are termed supratentorial PMTs. Children with medulloblastomas typically
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present with headache, vomiting, and lethargy of relatively short duration, and the mean age at diagnosis is younger than that for cerebellar astrocytomas. Infants may present with failure to thrive. Supratentorial PNETs present with increased intracranial pressure and focal neurologic signs depending on location. On a CT scan, medulloblastomas typically appear as wellmarginated homogeneously dense masses filling the fourth ventricle causing obstructive hydrocephalus; however, unlike ependymomas, they lack calcifications. They usually enhance brilliantly with contrast medium instillation. MRI shows variable signal characteristics. The images are often slightly hypointense on T1 weighting, becoming brighter on fluid-attenuated inversion recovery (FLAIR) sequences, and may be bright or dark on T2-weighted studies. They usually enhance on MRI (Fig. 41-2). MRI of the spine is indicated either preoperatively or postoperatively to evaluate for spinal metastases ("drop mets"). Treatment begins with biopsy and surgical excision. These tumors are not curable with surgery alone; and in cases with metastases at diagnosis or extensive brainstem involvement, the major mass should be debulked but no attempt should be made to resect tumor from vital areas. After the operation, radiation therapy is usually administered to the entire brain and spinal canal, with a boost to the tumor bed. Younger children suffer significant cognitive problems as a result of whole-brain irradiation in an age- and dose-dependent fashion." Because chemotherapy has proven effective in both newly diagnosed and recent trials have recurrent medulloblastornas,~4~~0~40~~3 attempted to reduce, eliminate, or delay radiation and replace it with chemotherapy, particularl; in the younger age groups.lZ In determining the best treatment, staging
An 8-year-old boy presented after several weeks of morning headaches and vomiting. An axial T1-weighted MR image with gadolinium shows a heterogeneously enhancing lesion occupying the fourth ventricle (arrows). The lesion does not "ooze" out of the lateral CSF pathways (foramen of Luschka) like an ependymoma. The pathologic diagnosis was medulloblastoma. -
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criteria are important to define risk groups. In the past, the Chang system was used, which used the surgeon's estimate of the tumor size at operation and the extent of metastatic disease based on postoperative imaging.9 In most centers today, patients are assigned to a high-risk group based on younger age, postoperative residual disease, and presence of disseminated disease.s1,39,40 The rate of progression-free survival ranges from more than 70% at 5 years in groups with favorable risk factors7 to less than 30% in certain high-risk groups.14 Recent reports suggest that intensive adjuvant chemotherapy results in improved survival in high-risk patients comparable to low-risk patients treated with radiation alone.40 Patients require long-term supportive care, which is best done in the setting of a multidisciplinary pediatric neurooncology clinic. Surveillance scanning is of unproven value, because patients with tumors that recur after primary therapy almost invariably die of their disease.64 Late sequelae of therapy include pituitary dysfunction," growth retardation,47 cardiomyopathy,28 cognitive delay,4~sychosocial adjustment and family problems, and radiation-induced meningiomas, astrocytomas, and sarc0mas.2~
Ependymomas Ependymomas occur in the region of the fourth ventricle or cerebellopontine angle (Fig. 41-3), spinal cord, or supratentorial compartment. Most are histologically
. ,
41
-
1
An 18-month-old boy presented after 3 days of
-
-
headaches and vomiting and 2 days , of gait ataxia: On the day of admission he was unresponsive at home. Emergent MRI revealed a large posterior fossa tumor. An axial T2-weighted MR image shows a tumor occupying the fourth ventricle and "oozing" out of the foramen of Luschka into the cerebellar pontine angle and encasing all of the posterior fossa cranial nerves (arrows). The patient was found to have an ependymoma.
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to ventricular obstruction and are usually treated with benign, but, despite this, they rank among the worst of either a ventriculoperitoneal shunt or endoscopic all pediatric brain tumors. They have a tendency to recur third ventriculostomy. These are usually extremely indoin the local tumor bed but may also disseminate throughlent, and treatment of the tumor itself is required only if out the neuraxis. The median age at diagnosis is between it progressively enlarges. 3 and 5 years,Z3 but tumors in infants and adults are not uncommon. When they arise in the posterior fossa (75% of cases), symptoms are similar to those of other tumors in this location. Cranial nerve and brainstem dysfunction Hypothalamic/Chiasmatic Astrocytomas suggest involvement of these structures. Vomiting may Suprasellar astrocytomas are usually low-grade neoplasms, arise without hydrocephalus, which suggests infiltration which may occur in association with neurofibromatosis of the region of the obex, which is characteristic of type 1 or as isolated tumors. The etiology of these tumors ependymomas. When they arise in the supratentorial is not well understood, but the association with neuroficompartment in children, they are often extremely large bromatosis type 1, which is localized to chromosome 17q, and, despite their presumed ependymal origin, may suggests a molecular genetics basis. These tumors may demonstrate no connection with the ventricle. present as primarily visual abnormalities (visual field cuts CT typically shows an isodense mass with flecks of calcior asymmetrical loss of visual acuity in association with fication and an inhomogeneous pattern of enhancement. optic atrophy) or as hypothalamic dysfunction (precoPosterior fossa lesions may extend through the foramina of cious puberty, growth failure, obesity, or the diencephalic Luschka into the cerebellopontine angle. On TI-weighted MRI, ependyrnomas are usually isointense to hypointense syndrome, which consists of failure of weight gain and loss and are hyperintense on TP/proton-weighted images.55 of subcutaneous tissue). Often visual and hypothalamic complaints coexist. They often enhance inhomogeneously. Imaging studies usually cannot distinguish hypothaTreatment is primarily surgical. Prognosis is strongly dependent on extent of surgical resection as determined lamic tumors from those arising from the visual apparaby postoperative imaging. The 5-year progression-free tus. The tumors typically do not calcify, which helps survival after complete resection is 60% to 80%, comdistinguish them from craniopharyngiomas, and appear as solid hypodense lesions on CT or T1-weighted MRI pared with less than 30% after incomplete resection.Z6 sequences with contrast agent enhancement. Extension Radical surgical resection may result in permanent neuroto the intraorbital optic nerves or along the optic radialogic damage and may not be possible in some cases. tions is diagnostic and rules out craniopharyngiomas, Unless the tumor has disseminated at diagnosis, postopergerminomas, or other tumors (Fig. 41-4). ative radiation is usually confined to the operative bed Treatment is controversial. Traditionally, treatment has with a generous margin. Adjuvant chemotherapy was been surgical biopsy, followed by radiation therapy. thought to be of little or no benefit,36but recent studies . ~ ~ ~ ~ ~Recently, chemotherapy with dactinomycin and vincristine, show improved outcomes with c h e m ~ t h e r a p yTrials of radiosurgery for unresectable tumors are under way in several centers.
Brainstem Gliomas It is now recognized that there are several types of brainstem gliomas, with very different outcome~.~"he most common variety is the dqfuse intm'nsicpontineglioma, which is not amenable to surgical resection. These tumors typically present as cranial neuropathies rather than hydrocephalus. Patients are young children with bilateral sixth nerve palsies, facial weakness, and ataxia. The diagnosis is established by MRI, which shows a swollen pons with diffuse signal abnormality (see Fig. 41-3). Surgery is not indicated. Radiation therapy provides symptomatic relief, but most children die within a year.37 Ceruicomedullary astrocytomas are considered to be rostral extensions of intrinsic spinal cord tumors and carry a favorable prognosis. Signs and symptoms may include vomiting, torticollis, slowly evolving motor weakness, or symptoms of hydrocephalus. MRI shows an enlarged upper cervical spinal cord, with a rostral extension presenting in the cisterna magna. These tumors are often amenable to aggressive surgical resection; and if the histology is benign, adjuvant radiation therapy is deferred. Tectal gliomas are now recognized to be a not infrequent cause of hydrotypically present as symptoms referable cephalus.4"hey
.
A
A 14month-old boy presented with a 1-week history
of lethargy and a 2-day history of vomiting. Sagittal TI-weighted MR image with gadolinium shows a large enhancing suprasellar and frontal tumor arising from the optic chiasm and hypothalamus (arrows). The diagnosis of a hypothalamic astrocytoma was confirmed at surgery.
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or other combinations, has shown promise, especially in infants and young children in whom radiation therapy is damaging to the brain.4,i Radical surgical resection as primary therapy has also been reported.'j8
Craniopharyngioma Craniopharyngiomas are histologically benign masses believed to arise from embryonic rests derived from the hypophyseal-pharyngeal duct. Symptoms arise from optic chiasm or nerve compression, hypopituitarism, hypothalamic dysfunction, or increased intracranial pressure in association with hydrocephalus. They also occur in adults, but the childhood form represents a distinct entity, characterized by large size and extensive calcification. There are two varieties of craniopharyngioma, the adamantinomatous and the papillary types. The most common variety in children is the adamantinomatous type. Histologically, they typically are composed of a squamous epithelial cyst wall, with cystic fluid composed of cholesterol crystals, and calcifications. They are usually inseparable from the pituitary gland and may have an interdigitating gliotic interface with the hypothalamus above. This makes complete surgical removal uncertain, because small rests of tumor may reside in the brain, and is also the explanation for hypothalamic dysfunction that may be seen after surgical excision. Radiographically, CT reveals either a rim-enhancing cystic mass with basal calcifications or an entirely solid tumor. MRI shows the sagittal anatomy well but may miss the calcifications (Fig. 41-5) .24 In some instances, imaging
A n 11-year-old boy presented with a several-month history o f headaches and lethargy and extreme thirst and high urine T1-weighted MR image shows a n output. Sagitral - with gadolinium enhancing intrasellar lesion enlarging the sella turcica (large amow). T h e tumor occupies the third ventricle and has a cystic component (small amou~s).T h e patient also has obstructive hydrocephalus with dilated lateral ventricles and a thinned corpus callosum (arrowheads). .
.
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cannot distinguish a craniopharyngioma from a hypothalamic glioma. Treatment is complete surgical excision via craniotomy, which is possible in a high percentage of cases.27 In cases in which complete resection is not possible, or when tumor recurs, radiation therapy is a useful adjunct.'j6Posttreatment problems include panhypopituitarism, obesity, visual problems, emotional lability," and pseudoaneurysms of the carotid artery60 Long-term survival is in the range of 90% at 10 but local recurrences are not uncommon. Recurrences are treated by reoperationF7 instillation of colloidal 32P into cysts, or radiosurgery.
Low-Grade Supratentorial Astrocytomas Low-grade astrocytomas and gangliogliomas of the cortical regions and temporal lobes often present as intractable seizures. CT may show masses of low density, which may or may not enhance with contrast medium instillation. MRI usually shows a mass of decreased signal on T1-weighted images and increased signal on T2 weighting. Complete resection is the goal of surgery, but this may be difficult owing to problems in defining the tumor margins and proximity to eloquent areas. Adjuncts to aid in this include language and motor mapping using implantable grids or intraoperative electrophysiologic monitoring techniques,2 functional MRI techniques, and imagedirected tumor resection.29 Tumors of the temporal lobe are often treated by formal temporal lobectomy to decrease the likelihood of seizures. Seizure mapping techniques have also been employed with cortical tumors, but simple removal of the tumor usually provides good seizure control,41and the value of these strategies is uncertain. The outcome of low-grade astrocytomas,g9 gangliogliomasm (Fig. 41-6), and DNETs (Fig. 41-7) that are
1
A 9-year-old boy presented with intractable seizures Axial TI-weighted M R image with gadolinium shows a minimally enhancing lesion i n the left temporal lobe (amoru).A ganglioglioma was completely resected, and the patient is s e i ~ u r efree.
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the pineal carry a good prognosis after irradiation, although in cases with disseminated disease whole-brain and spinal irradiation will be required." Treatment with chemotherapy alone is advocated in some centers. The other malignant germ cell tumors are usually fatal.% Pineoblastomas are treated like PNETs in other locations. Pineocytomas may be simply observed if totally resected or given focal radiation for residual tumor.
Rhabdoid/Atypical Teratoid Tumors
A 14year-old boy presented with left-sided headaches for months and a seizure. Axial T2-weighted image shows a hyperintense mesial temporal lobe lesion involving the cortex (arrow). The lesion was hypointense on TI-weighted images and did not enhance. The diagnosis was dysembryoplastic neuroepithelial tumor (DNET).
completely resected is favorable, although surveillance scanning is warranted. About 70% of children will be longterm survivors. Recurrent tumors can be treated by reoperation or reoperation followed by radiation
Pineal Region Tumors Tumors of the pineal region encompass a wide variety of histologic types. They can be divided into germ cell tumors (teratoma, germinoma, choriocarcinoma, embryonal cell carcinoma, yolk sac tumor), pineal parenchymal tumws ( pineocytoma, pineoblastoma) , tumors of surrounding structures (astrocytomas, meningiomas), and other benign conditions (cysts, vascular malformations). The older term pinealoma is no longer used. Patients present with signs and symptoms of hydrocephalus, upgaze paresis, and rarely precocious puberty. MRI confirms the presence of a tumor and excludes other possibilities but is nonspecific regarding the histologic type. Specific germ cell tumors may secrete "tumor markers," which may be measured in CSF obtained from lumbar puncture or ventriculostomy or blood. Elevated P-hCG (>50.0 IU/L) is seen in choriocarcinomas, elevated AFP (>25.0 IU/L) is seen in endodermal sinus tumors and embryonal cell carcinomas, and PLAP is elevated in germinomas. In the past, surgery in the pineal region was considered prohibitively dangerous and tumors were often treated without histologic confirmation. This region is now readily approachable using the supracerebellar/ infratentorial or interhemispheric-transcallosal routes with minimal morbidity, and in most centers biopsy is performed. As in the suprasellar region, pure germinomas of
These tumors have only recently been defined. They are highly malignant tumors with histologic resemblance to rhabdoid tumors of the kidney. They typically occur in the posterior fossa in young children and infants but may be located in the spine or supratentorial space. In the past, many of these were probably misclassified as PNETs but are distinguished by larger cells with pink cytoplasm that show immunohistochemical staining for smooth muscle actin, vimentin, and epithelial membrane antigen. Chromosomal analysis reveals monosomy 22 in a high percentage of cases.5 Treatment is surgical excision, chemotherapy, and irradiation in older children, but virtually all the patients in reported cases have died.
Malignant Supratentorial Astrocytomas Anaplastic astrocytomas and glioblastoma multiforme account for only about 6% of childhood tumors, which is a smaller incidence than that in adults. Clinical signs and symptoms reflect location. Imaging features are similar to those seen in adults, and the masses are often large, with enhancing rings and necrotic centers. ~isseminatgn occurs in about Treatment is maximal resection followed by radiation therapy, but the prognosis remains poor. Although more extensive resection confers better outcome, this may reflect the fact that more favorable tumors are more amenable to aggressive surgery. Chemotherapy prolongs life in children with high-grade astrocytomas, but overall 5-year progression-free survival is only 33%.17Trials of high-dose chemotherapy with autologous marrow rescue are ongoing.16
Choroid Plexus Tumors Tumors of the choroid plexus are divided into the benign choroid plexus papilloma and the malignant choroid plexus carcinoma. In children, they tend to arise in the trigone of the lateral ventricle, and they often present in infancy by producing hydrocephalus. The radiographic appearance is an intraventricular, homogeneously enhancing, lobulated mass. Carcinomas are typically larger and may disseminate. The vascular supply is the choroidal arteries, which may be seen with high-resolution MRI. Treatment is surgcal excision, which is curative for papillomas. The procedure is hazardous, because these tumors may be extremely vascular and the patients are typically small. Carcinomas are particularly difficult to remove
I
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because of extreme vascularity. This has prompted some to recommend biopsy, followed by chemotherapy, and later resection." Prolonged survival and even cure are possible after complete removal of malignant choroid plexus tumors.
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the TP53 suppressor gene.g In neuroblastoma, amplification of N-MYC correlates with tumor growth and aggressiveness. The continued collaboration between neurosurgeons, oncologists, radiologists, and molecular biologists is imperative to improving the fight against pediatric brain tumors.
Meningiomas Meningeal tumors are uncommon in childhood, accounting for about 2% of tumors. They may be associated with neurofibromatosis. Meningiomas occur in the orbit, sphenoid wing, or virtually any portion of the intracranial compartment and need not have a dural attachment. Radiographically, they typically enhance and may be extremely large. Treatment is surgical resection, which is curative if complete removal can be accomplished. Irradiation is of benefit in recurrences or when complete removal is not possible.44
Metastases Metastatic brain tumors are uncommon in children. Primary tumors that may metastasize to brain include Wilms' tumor, osteogenic sarcoma, and embryonal rhabdomyosarcoma. Presentation is often abrupt, often with catastrophic neurologic symptoms due to hemorrhage.
TUMOR GENETICS Despite rapid developments in imaging, navigational systems, and surgical instruments and techniques, many tumors, especially high-grade lesions, are still incurable with surgery alone and in conjunction with chemotherapy and radiation therapy. The future in treating brain tumors lies in better biologic and molecular understanding of the tumors. Such techniques have given us better understanding of neurofibromatosis type 2, which is associated with the development of meningiomas and acoustic neuromas in children. The gene locus was identified on chromosome 22,51 the same chromosome that has been identified in pediatric meningiomas in patients without neurofibromatosis type 2.4 The genetic abnormalities result in a loss of a tumor-suppressor gene. Monosomy 22 has been associated with rhabdoid and atypical teratoid tumors.~eurofibromatosis type 1 is associated with childhood gliomas, particularly of the hypothalamus, brainstem, and optic chiasm. The gene locus is at 17q11.2, which encodes for the protein neurofibromin. Neurofibromin is an "off switch" for the RAS oncogene. Tissue from astrocytomas frequently has abnormalities of chromosome 17, which are primarily in the short arm (p). The short arm of chromosome 1'7 is where the TP53 tumor suppressor gene is located. The possibility exists that mutation of a "control gene" leads to development of the brain tumor, and if one copy of the gene is already dysfunctional, as in neurofibromatosis type 1, the likelihood of a tumor arising is increased. Abnormalities of chromosome 17 are also found in medulloblastoma,6 but some work suggests that the locus is distinct from
REFERENCES 1. Abdollahzadeh M, Hoffman HJ, Blazer SI, et al: Benign cerebellar astrocytoma in childhood: Experience at the Hospital for Sick Children 1980-1992. Childs Nerv Syst 1994;10:380. 2. Berger MS, Ojemann GA, Lettich E: Neurophysiological monitoring during astrocytoma surgery. Neurosurg Clin N fun 1990;1:65. 3. Biegel JA, Burk CD, Barr FG, Emmanuel BS: Evidence for a 17p tumor related locus distinct from p53 in pediatric primitive neuroectodermal tumors. Cancer Res 1992;52:3391. 4. Biegel JA, Parmiter AH, Sutton IAN,et al: Abnormalities of chromosome 22 in pediatric meningiomas. Genes Chromosomes Cancer 1994;9:81. 5. Biegel JA, Rorke LB, Packer RJ, Emanuel BS: Monosomy 22 in rhabdoid or atypical tumors of the brain. J Neurosurg 1990;73:710. 6. Biegel JA, Rorke LB, Packer RJ, et al: Isochromosome 17q in primitive neuroectodermal tumors of the central nervous system. Genes Chromosomes Cancer 1989;1:139. 7. Bourne JP, Geyer R, Berger M, et al: The prognostic significance of postoperative residual contrast enhancement on CT scan in pediatric patients with medulloblastoma. J Neurooncol 1992;14:263. 8. Buetow PC, Smirniotopoulos JG, Done S: Congenital brain tumors: A review of 45 cases, AJNR Am J Neuroradiol 1990; 11:793. 9. Chang CH, Housepian EM, Herbert C Jr: An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology 1969;93:1351. 10. Crist WM, Kun LE: Common solid tumors of childhood. N Engl J Med 1991;324:461. 11. Duffner PK, Cohen ME, Voorhess ML, et al: Long-term effects of cranial irradiation on endocrine function in children with brain tumors: A prospective study. Cancer 1985; 56:2189. 12. Duffner PK, Horowitz ME, Krischer JP, et al: Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 1993;328:1725. 13. Epstein FJ, Farmer JP: Brain-stem glioma growth patterns. J Neurosurg 1993;78:408. 14. Evans AE, Jenkin RD, Sposto R, et al: The treatment of medulloblastoma: Results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone. J Neurosurg 1990;72:572. 15. Farwell JR, Dohrmann GJ, Flannery JT: Central nervous system tumors in children. Cancer 1977;40:3123. 16. Finlay JL, August C, Packer R, et al: High-dose multi-agent chemotherapy followed by bone marrow 'rescue' for malignant astrocytomas of childhood and adolescence. J Neurooncol 1990;9:239. 17. Finlay JL, Boyett JM, Yates AJ, et al: Randomized phase I11 trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugsin-1-day regimen. Children's Cancer Group. . -I Clin Oncol 1995;13:112.
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18. Freeman CR, Farmer JP, Montes J: Low-grade astrocytomas in children: Evolving management strategies. Int J Radiat Oncol Biol Phys 1998;41:979. 19. Geyer JR, Sposto R, Jennings M, et al: Children's Cancer Group. Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group. J Clin Oncol 2005;23:7621. 20. Giuffre R: Biological aspects of brain tumors in infancy and childhood. Childs Nerv Syst 1989;5:55. 21. Gjerris F, Klinken L: Long-term prognosis in children with benign cerebellar astrocytoma. J Neurosurg 1978; 49:179. 22. Gold EB, Leviton A, Lopez R, et al: Parental smoking and risk of childhood brain tumors. Am J Epidemiol 1993; 137:620. 23. Goldwein JW, Leahy JM, Packer RJ, et al: Intracranial ependymomas in children. Int J Radiat Oncol Biol Phys 1990;19:1497. 24. Harwood-Nash DC: Neuroimaging of childhood craniopharyngioma. Pediatr Neurosurg 1994;21(Suppl 1):2. 25. Hawkins MM, Draper GJ, Kingston JE: Incidence of second primary tumours among childhood cancer survivors. Br J Cancer 1987;56:339. 26. Healey EA, Barnes PD, Kupsky WJ, et al: The prognostic significance of postoperative residual tumor in ependymoma. Neurosurgery 1991;28:666. 27. Hoffman HJ, De Silva M, Humphreys RP, et al: Aggressive surgical management of craniopharyngiomas in children. J Neurosurg 1992;76:47. 28. Jakacki RI, GoldweinJW, Larsen RL, et al: Cardiac dysfunction following spinal irradiation during childhood. J Clin Oncol 1993;11:1033. 29. Kelly PJ: Image-directed tumor resection. Neurosurg Clin North Am 1990;1:81. 30. Krischer JP, Ragab AH, Kun L, et al: Nitrogen mustard, vincristine, procarbazine, and prednisone as adjuvant chemothera~v in the treatment of medulloblastoma. l A Pediatric Oncology Group study. J Neurosurg 1991; 74:905. 31. Laurent JP, Chang CH, Cohen ME: A classification system for primitive neuroectodermal tumors (medulloblastoma) of the posterior fossa. Cancer 1985;56:1807. 32. Laws ER Jr, Taylor WF, Clifton MB, Okazaki H: Neurosurgical management of low-grade astrocytoma of the cerebral hemispheres. J Neurosurg 1984;61:665. 33. Lee M, Wisoff JH, Abbott R, et al: Management of hydrocephalus in children with medulloblastoma: Prognostic factors for shunting. Pediatr Neurosurg 1994;20:240. 34. Legido A, Packer RJ, Sutton LN, et al: Suprasellar germinomas in childhood: A reappraisal. Cancer 1989;63:340. 35. Loftus CM, Copeland BR, Carmel PW: Cystic supratentorial gliomas: Natural history and evaluation of modes of surgical therapy. Neurosurgery 1985;17:19. 36. Nazar GB, Hoffman HJ, Becker LE, et al: Infratentorial ependymomas in childhood: Prognostic factors and treatment. J Neurosurg 1990;72:408. 37. Packer RJ, Allen JC, Goldwein JL, et al: Hyperfractionated radiotherapy for children with brainstem gliomas: A pilot study using 7,200 cGy. Ann Neurol 1990;27:167. 38. Packer RJ, Sutton LN, Atkins TE, et al: A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results.J Neurosurg 1989;70:707. 39. Packer RJ, Sutton LN, D'Angio G, et al: Management of children with primitive neuroectodermal tumors of the posterior fossa/medulloblastoma. Pediatr Neurosci 1985;12:272. i
40. Packer RJ, Sutton LN, Elterman R, et al: Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy. J Neurosurg 1994;81:690. 41. Packer RJ, Sutton LN, Pate1 KM, et al: Seizure control following tumor surgery for childhood cortical low-grade gliomas. J Neurosurg 1994;80:998. 42. Packer RJ, Sutton LN, Rorke LB, et al: Intracranial embryonal cell carcinoma. Cancer 1984;54:520. 43. Palma L, Russo A, Mercuri S: Cystic cerebral astrocytomas in infancy and childhood: Long-term results. Childs Brain 1983;10:79. 44. Perilongo G, Sutton LN, Goldwein JW, et al: Childhood meningiomas: Experience in the modern imaging era. Pediatr Neurosurg 1992;18:16. 45. Petronio J, Edwards MS, Prados M, et al: Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy. J Neurosurg 1991;74:701. 46. Pollack IF, Pang D, Albright AL: The long-term outcome in children with late-onset aqueductal stenosis resulting from benign intrinsic tectal tumors. J Neurosurg 1994;80:681. 47. Probert JC, Parker BR, Kaplan HS: Growth retardation in children after megavoltage irradiation of the spine. Cancer 1973;32:634. 48. Puce A, Constable RT, Luby MId,et al: Functional magnetic resonance imaging of sensory and motor cortex: Comparison with electrophysiological localization. J Neurosurg 1995; 83:262. 49. Radcliffe J, Bunin GR, Sutton LN, et al: Cognitive deficits in long-term survivors of childhood medulloblastoma and other noncortical tumors: Age-dependent effects of whole brain radiation. Int J Dev Neurosci 1994;12:327. 50. Ross AJ 3rd, Siege1 KR, Bell W, et al: Massive gastrointestinal hemorrhage in children with posterior fossa tumors. J Pediatr Surg 1987;22:633. 51. Rouleau GA, Wertelecki W, HainesJL, et al: Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22. Nature 1987;329:246. 52. Sandri A, Massimino M, Mastrodicasa L, et al: Treatment with oral etoposide for childhood recurrent ependymomas. J Pediatr Hematol Oncol 2005;27:486. 53. Scott RM, Hetelekidis S, Barnes PD, et al: Surgery, radiation, and combination therapy in the treatment of childhood craniopharyngioma-a 20-year experience. Pediatr Neurosurg 1994;21(Suppl 1):75. 54. Shiminski-Maher T: Patient/family preparation and education for complications and late sequelae of craniopharyngiomas. Pediatr Neurosurg 1994;21(Suppl 1):114. 55. Spoto GP, Press GA, Hesselink JR, Solomon M: Intracranial ependymoma and subependymoma: MR manifestations. AJR Am J Roentgen01 1990;154:837. 56. St. Clair SK, Humphreys RP, Pillary RK, et al: Current management of choroid carcinoma in children. Pediatr Neurosurg 1991;17:225. 57. Steinberg GK, Shuer LM, Conley FK, Hanbery JW: Evolution and outcome in malignant astroglial neoplasms of the cerebellum. J Neurosurg 1985;62:9. 58. Steinbok P, Boyd M, Cochrane D: Cervical spinal deformity following craniotomy and upper cervical laminectomy for posterior fossa tumors in children. Childs Nerv Syst 1989;5:25. 59. Sutton LN: Current management of low-grade astrocytomas of childhood. Pediatr Neurosci 1987;13:98. 60. Sutton LN, Gusnard D, Bruce DA, et al: Fusiform dilatations of the carotid artery following radical surgery of childhood craniopharyngiomas. J Neurosurg 1991;74:695. 61. Sutton LN, Packer RJ, Rorke LB, et al: Cerebral gangliogliomas during childhood. Neurosurgery 1983;13:124.
CHAPTER
62. Sutton LN, Wang Z, Gusnard D, et al: Proton magnetic resonance spectroscopy of pediatric brain tumors. Neurosurgery 1992;31:195. 63. Tait DM, Thomton-Jones H, Bloom HJ, et al: Adjuvant chemotherapy for medulloblastoma: The first multi-centre control trial of the International Society of Paediatric Oncology (SIOP I). Eur J Cancer 1990;26:464. 64. Torres CF, Rebsamen S, Silber JH, et al: Surveillance scanning of children with medulloblastoma. N Engl J Med 1994; 330:892. 65. Vertosick FT Jr, Selker RG: Brain stem and spinal metastases of supratentorial glioblastoma multiforme: A clinical 1990;27:516. series. Ne~~ros~irgery 66. Weiss M, Sutton I,, Marcia1 V, et al: The role of radiation therapy in the management of childhood craniopharyngioma. IntJ Radiat Oncol Biol Phys 1989;17:1313.
41
Brain Tumors
681
67. Wisoff JH: Surgical management of recurrent craniopharyngiomas. Pediatr Neurosurg 1994;21(Suppl 1):108. 68. Wisoff J H , Abbott R, Epstein F: Surgical management of exophytic chiasmatic-hypothalamic tumors of childhood. J Neurosurg 1990;73:661. 69. Wisoff JH, Epstein FJ: Pseudobulbar palsy after posterior fossa operation in children. Neurosurgery 1984;15:707. 70. YoungJL Jr, Percy CL, Asire AJ, et al: Cancer incidence and mortality in the United States, 1973-77. Natl Cancer Inst Monogr 1981;(57):1. 71. Zimmerman RA, Bilaniuk I,T, Bruno I>, Rosenstock J: Computed tomography of cerebellar astrocytoma. AJR Am J Roentgenol 1978;130:929.
Principles of Transplantation Jorge Reyes, Noriko Murase, andThomas E. Starzl
Histocompatibility matching, immunosuppression, tissue preservation, and techniques of implantation have been considered to be the generic struts of both organ and bone marrow cell transplantation. However, neither kind of transplantation could have emerged as a clinical service were it not for the induction by the graft itself of various degrees on donor-specific nonreactivity (tolerance). Without this fifth factor, no transplant recipient could survive for long if the amount of immunosuppression given to obtain initial engraftment had to be continued.
THE ENIGMA OF ACQUIRED TOLERANCE The variable acquired tolerance on which transplantation depends has been one of the most enigmatic and controversial issues in all of biology. This was caused, in part, by the unexpected achievement of organ engraftment at an early time-a decade before successful bone marrow transplantation and in ostensible violation of the very principles that would shape the impending revolution in general immunology. As a consequence, clinical organ transplantation was developed empirically rather than as a branch of classic immunology. This occurred in four distinct phases, each lasting more than a decade. Only at the end was it possible to explain organ engraftment and thereby eliminate the mystique of transplantation.
of bone marrow transplantation had to await discovery of the human leukocyte antigens (HLA). When this was accompli~hed,"2~,~~ the successfully treated human bone marrow recipients of 1968 were oversized versions of the tolerant chimeric mice. By the time of the clinical bone marrow transplant breakthrough of 1968, kidney transplantation22.23fi42,48x4g,64 already was an established clinical service, albeit a flawed 0ne.65 In addition, the first long survivals had been recorded after liver72 and heart transplantation5; these were followed in 1968-1969 by the first prolonged survival of a lung18 and a pancreas recipient" (Table 42-1). All of the organ transplant successes had been accomplished in the ostensible absence of leukocyte chimerism, without HLA matching and with no evidence of GVHD. By going
Phase 1: 1953-1968 Phase 1 began between 1953-1956with the demonstration that neonatal mice8*%ndirradiated adult micex develop donor-specific tolerance after successful engraftment o f donor hematolymphopoietic cells. The key observation was that the mice bearing donor cells (donor leukocyte chimerism) could now accept skin grafts from the original donor strain but from no other strain (Fig. 42-1). The chimeric neonatal mice and the irradiated adult mice were analogues of today's bone marrow transplantation into imm;ne deficient and cvtoablated humans, respectively. But because a good histocompatibility match was required for avoidance of graft-versus-host disease (GVHD) and of rejection," clinical application
-
A
The mouse models of acquired tolerance described
between 1953 and 1956. White cells (leukocytes) were isolated from the spleen or bone marrow of adult donor mice (up@ Lrft) and injected into the bloodstream of newborn mice (uppcr right) or of irradiated adult mice (middle right). Under both circumstances, the recipient immune system was too weak to reject the foreign cells (dark shaded). With engraftment of the injected cells (i.e., donor leukocyte chimerism), the recipient mice now could freely accept tissues and organs from the leukocyte donor but from no other donor (bottom 4).
686
Organ
PART
IV
City
TRANSPLANTATION
Date
Physician/ Surgeon Reference
Merrill/ Murray Liver Denver July 23, 1967 Starzl Barnard Heart Cape Town Jan. 2 , 1 9 6 8 Ghent Nov. 14, 1968 Derom Lung Pancreas Minneapolis June 3, 1969 Lillehei Kidney
Boston
Jan. 24, 1959
42, 4 8 72 5 18 34
beyond the leukocyte chimerism boundaries established by the mouse tolerance models, organ transplantation had entered unmapped territory.
"Pseudotolerant" Organ Recipients Two unexplained features of the alloimmune response had made it feasible to forge ahead precociously with organ tran~plantation.~~ The first was that organ rejection is highly reversible. The second was that an organ allograft, if protected by nonspecific immunosuppression, could induce its own acceptance. "Self-induced engraftment" was observed for the first time in 1959 in two fraternal twin kidney recipients, first in Boston by Joseph Murray48 and then in Paris by Jean Hamburger.22 These were the first successful transplantations in the world of an organ allograft, in any species. Both patients had been conditioned with 450 R sublethal total-body irradiation before transplantation. The renal allografts functioned for more than 2 decades without a need for maintenance drug therapy, which was, in fact, not yet available. A similar drug-free state was next occasionally observed after kidney transplantation (and more frequently after liver replacement) in mongrel dogs who were treated with a single immunosuppressive agent: Gmercaptopurine (6-MP) ,"Jfl a~athioprine,j036~ prednisone,fl3 or antilymphocyte globulin (ALG).70 After treatment was stopped, rejection in some animals never developed (Fig. 42-2A). Such results were exceedingly rare; less than 1% of the canine kidney experiments done under 6-MP and azathioprine up to the summer of 1962. However, the possibility that an organ could be inherently tolerogenic was crystallized by the human experience summarized in the title of a report in 1963 of a series of live donor kidney recipients treated in Denver: "The Reversal of Rejection in Human Renal Homografts with Subsequent " ~ ~ recipients Development of Homograft T ~ l e r a n c e . The had been given azathioprine before as well as after renal transplantation, adding large doses of prednisone to treat rejections that were monitored by serial testing of serum creatinine (Fig. 42-3A). Rejection occurred in almost every case, and 25% of the grafts were lost to uncontrolled acute rejection. However, the 1-year survival of 46 allografts obtained from familial donors over a 16-month period in 1962-1963was an unprecedented 75%. The development of partial tolerance in many of the survivors was inferred from the rapidly declining need
for treatment after rejection reversal (see Fig. 42-3A). Nine (19%) of the 46 allografts functioned for the next 4 decades, each depicted in Figure 42-4 as a horizontal bar. Moreover, all immunosuppression eventually was stopped in seven of the nine patients without rejection for periods ranging from 6 to 40 years (the solid portion of the bars). Eight of the nine patients are still alive and bear the longest surviving organ allografts in the world.92 What was the connection between the tolerant mouse models, the irradiated fraternal twin kidney recipients in Boston and Paris, the ultimate drug-free canine organ recipients (see Fig. 42-2A), and the unique cluster of "pseudotolerant" human kidney recipients in Denver (Fig. 42-4)? The mystery deepened with the demonstration in 1966 in France,I6 England,NJz," and the United States74 that the liver can be transplanted in about 20% of outbred pigs without any treatment at all (see Fig. 42-2B). None of the animal or human organ recipients, whether off or on maintenance immunosuppression, was thought to have donor leukocyte chimerism.
B
.
A, Caine recipient of an orthotopic liver homograft, 5 years later. The operation was on March 23, 1964. The dog was treated for only 120 days with a~athioprineand died of old age after 13 years. B, A spontaneously tolerant pig recipient described by Calne.12 -
1
CHAPTER
42
Principles of Transplantation
687
, A, Empirically developed immunosuppression used for kidney transplant recipients in 1962-1963. Note the reversal of rejection with the addition of prednisone to azathioprine. More than a third of a century later it was realized that the timing of drug administration had been in accord with the tolcrogcnic principles of immunosuppression (see text). B, Treatment revisions in immunosuppression made at the University of Colorado in December, 1963, that unwittingly violated principles of tolerogenic immunosuppression. Pretreatment was de-emphasized or eliminated, and high doses of prednisone were given prophylactically instead of as needed. Although the frequency of acute rejection was reduced, the drug-tree tolerance shown in Figure 4'2-4 was no longer seen. -
A
False Premises of Phase 1
been developed with azathioprine and prednisone (see Fig. 42-3B). The principal change was the use of large prophylactic doses of prednisone from the time of operation, instead of the administration of corticosteroids only when needed. In a second modification, the pretreatment was de-emphasized (see Fig. 42-3B). The incidence of acute rejection was greatly reduced after these changes. However, no cluster of drug-free kidney recipients like that shown in Figure 4 2 4 was ever seen again, anywhere in the world. More than 35 years passed before the long-term immunologic consequences of the modifications were realized.
Thus, organ transplantation became disconnected at a very early time from the scientific anchor of leukocyte chimerism that had been established by the mouse models and was soon to be exemplified by human bone marrow transplantation. The resulting intellectual separation of the two kinds of transplantation (Fig. 42-5) was an unchallenged legacy of phase 1, passed on from generation to generation ever since. There was another dark legacy of phase 1. This was a modified version of the treatment strategy that had
Nine (19%) of the 46 live donor kidney recipients treated at the University of Colorado over an 18-month period beginning in the autumn of 1962. The solid portion of the horizontal bars depicts the time off immunosuppression. Note that the current serum creatinine concentration (CR) is normal in all but one patient. *Murdered: kidney allograft normal at autopsy.
Recipient 1
[
~mrnunosuppression
No ~rnmunosuppression
Donor
CR
I Sister 4 . 5
2
1 Brother 4 . 5
3
[
Mother 4 . 5 Mother 4 . 5
4 5
1
1
w
--
Sister
6
7
8 9
Mother 2.5-3 c1.5
1 Gr. Aunt 4.5
< 9
1
1
I
0
10 20 30 Years post transplantation
I
I
40
Father
4.5
Uncle
4.5
688
PART
IV
TRANSPI.ANTATION Solid Organ
Bone Marrow
.
-
A
The developmental tree of
bone marrow (right) and organ transplantation (left) after it was demonstrated that rejection is an immunologic response. GVHD, graftversus-host disease.
Tissue match
Phase 2: 1969-1979 Throughout the succeeding phase 2 that began in 1969, immunosuppression for organ transplantation was based on azathioprine and prophylactic high-dose prednisone in about 15% of to which ALG was added after 196670,71 centers. Phase 2 was a bleak period. In the view of critics, the heavy mortality, and particularly the devastating morbidity caused by corticosteroid dependence, made organ transplantation (even of kidneys) as much a disease as
A
a treatment. Most of the liver and heart transplant programs that had been established in an initial burst of optimism after the first successful cases closed down. But in the few remaining centers, patients like the one shown in Figure 42-6 bore witness to what some day would be accomplished on a grand scale. Four years old at the time of her liver replacement for biliary atresia and a hepatoma in 1969, she is the longest surviving recipient of an extrarenal organ.
B
Four-year-old at the time of liver rep1acement for biliary atresia and a hepatoma but now in her 35th post-transplant year. She is the longest surviving recipient of an extrarenal organ. a
.
A
CHAPTER
42
Principles of Transplantation
689
Phase 3: 1980-1991
or a role of leukocyte chimerism. Although it was known that organs contain large numbers of passenger leukocytes, In fact, what had appeared to be the sunset of extrarenal these donor cells were largely replaced in the successfully organ transplantation was only the dawn of phase 3, which began with the clinical introduction of ~yclosporine,~~~~~,~~,~8 transplanted allograft by recipient leukocytes as shown in Figure 42-8A. followed a decade later by that of t a c r o l i m ~ s . 2 0 ~ ~ ~ ~~~~ ~ 2 The missing donor cells were thought to The use of these drugs was associated with stepwise have undergone immune destruction with selective improvements with all organs, but their impact was most sparing of the specialized parenchymal cells. As for conclusively demonstrated with liver and heart transplanbone marrow transplantation (see Fig. 42-8B), the ideal result had been perceived as complete replacement of tation. The results with liver transplantation shown in recipient immune cells (i.e., total hematolymphopoietic Figure 42-7 using azathioprine-, cyclosporine-, and chimerism). tacrolimus-based immunosuppression were presented at the meeting of the American Surgical Association in April 1994.10"~ then, intestinal transplantation under The Discovery of Microchimerism tacrolimus-based immunosuppression had become a Ser~Ce.104,10.5 A flaw in this historical dogma began to be exposed in the early 1990s. The first puzzling observation in Seattle56 As the new agents became available, they were simply and Helsinki107 was the invariable presence of a small incorporated into the modified formula of heavy proresidual population of recipient hematolymphopoietic phylactic immunosuppression that had been inherited cells in patients previously thought to have complete from phases 1 and 2. Used in a variety of multiple-agent bone marrow replacement (see Fig. 42-8D). This was combinations from the time of surgery, the better drugs followed in 1992 by the discovery of donor leukocyte fueled the golden age of transplantation of the 1980s microchimerism in long-surviving human organ recipand early 1990s. Acute rejection had become almost a ients. Now it was evident that organ engraftment (see "non" problem. However, the unresolved issues now were Fig. 42-86) and bone marrow cell engraftment (see chronic rejection, risks of long-term immunosuppression Fig. 42-8D) were mirror-image versions of leukocyte (e.g., infections and de novo malignancies), and drug chimerism, differing in the reversed proportion of donor toxicity (e.g., the nephrotoxicity of cyclosporine and and recipient cells. tacrolimus) . The discovery of microchimerism in organ recipients was made with a very simple clinical With the use of sensitive detection techniques, donor hematolymPhase 4: 1992-Present phopoietic cells of different lineages (including dendritic cells) were found in the blood, lymph nodes, skin, or It was clear that relief from the burden of lifetime other tissues of 30 of 30 liver or kidney recipients who immunosuppression would require elucidation of the had borne functioning allografts for up to 30 years. The mechanisms of alloengraftment and of acquired tolerance. An intensified search for the engraftment mechanisms donor leukocytes obviously were progeny of donor has dominated the current phase 4, which began in the precursor or pluripotent hematolymphopoietic stem cells that had migrated from the graft into the recipient early 1990s. after surviving a double immune reaction that presumably had occurred just after transplantation, years or The Historical Dogma decades earlier.35,45,57,94 It was concluded that organ engraftment had been Until this time, organ engraftment had been attributed the result of "responses of co-existing donor and recipito mechanisms that did not involve either the presence ent cells, each to the other, causing reciprocal clonal exhaustion, followed by peripheral clonal deleti~n."R"~~ The host response (the upright curve in Fig. 42-9) was the dominant one in most cases of organ transplantation but with the occasional exception of GVHD. In the conventionally treated bone marrow recipient, host cytoablation simply transferred immune dominance from the host to the graft (the inverted curve in Fig. 42-9), A CYA (n=1835) AZA (n=168) explaining the high risk of GVHD. All of the major differences between the two kinds of transplantation were caused by the recipient cytoablation. After an estrangement of more than a third of a century, the intellectual o 1 i i i i separation of bone marrow and organ transplantation Time after transplantation (years) was ended (Fig. 42-10). V
-
A
.
Patient survival: results with orthotopic liver trans-
plantation at the Universities of Colorado (1963-1980) and Pittsburgh (1981-1993), in periods defined by azathioprine (AZA)-, cyclosporine (CYA)., and tacrolimus (TAC)-basedimmune suppression. Stepwise improvements associated with the advent of these drugs also were made with other kinds of organs.
Immune Regulation by Antigen Migration and Localization But how was the exhaustion-deletion of the double immune reaction shown in Figure 42-9 maintained after its
690
PART
IV
TKANSPLANTATION
Single response (organ)
n
Proliferation of host
HVG (rejection)
Single response (bone marrow)
I \
Defenseless recipient
d
Double response (organ)
Double response (bone marrow)
lmmunosuppress~on
HVG (rejection)
2
HVG
2
.
Old ( A and B) and new views (Cand D)of transplantation recipients A, The early conceptualization of immune mechanisms in organ transplantation in terms of a unidirectional host-versus-graft (HVG) response. Although this readily explained organ rejection, i t limited possible explanations of organ engraftment. B, Mirror image of A depicting the early understanding of successful bone marrow transplantation as a complete replacement of the recipient immune system by that of the donor, with the potential complication of an unopposed lethal unidirectional graft-versus-host (GVH) response, that is, rejection of the recipient by the graft. C, Our current view of bidirectional and reciprocally modulating imrnune responses of coexisting immune competent cell populations. Because of variable reciprocal induction of deletiorial tolerance, organ engraftnlent was feasible despite a usually dominant HVG reaction. The bone silhouette in the graft represents passenger leukocytes of bone marrow origin. I), Our currently conceived mirror image of Cafter successful bone marrow transplantation. Recipient's cytoablation has caused a reversal of the size proportions of the donor and recipient populations of immune cells.
-.
---
'-, -,,-__-,,-*'-------------,GVH ----- -- -Donor
---_-- --__
1 Time after organ transplantation
-*Failure
.~erformed.15 salivary , cland hemangioma " Parotid hemangiomas often resolve spontaneously and do not require medical or surgical therapy. If they are
-
CHAPTER
.
53
Salivary Glands
839
.
Vascular malformation of the parotid gland, showing large, irregular vascular spaces. (Hematoxylin-eosin stain, ~ 5 0 . )
Pleomorphic adenoma (mixed tumor) of the parotid gland. Epithelial areas are mixed with myxomatoid and chondroid stroma. (Hematoxylin-eosin stain, ~ 5 0 . )
rapidly growing or are causing functional impairments such as facial nerve weakness, external auditory canal obstruction, or cutaneous breakdown, systemic therapy such as corticosteroids or interferon alfa-2a or -2b are viable options to inhibit vascular growth and promote involution of the tumor.5~3~ A less common vascular tumor is the kaposiform hemangioendothelioma. This is a benign, although locally aggressive, tumor that is firm to palpation with a nodular growth pattern and violaceous pigmentation. Therapy is controversial and may include systemic corticosteroids, interferon alfa, or surgical re~ection.~?
masses, most often in the parotid gland, with an average age at presentation of 9.5 years within the pediatric population.2"." The tumor presents as a painless, slowly growing mass and is rarely infiltrative.'? Treatment of superficial lobe tumors includes superficial parotidectomy with facial nerve dissection and preservation. Recurrence rates have been reported to be up to 4O%, so long-term follow-up is recommended.36," Rarely, recurrent pleomorphic adenomas may undergo malignant degeneration. The submandibular glands, minor salivary glands, tongue, and soft palate may also develop pleomorphic adenomas, although these are rare.g
Lymphatic Malformations Lymphatic malformations are less common than hemangiomas, and the biology of these congenital vascular malformations results in a clinical course that differs They do not undergo sponfrom that of hernangioma~.~j taneous involution, are usually present at or soon after birth, and grow with the growth of the child. They are not actual salivary lesions, but they are most commonly seen in the submandibular and parotid region in infants and young ~hildren.~"ecause they are lesions of the lymphatic system, they are susceptible to infection, with potential for cellulitis, intralesional bleeding, abscess formation, or lymphatic fluid extension to the floor of mouth or trachea with airway compromise. Treatment modalities have been an area of much investigation. Surgical resection must be complete to obviate recurrence. This is often difficult, owing to the fragility of the tumor lining and its proximity to major vessels and branches of the facial nerve.'3,'9 In an effort to avoid surgical morbidity, success with intralesional sclerotherapy has been demonstrated, resulting in reduction in tumor size and minimal scarring or r e c ~ r r e n c e . ~ '
Pleomorphic Adenomas Pleomorphic adenomas (benign mixed tumors) are the most common nonvascular benign salivary tumors in children (Fig. 53-6).j'z" They present as firm, rubbery
Monomorphic Adenomas Monomorphic adenomas are rare in children. Histologically, they may resemble adenoid cystic carcinoma, a highly aggressive malignant salivary tumor." Treatment includes complete surgical resection and close long-term follow-up.
Papillary Cystadenoma Lymphomatosum (Warthin's Tumor) These tumors are most commonly seen in men and are often bilateral parotid lesions. They may rarely present as is similar benign parotid tumors in children."reatment to that for pleomorphic adenomas.
Malignant Neoplasms Malignant salivary neoplasms are rare in children. When present, they are often low-grade lesions, located most commonly in the parotid gland, and have a female prep ~ n d e r a n c e Diagnostic .~~ evaluation should include CT or MRI and fine-needle aspiration biopsy. Treatment is surgical, with complete tumor excision with clear margins. Invasive malignancies may require sacrifice of the facial nerve branches, with subsequent nerve grafting to
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restore facial muscle function. Postoperative radiation therapy is recommended for high-grade lesions.27,4*
Mucoepidermoid Carcinoma Mucoepidermoid carcinoma is the most common pediatric salivary malignancy and is most commonly low grade and located in the parotid gland. Surgery with superficial or total parotidectomy, depending on tumor extent, is usually curative.",s4 For high-grade mucoepidermoid carcinomas, or those involving the submandibular or minor salivary glands, concomitant neck dissection and adjuvant radiation therapy is recommended by many institutions.l725,53
Acinic CeN Carcinoma
.
-
Rhabdomyosarcoma of the parotid gland showing
Acinic cell carcinornas present in a similar fashion as mucoepidermoid carcinomas. They tend to be low grade, and treatment is similar to that of mucoepidermoid carcinoma (Fig. 53-7).
spindle cell sarcoma with myogenous differentiation. (Hematoxylineosin stain, x100.)
Adenoid Cystic Carcinoma
SURGICAL CONSIDERATIONS
Adenoid cystic carcinoma is a rare, high-grade salivary gland tumor. Perineural invasion may result in facial paralysis or, for submandibular gland tumors, in lingual nerve, hypoglossal nerve, and marginal mandibular branch deficits. There is a high incidence of regional nodal metastases, as well as distant metastases to the lungs, liver, and bone. Treatment includes wide surgical resection, neck dissection, and adjuvant radiation therapy.Z7
The anatomic studies by Davis and colleag~es2~ and the contribution by Beahrs and Chong2have laid the foundations for parotid surgery. Careful facial nerve dissection and preservation intraoperatively is enhanced by routine use of the facial nerve monitor." Collaboration with anesthesia colleagues regarding reversal of muscle paralysis at the onset of surgery is crucial.
Parotid Gland Rhabdomyosarcoma Rhabdomyosarcoma may present as a parotid mass. Histologic variants include undifferentiated and embryonal types (Fig. 53-8). Treatment and outcomes depend on tumor stage and may include wide local surgical resection, with radiation and chemotherapy.
•
-
Acinic cell carcinoma of the parotid gland showing
invasive proliferation. (Hematoxylin-eosin stain, x100.)
An S-shaped incision is made, beginning in the preauricular crease and extending in a curvilinear fashion to the postauricular region, followed by an inferior extension to 2 fingerbreadths below the angle of the mandible (Fig. 53-9). Skin flaps are elevated in a plane deep to the subcutaneous tissue and superficial to the investing fascia of the parotid gland. Posteriorly, skin flaps are elevated in the subplatysmal plane until the anterior border of the sternocleidomastoid is visualized. The greater auricular nerve and posterior facial vein will be identified and may need to be sacrificed to expose the posterior border of the parotid gland. To identify the main trunk of the facial nerve, which will divide the superficial and deep lobes of the gland, the earlobe must be retracted superiorly and the parotid gland is retracted anteriorly. Blunt dissection along the tragal pointer and mastoid process will allow visualization of the main trunk of the facial nerve as it emerges from the stylomastoid foramen. Meticulous dissection along the facial nerve branches in an anterior direction will elevate the superficial lobe of the parotid gland. If deep lobe dissection is required, the nerve branches must be gently retracted to gain access to the deep extent of the tumor. Careful blunt dissection, with utilization of the bipolar cautery and facial nerve monitor, will maximize excellent surgical results with minimal morbidity.l*
CHAPTER
53
Salivary Glands
841
Sup. temporal v. and a
FACIAL NERVE
FACIAL NERVE Mastiod process
-
''4Techn~quefor parotidectorny.
Submandibular Gland For submandibular gland resection, a horizontal skin incision is made in a natural skin crease approximately 2 fingerbreadths inferior to the body of the mandible. The dissection plane is carried out below the subcutaneous
tissue and platysma, to the investing fascia of the submandibular gland. Exposure should reveal the mylohyoid muscle anteriorly, the sternocleidomastoid muscle posteriorly, and the digastric muscle inferiorly. The submandibular gland fascia is entered sharply. Identification and division
842
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of the anterior facial vein, just d e e p to this fascia, will facilitate protection a n d elevation of t h e marginal mandibular branch of t h e facial nerve. T h e hypoglossal nerve will b e visualized d e e p to the digastric muscle. Anterior retraction of the mylohyoid muscle a n d downward retraction o n the submandibular gland will enable identification of the lingual nerve a n d Wharton's duct. Division of the d u c t will free the lingual nerve from the gland a n d allow for complete blunt dissection of the gland.18
COMPLICATIONS AND RESULTS Although salivary gland disorders are rare in childhood, the surgeon's knowledge of the anatomy of the major salivary glands a n d understanding of both systemic a n d neoplastic physiology is critical in performing appropriate evaluation a n d therapy. Neoplasms of the salivary glands are very rare i n children a n d are commonly benign.5"valuation a n d management should b e tailored to the specific entity, whether it b e of systemic o r neoplastic origin. A multitude of diagnostic tools are available a n d may include radiologic o r pathologic studies. Inflammatory a n d infectious disorders are often treated medically, whereas neoplastic disorders require surgical intervention. T h e surgeon must have experience with facial nerve dissection a n d must have a n understanding of the variations of facial nerve anatomy i n infants, young children, a n d adolescents. Patients a n d families must b e counseled regarding potential short- a n d long-term complications of facial nerve injury, whether temporary from nerve traction o r permanent from nerve transection o r sacrifice. Despite the rigorous demands of parotid a n d submandibular gland surgery, in experienced hands, with adequate monitoring a n d meticulous dissection a n d hemostasis, surgical results a r e e ~ c e l l e n t . ~ ~
REFERENCES 1. Al-Khafaiji BM, Nestok BR, Katz RL: Fine needle aspiration of 154 parotid masses with histologic correlation: Ten year experience at the University of Texas MD Anderson Cancer Center. Cancer 1998;84:153. 2. Beahrs OH, Chong GC: Management of the facial nerve in parotidectomy. Am J Surg 1972;124:473. 3. Bentz BG, Hughes A, Ludemann JP, MaddalozzoJ: Masses of the salivary gland region in children. Arch Otolaryngol Head Neck Surg 2000;126:1435-1439. 4. Bianchi A, Cudmore RE: Salivary gland tumors in childhood. J Pediatr Surg 1978;13:512. 5. Blei F, Isakoff M, Deb G: The response of parotid hemangiomas to the use of systemic interferon alfa-2a or corticosteroids. Arch Otolaryngol Head Neck Surg 1997; 123:841-844. 6. Bower CM, Dyleski RA. Diseases of the salivary glands. In Bluestone CD, Stool SE, Kenna M (eds): Textbook of Pediatric Otolaryngology. Philadelphia, WB Saunders, 2004, pp 1251-1267. 7. Camacho AE, Goodman ML, Eavey RD: Pathologic correlation of the unknown solid parotid mass in children. Otolaryngol Head Neck Surg 1989;101:566571.
8. Candel A, Gattuso P, Reddy V, et al: Is fine needle aspiration biopsy of salivary gland masses really necessary? Ear Nose Throat J 1993;72:485. 9. Carlson GW: The salivary glands: Embryology, anatomy, and surgical applications. Surg Clin North Am 2000;80:261-273. 10. Casselman JW, Mancuso AA: Major salivary gland masses: comparison of MR imaging and CT. Radiology 1987; 165:183. 11. Castro EB, Huvos AG, Atrong EW, Foote FW Jr: Tumors of the major salivary glands in children. Cancer 1972;29:312. 12. Centers for Disease Control: Mumps prevention. MMWR Morb Mortal Wkly Rep 1989;38:338-392, 397-400. 13. CherryJD: Mumps virus. In Feigen RD, CherryJD, Demmler GJ, Kaplan SL (eds): Textbook of Pediatric Infectious Diseases, 5th ed. Philadelphia, WB Saunders, 2004, pp 2305-2314. 14. Chetty R, Vaithilingum M, Thejpal R: Epstein-Barr virus status and the histopathological changes of parotid gland lymphoid infiltrates in HIV-positive children. Pathology 1999;31:413-417. 15. Childers EL, Furlong MA, Fanburg-SmithJC: Hemangioma of the salivary gland: A study of ten cases of a rarely biopsied/excised lesion. Ann Diagn Pathol 2002;6:339-344. 16. Corr P, Cheng P, Metrweli C: The role of ultrasound and computed tomography in the evaluation of parotid masses. Aust Radiol 1993;37:195. 17. Conley J, Tinsley PP Jr: Treatment and prognosis of mucoepidermoid carcinoma in the pediatric age group. Arch Otolaryngol 1985;111:322-324. 18. Cunningham MJ: Tumors of the head and neck. In Bluestone CD, Stool SE (eds): Atlas of Pediatric Otolaryngology. Philadelphia, WB Saunders, 1995, pp 530-570. 19. Cvetinovic M, Jovic N, Mijatovic D: Evaluation of ultrasound in the diagnosis of pathologic processes in the parotid gland. J Oral Maxillofac Surg 1991;49;147. 20. Davis RA, Anson BJ, Budinger JM, Kurth LR: Surgical anatomy of the facial nerve and parotid gland based on 350 cervicofacial halves. Surg Gynecol Obstet 1956;102:358. 21. Dean GT, Briggs K, Spence RAG: An audit of surgery of the parotid gland. Ann R Coll Surg Engl 1995;77:188. 22. Ethunandan M, Ethunandan A, Macpherson D, et al: Parotid neoplasms in children: Experience of diagnosis and management in a district general hospital. IntJ Oral Maxillofac Surg 2003;32:373-377. 23. Fageeh N, Manoukian J, Tewfik T, et al: Management of head and neck lymphatic malformations in children. J Otolaryngol 1997;26:253-258. 24. Freling NJ, Molenaar WM, Verney A. Malignant parotid tumors: Clinical use of MR imaging and histological correlation. Radiology 1992;185:691. 25. Friedman M, Levin B, Grybauskas V, et al: Malignant tumors of the major salivary glands. Otolarpgol Clin North Am 1986;19:625-636. 26. Galick R: Salivary gland neoplasms in children. Arch Otolaryngol 1969;89:878. 27. Garden AS, el-Naggar AK, Morrison WH, et al: Postoperative radiotherapy for malignant tumors of the parotid gland. Int J Radiat Oncol Biol Phys 1997;37:79. 28. Gasser RF: The early development of the parotid gland around the facial nerve branches. Anat Rec 1992;15:244. 29. Giguere CM, Bauman NM, Smith RJ: New tfeatment options for lyrnphangioma in infants and children. Ann Otol Rhino1 Laryngol2002;111:10661075. 30. Greene AK, Rogers GF, Mulliken JB: Management of parotid hemangioma in 100 children. Plast Reconstr Surg 2004;113:53-60. 31. Haberal I, Gocmen H, Samim E: Surgical management of pediatric ranula. Int J Pediatr Otorhinolaryngol 2004;68: 161-163.
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32. Hicks J, Flaitz C: Mucoepidermoid carcinoma of the salivary glands in children and adolescents: Assessment and proliferation of markers. Oral Oncol 2000;36:454460. 33. Ilgit ET, et al: Digital subtraction sialography techniques: Advantages and results in 107 cases. Eur J Radiol 1992;15:44. 34. Jaques DA, Krolls SO, Chambers RG: Parotid tumors in children. Am J Surg 1976;132:469-471. 35. Kobayashi T, Ochi K, Komatsuzaki Y, et al: Blanket removal of the sublingual gland for treatment of plunging ranula. Laryngoscope 2003;113:386388. 36. Koral K, Sayre J, Bhuta S, et al: Recurrent pleomorphic adenoma of the parotid gland in pediatric and adult patients: Value of multiple lesions as a diagnostic indicator. AJR Am J Roentgen01 2003;180:1171-1174. 37. Krolls SO, Trodahl JN, Boyers R: Salivary gland lesions in children. Cancer 1972;30:459. 38. Lowe LH, Stokes LS,Johnson JE, et al: Swelling at the angle of the mandible: Imaging of the pediatric parotid gland and periparotid region. Radiographics 2001;21:1211-1227. 39. McGuirt WF, Whang C, Moreland W: The role of parotid biopsy in the diagnosis of pediatric Sjogren syndrome. Arch Otolaryngol Head Neck Surg 2002;128:1279-1281. 40. Megerian CA, Maniglia AJ: Parotidectomy: A ten-year experience with fine needle aspiration and frozen section biopsy correlation. Ear Nose Throat J 1994;73:377. 41. Mendenhall WM, Morris CG, Amdur RJ, et al: Radiotherapy alone or combined with carbogen breathing for squamous cell carcinoma of the head and neck: A prospective, randomized trial. Cancer 2005;104:332-337. 42. Metry DW, Hebert AA: Benign cutaneous vascular tumors of infancy: When to worry, what to do. Arch Dermatol 2000;136:905-914. 43. Modlin JF: Current status of mumps in the United States. Infection 1975;132:106. 44. Morita Y, Sato K, Kawana M, et al: Treatment of ranulaexcision of the sublingual gland versus marsupialization. Auris Nasus Larynx 2003;30:311-314. 45. Mulliken JB, Glowacki J: Hemangiomas and vascular malformations in infants and children: A classification based on endothelial characteristics. Plast Reconstr Surg 1982;69: 412420. 46. Orvidas LJ, Kasperbauer JI,: Pediatric lymphangiomas of the head and neck. Ann Otol Rhino1 Laryngol2000;109:411-421. 47. Orvidas LJ, KasperbauerJL, Lewis JE, et al: Pediatric parotid masses. Arch Otolaryngol Head Neck Surg 2000;126:177-184. 48. Pandit RT, Park AH: Management of pediatric ranula. Otolaryngol Head Neck Surg 2002;127:115-118.
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49. Pershall KE, Koopman CF, Coultard SW: Sialadenitis in children. J Pediatr Otolaryngol 1986;11:199. 50. Peter G (ed): 1997 Red Book: Report of the Committee on Infectious Diseases, 24th ed. Elk Grove Village, IL, American Academy of Pediatrics, 1997, pp 366-369. 51. Ribeiro Kde C, Kowalski LP, Saba LM, de Camargo B: Epithelial salivary gland neoplasms in children and adolescents: A forty-four year experience. Med Pediatr Oncol 2002;39:504600. 52. Rice DH: Non-neoplastic diseases of the salivary glands. In Paparella MM, et a1 (eds): Otolaryngology. Philadelphia, WB Saunders, 1991. 53. Rogers DA, Rao BN, Bowman L, et al: Primary malignancy of the salivary gland in children. J Pediatr Surg 1994;29: 4447. 54. Schuller DE, McCabe BF: Salivary gland neoplasms in childhood. Otolaryngol Clin North Am 1977;10:39. 55. Shikani AH, Johns ME: Tumors of the major salivary glands in children. Head Neck Surg 1998;10:257. 56. Siefert G, Sobin LH: The World Health Organization's Histological classification of salivary gland tumours: A commentary on the second edition. Cancer 1992;70:379. 57. Sung MW, Lee DW, Kim DY, et al: Sclerotherapy with picibinal (OK-432) for congenital lymphatic malformation in the head and neck. Laryngoscope 2001;111:1430-1433. 58. Tabor EK, Curtin HD: MR of the salivary glands. Radiol Clin North Am 1989;379:27. 59. Variend S, O'Neill D, Arnold P: The possible significance of cytomegaloviral parotitis in infant and early childhood deaths. Arch Path01 Lab Med 1997;121:1272. 60. Venkateswaran L, Gan YJ, SixbeyJW, Santana VM: EpsteinBarr virus infection in salivary gland tumors in children and young adults. Cancer 2000;89:463-466. 61. Watanabe Y, et al: Facial nerve palsy as a complication of parotid surgery and its prevention. Acta Otolaryngol Suppl (Stockh) 1993;504:137. 62. White AK: Salivary gland diseases in infancy and childhood. J Otorhinolaryngol 1992;21:422. 63. Woods JE: Parotidectomy: Points of technique for a brief and safe operation. Am J Surg 1983;145:678. 64. Work WP: Cysts and congenital lesions of the parotid gland. Otorhinolaryngol Clin North Am 1977;10:339. 65. Work WP: Newer concepts of first branchial cleft defects. Laryngoscope 1972;82:1581. 66. Yang WT, Ahuja A, Metreweli C: Sonographic features of head and neck hemangiomas and vascular malformations: Review of 23 patients. J Ultrasound Med 1997;16:39.
Lymph Node Disorders Kurt D. Newman and Andrea A. Hayes-Jordan
GENERAL APPROACH TO ADENOPATHY An enlarging or persistent neck mass in a child is a common source of concern for parents and pediatricians and is a frequent reason for referral to a surgeon. Most cervical masses in children are either congenital lesions (i.e., thyroglossal duct or branchial cleft origin) or enlarged lymph nodes. Clinically palpable cervical lymphadenopathy is extremely common during childhood, with a reported prevalence of 28% to 55% in otherwise normal infants and children.*3,3'Although reactive hyperplasia caused by presumptive or proven infection accounts for most cases of cervical lymphadenopathy, the possibility of a malignant condition must be considered in all clinically suspicious lesions that become chronic or persist despite antibiotic therapy.19 Surgical intervention is indicated in specific infectious conditions, such as atypical mycobacterial adenitis, and may be required in inflammatory lymphadenitis that is complicated by suppuration or fistula formation or is recalcitrant to appropriate medical management. Persistent lymphadenopathy despite 2 weeks of antibiotic therapy, unilateral adenopathy involving the supraclavicular or posterior triangle of the neck, and adenopathy in the presence of an unclear diagnosis are best treated by expedient excisional biopsy to exclude the possibility of malignancy. Diagnostic imaging may be helpful in distinguishing a solid versus cystic or mixed lesion.'"
This scheme describes nodal groups as follows: level Isubmental triangle nodes; levels 11, 111, and IV-upper, middle, and lower thirds of the internal jugular chain, respectively; level V-posterior cervical triangle nodes; level VI-tracheoesophageal groove nodes; and level VIIsuperior mediastinal nodes.
ACUTE LYMPHADENITIS The most common cause of self-limiting, acute, inflammatory lymph node enlargement is a viral infection.5 Acute bilateral cervical adenopathy is most often caused by a viral respiratory tract infection or streptococcal pharyngitis, whereas unilateral cervical lymphadenitis is usually caused by a streptococcal or staphylococcal infection in 40% to 80% of cases.ZgBilateral lymphadenopathy secondary to viral infections usually resolves spontaneously. Acute suppurative lymphadenitis is typically caused by
n ,
Submandibular Superficial parotid
Retro-auricular
ANATOMY The regional lymph node groups of the head and neck are shown in Figure 541. Drainage to lymphatic basins follows predictable, anatomic routes, with the nomenclature reflecting the site of the lymph nodes. The face and oropharynx drain predominantly to the preauricular, submandibular, and submental nodes: the uosterior scalp drains to the occipital nodal group; and the mouth, tongue, tonsils, oropharynx, and nasopharynx drain to suoerficial and deeo chains of the anterior cervical nodes. Significant lymphatic collateralization exists. A classification system for grouping cervical lymph nodes has been described by Shah and associates (Fig. 542).49
chain Regional lymph node groups of the head and neck. (From Bodenstein L, Altman RP: Cervical lymphadenitis in infants and children. Semin Pediatr Surg 1994;5:134. Used with permission.) -
1
CHAPTER
*"
54
Lymph Node Disorders
845
""a,,
, . A Lymphatic node levels of the neck. Level VI (tracheoesophageal) and level VII (superior mediastinum) groups are not shown. (From Shah JP, Medina JE, Shaha AR, et al: Cervical lymph node metastasis. Curr Prob Surg 1993;30:273.Used with permission.)
bacterial infection from penicillin-resistantstaphylococci, group A streptococci, or both.3 Staphylococcus infection leading to lymphadenitis seems to occur more commonly bacteria, group B streptococci, in infants.2"aerobic and Haemophilus influenzae type B are less frequent causal organisms.8.20~47Recently, a new pattern of resistance has been identified. Community-acquired methicillin-resistant, clindamycin-sensitive Staphylococcus aureus (MRSA) has been isolated from superficial abscesses and suppurative Regardless of the causative lymphadenitis in ~hildren.29,~~ bacterial agent, the local inflammatory signs of suppurative lymphadenitis strongly suggest the diagnosis. Children typically present with unilateral, tender adenopathy that involves the submandibular or deep cervical nodes (or both) draining the oropharynx. Erythema of the overlying skin may be present. Fever, malaise, and signs of systemic illness occur to varying extents. A careful search for a primary infection in the head and neck region, including the oropharynx and middle ear, should be conducted and treated appropriately. Initial therapy for uncomplicated cervical lymphadenitis should begin with an empirical 5- to 10-day course of an oral, p-lactamase-resistant antibiotic. Most patients can be treated safely and effectively on an outpatient basis. If systemic signs of infection, including associated cellulitis, are present or if infection occurs in very young infants, intravenous antibiotics may be more clinically appropriate. Response of the infectious process should be observable within the first 72 hours of therapy. Failure to note clinical signs of improvement indicates the need for further diagnostic testing, including ultrasonography or fine-needle aspiration (FNA) of the involved m a s s . T h e determination of the causative organism or organisms by aspirate culture allows for appropriate,
Although not necessary in the vast majority of cases, this CT scan demonstrates a deep cervical abscess from suppurative lymphadenitis. This 2-year-old child presented with diffuse unilateral cervical edema secondary to abscess, located posterior to the left carotid sheath. -
4
organism-specific antimicrobial therapy; however, FNA may require sedation or anesthesia to be performed safely in children. The aspirate should be sent for aerobic, anaerobic, and acid-fast bacterial stain and culture. Treatment should be based on aspirate results. If the aspirate reveals MRSA, clindamycin treatment should be ~ s e d . 2 ~ 8 ~ ~ Ultrasonography may help to differentiate between solid and cystic masses in the neck. In addition, identification of fluid associated with enlarged, inflammatory nodes may assist in determining the necessity for operative drainage. Other diagnostic methods such as computed tomography (CT) and magnetic resonance imagng (MRI) for suspected adenitis are unnecessary in most cases (Fig. 543). The enlarged lymph node will generally respond to appropriate antimicrobial therapy with prompt resolution of the lymphadenitis. The development of fluctuance caused by suppuration of the involved nodes can be effectively treated with repeated aspiration and antibiotics7 or more definitively with open incision and drainage. In a retrospective study of 110 children, 95 had 107 cervical infectious sites drained surgically. The remaining 15 improved with medical therapy. CT accurately predicted operative findings in only 81 ('76%)of cases. Of the 26 cases with a discrepancy between CT and operative findings, 18 showed false-positive findings in which the CT scan showed an abscess but only cellulitis was found at operation.l6
ATYPICAL MYCOBACTERIALADENITIS The genus Mycobacterium is characterized on light microscopy to be bacilli distinguished by their dense
846
PART
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HEADAND NECK
lipid capsules. The lipid capsules resist decolorization by acid alcohol after staining and thus are termed acid-fast bacilli.1 Atypical mycobacteria are now the most common causative agents in mycobacterial lymphadenitis. The more common atypical mycobacteria include M. auiumintracellulare, M. scrojulaceum, M.fortuitum, and M. che1onei.l In contrast to tuberculous adenitis, atypical (or nontuberculous) mycobacterial adenitis is generally considered a local infectious process, without systemic involvement in immunocompetent hosts.35Disseminated disease is more commonly observed in patients with underlying acquired or congenital immunodeficiency states. Atypical mycobacterial adenitis is not contagious, and the portal of entry in otherwise healthy children is presumed to be the oropharynx.2 Atypical mycobacterial adenitis usually occurs in young children between 1 and 5 years of age. The common clinical presentation is focal, unilateral involvement of the jugulodigastric, preauricular, or submandibular nodal group. In contrast to acute suppurative lymphadenitis, the involved nodal group with atypical mycobacterial disease is minimally tender, firm, and rubbery to palpation, is well circumscribed, and may adhere to underlying structures. Although remarkably nontender, these lesions occasionally present as a draining sinus tract.36 Signs of systemic illness or inflammation are usually minimal or nonexistent. Chest radiographs are typically normal. Skin testing with tuberculin purified protein derivative (PPD) or old tuberculin (tine) in patients with atypical mycobacterial adenitis may yield an intermediate reaction resulting from cross-reactivity.58 Specific, atypical mycobacterial antigens for skin testing have been developedj.26 but are not widely available for clinical use. An in-vitro whole-blood assay measuring increased lymphocyte production of interferon-y in patients with atypical mycobacterial adenitis has also been described.l5 FNA may yield acid-fast bacteria and provide a definitive diagnosis by aspirate culture. However, the preoperative clinical distinction between tuberculous and nontuberculous adenitis often remains difficult. Cervical lymphadenitis arising from infection with tuberculous and atypical mycobacteria has been reported but is extremely infrequent.35 Unlike tuberculous adenitis, atypical mycobacterial adenitis generally does not respond to chemotherapy. The treatment of choice is complete surgical excision with primary wound closure. In a literature review of the surgical treatment of atypical mycobacterial cervicofacial adenitis in children, excision, incision and drainage, curettage, and needle aspiration were compared among 16 studies. The cure rates were 92%, lo%, 86%, and 41%, respectively. Also, of 510 patients who underwent surgical excision, 11 transient and 1 permanent seventh nerve palsies were observed. Thirteen patients had persistent drainage after excision, and there were seven recurrences beneath the incision site.18At least 15 of 70 patients who underwent incision and drainage suffered draining sinuses. Of the 35 patients from four different studies who underwent curettage as treatment of atypical mycobacterial adenitis, 2 experienced delayed healing, in 1 a second curettage was necessary, and there was 1 recurrence.18 Incision and drainage alone should be avoided. Elliptical excision of the overlying skin, subcutaneous
tissue, and the involved node is required; formal lymph node dissection is not necessary. Curettage is recommended only if surgical excision is not possible. A nerve stimulator may be helpful for lesions at the angle of the mandible to avoid injury to branches of the facial nerve. Antituberculous chemotherapy or patient isolation is not required for confirmed cases of atypical mycobacterial adenitis treated with adequate local excision.
Tuberculous lymphadenitis, or scrofula, is almost exclusively caused by M. tuberculosis in developed countries (Fig. 54-4). Before control of bovine tuberculosis, the predominant cause of tuberculous adenitis was M. bouis. Occasional cases of M. bouis are observed in patients from underdeveloped regions in which consumption of contaminated raw milk occurs. Patients proven to have human tuberculous adenitis often report previous exposure to a known carrier of tuberculosis,48 but most patients have no evidence of active disease on a chest r a d i ~ g r a p hTuberculous .~~ adenopathy is generally associated with other clinical symptoms and signs, including a strongly positive tuberculin PPD skin test and hilar adenopathy or apical calcification on a chest radiograph.56 One study found a 92% sensitivity when two of three of the following criteria were fulfilled: positive PPD skin test, abnormal chest radiograph, or contact with someone Tuberculous with known infectious t~berculosis.4~ adenitis is therefore currently considered to be a local manifestation of a systemic disease and not an initial, primary focus of tuberculous infection.5J0 Clinically, patients
Cervical tuberculous adenitis (ear at right of photograph). Posterior cervical lymph nodes in a 7-year-old boy with a family history of contact and a positive PPD skin test. Medical management of tuberculosis with two-drug therapy for 7 months led to complete resolution. (From Jones PG: Glands of the neck. In Welch KJ, et a1 (eds): Pediatric Surgery, 4th ed. St. Louis, Mosby-Year Book, 1986. Used with permission.)
CHAPTER
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847
with tuberculous adenitis are usually older children and adolescents who present with nonsuppurative lymphadenitis,31 which may be bilateral. A retrospective review of 24 immunocompetent children with tuberculous lymphadenitis showed that no patient had bilateral disease and the submandibular (29%) and the anterior cervical (71%) sites were the only areas of lymph node involvement.44 However, posterior triangle nodal involvement does occur.34 The diagnosis of tuberculous adenitis can be made in the setting of an appropriate history, suspicious adenopathy associated with a strongly positive tuberculin PPD skin test, and positive acid-fast bacteria on stain or culture of nodal tissue. Diagnostic confirmation may be aided by FNA with aspirate culture and cytologic e ~ a m i n a t i o n . ' ~ , ~ ~ Rapid diagnosis of tuberculous adenitis by DNA amplification of nodal material using polymerase chain reaction (PCR) has been reported.42 In contrast, a negative tuberculin PPD test essentially excludes the diagnosis of tuberculous adenitis. If a diagnostic dilemma persists, Cervical lymph node involvement in a patient with excisional biopsy in the operating room with the patient cat-scratch disease. The organism responsible for this infection is the under general anesthesia is warranted. Incisional biopsy pleomorphic, gram-negative bacillus Bartonella henselae (formerly or incision and drainage should be avoided to prevent Rochalimaea). (From Jones PG: Glands of the neck. In Welch KJ, et al development of chronic, draining sinus t r a ~ t s . ~ , ~ ~ , ~ ~ [eds]: Pediatric Surgery, 4th ed. St. Louis, Mosby-Year Book, 1986. Fistula and cheloid formation can be seen in up to 100% Used with permission.) of patients who underwent incision and drainage of tuberculous infected lymph nodes.44 Tuberculous adenitis generally responds to medical Initial infection occurs at a portal of entry in the skin, management that consists of multiple-agent chemotherapy. such as a scratch or bite. Papule formation may be If tuberculous infection is directly observed, the World observed at the site of inoculation in 3 to 5 days, with Health Organization recommends directly observed development of subacute lymphadenopathy at regional short-course therapy, which includes isoniazid, rifampin, nodal drainage basins within 1 to 2 weeks. Early systemic and pyrazinamide for the first 2 months, followed by symptoms of fever, malaise, myalgia, and anorexia are isoniazid and rifampin for an additional 4 months60 commonly reported. Although most cases involve the Although antituberculous chemotherapy remains essenlymph node of the limbs, approximately 25% of cases tial, the role of complete surgical excision of involved involve the cervical lymph nodes." Diagnosis based on a nodes is more controversial.6J2 Complete excision of history of exposure to cats, presence of a site of inoculainvolved nodes is prudent when biopsy is required for tion (which may be healed by the time lymphadenopathy diagnosis; when a chronic, draining sinus tract evolves develops), and regional lymphadenopathy. Identification during medical treatment; or when optimal medical of Bartonella organisms from involved lymph nodes by management fails. Warthin-Starry silver impregnation stain has traditionally been used, but recently this stain has been found to be PCR for unreliable and found to lack species ~pecificity.~~ CAT-SCRATCH DISEASE B. henselae using paraffin sections from lymph nodes or other tissue is more reliable and accurate.40 Because of Cat-scratch disease is a common cause of lymphadenitis its usual benign, self-limiting course, lymphadenopathy in children, with an estimated incidence in the United States resolves in most cases within 6 to 8 weeks without specific of 9.3 per 100,000 ambulatory pediatric and adult treatment.39 Suppuration is unusual. Excisional biopsy is patientsAperyear.2' The highest ~g~-specific incidence is generally unnecessary but may be warranted if a draining among children younger than 10 years of age.32 Current sinus tract develops or if the diagnosis is uncertain and microbiologic and PCR-directed DNA analysis demonthe potential for malignancy cannot be excluded. strates that the pleomorphic, gram-negative bacillus Bartonella henselae (formerly Rochalimaea) is the causative ~ b s cases t can be organism of cat-sciatch dikea~e.~J~222 directly related to contact with a cat, and the usual site MISCELLANEOUS LESIONS of inoculation is a limb. Subseauent adenitis occurs at Various other infectious and inflammatory conditions regional lymphatic drainage basins (inguinal, axillary, can produce lymphadenopathy in infants and children. epitrochlear nodes) .I1 Similarly, cervical lymphadenopaMost patients with these disorders do not require surgithy is observed with scratches in the head and neck cal management or, in particular, excisional biopsy of the region (Fig. 545). Although the primary manifestation lesions. A systematic approach to evaluation of these of B. henselae infection is lymphadenopathy, some series patients, including a thorough history, physical examinareport up to 25% of cases result in severe systemic tion, and directed diagnostic tests, generally leads to the illnesses.30 ,
.
A
848
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HEADAND NECK
correct diagnosis. Surgical management of these lesions should be directed to patients who present diagnostic dilemmas, have nodal disease in suspicious areas (supraclavicular or posterior cervical triangle), or have persistent adenopathy despite adequate medical therapy. Lymphadenopathies caused by infectious agents include toxoplasmosis (caused by Toxo@lasmosisgondii), tularemia (caused by Francisella tularensis) , and infectious mononucleosis (caused by Epstein-Barr virus) .28,53,57 Infection with Actinomyces israelii in the head and neck may lead to cervicofacial actinomycosis that is characterized by a woody, indurated cervical mass and development of chronic, draining fistulas. Direct involvement of the lymph nodes is uncommon, but the induration can make clinical differentiation d i f f i c u l t . ~ n f e c t i o nwith human immunodeficiency virus can produce generalized lymphadenopathy in infants and children.17 Other less frequent disorders that present as lymphadenopathies include Kawasaki disease or mucocutaneous lymph node syndrome. Kawasaki disease is a febrile disorder of childhood that is characterized in part by the abrupt onset of erythematous changes in the oropharyngeal mucosa; acute vasculitis; and extensive, nonsuppurative, nontender cervical adenopathy.Z4 Histiocytic necrotizing lymphadenitis, or Kikuchi's disease, may present as cervical lymphadenopathy that resolves spontaneously. This disease can be clinically confused with malignant lymphadenopathy, and the patients often appropriately undergo diagnostic excisional lymph .~~ disease, node biopsy for definitive d i a g n o s i ~Castleman's or giant lymph node hyperplasia, may also occasionally present as a solitary, enlarged cervical node.45 These disorders do not require lymph node biopsy or excision. Lymphomas are one of the more common malignant conditions in children. They may present as primary neck adenopathy that does not resolve with antibiotics or is enlarging. Patients with congenital or acquired immunodeficiency states, including human immunodeficiency virus infection, are at greater risk for developing malignant lymphoproliferative conditions.17 The surgical management of Hodgkin's disease and non-Hodgkin's lymphoma is discussed in detail in Chapter 35. It is important to reiterate that although most neck masses in children are benign, a high index of suspicion regarding any neck mass that persists despite otherwise appropriate therapy must be maintained. Such masses must be assumed to be malignant until proven otherwise by excisional biopsy. Although lymphoma is the most common malignant disorder manifested by cervical adenopathy, neuroblastoma and thyroid carcinoma are other childhood cancers that can also present as enlarged cervical lymph nodes. In neuroblastoma, cervical adenopathy is often bilateral. These patients have stage 4 disease, and the abdominal adrenal primary may not be palpable. After imaging of the chest, abdomen, and pelvis, if an abdominal primary tumor is detected, excisional biopsy of cervical lymph nodes may be done for initial diagnosis of stage 4 neuroblastoma (see Chapter 28). A child with metastatic thyroid carcinoma may present with unilateral cervical lymph node enlargement that should not be mistaken for ectopic thyroid gland. If thorough neck
examination does not reveal a thyroid nodule, and a history of neck irradiation or other high-risk factors is obtained, thyroid ultrasound should be included in the evaluation of neck adenopathy.
REFERENCES 1. Albright JT, Pransky SM: Nontuberculous mycobacterial infections of the head and neck. Pediatr Clin North Am 2003;50:503-514. 2. Altman RP, Margileth AM: Cervical lymphadenopathy from atypical mycobacteria: Diagnosis and surgical treatment. J Pediatr Surg 1975;10:419. 3. Barton LL, Feigin RD: Childhood cervical lymphadenitis: A reappraisal. J Pediatr 1974;84:846. 4. Bergmans AM, Groothedde JW, Schellekens JF, et al: Etiology of cat-scratch disease: Comparison of polymerase chain reaction detection of Bartonella (formerly Rochalimaea) and Ajpia felis DNA with serology and skin tests. J Infect Dis 1995;171:916. 5. Bodenstein L, Altman RP: Cervical lymphadenitis in infants and children. Semin Pediatr Surg 1994;3:134. 6. British Thoracic Society Research Committee: Short course chemotherapy for tuberculosis of lymph nodes: A controlled trial. BMJ 1985;290:1106. 7. Brodsky L, Belles W, Broday A, et al: Needle aspiration of neck masses in infants and children. Clin Pediatr 1992; 31:71. 8. Brook I: Aerobic and anaerobic bacteriology of cervical adenitis in children. Clin Pediatr 1980;19:693. 9. Burden P: Actinomycosis.J Infect 1989;19:95. 10. Cantrell RW, Jensen JH, Reid D: Diagnosis and management of tuberculous cervical adenitis. Arch Otolaryngol 1975;101:53. 11. Carithers HA: Cat-scratch disease: An overview based on the study of 1,200 patients. Am J Dis Child 1985;139:1124. 12. Castro DJ, Hoover L, Zuckerbraun L: Cervical mycobacterial lymphadenitis: Medical vs. surgical management. Arch Otolaryngol 1985;111:816. 13. Dalton MJ, Robinson LE, Cooper J, et al: Use of Bnrtonclla antigens for serologic diagnosis of cat-scratch disease at a national referral center. Arch Intern Med 1995;155:1670. 14. Dasgupta A, Ghosh RN, Poddar AK, et al: Fine needle aspiration of cervical lymphadenopathy with special reference to tuberculosis. J Indian Med Assoc 1994;92:44. 15. Davidson PM, Creati K, Wood PR, et al: Lymphocyte production of gamma-interferon as a test for non-tuberculous mycobacterial lymphadenitis in childhood. Eur J Pediatr 1993;152:31. 16. Elden LM, Grundfast KM, Vezina G: Accuracy and usefulness of radiographic assessment of cervical neck infections in children. J Otolaryngol 2001;30:82. 17. Falloon J, Eddy J, Weinter K, Pizzo PA: Human immunodeficiency virus infection in children. J Pediatr 1989; 114:l. 18. Fergusson JAE, Simpson E: Surgical treatment of atypical mycobacterial cervicofacial adenitis in children. Aust NZ J Surg 1999;69:426. 19. Filston HC: Common lumps and bumps of the head and neck in infants and children. Pediatr Ann 1989;18:180. 20. Fishaut JM, Mokrohisky ST: Cervical lymphadenitis caused by Haemophilus influenzae type B. Am J Dis Child 1977; 131:925. 21. Fulcher AS: Cervical lymphadenopathy due to Kikuchi disease: US and CT appearance. J Comput Assist Tomogr 1993:17:131.
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22. Goral S, Anderson B, Hager C, et al: Detection of Rochalirnaea henselae DNA by polymerase chain reaction from suppurative nodes of children with cat-scratch disease. Pediatr Infect Dis J 1994;13:994. 23. Hartzog LW: Prevalence of lymphadenopathy of the head and neck in infants and children. Clin Pediatr 1983;22:485. 24. Hicks RV, Melish ME: Kawasaki syndrome. Pediatr Clin North Am 1986;33:1151. 25. Hieber JP, Davis AT: Staphylococcal cervical adenitis in young infants. Pediatrics 1976;57:424. 26. Huebner RE, Schein MF, Cauthern GM, et al: Usefulness of skin testing with mycobacterial antigens in children with cervical lymphadenopathy. Pediatr Infect DisJ 1992;11:450. 27. Jackson LA, Perkins BA, Wenger JD: Cat-scratch disease in the United States: An analysis of three national databases. Am J Public Health 1993;83:1707. 28. Jacobs RF, Condrey YM, Yamauchi T Tularemia in adults and children: A changing presentation. Pediatrics 1985;76:818. 29. Johnigan RH, Periera KD, Poole MD: Community-acquired methicillin-resistant Staphylococcus aureus in children and adolescents: Changing trends. Arch Otolaryngol Head Neck Surg 2003;129: 1049. 30. Kaplan S, Rawlings J, Paddock C, et al: Cat-scratch disease in children. MMWR 2002;51:212. 31. Lai KK, Stottmeier KD, Sherman IH, McCabe WR: Mycobacterial cervical lymphadenopathy: Relation of etiologic agents to age. JAMA 1984;251:1286. 32. Larsson LO, Bentzon MW, BergKelly K, Mellander L: Palpable lymph nodes of the neck in Swedish school children. Acta Paediatr 1994;83:1091. 53. Lau SK, Wei WI, Kwan S, Yew WW: Combined use of fineneedle aspiration cytologic examination and tuberculin skin test in the diagnosis of cervical tuberculous lymphadenitis. Arch Otolaryngol Head Neck Surg 1991;117:87. 34. Leung AK, Robson WL: Childhood cervical lymphadenopathy. J Pediatr Health Care 2004;18:3. 35. Lincoln EM, Gilbert LA: Disease in children due to mycobacteria other than Mycobacten'um tubmculosis. Am Rev Respir Dis 1972;105:683. 36. Mair IWS, Elverland HH: Cervical mycobacterial infection. J Laryngol 1975;89:933. 37. Margileth AW: Management of nontuberculous (atypical) mycobacterial infections in children and adolescents. Pediatr Infect Dis 1985;4:119. 38. Margileth AM: Cat-scratch disease: No longer a diagnostic dilemma. Semin Vet Med Surg 1991;6:199. 39. Margileth AM: Antibiotic therapy for cat-scratch disease: Clinical study of therapeutic outcome in 268 patients and a review of the literature. Pediatr Infect Dis J 1992;11:474. 40. Margolis B, Kuzu I, Herrmann M, et al: Rapid polymerase chain reaction-based confirmation of cat-scratch disease and Bartonella henselae infection. Arch Path01 Lab Med 2003;127:706-710. 41. Martinez-Aguilar G, Hammerman WA, Mason EO Jr, Kaplan SL: Clindamycin treatment of invasive infections
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caused by community-acquired methicillin-resistant and methicillin-susceptible Staphylococcus aureus in children. Pediatr Infect Dis J 2003;22:593. 42. Narita M, Shibata M, Togashi T, Kobayashi H: Polymerase chain reaction for detection of Mycobacterium tuberculosis. Acta Pediatr 1992;81:141. 43. Ord RJ, Matz GJ: Tuberculosis cervical lymphadenitis. Arch Otolaryngol 1974;99:327. 44. Panagiotis S, Maltezou HC, Hantzakos A, et al: Mycobacterial cervical lymphadenitis in children: Clinical and laboratory factors of importance for differential diagnosis. Scand J Infect Dis 2001;33:362. 45. Penfold CN, Cottrell BJ, Talbot R: Neonatal giant lymph node hyperplasia (Castleman's disease) presenting in the head and neck. Br J Oral Maxillofac Surg 1991;29:110. 46. Piersimoni C, Felici L, Giorgi P, et al: Mixed mycobacterial infection of the cervical lymph nodes. Pediatr Infect Dis 1991;10:544. 47. Rathmore MH: Group B streptococcal cellulitis and adenitis concurrent with meningitis. Clin Pediatr 1989;28:411. 48. Schuit KE, Powell DA: Mycobacterial lymphadenitis in childhood. Am J Dis Child 1978;132:675. 49. Shah JP, Mdina JE, Shaha AR, et al: Cervical lymph node metastasis. Curr Prob Surg 1993;30:273. 50. Sigalet D, Lees G, Fanning A: Atypical tuberculosis in the pediatric patient: Implications for the pediatric surgeon. J Pediatr Surg 1992;27:1381. 51. Siu KF, Ng A, Wong J: Tuberculous lymphadenopathy: A review of results of surgical treatment. Aust NZ J Surg 1983;53:253. 52. Speck WT: Tuberculosis. In Behrman RE, et a1 (eds): Nelson Textbook of Pediatrics, 14th ed. Philadelphia, WB Saunders, 1992. 53. Sumaya CV, EnchY Epstein-Ban-virus infectious mononucleosis in children: I. Clinical and laboratory findings. Pediatrics 1985;75:1003. 54. Taha AM, Davidson PT, Bailey WC: Surgical treatment of atypical mycobacterial lymphadenitis in children. Pediatr Infect Dis 1985;4:664. 55. Talmi YP, Cohen AH, Finkelstein Y, et al: Mycobacterium tuberculosis cervical adenitis: Diagnosis and management. Clin Pediatr 1989;28:408. 56. Telander RL, Filston HC: Review of head and neck lesions in infancy and childhood. Surg Clin North Am 1992; 72:1429. 57. Thomaidis T, Anastassea-Vlachou K, MandalenakiLambrou C, et al: Chronic lymphoglandular enlargement and toxoplasmosis in children. Arch Dis Child 1977;52:403. 58. Tomblin JL, Roberts FJ: Tuberculous cervical lymphadenitis. Can Med Assoc J 1979;121:324. 59. Wear DJ, Margileth AM, Hadfield TL, et al: Cat-scratch disease: A bacterial infection. Science 1983;221:1403. 60. World Health Organization: Global Tuberculosis Program: Global Tuberculosis Control. WHO report 1997, publication WHO/TB/225. Geneva, World Health Organization, 1997.
Surgical Diseases of the Thyroid andpParathyroidGlands Michael A. Skinner
Diseases of the thyroid or parathyroid gland are uncommon in the pediatric age group. In one population-based study of school-aged children in the United States, thyroid disease prevalence was 36.7 per 1000 individuals.36 Diffuse gland hypertrophy (goiter) was the most common diagnosis, occurring in about half of cases, and thyroiditis was the second most common abnormality. Thyroid nodules and thyroid hormone level disorders were less common, and malignant neoplasms were exceedingly rare; only two cases of papillary thyroid carcinoma were found in this population of nearly 5000 children observed clinically for 3 years. Surgical evaluation or treatment of thyroid disease may be necessary in patients with benign or malignant neoplasia or in children exhibiting a physiologic abnormality, such as increased hormone secretion.
EMBRYOLOGY The thyroid gland is the first endocrine organ to mature in embryologic development, arising at about 24 days' gestation as an outpouching of the embryonic alimentary tract at the primitive pharyngeal floor. As the embryo enlarges, the developing thyroid gland descends into the neck from the base of the tongue, passing ventrally to the hyoid bone and the laryngeal cartilages, and maintaining a tubular connection to the tongue known as the thyroglossal duct. The opening of this duct into the base of the tongue is called the foramen cecum. Typically, the thyroglossal duct changes from a hollow structure to a solid diverticulum; the original opening into the oropharynx usually remains as a blind pit at the base of the tongue. The thyroid gland has usually reached its final location in the neck by 7 weeks' gestation. Accessory thyroid tissue originating from remnants of the thyroglossal duct may appear in the tongue or anywhere along the course of caudal migration during development. Of occasional surgical importance, the gland fails to descend altogether, resulting in a lingual thyroid. Incomplete descent results in the gland appearing high in the neck or near the hyoid bone.
Histologically, in about the tenth week of gestation, the primordial thyroid cells begin to form discrete cords that further differentiate to form small cellular groups. Colloid begins to form, and thyroxine can be demonstrated in the embryo in about the 11th week. Early in the development of the thyroid gland, the ventral portions of the fourth pharyngeal pouches develop into the ultimobranchial bodies. These structures contain neural crest cells that fuse with the embryonic thyroid gland to form the parafollicular cells or C cells. The parathyroid glands derive from the third and fourth pharyngeal pouches beginning in about the fifth week of gestation. During the sixth week of development, the parathyroid glands associated with the third pair of pharyngeal pouches migrate caudally with the thymic primordium, finally coming to rest on the dorsal surface of the thyroid gland low in the neck. The parathyroid glands arising from the fourth pharyngeal pouches also descend in the neck, ultimately coming to rest at a position superior to the glands derived from the third pouches. Functioning chief cells are active during fetal development to assist in regulating calcium metabolism.
PHYSIOLOGY Production of thyroid hormone occurs in the thyroid gland at the interface between the follicular cell and the thyroglobulin or colloid. The initial step in thyroid synthesis is the iodination of tyrosine molecules to form either monoiodotyrosine, if there is one iodine molecule attached, or diiodotyrosine, if two iodine molecules are bound. These iodinated tyrosine molecules are then coupled to form the definitive thyroid hormones triiodothyronine (T3) and thyroxine (T4).If monoiodotyrosine is attached to diiodotyrosine, then T3 results; two diiodotyrosines bound together constitute a Tq molecule. The thyroid gland secretes primarily T4;approximately 80% of the Tg in the circulation represents metabolized T4,which has been partially deiodinated in the liver, kidney, or other peripheral tissues. In the circulation, most
CHAPTER
55
of the thyroid hormones are protein bound to increase their solubility. The most abundant hormone carrier is thyroid-binding globulin (TBG); other carriers include prealbumin and albumin. Because the protein-bound thyroid hormone is physiologically inactive, the plasma levels of these proteins must be considered when evaluating patients-for abnormalities of thyroid function. Whereas T4 is nearly 50-fold more concentrated in the plasma than T,, the latter moiety binds much more avidly to the thyroid receptor and therefore accounts for most effect of thvroid hormone. of the ~hvsio1og.i~ The produczon and secretion of T, and T4by the thyroid gland is chiefly controlled by thyroid-stimulating hormone (TSH). his protein is secreted by the anterior pituitary gland, principally in response to thyrotropinreleasing hormone (TRH), which is secreted by the hv~othalamus. Under the influence of TSH. thvroid foli l licular cells extend pseudopods into the colloid'to encircle the thyroglobulin and form vesicles that then fuse with protease-containing lysosomes. The thyroglobulin is then subjected to hydrolysis and proteolysis to release free thyroxine into the circulation. L
Surgical Diseases of the Thyroid and Parathyroid Glands
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in the serial evaluation of nodules managed nonoperatively. Radionuclide scintigraphy is another commonly used test. The three nuclides usually available for diagnoitic imaging include iodine-123 (lt31), iodine-131 (1311), and technetium-99m (9hTc). The radioiodines are most effective in detecting ectopic thyroid tissue or metastatic thyroid carcinoma, whereas g9mTc-pertechnetateis thought by some radiologists to enable superior imaging of thyroid gland nodules or tumors.
,
NON-NEOPLASTIC THYROID CONDITIONS The evaluation of a child with thyroid disease should begin with a physical examination of the neck to assess the size and consistency of the gland. Diffuse enlargement makes the diagnosis of simple colloid goiter more likely; or if the child is hyperthyroid, Graves' disease should be suspected. Chronic iymphocytic (Hashimoto's) thyroiditis is classically associated with a gland that feels granular or pebbly. Firmness in the gland suggests an infiltrative process, whereas a very hard gland is more suggestive of neoplasia. Tenderness in the thyroid gland is most commonly associated with an acute inflammatory process. Finally, the presence of enlarged neck lymph nodes should be noted; thyroid carcinoma may be associated with local metastases before the primary tumor can be palpated. Laboratory tests are essential to assess for altered thyroid function. The TSH is elevated in hypothyroid states. .. The plasma free T4 level is an accurate measure of the biologcally active hormone, because it is generally unaffected by the amount of protein binding in the circulation. Conversely, when plasma total T3 and T4 are measured, an evaluation of TBG may be necessary to gauge the level of biologically active (unbound) hormone. Plasma levels of TBG are altered in a number of conditions, affecting the level of total thyroxine. In particular, TBG is increased in the neonatal period and decreased in the presence of exogenous glucocorticoids, androgens, and anabolic corticosteroids. Other medications that affect thyroxine metabolism include phenytoin and phenobarbital, which induce hepatic degradation of T4 and decrease hormone binding to TBG. Finally, there exist rare conditions in which the TBG level is congenitally altered. Several radiologic modalities are available to assist in imaging the thyroid gland. Ultrasonography is increasingly used to assess for thyroid cysts and in the evaluation of multinodular glands. This modality is especially useful
~
~
~
~
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~
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i
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~
Disorders of hypothyroidism are rarely treated surgically and may result from a defect anywhere in the hypothalamicpituitary-thyroid axis. In rare cases, a hypothyroid state mav be seen in conditions of thvroid hormone unreswonsiviness, such as when there is a defect in the thiroid receptor gene; in such cases, the plasma thyroxine level is often elevated. The most common cause of hypothyroidism diagnosed in neonatal screening programs is thyroid gland dysgenesis, accounting for approximately 90% of these patients. In about a third of these infants, no thyroid tissue is seen on radionuclide scanning; in the rest of the patients, a rudimentary gland may be found in an ectopic location, such as at theubase of the tongue. Children dth complete thyroid agenesis are often asymptomatic at birth, owing to the transplacental passage of maternal thyroid hormone through development. In some cases, ectopically located thyroid tissue may supply a sufficient amount of thyroxine .for years or the ditinutive gland may fail in childhood. Such conditions may come to clinical attention with the discovery of a sublingual or midline neck mass, and surgeons should be mindful of this possibility when evaluating children with neck masses. Consideration should be given to performing radionuclide thyroid scanning before removing any unusual neck mass to ensure that the functioning thyroid tissue is not accidentally resected.
Goiter and Thyroiditis A goiter is found in about 3% of the population when children are specifically surveyed for abnormalities of the thyroid gland." Goiters may be classified as either diffusely enlarged or nodular, and they may be associated with normal hormone secretion or thyrotoxicosis. The differential diagnosis of diffuse thyroid enlargement is listed in Table 55-1. Physiologically, diffuse goiters may be related to autoimmune diseases or as a response to a nonautoimmune inflammatory condition, or the enlargement may be a compensation for some defect in hormone production. Most children with goiters are euthyroid, and surgical resection is rarely indicated. . In a population-based study of over 5000 Croatian schoolchildren, thyromegaly was found in 2.78% of the subjects.19The causes of thyroid enlargement in this population are presented in Table 55-2. As in other populations with adequate dietary iodine intake, most of these patients had simple colloid goiter, also frequently called
~
852
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HEADAND NECK
Autoimmune Mediated Chronic lymphocytic (Hashimoto's) thyroiditis Graves' disease Simple colloid goiter
Compensatory Iodine deficiency Medications Goitrogens Hormone or receptor defect
Inflammatory Conditions Acute suppurative thyroiditis Subacute thyroiditis
adolescent goiter or nontoxic goiter. The diagnosis is established after normal levels of TSH and thyroid hormone are documented and when the diffuse nature of the goiter is documented scintigraphically or by ultrasound. The natural history of colloid goiter is not well known, but in one study in which adolescents with the condition were reevaluated some 20 years later, nearly 60% of the glands were found to be normal in size." The spontaneous rate of colloid goiter resolution was not significantly different than the response rate in children treated with exogenous thyroid hormone. Thus, simple colloid goiters should generally not undergo any specific treatment. In rare cases, surgical resection of the gland may be indicated if there are symptoms related to the size of the goiter, if there is a suspicion of neoplasia, or for cosmetic reasons. Chronic lymphocytic thyroiditis, also known as Hashimoto's thyroiditis, is another common cause of diffusely enlarged thyroid glands in children. This condition occurs most commonly in adolescent females and is part of the spectrum of autoimmune thyroid disorders. Indeed, the condition is associated with the presence of other autoimmune disorders such as juvenile rheumatoid arthritis, Addison's disease, and type 1 diabetes mellitus. Patients are usually euthyroid and slowly progress to become hypothyroid. Approximately 10% of these patients are
Diagnosis Simple goiter Chronic lymphocytic thyroiditis Graves' disease Benign adenoma Cyst Total
Frequency (%) 2.3 0.35 0.07 0.04 0.02 2.78
Adapted from Jaksic J, Dumic M, Filipovic B, et al: Thyroid disease in a school population with thyromegaly. Arch Dis Child 1994;70:103-103.
hyperthyroid; this condition has been termed hashitoxicosis. Patients with chronic lymphocytic thyroiditis are characterized by high titers of the circulating antithyroglobulin and antimicrosomal autoantibodies, which are presumably responsible for the B-lymphocytic infiltrate found in the thyroid gland on histologic evaluation. Children with chronic lymphocytic thyroiditis generally come to clinical evaluation because of thyroid gland enlargement. The gland is generally pebbly or granular and may be mildly tender, and the diagnosis may be established by the discovery of high-titer antithyroid antibodies in association with the proper clinical and laboratory circumstances. Plasma thyroid hormone levels are generally not very useful, but the TSH level may be elevated in 70% of patients. Thyroid ultrasound demonstrates diffuse hypoechogenicity, and scintigraphy shows a patchy uptake of the tracer. In rare cases, fine-needle aspiration (FNA) of the gland may be needed to confirm the diagnosis if autoantibodies cannot be detected. The management of chronic lymphocytic thyroiditis is usually expectant; as many as a third of adolescent patients with the condition will resolve spontaneously, with normalization of gland size and disappearance of the antithyroid antibodies. Administration of thyroid hormone to euthyroid patients has not been shown to be useful in reducing the size of the goiter and is thus probably not indicated.39 Thyroid function studies should be obtained every 6 ~nurlths,and exogenous hormone should be administered if hypothyroidism develops. Subacute (de Quervain's) thyroiditis is caused by a viral infection and is very rarely seen in children. Physical findings include tender, painful swelling of the thyroid gland. Usually, there is mild thyrotoxicosis owing to injury to the thyroid follicles with leakage of thyroid hormone into the circulation. Radioactive iodine uptake is decreased, as a result of thyroid follicular cell dysfunction; this finding distinguishes subacute thyroiditis from Graves' disease. Histologically, granulomas and epithelioid cells may be seen. Treatment is symptomatic and generally consists of nonsteroidal anti-inflammatory agents or corticosteroids. The disease usually lasts 2 to 9 months, and complete recovery may be expected. Acute suppurative thyroiditis is caused by a bacterial infection of the gland, and the patient may have evidence of sepsis, with an acutely inflamed thyroid gland. Patients are usually euthyroid. The offending organisms are usually staphylococci or mixed aerobic and anaerobic flora. There may be a congenital pharyngeal sinus tract predisposing to infection. Treatment consists of antibiotics; if an abscess develops, incision and drainage may be necessary. The thyroid gland may be expected to recover completely.
Hyperthyroidism With rare exceptions, hyperthyroidism of childhood is caused by Graves' disease, which is also termed dqfuse toxic goiter Other possible causes of this condition are listed in Table 55-3. In these patients, the onset of the condition may be delayed until 2 to 3 weeks after birth.
CHAPTER
55
Graves' disease (toxic diffuse goiter) Toxic nodular goiter Subacute thyroiditis Chronic lymphocytic thyroiditis Neonatal thyroiditis Thyroid-secretinghormone-secreting pituitary tumor McCune-Albright syndrome Thyrotropin receptor mutation
Graves' disease occurs in girls about five times more often than in boys, and the incidence steadily increases throughout childhood, peaking in the adolescent years. The condition usually develops insidiously over several months, and initial symptoms include nervousness, emotional lability, and declining school performance. Later in the course of the disease there will be weight loss and increased sweating, palpitations, heat intolerance, and malaise. True exophthalmos is an unusual finding in children, but a conspicuous stare is common. The thyroid gland is smooth, firm, and nontender, and a goiter is evident on physical examination in over 95% of cases. A bruit may be heard on auscultation. Laboratory evaluation usually demonstrates elevated free Tqand a decreased TSH. In 10% to 20% of patients there is only elevation of T3, a condition known as Tg toxicosis. The diagnosis of Graves' disease is further supported by the presence of TSH-stimulating immunoglobulins. Graves' disease is an autoimmune disease caused by TSH receptor antibodies, which stimulate the thyroid follicles to increase iodide uptake and induce increased production and secretion of thyroid hormone. It has been suggested that the TSH-binding proteins are present in a number of gram-positive and gram-negative bacteria, and it is possible that infection with such organisms may elicit production of antibodies that cross-react with the TSH receptor.47An infectious cause of Graves' disease is further supported by some epidemiologic reports of disease c l ~ s t e r i n g . ~ ~ Graves' disease is currently managed by antithyroid medications, or the thyroid gland is ablated using either radioactive '"1 or surgical resection.ll Most pediatric endocrinologists initiate therapy with antithyroid medications, although there is increasing use of radioablation as the first line of treatment.Z6 The most commonly used antithyroid medications are methimazole or propylthiouracil (PTU), which reduce thyroid hormone production by inhibiting follicle cell organification of iodide and coupling of iodotyrosines. Methimazole is usually the preferred antithyroid medication because of its longer half-life and increased potency. The initial dose is 30 mg once daily, which should be reduced if the patient is younger than the usual adolescent. The TSH should be monitored carefully; rising levels signal overtreatment and may cause further increase in the goiter size. When the patient is euthyroid, as determined by normal Tg and Tq levels, the dose of methimazole should be reduced to 10 mg and maintained at a level to ensure normal thyroid hormone levels.
Surgical Diseases of the Thyroid and Parathyroid Glands
853
course of the drug. The onset of a sore throat with fevers should raise concern, and a neutrophil count should be obtained. Typically, the granulocyte count will rise 2 to 3 weeks after stopping the drug, but in rare cases, fatal opportunistic infections have been reported. Treatment with parenteral antibiotics during the recovery period has been recommended. Other adverse reactions to methimazole include nausea, minor skin reactions, urticaria, arthralgias, arthritis, and fevers. The length of medical treatment is controversial. Usually, treatment is continued for 3 to 4 years. Remission of Graves' disease is approximately 25% if medication is discontinued after 2 years of treatment, and the continuing remission rate is about 25% every 2 years. In most children, the remission of Graves' disease will occur within 6 months of discontinuing antithyroid therapy. The resolution rate is decreased in children who have persistent detection of TSH receptor antibodies during and after treatment. In patients with Graves' disease who do not respond to treatment with antithyroid medications, or if there is a severe reaction to the medication, then the thyroid gland must undergo definitive ablation. Current methods of definitively treating Graves' disease include either surgical resection or ablation with radioactive '3'1. Neither of these modalities is without complications. Whereas lSIItherapy is effective, and the disease remission rate is low, patients have a 50% to 80% incidence of long-term hypothyroidism after treatment.3 In some cases, larger doses of radioiodine have been administered to intentionally destroy the entire gland and to induce an easily managed state of permanent hypothyroidism.26 Recent studies demonstrate there is no scientific merit to concerns over the possibility of teratogenic or carcinogenic effects of 1311 therapy in these younger patient~.~,22 Surgical treatment may be occasionally recommended for pediatric patients with Graves' disease refractory to medical treatment. Subtotal thyroidectomy is the surgical procedure of choice for the treatment of Graves' disease and is appropriate treatment for patients who refuse radioiodine treatment or who fail medical management or if the thyroid is so large that there are symptoms related to compression. Patients should be rendered euthyroid with methimazole before undergoing surgery. Moreover, P-adrenergic blocking agents such as proprano101 may be used to ameliorate the adrenergic symptoms of hyperthyroidism. Finally, iodine in the form of Lugol's solution, 5 to 10 drops/day, should be administered for 4 to 7 days before surgery to reduce the vascularity of the gland. In large studies of adults treated with a subtotal thyroidectomy for Graves' disease, the rate of recurrent hyperthyroidism is 6% to 10% at 10 years' follow-up.3 Patients continue to relapse even later, and 30% of patients will exhibit recurrent hyperthyroidism 25 years after their subtotal thyroidectomy. * There is also a significant risk of permanent hypothyroidism in these patients, affecting approximately 5% of patients 1 year after surgery, increasing to as high as 50% of patients
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who are observed for 25 years. These findings demonstrate the importance of carefully observing such patients postoperatively to monitor thyroid status.
NEOPLASTIC THYROID CONDITIONS Thyroid Nodules Thyroid nodules are uncommon in children but can be the presenting finding in cases of thyroid cancer. In recent pediatric studies, the incidence of malignancy in This is a thyroid nodules has been 20% or less.2,8,16,53 much lower incidence of cancer than was reported in previous decades and probably reflects the decreased number of children whd have bken e x ~ o s e dto neck irradiation for trivial reasons. It is important to properly evaluate and manage these lesions, because the cancer may be at an easily curable stage. A summary of pathologic results from recent studies of children who underwent surgery for thyroid nodules is presented in Table 55-4. The differential diagnosis of solitary thyroid nodules is listed in Table 55-5. In most large pediatric series, females having nodules outnumber males approximately 2 to 1 ." The majority of patients will come to clinical attention because of the mass in their neck. A careful neck examination should be performed, with special attention directed to determine if there are enlarged cervical lymph nodes suspicious for locally advanced carcinoma. The serum TSH level should be measured to identify patients with unsuspected thyrotoxicosis resulting from an autonomously functioning nodule. Imaging studies are
No. of patients No. malignant (%) Histologic subtype Papillary Follicular Mixed Anaplastic Medullary No. benign (%) Diagnosis Thyroiditis Thyroglossal cyst Follicular adenoma Colloid nodule Branchial cyst Other
Yip et al., 1 9 9 4
Lafferty and Batch, 1 9 9 7
122 1 6 * (13)
52 1 7 (33)
12 3 0 0 0 1 0 6 (87)
7 7 0 0 3 35 (67)
17 0 26 57 0 6
1 2 16 2 0 14
L *One patient in this series had lymphoma of the thyroid gland. Data from Yip MIK, ReeveTS, Poole AG, Delbridge L: Thyroid nodules in childhood and adolescence. Aust NZJ Surg 1994;64:676-678;and Lafferty AR, Batch JA: Thyroid nodules in childhood and adolescence-thirty years of experience. J Pediatr Endocrinol Metab 1997:10:479-486.
Adenoma Carcinoma Thyroid cyst Ectopic thyroid gland Cystic hygroma Thyroglossal duct remnant Germ cell tumor
unreliable at distinguishing benign from malignant nodules. For example, malignant nodules may be either functioning or nonfunctioning on thyroid scintiscan. Ultrasonography is also nondiagnostic because malignant nodules may be either solid or cystic. Thus, such imaging studies should be interpreted carefully in the evaluation of thyroid nodules in pediatric patients. A therapeutic trial of exogenous thyroid hormone to induce nodule regression is not recommended. The use of FNA cytology to evaluate thyroid nodules is well established in adults, but the effectiveness of this technique is still being defined in children. Children are usually more difficult to evaluate than adults, owing to the smaller size of the nodules and the frequent need to sedate the child to allow safe and accurate aspiration. Moreover, the effectiveness of any diagnostic test is in part dependent on the pretest probability of a positive result. Because in young children there is a higher incidence of cancer in any thyroid nodule (when compared with adults), there is a slightly increased probability of a negative cytologic result that in fact may be associated with cancer. Such a false-negative cytologic result would delay the diagnosis and treatment of thyroid cancer. However, in light of the overall good clinical outcome in children with differentiated thyroid neoplasia, it must be acknowledged that such a delay will probably not result in any negative impact on survival. In adolescent patients, thyroid nodules may be safely evaluated with FNA. The pattern of thyroid disease in the adolescent age group is similar to that of adults, in whom the safety of FNA has been established. In one large series, the incidence of malignancy in thyroid nodules in patients from 13 to 18 years old was only 11%." In another study of 57 children with thyroid nodules evaluated by FNA, the incidence of malignancy was 18%.34There was one papillary carcinoma initially misdiagnosed as a benign lesion, which was eventually recognized as a malignancy with clinical follow-up. In another study of 57 children subjected to FNA for the evaluation of thyroid nodules, there was a similar incidence of cancer and 1 child initially had a false-negative FNA. In this case, the nodule was noted to increase in size over the ensuing 6 months, and excisional biopsy demonstrated the presence of Hiirthle cell carcinoma.20 Thus, these studies in mostly adolescent patients support the safety and effectiveness of FNA in this population. The results of FNA cytology either will indicate unequivocal cancer or a benign lesion or the diagnosis will be indeterminant for carcinoma. If the nodule is
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55
judged to be benign, then it can be followed with serial physical examinations and with ultrasound studies. Surgical resection should be performed if the nodule is malignant or indeterminant or if a benign nodule is shown to increase in size. Some endocrinologists suppress benign thyroid nodules with exogenous thyroid hormone, but this has not been shown to alter the natural history of such nodules. If a cystic lesion disappears after aspiration, then surgery may be deferred. The lesion should be removed if it recurs. Whereas cyst fluid may be sent for cytologic analysis, the sensitivity of this test is probably low for detecting the presence of cancer.25 In prepubertal children, there is increased difficulty in obtaining aspiration cytology and the pattern of benign disease is different than adults; thus, the natural history of these lesions is unknown and the safety of nonoperative treatment has not been demonstrated. Therefore, it is recommended that all thyroid nodules be removed in children younger than 13 years. Some surgeons obtain preoperative ultrasound examination and thyroid scintigraphy as an aid in determining the anatomy.16327 It cannot be overstated that if there is any question about the reliability of the cytologic evaluation, then excisional biopsy of all thyroid nodules irrespective of patient age should be performed.
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Recent research has elucidated some of the genetic events responsible for the neoplastic process in thyroid tumors. The RET proto-oncogene, a receptor tyrosine kinase molecule located on the 10th chromosome. is frequently rearranged in papillary cancers so that the intracellular portion of the gene is juxtaposed to one of several ubiquitously expressed genes. The fusion genes are termed RET/PTC and exhibit increased expression of the tyrosine kinase activity of the molecule. These genetic rearrangements involving RET are especially frequent in radiation-induced thyroid tumors. After the Chernobyl accident, children from Belarus with thyroid cancer were found to exhibit RET fusion genes in over 62% of cases." In some studies, the particular RETfusion gene combination has been correlated with particular histologic subtypes.41 The RET proto-oncogene is also important in the development of medullary thyroid carcinoma (MTC), and various mutations in RET are associated with the multiple endocrine neoplasia type 2 syndromes (MEN 2A, MEN 2B) and familial medullary thyroid carcinoma (FMTC). MTC is usually the first tumor to develop in these patients. Moreover, as many as 40% of patients with sporadic nonfamilial MTCs possess RE7'mutations.lO The RET mutations in the susceptible tissues perturb the intracellular signaling pathways to alter the proliferation or differentiation of the neural crest-derived tissues involved in the MEN 2 syndromes. Thyroid Carcinoma Carcinoma of the thyroid gland typically presents Carcinoma of the thyroid gland is relatively unusual in clinically as a thyroid mass, as enlarged cervical lymph children, and population-based studies in Wales and Los nodes, or with both of these findings. In one large clinical study of thyroid carcinoma in-children, the more Angeles demonstrate that the yearly incidence of thyroid recently diagnosed patients were somewhat less likely to carcinoma is between 1 and 2 cases per million individuals have enlarged regional lymph nodes at their initial presyounger than 20 years of age.l42" This represents only entation.'" compilation of the clinical aspects of several about 3% of all pediatric malignancies. The peak incirecent, large clinical series of pediatric patients with difdence of thyroid cancer in children occurs between 10 and ferentiated thyroid carcinoma is presented in Table 55-6. 18 years of age, and girls usually outnumber boys 2 to 1. Approximately 10% of all malignant thyroid tumors The pathologic diagnosis can be established either using FNA cytology or by frozen-section analysis of a biopsy occur in children. The incidence of thyroid tumors in specimen at the time of surgery. Recent studies have children has decreased over the past 2 decades owing to the reduced use of radiation to treat benign diseases. suggested that frozen-section analysis is less accurate in The importance of radiation as a cause of thyroid cancer evaluating follicular lesions. As shown in Table 55-6, was recently reemphasized by the marked increase of most of these patients will have papillary thyroid carcinoma. Before surgery, most children should have a such tumors noted in the Republic of Belarus following the 1986 Chernobyl nuclear power plant ~atastrophe.2"~~ thyroid scan, to determine if the thyroid mass contains The latency period for the development of thyroid functioning thyroid tissue. Some investigators also reccancer after radiation exposure is 4 to 6 years, and in ommend an ultrasound study to determine if the lesion the Belarus population there was a 62-fold increase in is cystic and to serve as a guide during the surgical procedure.z7 Because of the relatively high incidence thyroid tumor incidence after the Chernobyl accident. of pulmonary metastasis in children having thyroid Thyroid carcinoma also occurs at an increased incidence carcinoma, preoperative chest radiography or computed after treatment for a previous childhood malignancy. In tomography should be performed. one study, thyroid cancers constituted about 9% of second The surgical management of thyroid cancer in children malignancies occurring after treatment for childhood t~mors.~Wodgkin's lymphoma is the most common first is controversial, because there have been no prospective malignancy associated with the subsequent development clinical trials comparing more aggressive to less extensive of thyroid cancer, and most thyroid neoplasms follow the surgical management options. As show11in Table 55-6, the long-term outcome is usually excellent, irrespective of the previous use of radiation to the neck, but alkylating agents particular surgcal procedure employed. surgeons argualone also predispose to thyroid cancer. The median interval ing in favor of aggressive thyroid resections hold that total from radiation therapy to the recognition of thyroid disthyroidectomy, with lymph node dissection if the regional ease is about 12 years,l underscoring the importance of careful surveillance for second tumors in children who nodes are involved with cancer, is the most successful have been successfully treated for cancer. method of obtaining local control of the tumor.jJ3328.4'
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metastases, use of 1311radiotherapy in the initial management, or the antecedent exposure to radiation.Y8 On balance, it appears that tumor factors may be more important than treatment factors in determining the clinical outcome in children having differentiated thyroid Total number of patients cancer. Mean age Therefore, in the absence of controlled prospective Percent female trials, it is difficult to make firm recommendations regardHistology ing the surgical management of differentiated thyroid Papillary Follicular cancer in children. However, a consensus is emerging Medullary that more aggressive resections are preferred.I7 Surgeons Other and pediatric endocrinologists increasingly recommend % With metastasis either total or near-total thyroidectomy, followed by '"1 Surgical procedure remnant ablation in conjunction with long-term suppres178 Total thyroidectomy sive thyroxine therapy. A modified neck dissection Subtotal thyroidectomy 55 should be performed to remove as much gross disease as Lobectomy or other 96 possible if there are large lymph nodes suggestive of the Lymph node procedure 255 presence of regional metastasis. In patients with locally % Receiving radiotherapy 43 advanced disease, it is especially important to remove as Median follow-up (yr) 11.3 much of the thyroid gland as possible to allow subsequent 0.7 Cancer mortality (%) scanning and re-treatment with radioiodine as necessitated by tumor recurrence. Tumors involving the recurData from Newman KD, BlackT, Heller G, et al: Differentiatedthyroid cancer: rent laryngeal nerve should not be aggressively resected Determinantsof disease progression in patients 70 mm Hg) should be managed by changing ventilator strategy.
Ventilation The type of mechanical ventilator needed for the infant with a CDH is a matter of personal and institutional preference. Most infants can be successfully managed with a simple pressure-cycle ventilator using a combination of high rates (100 breaths per minute) and modest peak airway pressures (18 to 22 cm H 2 0 and no positive end-expiratory pressure [PEEP]) or 'rower rates (20 to 40 breaths per minute) and higher pressures (22 to 35 cm H 2 0 , 3 to 5 cm PEEP). The goal of such ventilatory support is to maintain minute ventilation while obtaining a preductal Po2greater than 60 mm Hg (Sao, 90% to 100%) with a corresponding Pco2 of less than 60 mm Hg.
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pH and Pco2 levels have been shown to be important in modifying pulmonary vascular t0ne.2~~ The successful clinical manipulation of these parameters in therapeutic interventions in neonates with persistent pulmonary hypertension represents an initial treatment strategy86 It is now clear, however, that the extremes of hyperventilation with induced alkalosis should be avoided because such therapy compounds the pulmonary problems with serious iatrogenic injury.I62A respiratory strategy based on permissive hypercapnea and spontaneous respiration has proven to be quite successful.31 If conventional mechanical ventilatory techniques cannot reverse the hypoxemia or hypercarbia, high-frequency techniques using an oscillating ventilator may be required. This technique may be effective in removing carbon dioxide and temporarily stabilizing an infant in severe respiratory distress. When such techniques have been used as initial therapy, survival results have been quite
Pharmacology A broad spectrum of drugs and antihypertensive agents has been used in attempts to modify the pulmonary vascular resistance in infants with CDH and respiratory failure. Experience has been extrapolated from clinical trials of infants with persistent pulmonary hypertension of the newborn (PPHN) and other forms of neonatal respiratory failure. In the past, agents such as tolazoline, which exerts its effects through a-receptor blockade, had been utilized to lower pulmonary vascular resistance in the face of ~ , 2efficacy ~~ in hypoxemia and respiratory f a i l ~ r e . 2 ~ Its CDH infants was marginal. Other drugs, such as nitroprusside, isoproterenol, nitroglycerin, and captopril, have not been effective.38 The administration of various prostaglandin derivatives, including prostaglandin D2 (PGD2), prostaglandin El (PGEI), and prostacyclin, and of the cyclooxygenase inhibitor indomethacin has also been disapp~inting.~~~~'~~ New management strategies for treating persistent pulmonary hypertension now undergoing clinical evaluation include various calcium channel blockers, prostacyclin derivatives, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors such as sildenafil.92,240
Surfactant Animal models have demonstrated that experimentally induced CDH lungs are surfactant deficient, but such results have not been replicated in human studies. Early reports in infants with CDH demonstrated alterations in ~ , 3 ~ ~ recent surfactant levels and ~ o m p o s i t i o n . 2 ~However, studies have indicated that the surfactant pool in infants with CDH is no different than control patients even in ~ J ~ ~may be infants requiring ECMO s ~ p p o r t . " J ~There alterations in synthetic and metabolic kinetics for individual components.53 In terms of improving respiratory function and outcomes, clinical and experimental investigations with surfactant administration have been mi~ed."J08J~~~2~6 A multicenter review of surfactant administration in CDH patients showed no overall benefit to its use and demonstrated a lower survival rate in
preterm infants compared to full-term infants.178At this time, there are no clinical data to support the administration of surfactant in the management of CDH infants.
Nitric Oxide NO is a potent mediator of vasodilatation and was originally identified as endothelialderived relaxing factor.145,289 Because it is a highly diffusible gas that is rapidly inactivated by binding to hemoglobin, it is particularly suited for administration to the pulmonary vasculature with mechanical ventilatory techniques. In clinical studies, NO was effective in improving oxygen saturation levels in In an neonates with respiratory failure due to PPHN.169,247 animal model of PPHN, NO decreased pulmonary artery pressures and increased arterial oxygen saturation without discernable side effects.lo3 Unfortunately, its effects in CDH infants with respiratory failure have been m i ~ e d . l , 8 0 , ~ ~ There , ~ ~ ~ , ~are 6 7 no data to show that NO administration improves survival or decreases the requirement for ECMO.97 The variable physiologic response to NO in these infants may be related to the method of its administration.155 NO administered through a nasal cannula has been utilized for the treatment of late pulmonary hypertension following extubation.'@ The exact role of NO in the treatment of pulmonary hypertension and respiratory failure in CDH infants has not been defined despite its widespread use.
Surgical Management Timing of Surgical Repair Historically, CDH was considered a surgical emergency. Infants were rushed to the operating room as soon as possible after birth in the belief that reduction of the abdominal contents from the chest would relieve the compression of the lungs. Frequently, after a brief postoperative honeymoon period marked by adequate gas exchange, progressive deterioration in the infant's respiratory status ensued with elevated pulmonary vascular resistance, right-to-left shunting, hypoxemia, and ultimately death due to respiratory failure. As management techniques for neonatal respiratory failure evolved, a period of medical stabilization and delayed surgical repair in an attempt to improve the overall condition of the infant with CDH was proposed.26-181 At the same time there was increasing evidence of the potential detrimental effects of early surgical repair on respiratory function.'" Since then, multiple single institutional studies have reported improved survival rates with delayed surgery as part of their treatment protocols, whereas others have found no changes in overall outcome.* Importantly, no study has shown a decrease in survival rates with this technique. Although-delayedsurgical repair is now widely practiced, there is no statistical evidence that supports this approach over immediate repair at this time.fl4
*See references 6, 31, 40, 48, 101, 109, 127, 224, 241, 246, 260, 313, and 320.
CHAPTER
The optimal timing of operative repair when employing a strategy of delayed repair also remains undetermined. The period of preoperative stabilization has varied from Some authors several days to several ~eeks.~O,22~,2~6,323 have reported waiting until the infant is successfully weaning off of mechanical ventilation and requiring low ventilator settings. Others follow the severity of pulmonary hypertension with serial echocardiographic examinations and wait until the hypertension has abated or at least s t a b i l i ~ e d . ~ ~ , l 2 ~
Operative Repair Most surgeons approach the defect through a subcostal incision, although the repair can be done through a thoracotomy incision as well. For rare cases in which
60
Congenital Diaphragmatic Hernia and Eventration
941
reduction of the herniated contents is difficult because of an abnormally shaped liver or spleen, a combined approach can be used. Both thoracoscopic and laparoscopic techniques have been used to repair these defects.21,1738228,245,259,324 Ideallv suited for older infants with delayed presentation, minimally invasive techniques may have a higher incidence of technical and physiologic consequences in the n e ~ b o r n . ~ ~ f t i rdivision of the abdominal wall muscles and entrance into the abdominal cavity, the viscera are gently reduced from the defect and completely eviscerated for adequate visualization. The spleen dn the' left side and the liver on the right " are usually the last organs to be mobi~ . k).Mobilization lized from the chest cavity i ~ i 60-5A, can be difficult and must be done without injury to either organ. On the right side, the kidney and adrenal gland
A, Schematic drawing of an unreduced left congenital diaphragmatic hernia as seen from the abdomen. B, The same hernia but now reduced, demonstrating that the spleen is usually the last organ to be reduced from the chest cavity. Sutures have been placed for a primary repair. C, Completed primary repair of a left congenital diaphragmatic hernia. D, Repaired left congenital diaphragmatic hernia using prosthetic material. (From Spitz L, Coran AG (eds):Rob & Smith's Pediatric Surgery. London, Chapman & Hall, 1996.)
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may be found in the chest as well. Abnormal drainage of the hepatic veins on either side may complicate mobilization of the liver. Once the abdominal contents are reduced, the defect in the diaphragm in the posterolateral position can be examined. In 20% of patients, a hernia sac formed by parietal pleura and peritoneum is present and must be excised to minimize chances of recurrence.237 Usually, there is an anterior rim of diaphragm of varylng size. The posterior rim of diaphragm must be searched for in the retroperitoneal tissue, because it may be rolled up like a window shade by the peritoneum. The peritoneum must be opened over this fold and the diaphragmatic tissue mobilized. When tissue is adequate, a primary repair with interrupted nonabsorbable suture material can be performed (see Fig. 60-5C). In some cases, the posterior rim of tissue may disappear along the lateral chest wall. If enough diaphragmatic tissue exists anteriorly, it can be sutured directly to the body wall with sutures placed around the ribs. If the defect is too large to be closed in a primary fashion, a number of reconstructive techniques have been described using various nearby stxuctures,such as prerenal fascia, rib structures, and various thoracic and abdominal wall muscle flaps.22,1",255,266,304,310 If there is any chance that ECMO support might be required in the management of the infant, however, the use of complex reconstructive techniques requiring extensive tissue dissection is contraindicated because of the risk of bleeding. The use of prosthetic material to complete the diaphragmatic closure has gained widespread acceptance (see Fig. 60-5D). A floppy, tension-free diaphragmatic repair can be accomplished that may lessen the degree of intra-abdominal pressure when closing the abdominal wall.19 Besides the risk of infection, the major drawback to using a prosthetic patch closure is the risk of dislodgment and subsequent reherniation." Complications of prosthetic patch repair occur in approximately 10% to almost 50% of cases. Patients who develop a recurrent hernia present with bowel obstruction or respiratory distress or may be a~ymptomatic.~~,2~~ With the loss of intra-abdominal domain, abdominal wall closure may not be possible at all or may result in unacceptable intra-abdominal pressure (i.e., abdominal compartment syndrome) even after extensively stretching the abdominal wall. In these situations, simple closure of the skin can be accomplished with repair of the resultant ventral wall defect some months later. If the skin cannot be closed successfully, temporary closure using prosthetic material such as a silo can be used. Biologic closure should then be obtained as soon as safely possible in the postoperative period. Drainage of the chest cavity on the repaired side with a tube thoracostomy is not indicated except for active bleeding or uncontrolled air leak. It has been proposed that such a tube with even a small degree of negative suction may add to the barotrauma and pulmonary hypertension imposed by mechanical ventilation on a hypoplastic lung.a3 Additional surgical procedures at the time of the repair such as correction of the nonrotation as well as appendectomy are not indicated and should be avoided if ECMO is to be considered.
The repair of recurrent defects can present a formidable surg&il challenge. Since the most common organ involved in recurrent herniation is either the small or large bowel, intestinal adhesions to the disrupted diaphragm or intrathoracic organs may compromise attempted closure. Repair is most commonly approached through the abdomen but can be accomplished through a thoracotomy as well. If adequate diaphragmatic tissue is present, then primary reapproximation should be attempted. Otherwise, different techniques for mesh insertion have been tried.68,24a2254
Anesthesia To avoid the stresses of transport and sudden changes in ventilation parameters imposed by a trip to the operating room, a number of centers have adopted the policy of performing surgical repair of CDH infants in the neonatal intensive care unit. This change in location allows for the lowest degree of disruption in the neonate's environment. Anesthesia is achieved by intravenous narcotic and muscle relaxant techniques. With intravenous anesthetics, the infant ventilator can be used continuously rather than a conventional anesthesia machine.
Postoperative Management Postoperative management should continue the trends and goals established before the operative procedure. Ventilator support should be tailored to keep preductal Po2 levels at least above 80 mm Hg and Pco2 levels less than 30 to 35 mm Hg. Echocardiograms should be obtained routinely to assess pulmonary hypertension, shunt flow, and ventricular performance. Therapeutic interventions discussed previously may be employed if respiratory decompensation develops. Weaning from ventilator support should be slow and deliberate as tolerated by the infant. Meticulous attention to fluid status must be maintained, particularly in the immediate postoperative period. As a result of surgical intervention, these infants are often hypovolemic and frequently require extra volume administration over time.
Extracorporeal Membrane Oxygenation Even with recent advancements in treatment strategies, overwhelming respiratory failure requiring ECMO support occurs in 15% to 45% of CDH infants.l4~"7.*~*41 Initially, infants were placed on ECMO after developing respiratory failure following the immediate repair of the diaphragmatic defect. With the evolution of delayed surgical repair, ECMO is now considered a part of the preoperative stabilization process. Clinical criteria for determining ECMO *usein infants with CDH have been based on factors predictive of at least an 80% mortality rate with mechanical ventilation. A number of parameters have been proposed, including the calculation of the oxygenation index (01) and the alveolar-arterial oxygen difference [ (A - a) DO^]. For CDH
CHAPTER
60
patients the most common reason for the initiation of ECMO was an 0 1 of 40 or greater, and it is often considered for an OI as low as 25." Generally accepted criteria for initiating ECMO support for neonatal respiratory failure based on [ (A - a)DO,] criteria include a value of 610 or greater despite 8 hours of maximal medical management. It must be realized that such criteria continue to be institutional specific and that no calculations can replace clinical judgment and frequent bedside assessment. Failure to improve in the setting of severe pulmonary hypertension and progressive hypoxemia despite maximum medical intervention remains a valid qualifying criterion for ECMO support. Controversy still exists as to whether ECMO support should be offered to all infants with CDH and respiratory failure. The issue of severe pulmonary hypoplasia incompatible with life must be kept in mind when ECMO is being" considered. This intervention is successful when used to support an infant with a reversible process of pulmonary hypertension. However, it is not a treatment for those infants with irreversible hypoplasia. Differentiating these infants on clinical parameters can be quite difficult. A newborn with a CDH who is unable to reach a preductal oxygen saturation level of at least 90% or a markedly ~ unresponsive to any type of ventilaelevated P C Olevel tory intervention during the pre-ECMO course has a high likelihood of having irreversible hypopla~ia.2~Wn the other hand, others have proposed that all infants should be ECMO candidates. Although widely accepted as a treatment for the respiratory failure associated with CDH, the impact of ECMO on improving overall survival continues to be debated. Over the past decade a number of studies have demonstrated improved survival rates in CDH infants with ECMO However, other as part of the treatment ~trategy.57J0~23~2 institutions have either not noted any improvements resulting from ECMO or have been able to manage their . ~ ~ sur~ ~ ~ infants without it with equivalent s ~ c c e s sOverall vival rates of infants treated with ECMO vary from 34% to 87% and are clearly, dependent on a number of variables, including gestational age and birth weight, respiratory function, and the degree of pulmonary development As and associated pulmonary hyperten~ion."~~~,l65,185,276 conventional treatment strategies continue to improve, ECMO utilization and concomitant survival rates may decrease.14 A number of surgical issues are involved in the management of CDH infants while on ECMO. Both venovenous and venoarterial techniques have been reported to be equally effective in supporting patients while on bypass.82J7* With venovenous bypass, severe right-sided heart failure can be managed temporarily with a PGEl infusion to keep the ductus open until the pulmonary hypertension resolves or by converting to venoarterial support. The timing of the surgical repair of the defect in relation to ECMO support remains variable. As a result of the acceptance of delayed surgical repair as a treatment strategy, more than 90% of CDH infants requiring ECMO support are placed on bypass before undergoing surgical repair.I8O Surgical repair of the defect while on ECMO can then be accomplished but has been associated with hemorrhagic L
Congenital Diaphragmatic Hernia and Eventration
943
complications in 60% of the patient~.I7"~~' Survival rates after surgery on ECMO have varied from 43% to 80%.M23132316 TO minimize the risk of hemorrhagic complications a number of techniques have been proposed, including the use of heparin-bonded ECMO circuits, performance of the surgical repair just before expected decannulation, and aggressive management of the anticoagulant status of the infant, including the use of antifibrinolytic therapy. Because of the coagulation problems, less than 20% of infants are reportedly repaired while on ECM0.51 The majority undergo repair after the completion of ECMO. This delayed operative approach sometimes not occurring until several days after decannulation has been extremely successful,with survival rates of almost 80% and higher.I,81,26However,there are currently no acceptable studies comparing either pathway.
Outcome Survival rates (discharge to home) for infants born with an isolated CDH have improved dramatically over the past decade when compared with the historical values of Survival rates as high as approximately 50%.3,11"1",261,319 80% to 93% are being reached with current treatment modalities.7~31,85,182,308 Nevertheless, variation in survival rates remains high, representing significant institutional differences in management strategies and patient accrua1.1*,275Further complicating t h e interpretation of most studies has been the continued evolution of respiratory care and medical treatment strategies. In addition, the presence of associated anomalies such as congenital heart disease remains a significant risk factor for a poor outcome in these infants."J5*Zm With improved overall survival rates, a greater number of physiologically compromised infants are surviving beyond the neonatal period, and late death in approximately 10% of initial survivors been reported mostly due to the consequences of ~has ~ ~ persistent pulmonary hypertension or iatrogenic complications.1503248.257 Before the widespread use of ECMO and newer treatment modalities, long-term survivors of conventional mechanical ventilation were reportedly healthy and withStudies out clinically evident respiratory di~ease.l~J02.24' have now shown that CDH survivors may be at risk for a number of long-term morbidities such as chronic pulmonary growth failure, neurodevelopmental delay, gastrointestinal problems, and orthopedic issues. The probability of respiratory, nutritional, and musculoskeletal morbidity is higher in CDH infants treated with ECM0.50 Pulmonary issues are by far the most common longterm problems in infants surviving beyond the neonatal period. Pulmonary developmental studies have shown that alveolar multiplication continues for several years after birth. A normal number, howeveq is never achieved in CDH hypoplastic lungs. Over time the alveoli become emphysematous, and there is gradual remodeling of the pulmonary bed.2~mphysematouschanges may affect both lung fields, because the contralateral lung may herniate across the mediastinum. Studies have shown
944
PART
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that even in infants with severe respiratory distress in the neonatal period lung volume will increase with time. However, pulmonary blood flow remains significantly decreased compared with the contralateral side, suggesting that vascular growth in severe cases does not match alveolar growth.217 Pulmonary function tests have been most useful in managing long-term survivors, because chest radiographs and ventilation-perfusion studies are almost always abnormal and therefore have had little influence on medical therapy. Although a number of infants may demonstrate compromised compliance early in their course, serial pulmonary function testing has demonstrated improved compliance over time associated with real lung growth.172 In long-term studies of survivors, many had normal pulmonary function tests In 30% to 50% of even with exercise testing.202,215,300.3'2 survivors there may be either obstructive or restrictive Increased bronchial hyperventilatory irnpairments.215~242~ reactivity has also been noted.l46,269 Treatment strategies for these patients have included the use of supplemental oxygen, bronchodilator therapy, corticosteroids, and diuretics. Clinically, chronic lung disease has been reported in CDH survivors, particularly in those requiring ECM0.63,'96,215 Whether this finding is related to the pathology of the disease or has been induced iatrogenically Regardless, ~~ owing to techniques of ventilation is ~ n c l e a r . 2 prolonged elevation in pulmonary artery pressure whether it results from pulmonary hypoplasia or bronchopulmonary dysplasia impacts long-term survival. Pulmonary artery pressures normalize in approximately 50% of all patients by 3 weeks of age but can remain elevated for months in as many as one third of surviving infants.81J48,258 This morbidity improves over time, and most survivors lead unaffected lives.172Jg" Studies have identified a number of nonpulmonary morbidities in CDH survivors with neurodevelopmental abnormalities being the most common. Developmental delay has been reported in a number of surviving infants.196 Abnormalities in both motor and cognitive skills have been identified.'j32279 Other neurologic problems reported include visual disturbances, hearing loss, seizures, abnormal cranial computed tomography (CT) and MRI, and abnormal electroencephalographic studies.63J43J96 Most studies have implicated ECMO as a factor in these neurologic problems, but CDH survivors treated without ECMO are also at ri~k.~,~"204,239 A high incidence of gastroesophageal reflux and foregut dysmotility has been found in CDH survivors (Fig. 60-6).63,93J961281,299Most infants have been managed with feeding regimen manipulations and prokinetic agents. Antireflux procedures have been reserved for medically unresponsive patients or those requiring gastrostomy tube placement for feeding purposes. Nutritional and growth-related problems have been found in a significant number of these survivors as we11.20 Long-term surveillance and aggressive nutritional management are required for these infants. Worrisome anecdotal reports are beginning to appear describing Barrett's esophagitis and chronic lung disease secondary to chronic gastroesophageal reflux.
Barium sulfate esophagogram in an infant with a left congenital diaphragmatic hernia demonstrating a dilated, ectatic esophagus. The stomach was oriented vertically and emptied slowly.
A number of skeletal disorders have been reworted. including chest wall defects (pectus anomalies) and s ~ o l i o s i s . ~ ~Treatment ,2~~,2~~ of these problems has included initial attempts at bracing followed by surgical correction. As interventional therapies have evolved, a new group of survivors has emerged with different patterns of longterm morbidities. Sicker infants who are physiologically compromised to varylng degrees are surviving in greater numbers. Resource management for these infants in the " future will be crucial as we attempt to determine and justify the impact of treatment strategies on survival rates and quality of life.z3l
Future Therapies Despite the advancements that have been made in treating infants with CDH, it still represents a frustrating and complex clinical problem. As the striking variance in survival rates attests, no currently employed therapeutic intervention or management strategy has emerged for widespread successful application. Even with the increasing success of current treatment strategies such as permissive hypercapnia, delayed operative repair, antihypertensive pharmacology, and advanced ventilatory techniques, a cohort of infants refractory to these interventions continue to be candidates for novel treatments. The concept of fetal surgical intervention evolved from the experimental observation in lambs that reduction of compressive forces on the lung resulted in continued pulmonary growth and development.2J1sAlthough technically and theoretically exciting, the clinical .trial of fetal diaphragmatic repair was disappointing.117 Significant problems were encountered with patient seleciion and- postoperative maternal management. A direct extension of these attempts at in utero repair was the observation that tracheal ligation accelerated
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CHAPTER
fetal lung growth and reversed the alveolar hypoplasia and abnormal pulmonary vascular pattern in fetal lamb Tracheal occlusion and rat models of CDH.77,78,171,315 or PLUG therapy (plug the lung until it grows) resulted in improved oxygenation and ventilation after birth when compared with untreated control animals.130 These observations ultimately led to a randomized, clinical trial comparing fetal endoscopic tracheal occlusion to current standard postnatal care for severe congenital diaphragmatic hernia.122 Fetuses qualified for enrollment if they were between 22 and 27 weeks' gestational age and had liver herniated into the left chest with an LHR below 1.4. The 90-day survival rate for the tracheal occlusion group was 73%, and it was 77% for the control group. Because there was no difference in survival between the two groups, the study was closed after 24 patients were treated. Nonetheless, there are reports of continued application of this intervention in European centers.72 Future research will determine whether fetal intervention has a role in the treatment of CDH. Liquid ventilation techniques have been attempted in CDH infants while on ECMO (Fig. 60-7).233 After perfluorocarbon administration, significant increases were reported in Pao, levels and in static total pulmonary compliance measurements accompanied by a fall in Pace, levels. No adverse side effects were noted. Extensive studies are required to examine this newest form of ventilation before its efficacy can be judged. Based on the observations of fetal lung growth induced by tracheal occlusion, inducement of postnatal lung growth with static distention has also been investigated. During the course of the liquid ventilation experiments, pulmonary distention as a result of perfluorocarbon
60
Congenital Diaphragmatic Hernia and Eventration
945
administration was observed. Its use as a potential treatH ment to induce postnatal lung growth ~ ~ - C Dpatients was then reported.94,135f303 Preliminary studies have shown significant radiographic enlargement of the lung and improved gas exchange. The same results have also been achieved using intra-alveolar albumin admini~tration.673~75 Further study of this potential intervention is required. Lung transplantation has also been used anecdotally in the surgical treatment of CDH.ls4,zg7Both unilateral and bilateral transplants have been attempted. Currently, not enough experience exists to recommend this form of treatment. The potential role of pharmacologic augmentation of pulmonary growth and development is currently being investigated. The combined administration of thyrotropinreleasing hormone and glucocorticoid therapy has been studied in a chemically induced rat model of CDH, It is also known with positive effects on lung gro~th.2~3 that a number of growth factors are crucial to normal pulmonary development. It has been proposed that perhaps selected administration of one or several of these pharmacologic agents or growth factors may be able to reverse the pulmonary hypoplasia of CDH.3g-z83 Continued experimental work using the nitrofen model of CDH may uncover new candidates to promote lung growth and development either prenatally or after birth. - Finally, given the current wide-ranging survival rates at various institutions, an in-depth study and evaluation of current management techniques and outcomes must be made. The efforts of the CDH Study Group to interpret very hetereogeneous data is an encouraging beginning. Such a study might result in the refinement and consolidation of current practices into a universally effective treatment strategy.
FORAMEN OF MORGAGNI HERNIA
Chest radiograph of a left congenital diaphragmatic hernia being supported with extracorporeal membrane oxygenation. The lungs have been opacified with perflubron for liquid ventilation. The pulmonary hypoplasia can be appreciated. (Courtesy of R. B. Hirschl, MD.)
The anterior diaphragmatic hernia of Morgagni is located anteromedially on either side of the junction of the septum transversum and the thoracic wall. The defect occurs through the embryologic space of Larrey. Occasionally, bilateral Morgagni hernias communicate in the midline, constituting a large anterior diaphragmatic defect extending all the way across the midline from right to left. Typically a sac is present, and herniation of the colon or small bowel is usually discovered to the right or left of the midline. Morgagni hernias account for less than 2% of diaphragmatic defects. Although this defect may be observed in neonates, it usually presents more commonly in older children or adults. Associated anomalies may be present and include malrotation. An anterior midline deficiency in the diaphragm with or without the other elements of the pentalogy of Cantrell with free pericardial and peritoneal communication may allow herniation of intestine into the pericardium. The hernia is often discovered incidentally as a mass or airfluid level on a chest radiograph. A barium enema or a CT scan may confirm the diagnosis. Operative correction is easily performed through an upper transverse abdominal incision. The diaphragm is
946
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sutured to the underside of the posterior rectus sheath at the costal margin after reduction of the hernia and resection of the sac. Laparoscopic and thoracoscopic techniques have also been used to repair this defect.70~144,191,221
EVENTRATION OF THE DIAPHRAGM Eventration of the diaphragm may be either congenital or acquired. The congenital form may be indistinguishable from a diaphragmatic hernia with a sac, and symptoms are usually similar. The acquired lesion is probably due to paralysis of the phrenic nerve that may occur from injury during repair of congenital heart defects, and some of the so-called congenital forms may be acquired through birth injury (Erb's palsy). The diaphragmatic muscle is usually present in its normal distribution, but it is attenuated and inactive. If a rim of diaphragm is present with a central defect to cover the pleural and peritoneal membrane, the lesion is probably a diaphragmatic hernia, although such a distinction may be moot. There may be no symptoms whatsoever even in the presence of a large eventration, although the findings may range from wheezing, frequent respiratory infections, and exercise intolerance to extreme respiratory distress. Diagnosis is usually made on fluoroscopy of the chest. In such cases, the diaphragm moves paradoxically with respiratory motion. This paradoxic movement may be so marked that it results in severe compromise of gas exchange. Although pneumoperitoneum was used frequently in the past, CT or MRI is used more often today. A small eventration may be left untreated. Repair is indicated when a large functional deficit in the function of the ipsilateral lung on ventilation/perfusion studies is found in an apparently asymptomatic patient. In such cases, the compressed lung will not grow well. For the same reason, a large eventration should be repaired even when asympte matic. Repair may be performed either through the abdomen or the chest, but, in most cases, a low thoracotomy is recommended. Through this approach the diaphragm is best plicated with nonabsorbable interrupted 2-0 sutures. A radial or peripheral incision may also be made in the diaphragm and the edges overlapped and sutured. It is important to reef up and overlap the diaphragm so that it is taut, overcorrecting it somewhat, because invariably the muscle will stretch and the eventration will recur if this is not done. Diaphragmatic plication for acquired eventration is frequently necessary to wean infants from ventilatory support. Plication can also be accomplished by either a laparocoscopic or thoracoscopic approach.
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286. Taira Y, Yamataka T, Miyazaki E, et al: Comparison of the pulmonary vasculature in newborn and stillborns with congenital diaphragmatic hernia. Pediatr Surg Int 1998;14:30. 287. Thebaud B, Azancot A, de Lagausie P, et al: Congenital diaphragmatic hernia: Antenatal prognostic factors. Does cardiac ventricular disproportion in utero predict outcome and pulmonary hypoplasia? Intensive Care Med 1997;23:10062. 288. Thibeault DW, Olsen SL, Truog WE, Hubbell MM: PreECMO predictors of nonsurvival in congenital diaphragmatic hernia. J Perinatol 2002;22:682. 289. Thorpe-Beeston JG, Gosden CM, Nicolaides KH: Prenatal diagnosis of congenital diaphragmatic hernia: Associated malformations and chromosomal defects. Fetal Ther 1989;4:21. 290. Thurlbeck WM: Postnatal human lung growth. Thorax 1982;37:564. 291. Touloukian RJ, Markowitz RI:A preoperative x-ray scoring system for risk assessment of newborns with congenital diaphragmatic hernia. J Pediatr Surg 1984;19:252. 292. Tracy TFJr, Bailey PV, Sadiq F, et al: Predictive capabilities of preoperative and postoperative pulmonary function tests in delayed repair of congenital diaphragmatic hernia. J Pediatr Surg 1994;29:265. 293. Turner GR, Levin DL: Prostaglandin synthesis inhibition in persistent pulmonary hypertension of the newborn. Clin Perinatol 1984;11:581. 294. Unger S, Copland I, Tibboel D, et al: Down-regulation of sonic hedgehog expression in pulmonary hypoplasia is associated with congenital diaphragmatic hernia. Am J Path01 2003;162:547. 295. Vacanti JP, Crone RK, Murphy JD, et al: The pulmonary hemodynamic response to perioperative anesthesia in the treatment of high-risk infants with congenital diaphragmatic hernia. J Pediatr Surg 1984;19:672. 296. van Dooren ME, Brooks AS, Tibboel D, et al: Association of congenital diaphragmatic hernia with limb-reduction defects. Birth Defects Res A Clin Mol Teratol2003;67:578. 297. Van Meurs KP, Rhine WD, Benitz WE, et al: Lobar lung transplantation as a treatment for congenital diaphragmatic hernia. J Pediatr Surg 1994;29:1557. 298. Vanamo K, Peltonen J, Rintala R, et al: Chest wall and spinal deformities in adults with congenital diaphragmatic defects. J Pediatr Surg 1996;31:851. 299. Vanamo K, Rintala RJ, Lindahl H, et al: Long-term gastrointestinal morbidity in patients with congenital diaphragmatic defects. J Pediatr Surg 1996;31:551. 300. Vanamo K, Rintala R, Sovijarvi A, et al: Long-term pulmonary sequelae in survivors of congenital diaphragmatic defects. J Pediatr Surg 1996;31:1096. 301. Vazquez WD, Cheu HW: Hemorrhagic complications and repair of congenital diaphragmatic hernias: Does timing of the repair make a difference? Data from the Extracorporeal Life Support Organization. J Pediatr Surg 1994;29:1002. 302. von Staak FH, de Haan AF, Geven WB, et al: Improving survival for patients with high-risk congenital diaphragmatic hernia by using extracorporeal membrane oxygenation. J Pediatr Surg 1995;30:1463. 303. Walker GM, Kasem KF, O'Toole SJ, et al: Early perfluorodecalin lung distension in infant? with congenital diaphragmatic hernia. J Pediatr Surg 2003;38:17. 304. Wallace CA, Roden JS: Reverse, innervated latissimus dorsi flap reconstruction of congenital diaphragmatic absence. Plast Reconstr Surg 1995;96:761. 305. Waller DK, Tita AT, Werler MM, et al: Association between prepregnancy maternal body mass index and the risk of having an infant with a congenital diaphragmatic hernia. Birth Defects Res A Clin Mol Teratol2003;67:73.
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306. Walsh DS, Hubbard AM, Olutoye 0 0 , et al: Assessment of fetal lung volumes and liver herniation with magnetic resonance imaging in congenital diaphragmatic hernia. Am J Obstet Gynecol 2000;183:1067. 307. Warkany J, Roth CB: Malformations induced in rats by maternal vitamin A deficiency. J Nutr 1948;35:1. 308. Weber TR, Kountzman B, Dillon PA, et al: Improved survival in congenital diaphragmatic hernia with evolving therapeutic strategies. Arch Surg 1998;133:498. 309. Weibel ER, Gomez DM: A principle for counting tissue structures on random sections.J Appl Physiol 1962;17:343. 310. Weinberg J: Diaphragmatic hernia in infants: Surgical treatment with use of renal fascia. Surgery 1938;3(4):78. 311. Wells LJ: Development of the human diaphragm and pleural sacs. Contr Embryo1 Carnegie Inst 1954;35:107. 312. Wenstrom KD, Weiner CP, Hanson JW, et al: A five year statewide experience with congenital diaphragmatic hernia. Am J Obstet Gynecol 1991;165:838. 313. West KW, Bengston K, Rescorla FJ, et al: Delayed surgical repair and ECMO improves survival in congenital diaphragmatic hernia. Ann Surg 1992;216:454. 314. WigglesworthJS, Desai R, Guerrini P: Fetal lung hypoplasia: Biochemical and structural variations and their possible significance. Arch Dis Child 1981;56:606. 315. Wilson JM, Difiore JW, Peters (2%Experimental fetal tracheal ligation prevents the pulmonary hypoplasia associated with fetal nephrectomy: Possible application for congenital diaphragmatic hernia. J Pediatr Surg 1993;28:1433. 316. Wilson JM, Bower LK, Lund DP: Evolution of the technique of congenital diaphragmatic hernia repair on ECMO. J Pediatr Surg 1994;29:1109.
317. Wilson JM, Fauza DO, Lund DP, et al: Antenatal diagnosis of isolated congenital diaphragmatic hernia is not an indicator of outcome. J Pediatr Surg 1994;29:815. 318. Wilson JM, Lund DP, Lillehei CW, et al: Congenital diaphragmatic hernia-a tale of two cities: Boston experience. J Pediatr Surg 1997;32:401. 319. Wilson JM, Lund DP, Lillehei CW, et al: Congenital diaphragmatic hernia: Predictors of severity in the ECMO era. J Pediatr Surg 1991;26:1028. 320. Wilson JM, Lund DP, Lillehei CW, et al: Delayed repair and preoperative ECMO does not improve survival in high-risk congenital diaphragmatic hernia. J Pediatr Surg 1992;27:368. 321. Witters I, Legius E, Moerman P, et al: Associated malformations and chromosomal anomalies in 42 cases of prenatally diagnosed diaphragmatic hernia. Am J Med Genet 2001; 103:278. 322. Wohl ME, Griscom NT, Streider DJ, et al: The lung following repair of congenital diaphragmatic hernia. J Pediatr 1977;90:405. 323. Wung JT, Sahni R, Moffitt ST, et al: Congenital diaphragmatic hernia: Survival treated with very delayed surgery, spontaneous respiration, and no chest tube. J Pediatr Surg 1995;30:406. 324. Yamaguchi M, Kuwano H, Hashizume M, et al: Thoracoscopic treatment of Bochdalek hernia in the adult: Report of a case. Ann Thorac Cardiovasc Surg 2002; 8:106. 325. Yamataka T, Puri P: Pulmonary artery structural changes in pulmonary hypertension complicating congenital diaphragmatic hernia. J Pediatr Surg 1997;32:387.
Cysts of the Lungs and Mediastinurn N. Scott Adzick and Diana L. Farmer
Familiarity with normal variations and potential pathologic abnormalities in the lung and mediastinum is necessary because questions frequently arise on evaluation of chest radiographs. The possibility of infection, respiratory difficulty, and airway obstruction from space-occupying lesions makes mandatory the expeditious evaluation and treatment of children with a mediastinal or pulmonary cystic mass. The prognosis of mediastinal and lung cysts in most children is good.
thymopharyngeal duct results in congenital cysts of the thymus.118 Prenatal lung development is described in Chapter 60, "Congenital Diaphragmatic Hernia and Eventration." A mixed lung lesion consisting of a combination of bronchogenic cyst, bronchopulmonary sequestration, and congenital cystic adenomatoid malformation suggests a common embryologic link for these malformations, but the precise embryologic causes are unknown.81
EMBRYOLOGY
CYSTIC LUNG LESIONS
Mediastinal and lung cysts are developmental in origin. Embryologic development pertinent to mediastinal masses is mostly related to the foregut and the thymus. The foregut is first recognizable as an epithelial-lined tube late in the third postconceptual week, by which time the respiratory groove (tracheal bud) is visible. Septation of the esophagus and the trachea occurs over the ensuing 2 weeks by a process of cephalocaudal growth of both structures, lateral infolding of the foregut, and caudocranial septation of the trachea and esophagus. During this interval, there is proliferation of foregut epithelium that almost completely obliterates the esophageal lumen before subsequent tubularization. Differentiation of both esophageal and tracheal epithelium is recognizable in the fourth week. The process is largely completed by day 32 to 34. It is presumed that incomplete tubularization after the epithelial proliferative phase results in foregut duplication cysts.l17 The thymus develops as paired primordia from the ventral third pharyngeal pouch. During the seventh postconceptual week, the primordia elongate caudad and ventromedially to their normal position anterior to the aortic arch. At that time, the two thymic lobes attach to each other by connective tissue but not parenchyma. Before complete descent, thymic primordia contain a thymopharyngeal duct, which is obliterated after complete descent. Incomplete descent may result in solid or cystic masses in the neck. Lack of obliteration of the
Diagnosis and Treatment The true incidence of cystic lung lesions is unknown because there are no population-based studies in the literature. Congenital cystic adenomatoid malformation was first described as a distinct pathologic entity by Chin and Tang in 1949." Before then, congenital cystic adenomatoid malformation was grouped under the general diagnosis of congenital cystic lung disease, along with bronche pulmonary sequestration, congenital lobar emphysema, and bronchogenic cyst. Prenatal diagnosis provides insight into the in utero evolution of fetal lung lesions such as congenital cystic adenomatoid malformation (CCAM), bronchopulmonary sequestration (BPS), and congenital lobar emphysema. Serial sonographic study of fetuses with lung lesions has helped define the natural history of these lesions, determine the pathophysiologic features that affect clinical outcome, and formulate management based on prognosis.1,34,86,112,128,131 A series of more than 175 prenatally diagnosed cases from the Children's Hospital of Philadelphia and the University o f TCalifornia, San Francisco, found that the overall prognosis depends on the size of the lung mass and the secondary physiologic derangement: a large mass causes mediastinal shift, hypoplasia of normal lung tissue, polyhydramnios, and cardiovascular compromise leading to fetal hydrops and death (Fig. 61-1).2
956
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VI
THORAX
A
B
A, Transverse ultrasonographic scan of the fetal thorax at 22 weeks' gestation. A large multicystic mass in the left hemithorax (open arrows) displaces the mediastinum to the right. H, heart. B, Sagittal ultrasonographic scan of the fetal thorax and abdomen shows an echogenic mass (open arrows) of the left hemithorax that flattens the left hemidiaphragm (D). A, aorta; Sp, spine. This lesion grew and resulted in fetal hydrops. Fetal surgical resection of the affected lobe was performed successfully at 23 weeks' gestation, delivery occurred at 35 weeks' gestation, and the infant survived.
Huge fetal lung lesions have reproducible pathophysiologic effects on the developing fetus. Esophageal comwression by the thoracic mass causes interference with fetal swallowing of amniotic fluid and results in polyhydramnios. Polyhydramnios is a common obstetric indication for ultrasonography, so a prenatal diagnostic marker exists for many large fetal lung tumors. Support for this concept comes from the absence of fluid in the fetal stomach in some of these cases, and the alleviation of polyhydramnios after effective fetal treatment.* The hydrops is secondary to vena caval obstruction and cardiac compression from large tumors causing an extreme mediastinal shift. Like CCAMs, a fetal BPS can also cause fetal hydrops, either from the mass effect or from a tension hydrothorax that is the result of fluid or lymph secretion from the BPS.2Hydrops is a harbinger of fetal or neonatal demise and manifests as fetal ascites, pleural and pericardial effusions, and skin and scalp edema. Although there is some association of both polyhydramnios and hydrops with fetal lung lesions, experience indicates that either can occur indewendentlv of the other. Smaller thoracic lesions can cause respiratory distress in the newborn period, and the smallest masses may be asymptomatic until later in childhood when infection, pneGmothorax, or malignant degeneration may occur. Large fetal lung tumors may regress in size on serial prenatal sonography illustrating that improvement can occur during fetal life.70,80,113In particular, many noncystic BPSs dramatically decrease in size before birth and may not need treatment after birth.2 However, fetal lung lesions that seem to disappear on prenatal ultrasound and are not seen on neonatal chest radiograph still require evaluation by chest CT scan, which will frequently detect a 1esi0n.l~~
Recently, fetal CCAM volume has been determined by sonographic measurement using the formula for a prolate ellipse (length x height x width x 0.52). A CCAM volume ratio (CVR) is obtained by dividing the CCAM volume by head circumference to correct for fetal size. A CVR greater than 1.6 is predictive of increased risk of hydrops, with 80% of these CCAM fetuses developing hydrops. The CVR may be useful in selecting fetuses at risk for hydrops and thus needing close ultrasound observation and possible fetal intervention." Serial CVR measurements have shown that CCAM growth usually reaches a plateau by 28 weeks' gestation. For fetuses at less than 28 weeks' gestation, the recommendation is twice-weekly ultrasound surveillance if the CYR is greater than 1.6 and initial weekly surveillance for fetuses with smaller CVR values. The finding that fetuses with hydrops are at very high risk for fetal or neonatal demise led to the performance of either fetal surgical resection of the massively enlarged pulmonary lobe (fetal lobectomy) for cystic/solid lesions or thoracoamniotic shunting for lesions with a dominant ~yst.2,~,~2 Lesions with associated hydrops that are diagnosed late in gestation may benefit from resection using an ex utero intrapartum therapy approach.53The fetus with a lung mass but without hydrops has an excellent chance for survival with maternal transport, planned delivery, and neonatal evaluation and surgery. Neonates with respiratory compromise due to a cystic lung lesion require prompt surgical resection, usually by lobectomy. In the most severe cases, ventilatory support with high-frequency ventilation or extracorporeal membrane oxygenation may be required. In asymptomatic neonates with a cystic lung lesion, we believe that elective resection is warranted because of the risks of infection
CHAPTER
and occult malignant tran~formation.7~ Malignancies consist mainly of pulmonary blastoma and rhabdomyosarcoma in infants and young children and bronchioloalveolar carcinoma in older children and adults.l5,31,89,106,132After confirmation of CCAM location by postnatal chest computed tomography (CT) with intravenous contrast, we recommend elective resection at 1 month of age or older. An experienced pediatric surgeon can safely perform a thoracotomy and lobectomy in infants with minimal risk of morbidity, and thoracoscopic resection has been perresection also maximizes compensatory f ~ r m e dEarly .~ lung growth; long-term follow-up has shown normal pulmonary function.66.71In contrast, we have usually followed patients with a tiny, asymptomatic, noncystic extralobar bronchopulmonary sequestration if we are confident of the diagnosis based on postnatal imaging studies. We do not favor the approach of catheterization and embolization for the treatment of larger bronchopulmonary sequestration lesions but instead opt for surgical resection.
Congenital Cystic Adenomatoid Malformation CCAM is characterized by an "adenomatoid" increase of terminal respiratory bronchioles that form cysts of various sizes. Grossly, a CCAM is a discrete, intrapulmonaiy mass that contains cysts ranging in diameter from less than 1.0 mm to over 10.0 cm. Histologically, CCAM is distinguished from other lesions and normal lung by (1) polypoid projections of the mucosa, (2) an increase in smooth muscle and elastic tissue within cyst walls, (3) an absence of cartilage (except that found i n "entrapped" normal bronchi), (4) the presence of mucus-secreting cells, and (5) the absence of inflammation.l22 Although the tissue within these malformations does not function in normal gas exchange, there are connections with the tracheobronchial tree, as evidenced by air trapping that can develop during postnatal resuscitative efforts. Cha has identified two histologic patterns of fetal CCAM: pseudoglandular and canalicular.26 Stocker defined three types of CCAM (types I to 111) based primarily on but this categorization has little clinical relcyst ~ize,122J2~ evance. Prenatally diagnosed CCAMs are divided into two categories based on gross anatomy and ultrasound findings.' Macrocystic lesions contain single or multiple cysts that are 5.0 mm in diameter or larger on prenatal ultrasound, whereas microcystic lesions appear as a solid echogenic mass on sonography. The overall prognosis for prenatally diagnosed lesions depends primarily on the size of the CCAM rather than on the lesion type, and the underlying growth characteristics are likely to be important. Resected large fetal CCAM specimens demonstrate increased cell proliferation and markedly decreased apoptosis compared with gestational-age-matched normal fetal lung tissue.z4 Examination of factors that enhance cell proliferation or down-regulate apoptosis in CCAM may provide further insights into the pathogenesis of this tumor and may suggest new therapeutic approaches. Fetal CCAMs that grew rapidly, progressed to hydrops, and required in utero resection showed increased platelet-derived growth factor (PDGF) gene expression and PDGF protein production
61
Cysts of the Lungs and Mediastinurn
957
compared with either normal fetal lung or term CCAM specimens.76 CCAM usually arises from one lobe of the lung, with the lower lobes being the most common site. Bilateral lung involvement is rare. CCAM lesions have an equal leftand right-sided incidence. For those children who are not diagnosed as a fetus or newborn, the usual clinical presentation is with infection in the CCAM area, probably due to failure of clearance of environmental bacterial pathogens. Other presentations include pneumothorax, reactive airway disease, and failure to thrive. There is no gender predominance. Associated anomalies in our experience are very uncommon.
Bronchopulmonary Sequestration A BPS is a mass of nonfunctioning lung tissue that is supplied by an anomalous systemic artery and does not have a bronchial connection to the native tracheobronchial tree. There are two forms of sequestration: extralobar and intralobar. Extralobar sequestrations are completely separate from the normal lung and are surrounded by a separate pleural covering, whereas intralobar sequestrations are incorporated into the normal surrounding lung. An extralobar sequestration may reside in the chest, within the diaphragm, or in a subdiaphragmatic location. Intralobar and extralobar sequestrations can occur simultaneously. An entire lung can be sequestered, and bilateral sequestrations have been reported but are very rare.8gBecause of the foregut derivation, communication between the esophagus or the stomach and a BPS may occur and, if suspected, should be delineated preoperatively by upper gastrointestinal series.121 Arterial blood supply to the BPS can arise from below or above the diaphragm, and venous drainage can be to either the pulmonary or the systemic venous circulation. The anomalous blood supply can result in high-output cardiac failure because of substantial arteriovenous shunting through the BPSlo4or bleeding with massive hemoptysis or hemothorax.log On prenatal ultrasonography, a BPS appears as a welldefined echodense, homogeneous mass. Detection by color flow Doppler of a systemic artery or arteries from the aorta to the fetal lung lesion is a pathognomonic feature of fetal BPS (Fig. 61-2).55 However, if this Doppler finding is not detected, then an echodense microcystic CCAM and a BPS can have an identical prenatal sonographic appearance. Ultrafast fetal magnetic resonance imaging (MRI) may help differentiate CCAM from BPS.Iw' Furthermore, there are prenatally diagnosed lung masses that display clinicopathologic features of both CCAM and sequestrationhybrid lesions-which suggests a shared embryologic basis for some of these lung masses.25,29,56The ability to differentiate intralobar and extralobar sequestration before birth is limited unless an extralobar sequestration is highlighted by a pleural effusion or is located in the abdomen (usually close to the left adrenal gland). There are no diagnostic hallmarks for the specific prenatal diagnosis of an intralobar sequestration. Extralobar BPS has a predominance in males (3:1), is more common on the left side, and can be associated
958
PART
VI
THORAX
By Doppler studies, a systemic artery (curved arrow) from the descending aorta (Ao) supplies the mass (*), consistent with the prenatal diagnosis of pulmonary sequestration.
with conditions such as congenital diaphragmatic hernia, vertebral deformities, and congenital heart disease. Approximately 5% of neonates with a congenital diaphragmatic hernia will have an extralobar BPS, which is usually an incidental intraoperative finding. An isolated, tiny noncystic extralobar BPS rarely requires treatment. An intralobar BPS is most commonly seen in the medial basal or posterior basal segments of the lower lobes, left side more frequent than the right side. Upper lobe involvement is present in only 10% to 15% of cases. For those cases that are not prenatally diagnosed, the usual postnatal presentation of an intralobar BPS is recurrent pneumonia and even abscess formation within the BPS; thus resection (usually by lobectomy) is warranted. It is mandatory to identify and ligate the feeding systemic arterial vessel(s), which usually is found within the inferior pulmonary ligament.
Congenital Lobar Emphysema Several causes for congenital lobar emphysema have been described,79but the fundamental mechanism is that the affected bronchus allows passage of air on inspiration but only limited expulsion of air on expiration leading to lobar overexpansion. Air trapping in the emphysematous lobe may be due to (1) dysplastic bronchial cartilages creating a ball-valve effect or a complete bronchial atre(2) endobronchial obstruction from inspissated sia35,133; mucus130or extensive mucosal proliferation and infolding54; (3) extrinsic compression of the bronchi from aberrant cardiopulmonary vasculature or enlarged cardiac chambers44;and (4) diffuse bronchial abnormalities that may or may not be related to infection.74
Careful preoperative bronchoscopy may help delineate an intrinsic obstructive lesion.35The most common site of involvement for congenital lobar emphysema is the left upper lobe (40% to 50%), followed by the right middle lobe (30% to 40%), right upper lobe (20%), lower lobes (I%),and multiple sites for the remainder. Barotrauma associated with the treatment of bronchopulmonary dysplasia in preterm infants can result in acquired ernphyscma in which multiple areas of hyperinflation may be present." Because of endotracheal tube positioning, right lower lobe involvement is common in these cases, which helps to differentiate acquired from congenital disease. Polyalveolosis or the polyalveolar lobe first described by Hislop and Reid has been found in some . ~ ~ total alveolar cases of congenital lobar e m p h y ~ e r n aThe number is increased severalfold in this condition, but the airways and arteries are normal for age in number, size, and structure. The polyalveolar lobe becomes overinflated and hyperlucent on chest radiography because of impaired air exchange in the affected lobe. Congenital lobar emphysema can be distinguished prenatally from other cystic lung lesions on ultrasonography by increased echogenicity and reflectivity compared with a microcystic C W and the absence of systemic arterial blood supply compared with a BPS.s,92Progressive enlargement of these lesions prior to 28 weeks' gestation may be due to fetal lung fluid trapping in the lobe analogous to the air trapping seen postnatally. Late in gestation, lobar emphysema may regress in the size and the character of the mass, rendering it indistinguishable from adjacent normal fetal lungg2Postnatal assessment is important because of the risk of postnatal air trapping in the emphysematous lobe. At the time of birth, the affected lobe may be radiopaque on chest radiography because of delayed clearance of fetal lung fluid. Prenatally diagnosed mainstem bronchial atresia results in massive lung enlargement, hydrops, and fetal death; ultrafast fetal M I R I demonstrates that the entire lung is involved and that there are dilated bronchi distal to the mainstem atresia.65 Congenital lobar emphysema is diagnosed at birth in about 25% of cases and by age 1 month in about 50%. The diagnosis is sporadic after 6 months of age. The earlier the onset of symptoms, the more likely the progression of lobar emphysema and the need for resection. Nevertheless, some infants have very mild symptoms that do not progress, and the emphysematous lobe remains stable and does not encroach on adjacent lung, so resection is not required in these cases.93 Besides chest radiography and CT (Fig. 61-3), a ventilation-perfusion scan can demonstrate delayed uptake and washout of the xenon radioisotope from the affected lobe and little blood flow through it. If the presentation is respiratory distress and pulmonary lobar hyperinflation, then the mainstay of management is resection of the emphysematous lobe. Positive-pressure ventilation may result in abrupt exaggerated air trapping in the lobe with sudden cardiopulmonary decompensation, so it is important for the surgeon to be present during anesthetic induction in the event that urgent thoracotomy is needed. At operation, the affected lobe will characteristically "pop out" through the thoracotomy wound. High-frequency ventilation,45 selective bronchial intubation+? and endoscopic decompression
CHAPTER
61
Cysts o f the Lungs and Mediastinum
959
which a retrospective review compared the 60-year experience before and after 1970. The best estimate of prevalence of mediastinal masses is provided by a retrospective pathology study of mediastinal masses from Victoria in Australia, which had an estimated pediatric population of 900,000. In that series, 50% of mediastinal masses were lymphoma followed by 20% of neurogenic origin, 8% foregut duplication cysts, and 6% teratomas.l16This prevalence is similar to the recent U.S. series (see Table 61-1).
Anatomic Considerations A clear understanding of the anatomic subdivisions of the mediastinum is useful in differential diagnosis and selection of diagnostic studies. The mediastinum is the central thoracic space bounded laterally by the right and left parietal pleura, anteriorly by the sternum, posteriorly by Chest CT scan from a neonate with congenital lobar the vertebral bodies to include the transverse processes, emphysema involving the right middle lobe. There are dilated superiorly by the thoracic inlet, and inferiorly by the airspaces in the right middle lobe with compressive atelectasis of the diaphragm. Although several classificationsfor subdividing right lower lobe. The mediastinum is shifted to the left, and a portion the mediastinum exist, the classic anatomic description is of the emphysematous lobe herniates across the midline posterior to used here.82 The value of any system of anatomic subdivithe heart (arrow). sion is to provide insight into the contents of that region, which simplifies differential diagnosis. The superior mediastinum is delimited by the thoracic inlet superiorly and the plane between the sterof the emphysematouslobeg6may be useful adjuncts in the nomanubrial junction and the inferior limit of the fourth preoperative management of patients with respiratory disthoracic vertebra inferiorly. The lateral boundaries are the tress. Long-term pulmonary growth and function after lobectomy for congenital lobar emphysema is e ~ c e l l e n t . ~ ~parietal pleurae. Normal anatomic contents of this s u b division are the thymus, .other lymphatic structures, and mesenchymal derivatives, including vasculature, diffusely found throughout the entire mediastinum. CYSTIC MEDIASTINAL LESIONS The anterior mediastinum is the zone posterior to the sternum, anterior to the pericardium, superior to the Clinical Features diaphragm, and inferior to the plane through the sternomanubrial junction. This space normally contains The clinical manifestations of mediastinal lesions are the mesenchymal derivatives, fat, and connective tissue. result of mass effects and are influenced by the location The middle mediastinum is delimited by the periof the lesion within the chest. Many are asymptomatic, cardium and origins of the great vessels. Therefore, its although the most important symptom of anterior and normal contents are the pericardium, heart, great vessels, middle mediastinal masses is respiratory distress, particulymphatics, and mesenchymal derivatives. larly in infants when noisy, stridorous breathing or cyanosis The posterior mediastinum is outlined by the periwhile feeding is observed.67 In older children, cough, chest pain, dyspnea, orthopnea, or, rarely, hemoptysis 0ccurs.2~ cardium and great vessels anteriorly, the vertebral column posteriorly, and, as in each of the prior subdivisions, the Respiratory distress may be life threatening in all age parietal pleurae laterally. Its contents include the trachea gro~ps.9,*0,67,98,~~ Rapid onset of respiratory distress or and main bronchi, esophagus, widely distributed lymphatic symptoms of superior vena caval obstruction suggest lymstructures, sympathetic nervous ganglia, descending aorta, Although rare, infected teratomas have been azygous venous system, and thoracic duct. reported to rupture into the bronchus, pleura, pulmonary Large masses or diffuse processes may transgress multiartery, and pericardium.20,94JlO Posterior mediastinal massks can be quite large and yet asymptomatic, often disple subdivisions. An additional caveat to aid in differential covered incidentally on a chest radiograph taken for other diagnosis is age. With the exception of posterior mediastinal neuroblastoma, mediastinal masses in young children indications. Less frequently, pain or symptoms of spinal are most likely to be developmental in origin. Mediastinal cord compression lead to r e ~ o g n i t i o n . ~ ~ J l ~ Reports from individual institutions regarding masses that are not cystic will also be mentioned. mediastinal masses may be biased by selection. If more recent series are compared with those published before 1967 (Table 61-l), an increase in malignancy, Diagnosis and Treatment particularly of lymphomas and neuroblastoma, is eviRecognition of cystic mediastinal masses may first occur on dent.l9,48,4g,51,67,100,110~114,115Such is the case in a single large The fetus who develops progressive fetal ultra~ound.6g~8"8~ institutional series from Walter Reed Army Hospital28 in
960
PART
VI
THORAX
Cyst/Neoplasm Neurogenic Tumors Neuroblastoma/ganglioneuroblastorna Ganglioneurorna Neurofibrorna Neurilemoma/schwannoma Paragangliorna (pheochromocytoma) Primitive neuroectodermal turnor/neurosarcoma
King et at.,
Simpson and Campbell,
Saenz et al.,
Cohen et al.,
Grosfeld,
1982e7
1991116
1993-
199128
199447
Total
%
16 9 4 1
32 14 3 3 2 2
13 8
50 14 2 5
227
33
105
62
201
677
20 17 4 6 1
1
Lymphomas Hodgkin's d~sease Non-Hodgkin's lymphoma Germ Cell Tumors Teratodermoid Benign Malignant Seminorna/ernbryonal carcinoma Mesenchymal Tumors Lymphangiorna/cystic hygroma Hernangioma Fibrorna/fibrosarcoma Liporna/Iiposarcoma/sarcoma Rhabdomyosarcoma Cysts Pericardial Bronchogenic Enteric Neurenteric/misc. cyst Thymic Lesions Thymic cyst Hyperplasia Thymoma Thymic carcinoma Miscellaneous Granulomas, abscess, fibrosis Total
188
121
nonimmune hydrops, cardiac failure, or mediastinal shift with compression of developing lung tissue may benefit from in utero decompression or resection of a cystic mediastinal lesion.84 For cystic mediastinal masses, the initial postnatal diagnostic study should be anteroposterior and lateral chest radiographs. A presumptive diagnosis can often be made based on the location of the lesion on the plain radiograph. CT has now largely replaced endoscopy and esophagograms as part of the preoperative evaluation. Several studies comparing contrast medium-enhanced CT to MRI suggest that CT is superior, given its ability to define calcification within a mass.13,5g MRI is useful if spinal involvement is in question or if vascular lesions are being considered. An esophagogram reveals the characteristic extrinsic mass effect of a foregut duplication cyst, but CT is probably the most useful study for this diagnosis. Echocardiography has value in defining the rare
intrapericardial teratoma in the neonate with an enlarged pericardial silhouette47 and can detect congenital heart disease if present. The goal of the preoperative diagnostic workup is to help define the optimal surgical approach. When the nature of a mediastinal mass is uncertain or if the potential of malignancy exists, a preoperative serum sample should be drawn for determination of alpha fetoprotein or P-human chorionic gonadotropin levels, particularly in the case of anterior mediastinal tumors. Similarly, urinary catecholamine catabolites should be obtained in suspect posterior mediastinal masses. Surgical resection at the time of diagnosis is the preferred treatment of benign mediastinal cysts and tumors. When indicated, thoracoscopic resection or biopsy can be performed with adequate results and minimal morLarge anterior mediastinal masses are best bidity.32~64,~~ approached through median sternotomy, and middle
CHAPTER
61
Cysts of t h e Lungs a n d Mediastinum
961
and posterior mediastinal masses are best approached through posterolateral thoracotomy.
a cosmetically unacceptable appearance. The cysts are lined with ciliated, respiratory epithelium; contain lymphocytes as well as normal thymic tissue; and often show inflammatory and granulomatous changes. Thymolipoma is a benign tumor, possibly hamartoma, of mixed fatty and ANTERIOR AND SUPERIOR MEDlASTlNUM thymic tissue. Resection results in diagnosis and cure. Thymomas are rare in children, accounting for less than The anterior and superior mediastinum contains the 1% of mediastinal tumors, with only 20 well-documented thymus, great vessels, and a network of lymphatic struccases of malignant thymoma in children in the literatures, as well as connective and adipose tissue. Lymphomas ture.61,72,103,1*6These tumors originate in the thymic are the most common tumors, followed by teratomas, epithelium and are usually aggressive.21 Treatment is germ cell tumors, cystic hygromas, and thymic lesions multimodal, but outcome is poor. (Fig. 61-4). Anterior mediastinal masses in infants are Although the thymus is located in the anterior and usually either a teratoma or a thymic enlargement. superior mediastinum, ectopic thymic tissue can be found Foremost in evaluation of masses of the anterior in the neck and posterior mediastinum as we11.7~12Jlg mediastinum is assessment of the risk of malignancy. Benign thymic hyperplasia is a physiologic enlargement of Malignant disease such as lymphoma generally presents the thymus gland no longer believed to cause respiratory in the older child, is often associated with systemic symp toms and adenopathy elsewhere, and is frequently embarrassment, although rapid enlargement has led some authors to recommend resecti0n.77,~07If necessary, a associated with symptoms of airway compromise. When short course of prednisone shrinks the normal thymus possible, the diagnosis should be sought from nonmediastigland and helps differentiate it from nonlymphoid medinal sources, such as bone marrow, pleural fluid, or other masses. MRI can also be h e l p f ~ l .Mediastinal ~~,~~ ~ ~ , ~astinal ~ nodal tissues, thus avoiding a general a n e s t h e t i ~ . " If radiation is of historical interest only because it had an a diagnosis is still lacking in the presence of airway comprounacceptably high association with thyroid carcinoma. mise, corticosteroid administration reduces the risk of Exploration is recommended only when malignancy open biopsy yet does not affect diagnostic accuracy. cannot be ruled out, as in benign nodular thymic hyperLymphomas are discussed in Chapter 35. plasia. Nodular thymic hyperplasia is usually asymptomatic and is usually recognized as a superior mediastinal mass on an incidental chest film. CT reveals a solid, asymmetrical, Thymus nonenhancing mass within a thymic lobe. Peripheral blood and bone marrow studies are normal. Operation in these Thymic cysts are seen in the anterior mediastinum and instances reveals a lymphoid mass within one lobe of the the neck (Figs. 61-5 and 61-6). They are usually asymptothymus with histologic compression of adjacent normal matic but can become infected or hemorrhagic or thymus. Analysis of lymphocytes in the mass reveals a produce symptoms owing to mass effects and can create
A
B
A 5-year-old boy presented with a superoanterior mediastinal mass noted to be separate from the pericardial silhouette on an anteroposterior chest film ( A ) . Lateral chest radiograph (B) reveals sternomanubrial prominence and a mass anterior to the trachea. This mass turned out to be a teratoma.
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B Fullness in the left neck led to these CT scans, which delineated a left thymic cyst anterior to neck vessels with extension into anterior mediastinum (A) at and below the level of the carina (B).
normal ratio of T and B lymphocytes. Today, most thymic lesions can be resected using thoracoscopic techniques.
Teratomas, Dermoid Cysts, and Germ Cell Tumors After lymphoma, teratomas are the most common tumors of the anterior mediastinum. They also have been reported .~~ in other subdivisions of the m e d i a s t i n ~ mTeratomas characteristically have both cystic and solid components and are derived from at least two and, most often, all three germ cell layers." Some controversy exists about the origin of teratomas because they may occur near or at the midline from brain to anus. One view is that they
Thymic cyst mobilized from the mediastinum in the same patient as in Figure 61-5 through sternotomy before removal of the cervical extension.
represent a mature form of extragonadal germ cell tumor.32 The other is that they arise from undifferentiated embryonic cells. The World Health Organization classifies are, by definiteratomas as germ cell variant~.~Wermoids tion, composed of ectodermal and mesodermal derivatives only. They are mature, benign masses often encased in a fibrous, thick cyst wall containing various skin appendages including hair or teeth. True teratomas can be some of the largest and most unusual tumors with malignant elements, particularly when diagnosis is delayed. In the young patient, teratomas are usually benign. Only 25% are malignant in all age gr0ups.l2~Because it is not always possible to determine if a tumor is fully mature preoperatively, alpha-fetoprotein and P-human chorionic gonadotropin levels should be obtained in all patients. When malignant elements are present, they are most commonly yolk sac in origin, currently termed endodermal sinus tumors.36 The signs and symptoms of extrapericardial teratomas are that of any compressive, anterior mediastinal mass, such as tachypnea or stridor. Although rupture of teratomas into adjacent structures has been reported, this is a rare e~ent.~*J29 Intrapericardial tumors are more common in neonates and young infants and present as low cardiac ~ u t p u tIntrapericardial .~ teratomas are invariably benign and arise in the sulcus between the origins of the aortic root and the main pulmonary artery. On chest radiograph and CT, the mass is generally asymmetrically placed in the anterior mediastinum, commonly with extension into the right or left hemithorax. Flocculent calcifications are often seen. Anterior mediastinal teratomas are generally best approached through a sternum-splitting incision. Despite their large size, the vascular supply is often scant. Exceptions are those tumors with malignant elements, in which preoperative
CHAPTER
aortography may reveal a posterior mediastinal teratoma with arterial supply from the aorta.60~62
MIDDLE MEDlASTlNUM In the classic anatomic description, the middle mediastinum is circumscribed by the pericardium.82As such, pericardial cysts may be the only true common middle mediastinal cysts. Pericardial cysts are benign, thinwalled, fluid-containing cysts lined with mesothelium. It is postulated that the pericardium forms from a series of disconnected lacunae in the mesenchyme that later coalesce to form the pericardial sac. Occasionally, one of these lacunae persists as a pericardial cyst. They are nearly always asymptomatic and are often discovered on routine chest films or at autopsy. The classic description is that of a cystic mass lying anteriorly in the chest at either cardiophrenic sulcus, although the right side is more common. Historically, thoracotomy was recommended to establish a definitive diagnosis. Currently, CT provides a sufficiently characteristic appearance to allow accurate diagnosis, thus allowing nonintervention unless the cyst is large. If the diagnosis is uncertain, these can be excised or unroofed thoracoscopically as well.
61
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963
inflammatory processes in children. Most common of these lesions is the spectrum of benign to malignant neurogenic tumors of the sympathetic nervous system. In the young, the most common tumor is a malignant neuroblastoma, and in the older child, the most common tumors are benign ganglioneuromas; both of these lesions are discussed in Chapter 28.
Foregut Duplication Cysts Foregut duplication cysts are reasonably common in pediatric specialty centers. The nomenclature of these lesions varies considerably. They can be subdivided clinically and pathologically into (1) enteric duplications and cysts (lined by intestinal epithelium), (2) bronchogenic cysts (lined by respiratory epithelium), and (3) neurenteric cysts (associatedwith vertebral anomalies or having a connection with the nervous system). Enterogenous is a confusing historical term and in various reports has included each of the aforementioned categories. The generic term fuvegut duplication cyst is a more accurate embryologic description with subdivision into bronchogenic or enteric cysts determined by the histology of the mucosa lining the cyst wall. In fact, all three endodermal derivatives may be found in the occasional foregut duplication, supporting a common embryologic derivation for foregut duplication cysts.
POSTERIOR MEDlASTlNUM The posterior mediastinum lies behind a plane passing in front of the tracheal bifurcation and extending posteriorly to the paravertebral sulci.82 The posterior mediastinum is the site of a heterogeneous group of cysts, neoplasms, and
~
~
cystS ~ ~
,
,
~
~
Bronchogenic cysts (Fig. 61-7) develop from abnormal budding of the tracheal diverticulum or ventral portion
A, Bronchogenic cyst. Central tracheobronchial compression with respiratory distress was demonstrated in this 15-month-old boy transferred to the intensive care unit in critical condition. He had been treated for a year for symptoms of asthma. B, Lateral view shows remarkable tracheal compression with tracheoesophageal separation confirmed by contrast agent in the esophagus.
~
964
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of the foregut. These cysts can be found in a variety of locations from paraesophageal to paratracheal, perihilar, or intraparenchymal?l depending on the level at which the abnormal budding occurred in the development of the foregut or tracheobronchial tree. It has been reported that about two thirds of bronchogenic cysts are located within the lung parenchyma, with the remainder in the mediastinum; but this distribution varies between different reports. Rarely, they can be found in remote locations, such as the tongue, neck, back, and even below the diaphragm.l~.40,51,1011127 Histologically, bronchogenic cysts are thin walled, lined with bronchial epithelium, and filled with mucus. They can be single or multiple and are white or pinkish. Cartilage has been reported in the wall of these cysts, and air-fluid levels may be present. The cysts have no predilection for the right or left side. Although they do not usually communicate with the tracheobronchial tree, they may do so from inception or the communication may be acquired from superinfection. Diagnosis in older children often results from identification of an incidental mass on chest radiograph obtained for an unrelated reason. Infants usually present with respiratory symptoms, and the mass may be obscured on plain film by associated atelectasis and infection (Figs. 61-8 and 61-9).37,7"120 In this case, the diagnosis can be delayed, but CT usually confirms the diagnosis. ~ r o n c h d ~ e ncysts i c have also been recognized on antenatal ultrasound5 and on esophagogram for other indications. The differential diagnosis includes foreign body, lobar emphysema, pneumonia, bronchial stenosis, and pneumothorax. Bronchogenic cysts should be excised to avoid the complications of infection, hemorrhage, or sudden death from rapid expansion under tension. A risk of malignant
Microscopically, this bronchogenic cyst wall is lined by ciliated respiratory epithelium and contains bronchial cartilage, characteristic of bronchogenic cysts and evidence that they are central bronchial developmental anomalies (in contrast to cystic adenomatoid malformation, which is a peripheral parenchymal anomaly).
transformation does exist, as malignancy has been reported in two adult patients with bronchogenic cysts and adenocarcinoma has been reported arising from a bronchogenic cyst in an 8-year-old girl.l25 Excision should be accomplished without injury to the bronchial or esophageal wall. Small cysts in the pulmonary hilum may not be visualized until the mediastinal pleura is opened. Cyst resection is usually straightforward, but occasionally limited parenchymal lung resection or lobectomy may be required. In the majority of patients, bronchogenic cysts are amenable to thoracoscopic resection."^^^ An error in recognition may lead to unnecessary resection of emphysematous lung tissue rather than removal of a cyst producing bronchial obstruction. Complete excision is recommended; recurrence 25 years after incomplete resection has been reported.105 Although there are reports of transbronchial drainage, we do not recommend that approach.95
Enteric Duplication Cysts
Urgent thoracotomy in the same patient as in Figure 61-7 showed a large unilocular cyst. It was aspirated of infected mucus to relieve bradycardia and then removed from its attachment to the posterior trachea. The microscopic appearance is shown in Figure 61-9.
Enteric cysts arise from failure of coalescence of vacuoles early in development of the foregut. They are lined by esophageal or gastric epithelium surrounded by smooth muscle. They have been called variously enterogenic or enterogenous cysts, esophageal cysts, enteric cysts, and esophageal duplications. Gastric mucosa is often seen, and intramural adrenal cortical rests have been reported.13qnteric cysts may be located throughout the posterior mediastinum and in the neck. Although most commonly integral to the wall of the esophagus, they may communicate with the lumen of the esophagus or exist completely separate from the structure of origin. A number of large thoracoabdominal enteric cysts have been reported, either ending blindly in the abdomen or
CHAPTER
connecting with the lumen of the stomach, jejunum, ileum, or pancreatic duct.5l,gg Biliary reflux during bronchoscopy was reported in a case of an enteric duplication cyst that penetrated the diaphragm and connected the carina with the biliary tree.73Thereis a 12%incidence of associated malformations. Most of these are additional enteric duplication^.^^ Two cases of prenatally diagnosed intrathoracic enteric duplication cyst associated with hydrops have been treated with placement of a thoracoamniotic shunt in ~ t e r o . ~ ~ In most series, enteric cysts are asymptomatic at presentation. Chest radiograph and CT are the mainstays of diagnosis (Figs. 61-10 to 61-12). Although ggmTc pertechnetate, abdominal ultrasound, barium swallow, or MRI may occasionally be useful adjunctive procedures, the goal of preoperative studies is less an attempt to make a definitive diagnosis than to provide information to aid in operative planning. Treatment consists of complete surgical excision either by thoracotomy or thoracoscopy. If necessary, as in long tubular duplications, the mucosal lining of a foregut duplication may be stripped, leaving the common muscular wall intact.lZ4
A
61
Cysts of t h e Lungs a n d Mediastinum
965
Marsupialization is no longer recommended. These are benign lesions, and esophageal integrity should be preserved.
Neurenteric Cysts Neurenteric cysts are rare foregut duplications that also have connections to the spinal canal, sometimes with the dura. Although they most commonly present as intrathoracic masses, they may also present as an intraspinal mass. The coexistence of a cystic posterior mediastinal mass with adjacent hemivertebrae should raise suspicion of a neurenteric cyst as well as anterior rnyel~meningocele.~~ Neurenteric cysts are thought to form early in develop ment when the notochord and foregut are in apposition, either by failure of complete separation or by herniation of foregut endoderm intothe dorsal e c t ~ d e r m . ~ ~ , ~ ~ Histologically, neurenteric cysts have alimentary tract mucosa, well-developed muscle walls, and no serosa. Gastric mucosa may be present, so signs of inflammation and ulceration may occur.@Symptoms often include pain
B
A, Incidental finding of an asymptomatic mediastinal mass behind the cardiac silhouette on anterior chest radiograph (arrow). B, On lateral film, the lesion was located just inferior and posterior to the base of the heart (arrow) and adjacent to the esophagus.
966
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A
. -.
VI
THORAX
B
A and B, CT scan further delineates the lesion in the patient shown in Figure 61-10 (ring marker). CT is probably the most useful imaging approach for patients with mediastinal tumors.
or neurologic findings (or both). MRI is suggested when Miscellaneous Mesenchymal Cystic Tumors a posterior mediastinal mass is associated with vertebral Mesenchymal tumors may occur throughout the medianomalies. Prompt excision is indicated. Paraplegia and death owing to meningitis have been rep~rted.~~Althoughastinum and may compromise the airway. They originate some authors report leaving the neural connections from connective tissue, lymphatic tissue, smooth and intact, most recommend total excision with simultaneous striated muscle, fat, and blood vessels. As a group, laminectomy if necessary.l4~l6,38 they constitute less than 5% of mediastinal masses in Other miscellaneous entities enter into the differential children. diagnosis of rare posterior mediastinal cystic masses. Mesenchymal tumors derived from blood and lymph Anterior thoracic meningoceles are seen in older children vessels are the most common varieties in children, espeand are thought to be progressive degenerative lesions cially lymphangiomas (cystic hygroma). In most patients, associated with vertebral anoma1ies.l" MRI should distinlymphangioma presents as a superior or posterior mediguish this lesion from a neurenteric cyst. astinal extension of a cervical lesion; however, primary ~ ~ , tumors ~ mediastinal lymphangiomas do o ~ c u r .These grow by proliferation of endothelial cell-lined buds within tissue planes. Symptoms relate to the size and invasiveness of the tumors or relate to i n f e ~ t i o n Hemorrhage .~~,~~ into these tumors can cause obstruction from rapid increase in size. Diagnostic steps include CT with intravenous contrast material or MRI. Fibrous reaction and neovascularization may make surgical resection tedious, although it remains the best therapy. Sclerotherapy with OK-432 is under investigational use in the United States and has been shown to have dramatic results in other countries. The most common complication after surgical resection of mediastinal lymphangioma is lymphatic fluid leak. Treatment of this complication by aspiration, chest tube drainage, and fibrin glue application (if drainage alone fails) is usually effective. Lymphangiomas recur in at least 15%of cases after resection, so long-term follow-up is important. There have been rare reports of mediastinal hemangiomas. The preOperative findings revealed a single cyst with ferred treatment of hemangiomas is nonoperative when esophageal mucosal lining, and microscopic examination confirmed possible, including the use of pulse corticosteroids or the presence of esophageal mucosa. interferon-a.
-.
CHAPTER
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64. Kern JA, Daniel TM, Tribble C, et al: Thoracoscopic diagnosis and treatment of mediastinal masses. Ann Thorac , Surg 1993;56:92-96. 65. Keswani SG, Crombleholme TM, Pawel BR, et al: Prenatal diagnosis and management of mainstem bronchial atresia. Fetal Diagn Ther 2005;20:7478. 66. Khosa JK, Leong SL, Borzi PA: Congenital cystic adenomatoid malformation of the lung: Indications and timing of surgery. Pediatr Surg Int 2004;20:505-508. 67. King RM, Telander RL, Smithson KA, et al: Primary mediastinal tumors in children. J Pediatr Surg 1982;5:512-520. 68. Kropp J, Emons D, Winkler C: Neurenteric cyst diagnosed by technetium-99m pertechnetate sequential scintigraphy. J Nucl Med 1987;28:1218-1221. 69. KullerJA, LaiferJA, Martin JG, et al: Unusual presentations of fetal teratoma. J Perinatol 1991;11:294296. 70. Laberge JM, Flageole H, Pugash D, et al: Outcome of the prenatally diagnosed congenital cystic adenomatoid lung malformation: A Canadian experience. Fetal Diagn Ther 2001;16:178-186. 71. Laberge JM, Bratu I, Flageole H: The management of asymptomatic congenital lung malformations. Paediatr Respir Rev 2004;5(Suppl)5305-S312. 72. Lam WW, Chan EL, Lau YL, et al: Paediatric thymoma: Unusual occurrence in two siblings. Pediatr Radiol 1993;23: 124126. 73. Lazar RH, Younis RT, Bassila MN: Bronchogenic cysts: A cause of stridor in the neonate, Am J Otolaryngol 1991; 12:117-120. 74. Leape LL, Longino LA: Infantile lobar emphysema. Pediatrics 1964;34:24&251. 75. Lemoine G, Montupet P: Mediastinal tumors in infancy and childhood. In FallisJC, Filler FM, Lemoine G (eds): Pediatric Thoracic Surgery. New York, Elsevier, 1991, pp 103-110. 76. Liechty KW, Quinn TM, Cass DL, et al: Elevated PDGF-P in congenital cystic adenomatoid malformations requiring fetal resection. J Pediatr Surg 1999;34:805-810. 77. Linegar AG, Odell JA, Fennel1 WM, et al: Massive thymic hyperplasia. Ann Thorac Surg 1993;55:1197-1199. 78. Lobe TE: Pediatric thoracoscopy. Semin Thorac Cardiovasc Surg 1993;5:298-302. 79. Mani H, Suarez E, Stocker JT: The morphologic spectrum of infantile lobar emphysema: A study of 33 cases. Paediatr Respir Rev 2004;5(Suppl):S313-S320. 80. MacGillivray TE, Harrison MR, Goldstein RB, et al: Disappearing fetal lung lesions. J Pediatr Surg 1993;28: 1321-1324. 81. MacKenzie TC, Guttenberg ME, Nissenbaum HL, et al: A fetal lung lesion consisting of bronchogenic cyst, bronchopulmonary sequestration, and congenital cystic adenomatoid malformation: The missing link? Fetal Diagn Ther 2001;16:193-195. 82. McVay CB: Mediastinum. In Anson BJ, McVay CB (eds): Surgical Anatomy, 6th ed. Philadelphia, WB Saunders, 1984, pp 296-308. 83. Meizner I, Levy A: A survey of non-cardiac fetal intrathoracic malformations diagnosed by ultrasound. Arch Gynecol Obstet 1994;255:31-37. 84. Merchant MI, Hedrick HL, Crombleholme TM, et al: Management of fetal mediastinal teratoma: A report of two cases. J Pediatr Surg 2005;40:228-231. 85. Messineo A, Wesson DE, Filler RA, et al: Juve,nile hemangiomas involving the thoracic trachea in children: Report of two cases. J Pediatr Surg 1992;27:1291-1295. 86. Miller JA, Corteville JE, Langer JC: Congenital cystic adenomatoid malformation in the fetus: Natural history and predictors of outcome.J Pediatr Surg 1996;31:805-808.
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87. Moran CA, Suster S: Mediastinal hemangiomas: A study of 18 cases with emphasis on the spectrum of morphological features. Hum Pathol 1995;26:416-420. 88. Muraskas JK, Gianopoulos JG, Husain A, Black PR: Mediastinal cystic hygroma: Prenatal decompression with neonatal resection and recurrence at 19 months of age. J Perinatol 1993;13:381-383. 89. MurphyJ, Blair GK, Fraser GC, et al: Rhabdomyosarcoma arising within congenital pulmonary cysts: Report of three cases. J Pediatr Surg 1992;27:13641367. 90. Murray ME: Bilateral communicating bronchopulmonary foregut malformation in an infant with multiple congenital anomalies. Pediatr Radiol 1994;24:128-132. 91. Nuchtern JG, Harberg FJ: Congenital lung cysts. Semin Pediatr Surg 3:233, 1994. 92. Olutoye 0 , Coleman B, Hubbard AM, et al: Prenatal diagnosis and management of congenital lobar emphysema. J Pediatr Surg 2000;35:792-795. 93. Ozcelik U, Gocmen A, Kiper N, et al: Congenital lobar emphysema: Evaluation and long-term followup of thirty cases at a single center. Pediatr Pulmonol2003;35:384391. 94. Paterson IM, Cockburn JS: Acute pericarditis due to perforation of a benign mediastinal teratodermoid into the pericardial sac. Thorax 1982;37:863-865. 95. Philippart AI: On foregut duplications. J Pediatr Pulm 1994;18:45. 96. Phillipos EZ, Libsekal K: Flexible bronchoscopy in the management of congenital lobar emphysema in the neonate. Can Resp J 1998;5:219-221. 97. Piramoon AN, Abbassioun K: Mediastinal enterogenic cyst with spinal cord compression. J Pediatr Surg 1974;9: 543-545. ' 98. Pokomy WJ: Mediastinal tumors. In Ashcraft KW, Holder TM (eds): Pediatric Surgery, 2nd ed. Philadelphia, WB Saunders, 1993, pp 218-227. 99. Pokorny WJ, Goldstein IR: Enteric thoracoabdominal duplications in children. J Thorac Cardiovasc Surg 1984; 87:821-825. 100. Pokorny WJ, Sherman JO: Mediastinal masses in infants and children. J Thorac Cardiovasc Surg 1974;68: 869-873. 101. Pul N, Pul M: Bronchogenic cyst of the scapular area in an infant: Case report and review of the literature. J Am Acad Dermatol 1994;3:120-122. 102. Quinn TM, Hubbard AM, Adzick NS: Prenatal magnetic resonance imaging enhances prenatal diagnosis. J Pediatr Surg 1998;33:312-316. 103. Ramon Y, Cajal S, Suster S: Primary thymic epithelial neoplasms in children. Am J Surg Pathol 1991;15:466471. 104. Ransom JM, Norton JB: Pulmonary sequestration presenting as congestive heart failure. J Thorac Cardiovasc Surg 1978;76:378-381. 105. Read CA, Moront M, Carangelo R, et al: Recurrent bronchogenic cyst: An argument for complete surgical excision. Arch Surg 1991;126:1306-1308. 106. Ribet ME, Copin MC, Soots JG, et al: Bronchioloalveolar carcinoma and congenital cystic adenomatoid malformation. Ann Thorac Surg 1995;60:11261128. 107. Rice HE, Flake AW, Hori T, et al: Massive thymic hyperplasia: Characterization of a rare mediastinal mass. J Pediatr Surg 1994;29:1561-1564. 108. Robie DK, Gursoy MH, Pokorny WJ: Mediastinal tumors: Airway obstruction and management. Semin Pediatr Surg 1994;3:259-263. 109. Rubin EM, Garciatt C, Horowitz MD, et al: Fatal massive hemoptysis secondary to intralobar sequestration. Chest 1994;106:954955.
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110. Rubush JL, Gardner IR, Boyd WC, et al: Mediastinal tumors: Review of 186 cases. J Thorac Cardiovasc Surg 1973;65:216-222. 111. Saenz NC, Schnitzer JJ, Eraklis AE, et al: Posterior mediastinal masses. J Pediatr Surg 1993;28:172-176. 112. Sakala EP, Perrott WS, Grube GL: Sonographic characteristics of antenatally diagnosed extralobar pulmonary sequestration and congenital cystic adenomatoid malformation. Obstet Gynecol Surv 1994;49:647-655. 113. Saltzman DH, Adzick NS, Benacerraf BR: Fetal cystic adenomatoid malformation of the lung: Apparent improvement in utero. Obstet Gynecol1988;71:1000-1003. 114. Shamberger RC, Holzman RS, Griscom NT, et al: CT quantification of tracheal cross-sectional area as a guide to the surgical and anesthetic management of children with anterior mediastinal masses. J Pediatr Surg 1991;26: 138-142. 115. Shields TW: Primary Tumors and Cysts of the Mediastinum. Philadelphia, Lea & Febiger, 1972, p 32. 116. Simpson I, Campbell PE: Mediastinal masses in childhood: A review from a paediatric pathologist's point of view. Prog Pediatr Surg 1991;27:92-96. 117. Skandalakis JE, Gray SW, Ricketts R: The esophagus. In SkandalakisJE, Gray SW (eds): Embryology for Surgeons. Philadelphia, WB Saunders, 1994, pp 65-112. 118. Skandalakis JE, Gray SW, Todd NW: The pharynx and its derivatives. In Skandalakis JE, Gray SW (eds): Embryology for Surgeons. Philadelphia, WB Saunders, 1994, pp 17-64. 119. Slovis TL, Meza M, Kuhn JP: Aberrant thymus--MR assessment. Pediatr Radiol 1992;22:490-494. 120. Snyder ME, Luck SR, Hernandez R, et al: Diagnostic dilemmas of mediastinal cysts. J Pediatr Surg 1985;20: 810-815. 121. Srikanth MS, Ford EG, Stanley P, et al: Communicating bronchopulmonary foregut malformations: Classification and embryogenesis. J Pediatr Surg 1992;27:732-736. 122. StockerJT, ManewellJE, Drake RM: Congenital cystic adenomatoid malformation of the lung: Classification and morphologic spectrum. Hum Pathol 1977;8:155-161. 123. Stocker JT: Congenital pulmonary airway malformation: A new name and an expanded classification of congenital cystic adenomatoid malformations of the lung. Histopathology 2002;41:424431. 124. Stringer MD, Spitz L, Abel R, et al: Management of alimentary tract duplications in children. Br J Surg 1995; 82:7478. 125. Suen HC, Mathisen DJ, Grillo HC, et al: Surgical management and radiological characteristics of bronchogenic cysts. Ann Thorac Surg 1993;55:476-481. 126. Suster S, Rosai J: Thymic carcinoma. Cancer 1991;67: 1025-1028. 127. Swanson SJ 3d, Skoog SJ, Garcia V, et al: Pseudoadrenal mass: Unusual presentation of bronchogenic cyst. J Pediatr Surg 1991;26:1401-1403. 128. Taguchi T, Suita S,Yamanouchi T, et al: Antenatal diagnosis and surgical management of congenital cystic adenomatoid malformation of the lung. Fetal Diagn Ther 1995;10:400-404. 129. Thompson DP, Moore TC: Acute thoracic distress in childhood due to spontaneous rupture of a large mediastinal teratoma. J Pediatr Surg 1969;4:416-419. 130. Thompson J, Forfar JO: Regional obstructive emphysema in infancy. Arch Dis Child 1958;33:97-101. 131. Thorpe-Veeston JG, Nicolaides KH: Cystic adenomatoid malformation of the lung: Prenatal diagnosis and outcome. Prenat Diagn 1994;14:677-681.
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132. Ueda K, Gruppo - R, Martin L, et al: Rhabdomyosarcoma arising in a congenital cystic adenomatoid malformation. Cancer 1977;40:383-388. 133. WarnerJO, Rubin S, Heard BE: Congenital lobar emphysema: A case with bronchial atresia and abnormal bronchial cartilages. B r J Dis Chest 1982;76:177-181. 134. Weimann RB, I-Iallman GL, Bahar D, et al: Intrathoracic meningocele: A case report and review of the literature. J Thorac Cardiovasc Surg 1963;46:40-49. A
135. Winters WD, Effmann EL, Nghien HV, et al: Disappearing fetal lung masses: ~ m ~ o r t a n cofe postnatal ima,$ng studies. Pediatr Radio1 1997;27:535-539. 136. Wright JR Jr, Gillis DA: Mediastinal foregut cyst containing an intramural adrenal cortical rest: A case report and review of supradiaphragmatic adrenal rests. Pediatr Path01 1993;13:407-409.
Laryngoscopy, Bronchoscopy, and Thoracoscopy Bradley M . Rodgers and Eugene D. McGahren Ill
The ability to view the larynx and tracheobronchial tree directly in living subjects has long intrigued physicians. Bozzini, in 1806, is credited with being the first to design an instrument specially to visualize the larynx and upper a i r ~ a yHis . ~ hollow tube was illuminated by a wax candle whose light was reflected with a mirror down the axis of the instrument. Babington, in 1829, devised the laryngeal mirror, which used reflected light. Several physicians subsequently developed rigid tubes with reflected light for observation of the esophagus and proximal part of the stomach. The major breakthrough, however, in the evolution of endoscopy came in 1879 when Nitze developed a cystoscope with a distal lens illuminated by a heated platinum Shortly thereafter, Nitze adapted Thomas Edison's discovery of the incandescent light bulb to his telescopic instrument by placing a bulb with a miniature filament at the end of the tube. Kirstein developed a laryngoscope with a blade, similar to our modern Miller blade, that was illuminated by an incandescent bulb in the handle, and Chevalier Jackson modified this instrument by placing the bulb on the distal portion of the blade and adding a removable floor to the laryngo~cope.2~ The final significant advance in rigid endoscopic technology was development of the Hopkins rod-lens system. Hopkins constructed a rigid endoscopic telescope with a series of lenses separated by quartz glass that enormously improved transmission of light through the instrument and allowed more magnification and better image resolution than had ever before been possible. In turn, this development allowed for miniaturization of endoscopes, applicable for use in children, and recording of highresolution images on film and television. Hopkins was also instrumental in development of the early flexible fiber-optic endoscopes. In 1930 Lamm discovered that images could be transmitted through thin fiberglass threads that were oriented and bound tightly t0gether.2~A prototype flexible gastroscope using this fiber-optic technology was developed by Hopkins in 1954 and was first used clinically by Hirschowitz et al. in 1958.18Ikeda adapted this same technology to the development of a flexible fiber-optic bronchoscope in 1970.21
Subsequent refinement in this technology allowed the development of truly miniaturized flexible fiber-optic laryngoscopes and bronchoscopes, suitable for use in infants and children of any size. The history of the development of thoracoscopy, in significant measure, parallels that of airway and gastrointestinal endoscopy. In 1910 HansJacobaeus used Nitze's cystoscope to visualize the pleural space in patients with pulmonary tuberculosis.22 In that era, artificial pneumothorax was known to be effective in treating many patients with cavitary tuberculosis, and Jacobaeus quickly perfected techniques to perform "closed intrapleural pneumolysis" with the cystoscope and a galvanic cautery. Jacobaeus coined the term "thoracoscopy" and by 1921 was able to of show the utilitv of this ~ro'edure for the diagnosis " intrathoracic carcinoma by observation and direct biopsy.z3 Rodgers and Talbert used the Hopkins rod-lens tele&ope for~horacoscopyand suggested the use of this technique for lung biopsy for the diagnosis of pulmonary infiltrates in immunocompromised children and reported its successful application in this clinical setting in 1976.59
LARYNGOSCOPY Indications Laryngoscopy is used for both diagnostic and therapeutic purposes in pediatric patients. The most common indication for laryngoscopy in infants and children is for the evaluation of stridor.17a32The term stm'dor refers to a highpitched respiratory sound created by turbulence of airway gases. Laryngeal and supraglottic pathology usually creates inspiratory stridor, which may change in nature with different positions or certain activities. Tracheal narrowing is generally manifested as expiratory stridor. Most infants and children with persistent inspiratory stridor should undergo laryngoscopy to establish a precise anatomic diagnosis. Other common indications for diagnostic laryngoscopy in children include a change in cry or voice, acute respiratory distress, or repeated episodes
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of aspiration. Indications for therapeutic laryngoscopy in children include the treatment of congenital or acquired subglottic stenosis, laryngeal webs, laryngoesophageal clefts, and laryngeal papilloma. Laryngeal foreign bodies, though uncommon, can be a cause of sudden respiratory distress and are thus an important indication for emergency laryngoscopy.
Instrumentation A surgeon performing laryngoscopy in infants and children must be skilled in the use of both flexible and rigid endoscopes and must have a broad array of instrumentation available. Often, rigid and flexible instruments are used in conjunction with each other because each has advantages and disadvantages in certain clinical situations. The standard rigid laryngoscopes used in pediatric practice are open sided with blades varying between 8 and 13.5 cm in length. Illumination is provided by a high-intensity light source aimed down the blade from a prism in the handle of the instrument (Fig. 62-1). Certain specialized laryngoscopes, such as the pediatric Dedo laryngoscope, allow suspension laryngoscopy for more complex operative procedures. The anterior commissure endoscope has an 1lcm-long blade with a keel configuration of the distal portion (Fig. 62-2). This endoscope is helpful in exposing
Anterior commissures endoscope. This instrument has an 11-cm-longblade with a keel configuration of the distal portion (inset).Illumination is provided by a prism in the handle. This instrument may be suspended.
-
cmo
I
2
3
4
5
Pediatric rigid laryngoscopes. These instruments have blades ranging from 8 cm (A) through 13.5 cm (C) in length. Illumination is provided by a light prism in the handle of the instrument. These instruments may be suspended.
the anterior aspect of the larynx in small infants. In addition, the configuration of the blade allows abduction of the vocal cords for the diagnosis of a laryngoesophageal cleft. The flexible instruments used for laryngoscopyin infants and children vary in size from the 2.0-mm-outerdiameter ultrathin bronchoscope to the 3.6mm-outerdiameter pediatric bronchoscope. The ultrathin endoscope does not have an instrument or suction channel and has only tweway deflection of the tip, thus limiting its use to diagnostic examinations. The standard pediatric flexible bronche scope has two-way tip deflection and a suction or instrument channel. This endoscope can be used satisfacte rily to visualize the larynx in all but very small premature infants (lo0 mL/day) over days to weeks.362 It occurs in approximately 1% of patients with CF and is more frequent in those patients with severe lung disease.lz4 Most of these patients are older than the age of 10 years. The pathogenesis is related to the enlargement and tortuosity of the bronchial arteries and the multiple anastomoses that form between these vessels and the pulmonary arteries (Fig. 6410) .407Nonbronchial arteries may also form collaterals with the bronchial circulation or enter the lung through granulation tissue. Most episodes of major hemoptysis resolve spontaneously, but sedation and the discontinuation of medications that impair coagulation should be initiated. Hemoptysis usually indicates deteriorating lung function, and thus antibiotics may be used at this time to treat underlying infection. Vasopressin, endobronchial balloon tamponade, selective mainstem intubation, and topical a-adrenergic agonists have also been used.Z1 Bronchial artery embolization has emerged as a highly successful nonsurgical intervention for the short-term control of hemoptysis.177 Several series have demonstrated that this technique is safe and effective for the control of massive hemoptysis."~s6~41°However, up to 20% of these patients require repeated embolization. Failure of embolization is mainly attributable to nonbronchial colwith the lateral~.",~ogBronchoscowv can be used to h e l ~ preoperative localization of bleeding. Surgery with lobectomy may be lifesaving for patients who fail embolization or for those patients with fkminant, massive hemoptysis. ' i
Complications of Pneumonia Pneumatocele Pneumatoceles are small, thin-walled structures consisting of single or multiple cysts within an air-lined cavity secondary to alveolar and bronchiolar necrosis. These abnormalities are seen frequently as a consequence of infection by S. aureus, group A Streptococcus, and occasionally H. influenzae. Pneumatoceles secondary to S. aureus infections may be identified early in the disease process and occur in up to 80% of patients.*03 Pneumothorax and pyopneumothorax are complications resulting from the
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64
Infections a n d Diseases of the Lungs, Pleura, and Mediastinum
A
1015
B
A, Arteriogram obtained to identify the cause of hemoptysis in a 10-year-old girl with cystic fibrosis. Note the tortuous bronchial artery. B, After successful Gelfoam embolization, the peripheral branches of the artery are not visualized.
rupture of infected pneumatoceles.334 These lesions can be difficult to distinguish from congenital cysts of the lung. However, pneumatoceles are prone to spontaneous resolution whereas congenital abnormalities should not involute. Follow-up of chest radiographs are required until the resolution of the pneumatocele, and a CT scan may be useful in suspicious instances (Fig. 6 4 11) .
Lung Abscess A pulmonary abscess develops when a localized infection in the lung parenchyma becomes necrotic and then cavitates. Classically,pulmonary abscesses were classified into primary (occurring in healthy children) or secondary (occurring in otherwise compromised children).ze However, it is now clear that lung abscesses occur almost exclusively in areas of pneumonia.27 When appropriate antibiotic therapy is administered early, the frequency of lung abscesses decreases considerably. Abscesses developing in immunocompromised, severely ill, or occasionally very young patients have recently become a more frequent problem. Occasionally, congenital bronchogenic or pulmonary cysts may become secondarily infected. These lesions may be indistinguishable from lung abscess on chest radiographs (see Fig. 6 4 1 1C and Fig. 6412).
History In the 17th century, Bonet described two patients whom he cured of lung abscess by external drainage.165In the 1930s, Neuhoff and TourofP68 reported good results with one-stage surgical drainage of acute putrid abscess of the lung. A two-stage procedure, the first step to induce pleural symphysis, was used by Welch,3gl with a mortality rate of 40%. The treatment of lung abscess by resection in the early 1940s gave way to almost total reliance on antibiotics, which is still the approach now.306
Pathogenesis The aspiration of gastric contents is a leading cause of chronic pneumonia and lung abscess in children,27
particularly in those with neurologic deficits.sfioAspiration may occur acutely during trauma, anesthesia, or epileptic seizures or in those children with severe gastroesophageal reflux. Patients with repaired esophageal atresia or esophageal dysmotility are also at risk of a~piration."~ The aspiration of foreign bodies, including blood or tissue after tonsillectomy, were previously common antecedents of lung abscess.27,"fi Such abscesses are now infrequent because they are prevented by prompt bronchoscopic removal of foreign objectsgi and by endotracheal intubation and pharyngeal packing, which protects against aspiration during operations on the oropharynx. Lung abscess is an occasional complication of bacterial pneumonia and is much less frequent in the pediatric population than in adults.36oThe most common causative organisms are anaerobes," followed by S. aureus, Pseudomonas, streptococcalspecies, pneumococci, and occasionally H. influenzae. Other bacteria implicated in lung abscess include Klebsiella, Eschen'chia coli, Peptostreptococcus, and Peptococcus. Children with cellular or humoral immune deficiencies, either congenital or acquired, are occasionally unable to eradicate a pulmonary infection despite appropriate antibiotics, leading to inflammation, the breakdown of pulmonary parenchyma, and eventual abscess formation. Histologically, a lung abscess may be identified 18 to 36 hours after the inciting event but may only be apparent on chest radiographs after 7 days.27 When a lung abscess occurs in infants, an underlying congenital anomaly, such as a bronchogenic cyst or congenital cystic adenomatoid malformation, should be suspected (see Fig. 6 4 1 1).84These lesions require resection but initial treatment with antibiotics with or without drainage is usually indicated. The position of the child at the moment of aspiration determines the location of the lung abs~ess.")~ In supine patients, the superior segments of the lower lobes are most often involved. If the child is on the right side, the right upper lobe is at risk; if the child is on the left side, the apical posterior segment of the left upper lobe may be the site. The upright child aspirates into basilar segments of the lower lobes. The distribution of lung abscesses in various lobes and segments in children is similar to
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A, A 5-year-old child presented with a right lower lobe pneumonia that responded to Intravenous antibiotics. B, During outpatient monitoring, small cysts were noted 6 weeks later and appeared to coalesce in a larger pneumatocele on this radiograph, taken 11 weeks after the initial study. Follow-up was recommended. C, At 14 years of age, the patient presented with a new episode of infection with a large air-fluid level and some smaller ones. Intravenous antibiotics were required for more than 2 weeks. CT confirmed the presence of three cysts. Six weeks later a right lower lobectomy was performed and microscopic examination confirmed a type I congenital cystic adenomatoid malformation.
that in adults. Lung abscesses often occur at the periphery of a segment or lobe, making them amenable to external drainage procedures.
Diagnosis The most common symptoms caused by lung abscess include fever, cough, chest pain, anorexia, productive sputum, weight loss, malaise, hemoptysis, and chills. Purulent sputum may be easily obtained from older children to help with a bacteriologic diagnosis; younger patients usually swallow their secretions. Putrid sputum is characteristic of an anaerobic abscess. The affected area of the chest may be dull to percussion and have decreased breath sounds. Leukocytosis is common. Patients may also present with restrictive lung disease patterns from the enlarging abscess or secondary to pleuritic chest pain. The diagnosis of lung abscess is established by a chest radiograph that shows a cavity, commonly with an air-fluid level (see Fig. 6412). An abscess should be distinguished
from pneumatocele, a localized collection of intrapulmonary air that usually does not have an air-fluid level, and from empyema with an air-fluid level. CT has become a valuable adjunct in the diagnosis and characterization of lung disease in complicated pneumonia, revealing pathology that may not be apparent on plain chest radiographs.lol
Treatment A specific bacteriologic diagnosis should be established before treatment whenever possible. Diagnostic bronchoscopy with direct aspiration of purulent fluid from the parent bronchus should be performed, except in those older children who are able to induce a satisfactory sputum sample. The needle aspiration of a peripheral abscess cavity under imaging guidance to isolate bacterial species and drain collections has been used with moderate su~cess.2~Vsolation of the causative organism is possible with this technique even if patients are concurrently receiving antibiotic therapy.
CHAPTER
64
Infect ions a n d Diseases of the Lungs, Pleura, a n d Mediastinurn
1017
This may take from 1 to 6 months.28 The most effective antibiotic for the treatment of lung abscess has been clindamycin. Aminoglycosides are usually recommended for coliform bacteria. If Pseudomonas is strongly suspected, then an appropriate p-lactam with an aminoglycoside is recommended."O Medical therapy for lung abscesses is frequently unsuccessful in neonates and immunocompromised children, in whom the mortality approaches 20%.391Percutaneous catheter drainage of the abscess may be helpful in acutely ill children,"".O99.3R6.41' particularly for those who experience rapid progression of the disease despite maximal antibiotic therapy. The complications related to percutaneous techniques occur occasionally and include pneumothorax, hemothorax, incomplete drainage, and ~ ~ ~ ~ ~resection ~ of the bronchopleural f i s t ~ l a s . 2Surgical lung abscess by segmental resection or lobectomy is recommended for the chronic, large, and thick-walled abscesses or for those few patients who do not respond to intensive antibiotic therapy or percutaneous d ~ - a i n a g e . ~ ~ , z ~ ~ Other indications for resection include chronic abscesses lasting longer than 3 months, persistent significant hemoptysis, bronchial stenosis, significant bronchiectasis, and massive pulmonary necrosis.
Empyema
History Even during the ancient times of Hippocrates, Paul of Aegina, and Fabricius, empyema was a known complication that followed pulmonary infections and required external drainage for cure. In the 16th century, Park manually evacuated a putrid hematoma from the pleural cavity of a French soldier.165 Formal decortications were performed by Kuster in 1889 and Fowler in 1891.E5 Until the antibiotic era, discussions of therapy for empyema largely centered on the relative advantages of open drainage, various types of closed drainage, and the optimal time for the use of these measures.93
Definition and Pathogenesis B Lung abscess after aspiration in an infant. A, A thick-walled cavity is present on the anteroposterior supine view. B, An air-fluid level is visible on the lateral decubitus view.
The preferred treatment of lung abscess is appropriate intravenous antibiotic therapy and drainage. Satisfactory drainage can usually be accomplished by chest physiotherapy with postural drainage and percussion and by occasional bronchoscopic aspiration. For children who are unable to cough adequately, therapeutic bronchoscopy or transbronchial drainage may be necessary. Intravenous antibiotics are recommended for 2 to 4 weeks, followed by oral antibiotics for a total treatment period of 6 to 8 weeks. Antibiotics are discontinued when the child is symptom free and the chest radiographs are clear.
An empyema is the accumulation of purulent fluid in the pleural cavity and complicates pneumonia in up to 30% of children.359 It may also occur after trauma, neoplastic processes, intrathoracic esophageal perforation, or surgeries on the chest. Normally, the pleural membranes are permeable to liquid and a small amount of fluid exists between the visceral and parietal pleura to minimize friction during respiration. When the adjacent lung is healthy, the pleural cavity is generally resistant to infection. Empyema, once established, exhibits three characteristic stages67.314: (1) an exudative or early stage when the fluid is thin and of low cellular content; (2) an intermediate or fibrinopurulent stage during which large numbers of polymorphonuclear cells and fibrin are deposited in the pleural space, progressively impairing lung expansion and leading to the formation of fluid loculations; and (3) a final stage or organizing empyema during which a thick exudate forms and fibroblasts invade the fibrinous peel. The empyema may be diffuse and involve the entire
1018
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pleural space, or it may be localized and encapsulated in an interlobar, diaphragmatic, or paramediastinal location. Currently, the most common organisms in childhood empyema are S. pneumoniae, S. aureus, and H. influen~ae.l2~ Other streptococci, mixed oral flora, and anaerobes have also been classically associated with the development of empyema. The changes in bacteriology are likely due to changing antibiotic resistance patterns. However, the incidence of empyema may be increasing,l0"292 and the virulence of the causative organisms appears to impact the natural course and, ultimately, the management of these patients.241 Tuberculous empyema is much more rare than effusion and is associated with a high bacterial load within the pleural space. Mycobacterial resistance is a problem in this situation owing to the poor pleural penetration of standard chemotherapeutic agents.174
Clinical Manifestations and Diagnosis The symptoms of empyema in a child are usually those of a short history of pulmonary infection followed by respiratory distress, fever, and cough. Chest or shoulder pain coupled with abdominal pain, distention, and ileus may intensify the respiratory difficulty. The radiographic appearance often includes bilateral pulmonary involvement with pneumatoceles occasionally identified within the lung. Haziness of a hemithorax may represent either pulmonary consolidation or pleural fluid. In the early exudative phase, the pleural fluid flows freely along the lateral chest wall on decubitus views (Fig. 6413). In advanced empyema, the exudate is a solid mass of fibrin and does not move with changes in position. In the intermediate fibrinopurulent stage, loculations typically develop (see Fig. 6413C). Air-fluid levels within the loculations suggest the presence of anaerobes in the pleural contents. Thoracentesis may provide valuable information on the quality of pleural fluid. The progression to advanced-stage empyema may be suspected if the fluid demonstrates any of the following characteristics after diagnostic thoracentesis: (1) gross pus, (2) pH < 7.0, (3) lactate dehydrogenase > 1000 U/mL, (4) glucose < 40 mg/dL, and (5) bacteria visible on Gram stain.
Treatment Primary therapy for empyema is the administration of high-dose intravenous antibiotics. Effective drainage of the pleural space also speeds the resolution of the empyema. Fluid that layers in the decubitus position may be amenable to chest tube drainage alone. Loculated fluid collections may not be sufficiently drained in such a manner, and the optimal managemen.t of these patients is still debated. Fibrinolytic therapy was recommended as early as the 1940s to improve the drainage of pleural fluid.3" Currentlv. ,, the use of fibrinolvtics remains controversial. Cameron and Davies64 reviewed the four randomized trials involving patients aged over 14 years conducted to date52,j"88,371and concluded that fibrinolytic therapy conferred significant benefit (shorter lengths of stay, increased chest tube drainage) without morbidity when compared with saline controls. However, routine use of this therapy could not be recommended owing to
the small numbers of patients involved in this metaanalysis. Several retrospective case series in children have also demonstrated inkeased pleural drainage with the use and streptokinase,76.2" with an average of ~rokinase20~,2~l 20% failure rate of therapy. Recombinant tissue plasminogen activator (alteplase) may provide even more effective drainage but has not been extensively evaluated thus far.394 Thomson and colleagues, in the only randomized trial in children to date,-assessed the efficacy of .~~~ urokinase in 60 children with e m ~ y e m a Although a significantly shorter length of stay was noted in the treatment group, control group patients had a much longer duration of prehospital illness (9 versus 5 days). Interestingly, this study also demonstrated a shorter length of stay for those patients receiving smaller-caliber chest tubes. In the end, there is evidence to support the use of fibrinolysis as an adjunctive therapy for children with complicated pleural effusions or empyema. The major reported complications with fibrinolytic therapy, including anaphylactic/allerplc reactions (with streptokinase), chest pain, hemorrhage, and bronchopleural fistula occurred rarely in these reports. Urokinase is no longer available on the market, whereas alteplase is very expensive. Decortication has been recommended in the treatment of complicated pleural effusions and empyema not responsive to medical therapy and attempts at pleural drainage. Indeed, using an empyema score, Hoff and colleagues demonstrated shorter and less complicated hospital stays for patients undergoing thoracotomy, particularly in severe disease.16Wideo-assistedthoracosco~ic surgery (VATS) is an excellent alternative to thoracotomy for this purpose and has been advocated by many as a primary intervention in pediatric patient~.77,104,14~,204,229,352 Given that patients with nonlocuiated effusions (stage 1) tend to recover with appropriate antibiotic therapy and chest tube drainage,67 VATS may play more of a role in late-stage empyema. Chen and colleagues7l noted that 70% of these patients eventually required surgery and that delay to surgical treatment increased length of stay. Patients in this series who were treated with VATS experienced the shortest lengths of stay, despite later intervenkon. Gates and colleagues systematically reviewed the English and Spanish language literature from 1987 to 2002 to determine the most effective treatment strategy for pediatric patients with empyema.l% In their analysis of 44 studies involving 1369 patients, only the length of stay could be shown to be statistically shorter for those patients treated by either thoracotomy or VATS. Unlike in adults for whom the American College of Chest Physicians has established guideline^,'^ treatment algorithms for pediatric patients with empyema vary widely and are often institution based. Interestingly, in a study from the Arkansas Children's Hospital,l22 a clinical pathway for the appropriate management of childhood empyema has been developed (Fig. 6414). In this prote col, if an empyema is identified on chest radiographs it is then assessed by ultrasound for the presence of loculations. If loculations are identified, early VATS is advocated. The results of this pathway have demonstrated significantly reduced lengths of stay and hospital costs when compared with the national children's database. However, others maintain that antibiotics and chest tube drainage
CHAPTER
64
Infections a n d Diseases of the Lungs, Pleura, a n d Mediastinum
1019
C A and B, An 11-year-old boy presented with left-sided pleuritic pain and fever. A, Chest radiograph shows a large left-sided effusion with mediastinal shift. B, Because of concern about an underlying malignancy, a CT scan was obtained that showed a large nonloculated fluid collection, with a collapsed lower lobe; fluid can be seen in the fissure. A chest tube was inserted and drained 400 mI, of serous fluid, with a lactate dehydrogenase of 4000 U/L, thus qualifying it as a fibrinopurulent empyema. There were no bacteria on Gram stain, but cultures grew Streptococcus. The patient improved with intravenous antibiotics, and the chest tube was removed 8 days later. Cand I), A 3-year-old girl had a more fulminant course. Loculations (arrow) and debris in the pleural fluid were evident on ultrasound in C. Despite early thoracoscopic drainage, she developed lung necrosis (seen on CT with intravenous contrast in D) with a persistent air leak, requiring 10 days in the intensive care unit and 1 month in hospital.
1020
PART
VI
THORAX ( ~ ~ 1 t i cpitI~\\,:i~ ~11 tor
Symptoms: cough, dyspnea, fevers
management of empyema in children. (From Finck C, Wagner C, Jackson R, Smith S: Empyema: Development of a critical pathway. Semin Pediatr Surg 2002;11:25-28,with permission.)
CXR - ?effusion
Yes
No
Obtain ultrasound iiLoculated
Treat underlying condition Pneumonia/antibiotics
Yes
4 VATS drainage
Thoracentesis
\
Yes
\
NO
Tube thoracostomy remove chest tube when < 50 mllday
Follow-up 4-6 weeks with CXR
are still the most cost-effective strategies for the treatment of empyema.248 Because of the lack of any prospective studies, there is a need for a multicenter, prospective, and randomized trial to answer ongoing questions regarding the best treatment of pediatric patients with empyema.
PEDIATRIC SPONTANEOUS PNEUMOTHORAX Primary spontaneous pneumothorax is defined as a pneumothorax occurring secondary to apical blebs or bullae It can without evidence of other lung pathology.293,332,3'J9 also occur in term neonates without any risk factors. In contrast, secondary spontaneous pneumothoraces occur in the context of underlying lung disease, such as cystic fibrosis or P jiroveci (carinii) pneumonia. Other lung infections, bronchiolitis, asthma (even mild), connective tissue disorders, congenital cystic adenomatoid malformations, and traumatic lung contusions are risk factors.8~."4~"? The incidence of primary spontaneous pneumothorax is estimated to be 7.4 to 18 per 100,000boys
Follow-up 4-6 weeks with CXR
and 1.2 to 6.0 per 100,000 girls in the United state^.^^"^^" Typically, the patient is a thin, lean adolescent who presents with an acute onset of ipsilateral pleuritic chest pain and nonproductive cough. Most patients are clinically stable on initial assessment. However, a small number may present in fulminant distress, including hypotension and respiratory failure, secondary to a tension pneumothorax. Other clinical findings in patients with pneumothorax include tachypnea and tachycardia. Chest radiographs confirm the diagnosis and may identify a secondary pathologic process within the lung. Expiratory films may be helpful to identify small pneumothoraces. Different methods are available to quantitate the size of the pneumothorax, because this factor is most likely to influence subsequent management. Indeed, a Light Index has been described that compares the diameter of the lung to the ipsilateral hemithorax as a means of quantitating the size of the pneumothora~.?2~227'1 Patients who present with an acute pneumothorax require supplemental oxygen and intravenous access. For those few patients presenting with a tension
CHAPTER
64
Infections and Diseases of the Lungs, Pleura, and Mediastinurn
pneumothorax, immediate needle decompression in the second intercostal space (midclavicular line) is necessary even before chest radiograph confirmation, followed by the prompt placement of a chest tube. A pneumothorax of less than 15% can often be managed by observation with or without supplemental oxygen, especially if the initial symptoms occurred more than 24 hours before presentation. Needle aspiration and the insertion of small pleural drains has also been used,2g3but the Delphi Consensus Statement (2001) does not support the routine use of needle decompression in this instance.10 Heimlich valves connected to the pleural drain allow for outpatient management of small pneumothoraces in compliant patients. Large pneumothoraces require the placement of a chest tube with underwater seal and drainage. An air leak that persists for more than 5 to 7 days may require further intervention, or at least confirmation that the For most chest tube in place is functioning pr0perly.2~~ young children (~),ii by inhibiting inflammation, scar formation, and infecmanagement strategies for ingestion are now well defined, tion. 16,lX,21.24.ii2,.i6.67,70,Y9 However,mortalim still occurs from particularly the use of fiber-optic endoscopy to assess the pharyngeal and laryngeal burns resulting in edema and ever, extent and severity of i n j ~ r y . ~ ~ ~ ~ J 2 W o wcontroairway obstruction, massive ingestion with perforation, versy still surrounds the use of steroids, antibiotics, and and complications after stricture dilatation or surgical esophageal stents and the timing, frequency, and method bypass of an irreversibly damaged esophagus.4.9~31~,"'48,4*7g of esophageal dilatation in the prevention and management of caustic strictures. Indications for definitive esophageal surgery or bypass and the type of procedure to use are also subjects of ongoing debate.31 EPIDEMIOLOGY The ingestion of corrosive substances remains a major health hazard in children, despite aggressive educational programs aimed at both children and adults, preventive labeling and packaging, and even legislation limiting the strength and availability of caustic SUbStanCeS.26,7.i.~~)~S~~2Z,~~91)~22,~23 In rural areas and in developing countries, caustic soda in both crystal and liquid form is used in home industry for soap making, fruit drying, and container cleaning on farms. In addition, the availability of innumerable over-the-counter caustic cleaning agents virtually ensures that children will continue to be at risk. The most distressing aspect is that the majority of ingestions occur in children younger than 3 years and are entirely preventable. Boys are more frequently i n v o l v e d . 2 ~ ~ 2 ~ ~ingestion ~ o x i c in children older than 5 years is suspect, and ingestion in adolescents (where girls predominate) is usually intentionalMji7";in these cases, larger volumes and more potent corrosive and caustic materials tend to be used. Although mortality is rare,
CAUSE Strong alkalis that are sold in both liquid and granular form are the principal cause of severe injury (Table 68-1).2" Household bleach, dishwasher detergents, and other cleaning agents, all of which are moderately alkaline, are the most frequent corrosive material ingested. However, these bums are usually limited to the esophageal mucosa, without extensive necrosis or subsequent stricture formation.26,e A wide variety of caustic substances can cause direct injury to living tissues and particularly to moist mucous membranes, including corrosives such as potassium and sodium hydroxide (lye) and phenols; reducing agents such as hydrochloric and nitric acids; desiccants such as sulfuric acid; oxidizing agents such as chromic acid, sodium hypochlorite, and potassium permanganate; and protoplasmic poisons such as acetic and formic a~ids.~'.O':J"The physical form of the substance ingested and its pH play a
CHAPTER
68
Caustic Strictures of the Esophagus
1083
and alkaline substances differs considerably. With acid ingestion, coagulation necrosis of the musoca, hard eschar formation, and usually limitation of acid penetration through the mucosa occur. With alkali ingestion, tissue Caustic Commercially penetration with liquefactive necrosis is followed by Substance Type Available From -destruction of the epithelium and submucosa, which may Acids Sulfuric Batteries extend through the muscle layer.1".9"fi1A friable disIndustrial cleaning agents colored eschar develops, under which tissue destruction Metal plating continues until the alkali is neutralized. The esophagus is Oxalic Paint thinners, strippers damaged principally at the areas of holdup: the cricophaMetal cleaners ryngeal area, the midesophagus where it is crossed by the Hydrochloric Solvents aortic arch and left mainstem bronchus, and immediately Metal cleaners Toilet and drain cleaners above the esophagogastric junction. Immediate spasm Antirust compounds and disorganized motility occur; these events may result Phosphoric Toilet cleaners in delayed emptying and even gastric reg~rgitation.~' Alkali Sodium hydroxide Drain cleaners Hemorrhage, thrombosis, and marked inflammation Potassium hydroxide Oven cleaners with edema may be seen in the first 24 hours after injury. Washing powders Depending on the degree of burn, inflammation may Sodium carbonate Soap manufacturing extend through the muscle layer until perforation occurs. Fruit drying on farms After 48 hours, there is evidence of thrombosis of submuAmmonia Commercial ammonia Household cleaners cosal vessels, which gives rise to local necrosis and gangrene. Ammonium hydroxide Bacterial contamination leads to the development of small Detergents, Sodium hypochlorite Household bleach, bleach cleaners intramural abscesses, which may extend to the mediSodium polyphosphate Industrial detergents astinum with full-thickness injury.'Ufter several days, Condy's Potassium Disinfectants, hair dyes necrotic tissue is sloug.hed, ed;ma decreases. and neovascrystals permanganate cularization begins. This early reparative or subacute phase is evident from the end of the first week through the second week after injury. Scar formation begins in the third substantial role in the site and type of postingestion week, when fibroblast proliferation replaces the submuesophageal injury, with a pH greater than 12 or less than cosa and muscularis and stricture formation commences. 1.5 being associated with severe corrosive injurie~.10."~~""6*~7s Mucosal re-epithelialization begins during the third week Crystalline drain cleaners in the form of concentrated and is usually complete by the s&th weekr~tis during this sodium hydroxide tend to adhere to the oropharynx or period that adhesions may form, narrowing or obliterating become lodged in the upper esophagus, where injury is the esophageal lumen. The end result may be a fibrotic most severe."2.4-4."")-127Highly concentrated caustic liquids stricture and a shortened e s o p h a g u s . l ~ fthe injury is usually pass rapidly through the oropharynx and cause transmural, necrosis may extend to the surrounding injury to the entrance of the esophagus, the midesophagus, mediastinum, leading to mediastinitis, or in an anterior and immediately proximal to the esophagogastricjunction. direction into the trachea, giving rise to tracheoesophageal Unlike alkaline solutions,which do not have much taste, or even aortoesophageal fist~las.".").~"~~ strong acids are bitter, burn on contact, and are usually Steroids have been used to modify the inflammaexpectorated. However, when swallowed, they pass rapidly tory response both at the site of the burn and in the through the esophagus and cause the most substantial deeper tissues, with the ultimate goal of less extensive damage in the antrum of the stomach. The injury tends ~ c a r r i n g . ~ 8 , " ~ " , ~ ~ , ~ ~ , ~ ~ )the W oextent w e v e rof , the initial to be worse when the stomach is empty.:)l The duodenum injury largely determines the outcome of the healed injury; and proximal small intestine are relatively protected by this can range from mucosal re-epithelialization,with loss pyloro~pasm.'"~2~"~~0~ Ferrous sulfate as tablets (Clinitest) of esophageal glands and some submucosal fibrosis but or capsules may also induce caustic injury to the esophapreservation of the muscularis, to complete replacement of gus or stomach.l!) Disk batteries contain concentrated the esophageal wall by fibrous t i s s ~ e .Once ~,~~ the muscle potassium or sodium hydroxide, but they rarely lodge in of the esophagus has been destroyed, it cannot regenerate; the esophagus because of their small size.'"f charged, at that point, maturation of the fibrous replacement with these batteries may also cause injury to adjacent mucosa epithelialization of the luminal surface is the only "positive" because of hydrolysis at the negative electrode. 0utcome.2~Reduction of scar tissue formation by induced inhibition of intermolecular covalent bonding of' collagen with lathyrogens and mitomycin C has been demonstrated experimentally but not clinically.'l,"-~',44 PATHOPHYSIOLOGY u
Much of what is known about the pathology of caustic injury in children has been derived from adult experience with self-inflicted injury and experimental studies in animals.3x..i:+.57,64,66,65j,78,Y7,106 Injury to mucosal surfaces occurs within seconds after contact with a strong acid or alkali..3~~""he nature of the injury caused by acidic
.
CLINICAL PRESENTATION Most infants and children who ingest caustic substances present with few symptoms or Only approximately one quarter have substantial objective evidence
1084
PART
VI
THORAX
of corrosive inge~tion.~"7~ The extent and severity of injury depend on the concentration and form of the ingested substance. Crystalline alkalis tend to adhere to moist surfaces and cause immediate pain; in this case, orophaGrade Description ryngeal burns and primarily upper esophageal injury result. 0 Normal Esophageal burns in the absence of objective oropharynI Edema and hyperemia of mucosa geal evidence may occur in a small percentage (510%)of Ila Friability: hemorrhage; erosion blisters, exudates, patients and should not deter the clinician from taking or whitish membranes; superficial ulcers the appropriate diagnostic steps. However, most patients Ilb Grade Ila plus deep, discrete or circumferential with extensive oropharyngeal injury present with substanulceration tial esophageal damage; esophageal injury is unlikely if llla Small scattered areas of necrosis; areas of brownish only the tongue and soft palate are involved.I,40,43,77 black or gray discoloration lllb Extensive necrosis The viscosity and specific gravity of corrosive acids are lower than those of liquid alkalis. As a result, acid ingestion is associated with rapid transit through the esophagus; thus, this organ may be largely spared. Damage occurs primarily in the antrum of the stomach because of the patients with a history of ingestion require endoscopy. pooling of swallowed acid proximal to the pylorus, which Some advocate endoscopy only in symptomatic patients.Ws74 goes into spasm on contact with the ingested a~id.~9,62,97,113 Technetium-labeled sucralfate radioisotope scanning Obvious signs and symptoms of injury may be evident, of the esophagus has been used successfully as a screenwith inflammatory mucosal edema in the oropharyngeal ing device, with lack of sucralfate adherence indicating area and severe pain in the mouth and in a retrosternal the absence of significant injury." Using endoscopy directi0n.2~2~~ This is often associated with agitation and findings to grade the severity of the injury, one can predict tachycardia. Drooling and inability to swallow indicate the long-term outcome, particularly with regard to subsevere posterior pharyngeal or upper esophageal injury.rn0.90 sequent stricture formation; however, it is sometimes Acute obstruction of the upper airway may result from difficult in practice to obtain an accurate assessment posterior pharyngeal and laryngeal edema caused by An attempt is made to visualize the (Table 68-2).37,m254 spillage of the caustic agent into the upper airway.54Jl" entire upper gastrointestinal tract, but identifying cirConcentrated ammonia fumes may be inhaled, causing cumferential or grade I11 injuries provides sufficient nasopharyngeal edema and leading to respiratory injury.54 information to initiate treatment protocols; attempts Although rare, esophageal perforation with mediastinitis, at further visualization are unnecessary and potentially peritonitis, and shock may occur.9~90 d a n g e r o ~ s Perforation . ~ ~ ~ ~ ~ in this situation is a severe complication that may be accompanied by mediastinitis and even mortality. In the presence of visual evidence of a pharyngeal burn with stridor, early esophagoscopy is INITIAL MANAGEMENT AND DIAGNOSIS contraindicated because of the risk of aggravating the Initial management is directed at maintaining an adequate airway 0bstruction.l2~Indirect fiber-optic laryngoscopy is airway and oxygenation and ensuring cardiovascular stauseful to assess the upper airway.g0Esophagoscopy may bility. A few patients may require immediate intervention be done at the same time if intubation is required, or it to maintain the airway. Once respiratory and hemodymay be done later, when edema of the upper airway has namic stability has been achieved, the noxious agent, its resolved. Initial radiographic studies should be restricted composition and concentration, and the circumstances to the neck, chest, and abdomen if aspiration or respiof ingestion should be investigated. Although the careratory burn is suspected. If fever, systemic sepsis, and giver should be able to identify the ingested substance, upper abdominal signs are present, perforation may have this information is often lacking. Many health regions occurred, and a water-soluble contrast esophagogram may have poison centers where detailed product information ~) be useful to provide evidence of p e r f o r a t i ~ n .A~ contrast is available.l17 In cases of caustic ingestion, inducing esophagogram is usually done after 10 to 14 days, when vomiting or encouraging the ingestion of any liquid is an assessment of the entire esophagus and upper gastroincontraindicated because the alkali is mostly neutralized testinal tract can identify the extent of injury and may by gastric acids, and the consequences of acid regurgitahelp in choosing the appropriate therapy (Fig. 68-1).71 tion may cause further injury. Also, inhaled or aspirated vomitus may introduce corrosive matter into the upper airway, leading to acute inflammation and edema with TREATMENT airway obstruction. Because the history and physical examination are unreIf a known mild irritant, such as hypochlorite bleach, has liable in assessing the degree of esophageal involvement, been ingested without evidence of injury, treatment can be endoscopic examination of the oropharynx and upper e~pectant.~3,",~28 If the substance ingested is not known gastrointestinal tract is crucial.' Fiber-optic endoscopy and symptoms are apparent, endoscopy is indicated."~37,92~96 is both accurate and safe, especially when done within For patients with first-degree burns (grade I injury), no 24 to 48 hours after i n g e ~ t i o n . ~ , ~ 0 ~ 9 j , ' 2Unnecessary 7-*28 specific treatment is necessary. Liquid oral intake is inititreatment is avoided when esophageal injury can be ated and extended to solids. If solid foods are tolerated, excluded; however, there is still debate about which the child can be discharged. Clinical follow-up at 2 to
CHAPTER
68
Caustic Strictures of t h e Esophagus
1085
use of very high dose steroids (dexamethosone 1 mg/kg for 4 to 6 weeks) has been a d v o ~ a t e d . * 2 ,However, *~~~ the number of patients in these studies was small, and morbid conditions, such as mycotic infection of the esophagus, osteitis, peptic ulceration, and osteoporosis, were significant. For patients with severe injuries, a nasogastric tube may be passed for early feeding purposes. In patients who are unable to swallow, the tube can be used for enteral feeding, to serve as a guide for prograde dilatation,and, to some degree, to maintain patency of the esophageal lumen. In most cases, oral feeding commences as soon as the patient is able to swallow saliva. If dysphagia occurs, an esophagogram can identify the extent of involvement. Concomitant use of antifungal agents, antacids, and acidsecreting inhibitors (H2receptor blockers or proton pump inhibitors) is widespread, but their efficacy has not been proved.g~,96~103,123
COMPLICATIONS OF INJURY AND TREATMENT If a stricture is demonstrated on contrast radiography done 10 to 14 days after injury, a program of dilatation is commenced (Fig. 68-2).g6Various methods can be used,
Localized stricture from ingestion of caustic crystals in a 4year-old. The patient was managed successfully by local resection and primary esophageal anastomosis.
3 weeks is indicated, and contrast examination is done if residual clinical symptoms of dysphagia are noted. Patients with moderate (grade IIa) or severe (grade IIb and 111) injuries require further treatment aimed at .~~ most the prevention of stricture f ~ r m a t i o n Although patients with grade IIa injuries recover completely, close follow-up is required, and endoscopy and dilatation must be done as prophylactic measure^.^^^^^ Major controversy surrounds the treatment options for severe injuriesnamely, the use of steroids and antibiotics, esophageal stents, and esophageal dilatation.ll* Grade IIIb injuries are rare in the pediatric age group and usually occur in adolescents attempting suicide. These injuries may require immediate and aggressive surgery if extensive necrosis and perforation are present, especially if the stomach is also invol~ed."3"~~ The use of systemic steroids is based on the knowledge that they inhibit the inflammatory response, which is However, in clinbacked by animal experiments.16,18~52,53,111 ical trials using a variety of dosing regimens, no statistical difference in the prevention of stricture formation was evident.5J20 Extensive retrospective reviews have also failed to show any significant benefit of steroid therapy for patients with severe injuries.38xgO More recently, the
A
B
A, Early esophagogram after caustic ingestion. B, Several areas of'full-thickness ulceration progressed to extensive strictures, which required esophageal bypass.
1086
PART
VI
THORAX
ranging from mercury-filled bougies, flexible-graded bougie dilatation, guidewire-directed metal olives (Eder-Puestow system), or various balloon dilators." Dilatation should always be attempted with great care. Initial passing of bouges for prograde dilatation should never be done blindly. If there are several strictures and visualization is difficult, it is much safer to place a transesophageal string, which is then used to guide the dilators either retrograde through the gastrostomy or antegrade through the mouth.' lYThis is best done by initially passing a soft-tipped, flexible guidewire into the distal esophagus through a ga~trotomy.~~.ll~ Easy access to the gastroesophageal orifice is gained by advancing a polyvinyl chloride endotracheal tube up the lesser curve through the gastrotomy." For satisfactory dilatation of a stricture, a general anesthetic is required in the early stages to protect the airway. To be effective, dilatations should be done at least once a week, commencing with catheters that are one or two French sizes smalle; than the estimated diameter of the stricture. It is generally prudent not to dilate more than two to three sizes larger than the size of the first dilator meeting resistance. Initially, dilatation should be continued as long as esophageal healing and a progressive increase in esophageal caliber are noted, along with re-establishment of normal feeding. Poor prognostic factors are delay in presentation, extensive grade I11 injury, ongoing esophageal ulceration, a densely fibrotic stricture that cracks on dilatation, a stricture longer than 5 cm, and inadequate lumen patency despite repeated dilata~ .data ~ support the tions over a 9- to 12-month p e r i ~ d .No routine use of prophylactic antibiotics; however, if systemic infection or transmural necrosis occurs, appropriate antibiuring otic therapy should be c ~ m m e n c e d . ~ ~ . ~ " ~ Wrecovery, it is essential to provide adequate nutrition; in most cases, the gastrointestinal tract can be used, with access through the nasogastric tube or by placement of a feeding gastrostomy or jejunostomy tube. If dilatation fails and a dense stricture develops, it requires treatment." As with other benign esophageal strictures, the incidence and severity of gastroesophageal reflux must be investigated and excluded as a contributing cause Gastroesophageal ,~~,~~ reflux of the persisting s t r i ~ t u r e . 2 ~ should be managed surgically, if necessary, before definitive procedures are attempted.I0l Localized strictures may be resected with an end-to-end anastomosis. the whole esophagus must first be carefully assessed endoscopically to confirm that the stricture is localized, because the fibrotic injury may be much more extensive than is evident on radiography.9." A healthy color of the esophageal mucosa and distensibility with air insufflation at esophagoscopy are useful signs when assessing the esophagus. Local injection of steroids (1% triamcinolone acetate) into short strictures has had some success when combined with dilatation but has not been assessed prospectively.13.20,42.5668,80 Some investigators advocate the use of esophageal stenting by means of an indwelling nasogastric t~be.2~,"3,"The lumen is maintained, and adhesion of de-epithelialized areas of the esophagus is prevented; simultaneously, tube feedings can be given. Over the years, various types of
stents have been used (e.g., silicone, polytetrafluoroethylene) .1412739344.8,1*5If used, stents should remain in place for at least 6 weeks, at which time epithelial healing should be complete and fibrosis will have begun to mature. However, in many cases, these tubes are not well tolerated; they may gastroesophageal reflux, and if an extensive inflammatory response through the muscle occurs, the stent must be in place for much longer to be effective. Stents have also been used in the management of esophageal fistulas resulting from caustic injury or dilatation therapy, mainly as a temporizing measure before surgical repair or esophageal bypass (Fig. 68-3).87
LONG-TERM OUTCOME Extensive caustic injury may heal without stricture or may respond to the various prophylactic and therapeutic measures outlined. However, residual motility dysfunction can be expected, and an achalasia-like picture has been described,B344j.85 Carcinoma of the previously injured esophagus is a real risk, but the disease has a latency period of 15 to 40 years.8,'*,15,46,58,69,73,96,118 Also, Barrett's esophagus has
ow ever.
-
-
A
B
A, Contrast esophagogram of a persistent caustic stricture of the midesophagus, with esophageal shortening and marked gastroesophageal reflux (arrow). £3, This resolved after antireflux surgery and dilatation.
CHAPTER
68
Caustic Strictures of the Esophagus
1087
been observed following lye-induced i n j ~ r y .Thus, ~ ~ ~ ~ used ( ~ for less extensive but persistent strictures." Deciding long-term surveillance with esophagoscopy is advocated. which procedure to use and whether to bypass or resect In this regard, two prudent questions arise: To what the injured esophagus is influenced by local practice and extent should the clinician try. to -preserve the damaged the morbidity and mortality from esophageal resection. esophagus? When should attempts at dilatation-be Clearly, the risks associated with resection must be less abandoned?"-94 than the risk of cancer in the retained but bypassed esophagus.&.8,",."2,102 Currently, there is a trend toward earlier esophageal bypass in a severely injured esophagus, with the addition of resection of the damaged esophagus.9~95~109~~~~ Complications such as abscess or cyst formation in the RESULTS bypassed but retained esophagus are rare, and carcinoma has not been reuorted.".":! Between 1957 and 2003,327 children with caustic injuries Esophageal perforation, as evidenced by pain, fever, and of the esophagus were treated at the University of Cape tachycardia, is a life-threatening iatrogenic complication Town teaching hospitals (Red Cross Water Memorial of esophageal dilatation (Fig. 68-4).",m With immediate Children's Hospital and Groote Schuur Hospital). The . recognition by endoscopy-or contrast swallow, many average age was 35 months, with a range of 9 to 144 months. patients with a perforated esophagus can be treated Forty-eight percent were younger than 2 years. In recent conservatively with systemic antibiotics and parenteral years (1990 to 2003) there has been a trend toward an n~trition.9"~()7.~2~ Established methods of management increasing number of caustic ingestions (832), but only with either thoracostomy drainage or primary repair with 305 patients (36%) required hospitalization, and of these, proximal and distal esophageal and gastric diversion are only 24 (8%) developed strictures. The mean age was reserved for patients with delayed recognition or exten3.1 years, with a slight male predominance (58%). Most al irrigation with or sive disruption. ~ r a n s e s o ~ h a g ewater children ingested household cleaners or disinfectants without chest drainage as a supplement to conservative (Table 68-3). measures has also been advocated.'j3If dilatation has failed Overall, 82 of the 327 (25%)patients developed fibrous or if the esophagus cannot be salvaged, esophageal bypass strictures of the esophagus. Caustic soda was the most or substitution is indicated. O~erationscurrentlv used are common corrosive agent (78 of 82 patients) and was taken colonic interposition, gastric tube esophagoplasty, jejuin the crystal form by 31 children. This form of caustic nal interposition, and gastric advancement (see Chapter soda was used extensively on orchards and sheep farms. Colonic patch procedures have also been 69).y'.X"~~lOOJ1l.ll~ Acid burns were responsible for only four strictures.
A
B
C
Left-sided tension pneumothorax secondary to perforation after dilatation of an upper esophageal caustic stricture. A, Treatment by thoracotomy drainage. B, Contrast study 10 days later shows that the leak has been contained. C, Healed esophagus 12 weeks after perforation. Esophageal replacement was not required in this case.
1088
PART
VI
THORAX
Substance
No. of Patients
Acids (toilet bowl cleaner, soldering flux, antirust compounds, battery acid) Anionic surfactants and polyphosphates (household cleaning agents) Sodium hydroxide (drain and oven cleaners) Ammonium hydroxide (bleach, cleaning agents) 2% to 3.5% sodium hypochlorite (bleach) 3.2% phenols, 2% alkali (household cleaners and disinfectants) Permanganate crystals Dishwasher detergent granules* Unknown *Very corrosive because of granular form and alkalinity of binders.
One patient with an acid burn who had extensive esophageal injury developed a severe stricture of the stomach antrum and upper jejunum; another patient presented 8 months after ingesting soldering acid with a near-complete antral stricture. Early management did not include steroids or the routine use of antibiotics; antibiotics were administered only in cases of infection, usually of the respiratory tract. Recently, we have empirically used an antifungal agent (nystatin [Mycostatin]) prophylactically and an antacid coating agent (sucralfate) to protect the esophagus from fungal infection and gastroesophageal reflux. Most patients had endoscopy only as far as the first grade I1 lesion encountered. A nasogastric tube was inserted into the stomach for feeding purposes and to prevent total occlusion of the esophageal lumen. Strictures were initially treated by regular prograde dilatation. Bougienage commencing 10 to 14 days after injury was performed with the patient under general anesthesia. Antegrade dilatation was initially performed through a rigid esophagoscope using gum elastic bougies; for the last 2 decades, however, this has been done using a fiber-optic endoscope with balloon dilators, the Eder-Puestow wire-guided dilator system, or string-guided dilatation with a transesophageal string and gastrostomy. Successful dilatation was usually accompanied by a steady lengthening of the interval between successive treatments and was confirmed by contrast-swallow radiography. Over the past decade, we have been using the string-guided system through the mouth because we found that the gastrostomy aperture is often too small for the largerdiameter bougies. The Eder-Puestow system is useful on occasion, but for the most part, it is too rigid and does not allow sufficient "feel" for safe dilatation. The esophageal balloon dilator was ineffective for established fibrotic strictures. Patients with an ulcerated esophagus requiring repeated dilatations were given prophylactic antibiotics with each dilatation as a precautioil against dissemination of bacteria, after a brain abscess occurred in one of our patients.' Two patients received a local injection of the steroid 1% triamcinolone-one into a very scarred supraglottic area, and the other into a fairly localized esophageal stricture-but neither patient had
sustained effects. An esophageal stent was used for 6 weeks in one patient with an extensive grade I11 injury, but within weeks of removal, complete obliteration of the lumen recurred. Of the 82 patients with strictures, 38 (46%) responded to repeated dilatations, whereas the other 44 required operative management. Ten of the 44 had severe oiopharyngeal burns in addition to the scarred esophagus, and 6 of these patients required tracheostomy. The 82 patients had an average of 18 dilatations (range, 1 to 38). The 38 who responded to dilatation had an average of 17 dilatations over a period of 15 months (range, 0.5 to 20 months); the 44 children with strictures who required esophageal replacement were dilated an average of 12 times-(range, 1 to 31) over a 13month period (range, 0.5 to 87 months). The outcome was poor when presentation was delayed for more than 1 month, with 8 of 10 such patients requiring esophageal bypass. Length of stricture greater than 5 cm was another adverse factor; 1'7 of 18 patients with this finding did not respond to dilatation. The most significant complication was esophageal perforation, which occurred in 11 patients (Table 68-4). Perforation occurred after an average of six dilatations. Two perforations occurred during the first dilatation, and others occurred after as manv as 14 dilatations, indicating that perforation can occur at any stage. With early recognition, perforation was associated with minimal morbidity, and some patients could be treated conservatively with intravenous antibiotics alone. If extension of the inflammatory process or perforation into the mediastinum or pleura occurred, these areas were drained. One patient developed a tracheoesophageal fistula and had esophagectomy of an extensively scarred esophagus, followed by retrosternal left colonic interposition; no complications such as cyst or abscess formation have occurred in the retained esophagus. Seven patients developed gastroesophageal reflux, six of whom underwent antireflux surgery. Four subsequently responded to dilatations, whereas the other three required esophageal replacement. Since 1969, we have performed an isoperistaltic retrosternal left transverse and left descending colon interposition based on the ascending branches of the left colonic vessels in 35 cases and local resection with end-to-end anastomosis in 1 case. Details of the operative procedure have been reported." Colonic interposition has proved to be a successful conduit for all nutritional needs, with satisfactory long-term results (Fig. 68-5; Table 68-5).
Complication Perforation Tracheoesophageal fistula Gastroesophageal reflux Pneumonia Cerebral abscess Hemorrhage Tracheostomy
No. of Patients 11
1 7 8 1 1 6
CHAPTER
68
Caustic Strictures of t h e Esoptlagus
1089
Some practical aspects of the operation are worthy of mention and should be emphasized, because most complications can be prevented. The feeding vessels of the conduit must be carefully selected and preserved with some adjacent mesentery. Usually, two of the ascending branches of the left colic artery can be retained. The colonic segment required to reach the upper esophagus and pharynx should be measured on the mesenteric border while the pedicle is being pulled taut. As this is being done, the bowel contracts circumferentially and shrinks in length after decompression and irrigation. Care must be taken to avoid entering the pleura when tunneling digitally in a substernal direction, because a tear into the pleural cavity sucks the colon into the adjacent thorax and may result in tortuosity of the graft. Redundancy of the lower end of the conduit should be avoided by resecting any distal redundancy before cologastric anastomosis is performed. The upper anastomosis is performed as a primary procedure in a meticulous manner with an inverted U-shaped inlay of colon into the anterolateral proximal esophagus or pharynx, thereby extending the length of the anastomosis and reducing the incidence of stricture. Pyloroplasty should be done as an adjunct to ensure adequate gastric emptying, thus preventing gastrocolonic reflux or reflux into the retained distal esophagus. Tight closure of the abdominal sheath in the epigastrium should be av0ided.303:~At the end of the procedure it is useful to hitch the stomach to the anterior abdominal wall with sutures or by placing a gastrostomy to avoid a posteriorly directed "bow" of the inferior aspect of the graft.
REFERENCES
Young man 21 years after substernal left colonic esophageal replacement for caustic injury, with accompanying esophagogram. He recently developed fatal squamous carcinoma of the cricopharynx nearly 30 years after caustic ingestion.
No. of Patients Early Death
Leaks (upper anastomosis) Recurrent laryngeal nerve palsy Late Stricture (upper anastomosis) Significant gastrocolonic reflux Intestinal obstruction (adhesions) Peptic ulceration (distal cologastric)
2 ( 1 small bowel volvulus; 1cardiac tamponade of PVC central line) 2 1
4 (2 revisions) 1 1 1
1. Adams JS, Brick HG: Pediatric caustic ingestion. Ann Otol Rhinolaryngol 1982;91:656. 2. Aghaji MAC, Chuklwu OC: Oesophageal replacement in pediatric patients. J R Coll Surg Edinb 1992;37:101. 3. Allen RE, et al: Corrosive injuries of the stomach. Arch Surg 1970;100:409. 4. Amoury RA, et al: Tracheoesophageal fistula after lye ingestion. J Pediatr Surg 1975;10:273. 5. Anderson KD, Rouse TM, Randolph JG: A controlled trial of corticosteroids in children with corrosive injury of the esophagus. N Engl J Med 1990;323:637. 6. Anderson KD, et al: Long-term follow-up of children with colon and gastric tube interposition for esophageal atresia. Surgery 1992;111:131. 7. Angel C, Wrenn E, Lobe T: Brain abscess: An unusual complication of multiple esophageal dilatations. Pediatr Surg Int 1991;6:42. 8. Appelqvist P, Salmo M: Lye corrosion carcinoma of the esophagus: A review of 63 cases. Cancer 1980;43:2655. 9. Ashcraft KW: Chemical esophageal injuries. In Ashcraft KW, Holder TM (eds): Pediatric Surgery, 2nd ed. Philadelphia, WB Saunders, 1993. 10. Ashcraft KW, Padula RT: The effect of dilute corrosives on the esophagus. Pediatrics 1974;53:226. 11. Bahnassy AF, Bassiouny IE: Esophagocoloplasty for caustic stricture of the esophagus: Changing concepts. Pediatr Surg Int 1993;8:103. 12. Benirschke T: Time bomb of lye ingestion? Am J Dis Child 1981;135:17.
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13. Berenson GA, et al: Intralesional steroids in the treatment of refractory esophageal strictures. J Pediatr Gastroenterol Nutr 1994;18:250. 14. Berkovits RN, et al: Caustic injury of the esophagus: Sixteen years' experience, an introduction of a new model oesophageal stent. J Laryngol Otol 1996;110:1041. 15. Bigelow NH: Carcinoma of the esophagus developing at the site of lye stricture. Cancer 1953;6:1159. 16. Bosher LJ Jr, Burford TH, Ackerman L: The pathology of experimentally produced lye burns and strictures of the esophagus. J Thorac Surg 1951;21:483. 17. Broor SL, et al: Long term results of endoscopic dilatation for corrosive oesophageal strictures. Gut 1993;34:1498. 18. Burford TH, Webb WR, Ackerman L: Caustic burns of the esophagus and their surgical management: A clinicoexperimental correlation. Ann Surg 1953;138:453. 19. ~ i n i n g t o JD: n Clinitest bums of the-esophagus. Ann Thorac Surg 1975;20:400. 20. Burrington JD, Raffensberger JG: Surgical management of tracheoesophageal fistula complicating caustic ingestion. Surgery 1978;84:329. 21. Butler C, et al: Morphologic aspects of experimental esophageal lye strictures. 11. Effect of steroid hormones, bouginage and induced lathyrism on acute lye burns. Surgery 1977;81:431. 22. Cadranel S, et al: Treatment of esophageal caustic injuries: Experience with high-dose dexamethasone. Pediatr Surg Int 1993;8:97. 23. Capella M, et al: Persistence of corrosive esophageal stricture due to gastroesophageal reflux in children. Pediatr Surg Int 1992;7:180. 24. Cardona JC, DalyJF: Management of corrosive esophagitis: Analysis of treatment, methods and results. N Y StateJ Med 1964;4:2307. 25. Chodak GW, Paesaro E Jr: Acid ingestion, need for gastric resection. JAMA 1978;239:225. 26. Christensen HBT: Epidemiology and prevention of caustic ingestion. Acta Pediatr 1994;83:212. 27. Coln D, Chang JHT: Experience with esophageal stenting for caustic burns in children. J Pediatr Surg 1986;21:588. 28. Cox JGC, et al: Balloon or bougie for dilatation of benign esophageal stricture. Dig Dis Sci 1994;39:776. 29. Crain EF, Gershel JC, Mezey AP: Caustic ingestions: Symptoms as prediction of esophageal injury. Am J Dis Child 1984;138:863. 30. Curtis JA, et al: Endocrine complications of topical and intralesional corticosteroid therapy. Arch Dis Child 1982; 57:204. 31. Cywes S: Challenges and dilemmas for a pediatric surgeon. J Pediatr Surg 1994;29:957. 32. Cywes S, et al: Corrosive strictures of the esophagus in children. Pediatr Surg Int 1993;8:8. 33. Dantas RO, Mamede RC: Esophageal motility in patients with esophageal caustic injury. 6J ~astroe-nterol1996; 91:1157. 34. Davis WM, Madden JW, Peacock EE Jr: A new approach to control of esophageal stenosis. Ann Surg 1972;176:469. 35. Demitbilek S, et al: Effects of estradiol and progesterone on the synthesis of collagen in corrosive esophageal burns in rats. J Pediatr Surg 1994;29:1425. 36. De Peppo F, et al: Conservative treatment of corrosive esophageal strictures: A comparative study of endoscopic dilatationsand esophageal stenting. Pediatr Surg Int 1993;8:2. 37. DiConstanzoJ, et al: New therapeutic approach to corrosive burns of the upper gastrointestinal tract. Gut 1980;21:370. 38. Estrera A, et al: Corrosive burns of esophagus and stomach: A recommendation for an aggressive surgical approach. Ann Thorac Surg 1986;41:276.
39. Fell SC, et al: The effect of intraluminal splinting in the prevention of caustic stricture of the esophagus. J Thorac Cardiovasc Surg 1966;52:675. 40. Ferguson MK, et al: Early evaluation and therapy for caustic esophageal injury. Am J Surg 1989;157:116. 41. Fyfe AH, Auldist AW: Corrosive ingestion in children. Z Kinderchir 1984;39:229. 42. Gandhi RE', Cooper A, Barlow BA: Successful management of esophageal strictures without resection or replacement. J Pediatr Surg 1989;24:745. 43. Gaudreault P, et al: Predictability of esophageal injury from signs and symptoms: A study of caustic ingestion in 378 children. Pediatrics 1983;71:767. 44. Gehanno P, Guedon C: Inhibition of experimental esophageal lye strictures by penicillarnine. Arch Otolaryngol1981;107:145. 45. Genc A, Mutaf 0 : Esophageal motility changes in acute and late periods of caustic esophageal burns and their relation to prognosis in children. J Pediatr Surg 1998;37:1526. 46. Gerzic Z, et al: Post corrosive stricture and carcinoma of the esophagus. In SiewertJR, Holsher AH (eds): Diseases of the Esophagus. New York, Springer Verlag, 1988. 47. Guelrud M, Ardeha M: Motor function abnormalities in acute caustic esophagitis. J Clin Gastroenterol 1980;2:247. 48. Gundogdu HZ, et al: Colonic replacement for the treatment of caustic esophageal strictures in children. J Pediatr Surg 1992;27:771. 49. Gupta S: Total obliteration of esophagus and hypopharynx due to corrosives.J Thorac Cardiovasc Surg 1970;60:264. 50. Gupta SK, Croffie JM, Fitzgerald JF: Is esophagogastroduodenoscopy necessary in all caustic ingestions? J Pediatr Gastroenterol Nutr 2001;32:50. 51. Hall RJ, LillyJR: Treatment of acid burns of the stomach in children by pedicle pyloroplasty. Surg Gynecol Obstet 1988; 167:153. 52. Haller JA Jr, Bachman K: The comparative effect of current therapy on experimental burns of the esophagus. Pediatrics 1964;34:236. 53. HallerJA Jr, et al: Pathophysiology and management of acute corrosive burns of the esophagus: Results and treatment of 285 children. J Pediatr Surg 1971;6:578. 54. Hawkins DB, Demerer MJ, Barnett TE: Caustic ingestion: Controversies in management. A review of 214 cases. Laryngoscope 1980;90:98. 55. Hill JL, et al: Clinical technique and success of the esophageal stent to prevent corrosive strictures. J Pediatr Surg 1976;11:443. 56. Holder TM, Ashcraft KW, Leape L: The treatment of patients with esophageal strictures by local steroid injections.J Pediatr Surg 1969;4:646. 57. Holinger PH: Management of esophageal lesions caused by chemical burns. Ann Otol Rhinolaryngol 1968;77:819. 58. Hopkins RA, Postlethwaite RW: Caustic burns and carcinoma of the esophagus. Ann Surg 1981;194:146. 59. Imre J, Kopp M: Arguments against long term conservative treatment of esophageal strictures due to corrosive burns. Thorax 1972;27:594. 60. Jackson C: Esophageal stenosis following swallowing of caustic alkalis. JAMA 1971;77:22. 61. Jelenko C: Chemicals that "burn." J Trauma 1974;14:65. 62. Jena GP, Lazarus C: A case report: Acid corrosive gastritis. S Afr Med J 1985;67:473. 63. Johnsen A, Jensen LI, Mauritzen K: Balloondilatation of esophageal strictures in children. Pediatr Radio1 1986;16:388. 64. Johnson EE: A study of corrosive esophagitis. Laryngoscope 1963;73:1651. 65. Kim 1-0, et al: Perforation complicating balloon dilatation of esophageal strictures in infants and children. Radiology 1993;189:741.
CHAPTER
66. Kirsch MM, Ritter F: Caustic ingestion and subsequent damage to the oropharyngeal and digestive passages. Ann Thorac Surg 1976;21:74. 67. Kirsch MM, et al: Treatment of caustic injuries of the esophagus. Ann Surg 1978;188:675. 68. Kirsch MM, et al: Intralesional steroid injections for peptic oesophageal strictures. Gastrointest Endosc 1991;37:180. 69. Kiviranta UK: Corrosion carcinoma of the esophagus. Acta Otolaryngol 1952;42:88. 70. Krey H: Treatment of corrosive lesions of the esophagus. Acta Otolaryngol 1952;102(Suppl):l. 71. Kuhn JR, Tunell WP: The role of initial cine-esophagography in caustic esophageal injury. Am J Surg 1983;146:804. 72. Landau G, Saunders W: The effect of chlorine bleach on the esophagus. Laryngol Rhinol Otol 1978;92:499. 73. Lansing PB, Ferrante WA, Ochsner JL: Carcinoma of the esophagus at the site of lye stricture. Am J Surg 1969;118:108. 74. Larimeau T, et al: Accidental caustic injury in children: Is endoscopy always mandatory? J Pediatr Gastroenterol Nutr 2001;33:81. 75. Leape LL, et al: Hazard to health-liquid lye. N Engl J Med 1971;284:578. 76. Litovitz R, Schmitz BF: Ingestion of cylindrical and button batteries: An analysis of 2382 cases. Pediatrics 1992;89:747. 77. Mansson I: Diagnosis of acute corrosive lesions of the esophagus. J Laryngol Otol 1978;92:499. 78. Marshall F: Caustic burns of the esophagus: Ten-year results of aggressive care. South Med J 1979;72:1236. 79. McCabe RE, Scott JR, Knox WC: Fistulation between the esophagus, aorta and trachea as a complication of acute corrosive esophagitis: Report of a case. Ann Surg 1969;35:450. 80. Mendelsohn HJ, Maloney WH: The treatment of benign strictures of the esophagus with cortisone injection. Ann Rhinol Laryngol 1970;79:85. 81. Middlekamp JN, et al: The management and problems of caustic burns in children. J Thorac Cardiovasc Surg 1969; 57:341. 82. Millar AJW, et al: Negotiating the "difficult" oesophageal stricture. Pediatr Surg Int 1993;8:445. 83. Millar AJW, et al: Detection of caustic oesophageal injury with technetium 99m-labelled sucralfate.J Pediatr Surg 2001; 36:262. 84. Mills LJ, Estrera SA, Platt MR: Avoidance of esophageal stricture following severe caustic burns by use of an intraluminal stent. Ann Thorac Surg 1979;28:60. 85. Moody FG, Garrett JM: Esophageal achalasia following lye ingestion. Ann Surg 1969;17:775. 86. Mutaf 0 : Esophagoplasty for caustic esophageal burns in children. Pediatr Surg Int 1992;7:106. 87. Mutaf 0 , et al: Management of tracheoesophageal fistula as a complication of esophageal dilatationsin caustic esophageal burns. J Pediatr Surg 1995;30:823. 88. Mutaf 0 , et al: Gastroesophagealreflux: A determinant in the outcome of caustic esophageal burns. J Pediatr Surg 1996; 31:1494. 89. Naef AP, Savary M, Ozzello L: Columnar lined lower esophagus: An acquired lesion with malignant predisposition: Report of 140 cases of Barrett's esophagus with 12 adenocarcinomas. J Thorac Cardiovasc Surg 1975;70:826. 90. Oakes DD, Sherck JP, Mark JBD: Lye ingestion: Clinical patterns and therapeutic implications. J Thorac Cardiovasc Surg 1982;83:194. 91. Orringer MB, Orringer JS, Arbor A: Esophagectomy without thoracotomy: A dangerous operation? J Thorac Cardiovasc Surg 1983;85:72. 92. Othersen BH Jr, Parker EP, Smith CD: The surgical management of esophageal stricture in children. Ann Surg 1988; 207:590.
68
Caustic Strictures of the Esophagus
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93. Panieri E, et al: Iatrogenic esophageal perforation in children: Patterns of injury, presentation, management and outcome. J Pediatr Surg 1996;31:890. 94. Panieri E, et al: Oesophageal replacement in the management of corrosive strictures: When is surgery indicated? Pediatr Surg Int 1998;13:336. 95. Pintus C, et al: Caustic ingestion in childhood: Current treatment possibilities and their complications. Pediatr Surg Int 1993;8:109. 96. Rappert P, et al: Diagnosis and therapeutic management of oesophageal and gastric caustic burns in childhood. Eur J Pediatr Surg 1993;3:202. 97. Ray JF, et al: The natural history of liquid lye ingestion. Arch Surg 1974;109:436. 98. Ritter F, Newman MH, Newman DE: A clinical and experimental study of corrosive burns of the stomach. Ann Otol Rhinol Laryngol 1968;77:830. 99. Rivosecchi M: Lye strictures (part 1) [editorial]. Pediatr Surg Int 1993;8:1. 100. Rode H, et al: Colonic oesophageal replacement in children-functional results. Z Kinderchir 1986;41:201. 101. Rode H, et al: Reflux strictures of the esophagus in children. J Pediatr Surg 1992;27:462. 102. Rodgers BM, Ryckman FC, Talbert JL: Blunt transmediastinal esophagectomy with simultaneous substernal colon interposition for esophageal strictures in children.J Pediatr Surg 1981;16:184. 103. Rothstein FC: Caustic injuries to the esophagus in children. Pediatr Clin North Am 1986;33:665. 104. Saeed ZA, Graham DY: Treatment of benign esophageal stricture: Where do we go from here? Dig Dis Sci 1994; 39:2099. 105. Sato Y, et al: Balloon dilatation of esophageal stenosis in children. AJR Am J Roentgen01 1988;150:639. 106. Sellars SL, Spence RAJ: Chemical burns of the oesophagus. J Laryngol Otol 1987;lOl:1211. 107. Shaffer HA, Valenzuela G, Mittal RK: Esophageal perforation: A reassessment of the criteria for choosing medical or surgical therapy. Arch Intern Med 1992;152:757. 108. Shemesh E, Czerniak A: Comparison between Savary-Gilliard and balloon dilatation of benign esophageal stricture. World J Surg 1990;14:518. 109. Spain DM, Molomut N, Haber A: The effect of cortisone on the formation of granulation tissue in mice. Am J Path01 1957;26:710. 110. Spechler SJ, et al: Barrett's epithelium complicating lye ingestion with sparing of the distal esophagus. Gastroenterology 1981;81:580. 111. Spitz L: Gastric transposition via the mediastinal route for infants with long-gap esophageal atresia. Pediatr Surg 1984;19:149. 112. Spitz L, Lakhoo K: Caustic ingestion. Arch Dis Child 1993;68:157. 113. Syrnbas PN, Vlasis SE, Hatcher CR Jr: Esophagitis secondary to ingestion of caustic material. Ann Thorac Surg 1983;36:73. 114. Tanyel FC, Buyukpamukcu NB, Hicsonmez A: An improved stringing method for retrograde dilatations of caustic esophageal strictures. Pediatr Surg Int 1987;2:57. 115. Thomas AN, Dedo HH: Pharyngogastrostomy for treatment of severe stricture of the pharynx and esophagus. J Thorac Cardiovasc Surg 1977;73:817. 116. Thomas AN, et al: Pharyngoesophageal caustic stricture. Am J Surg 1976;132:195. 117. Thompson DF, et al: Evaluation of regional and nonregional poison centers. N Engl J Med 1983;308:191. 118. Ti TK: Esophageal carcinoma associated with corrosive injury-prevention and treatment by esophageal resection. Br J Surg 1983;70:223.
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119. Tucker JA, et al: Tucker retrograde esophageal dilatation 19241974: A historical review. Ann Otol Rhinol Laryngol 1974;83(Suppl 16):1. 120. Ulman I, Mutaf 0 : A critique of systemic steroids in the management of esophageal burns in children. Eur J Pediatr Surg 1998;8:71. 121. Van der Zee DC, et al: Management of pediatric esophageal perforation. J Thorac Cardiovasc Surg 1988;95:692. 122. Walton WW: An evaluation of the poison prevention packaging act. Pediatrics 1982;69:363. 123. Wasserman RL, Ginshurg CM: Caustic substance injuries. J Pediatr 1985;107:169. 124. Webb WA: Esophageal dilatation: Personal experience with current instruments and techniques. Am J Gastroenterol 1988;83:471.
125. Wijburg FA, Heymans HAS, Urbanus NAM: Caustic esophageal lesions in childhood: Prevention of stricture formation. J Pediatr Surg 1989;24:171. 126. Yarrington CT Jr: The experimental causticity of sodium hypochloride in the esophagus. Ann Otol Rhinol 1970; 179:895. 127. Zarger SA, et al: Ingestion of strong corrosive alkalis: Spectrum of injury to upper gastrointestinal tract and natural history. Gastroenterology 1989;97:276. 128. Zarger SA, et al: The role of fibreoptic endoscopy in the management of corrosive ingestion and modifikd endoscopic classification of burns. Gastrointest Endosc 1991; 37:165.
Esophageal Replacement Lewis Spitz
The need to replace the esophagus is becoming increasingly I-are, mainly because of improved methods of retaining the native esophagus in infants born with l o n g gap esophageal atresia. In addition, general awareness of the damage that can occtu- as a consequence of intractable gastroesophageal reflux has resulted in more aggressive approaches in antireflux surgery, and with the introduction of childproof containers, fewer lye and caustic injuries to the esophagus occur. Nevertheless, there continue to be instances in which substitution of the esophagus is required, and it is therefore important for the pediatric surgeon to be aware of the various options available for replacement.
now possible to perform a primary interposition procedure, or if circumstances do not permit, a cervical esophagostomy is performed with a later replacement procedure. Although it is obvious that the patient's own esophagus is the best esophagus, persisting with futile attempts to retain the native esophagus in the presence of major complications (such as empyema, intractable stricture, and repeated recurrent fistulas) is occasionally detrimental to the wellbeing of the infant. In such situations, it is clearly in the patient's best interest and safety to abandon the esophagus and perform a replacement procedure at a later stage.
Peptic Strictures INDICATIONS FOR ESOPHAGEAL REPLACEMENT Esophageal Atresia Infants with long-gap esophageal atresia constitute the maill group that requires esophageal replacement because of failure to achieve end-to-end anastomosis. Numerous maneuvers have been adopted to ~ \ ~ e r c o mthe e long gap and achieve a primary anastomosis to allow retention of the infant's native esophagus. A list of these techniques is presented in Table 69-1. For isolated esophageal atresia, it is important to exclude an upper pouch tracheoesophageal fistula. When only a small nubbin of distal esophagus is present above the hiatus or there is no intrathoracic esophag~sat all, a replacement is clearly going to be required, and it is best to perform a cervical esophagostomy at an early stage and allow the infant to go home pending a later replacement procedure. The infant is now free of the danger of aspiration, and appropriate bonding with the fanlily can take place at home. If an anastomosis cannot be achieved even under extreme tension, current opinion favors an attempt at delayed primary repair. The infant is fed by gastrostomy while suction is applied to the upper esophageal pouch for a period of 6 to 12 weekx During this time, the gap between the two ends o f the esophagus gradually diminishes. If primary anastonlosis is i~npossibleat this stage, f ~ ~ r t h edelay r is t~~lprodt~ctive and esophageal stibstitution is required. It is
Antireflux surgery is usually performed for pathologic gastroesophageal reflux before intractable strictures develop. However, in children with severely scarred and
During the Initial Procedure Anastomosis under tension40.69.112 Tension-relieving p r o c e d ~ r e s 2 ~ , ~ 0 ~ ~ ~ ~ ~ ~ Flap techniq~e25.~~ Suture fistula48,100.103.104 Delayed Primary Anastomosis With bougienage: proximal,51,70 proximal and dista1,43 magnetic47 Without bougienageE9 Esophageal-lengthening techniques (e.g., flap,22.36 spiral m y ~ t o m y ,gastric l ~ ~ divisionlo1) Transmediastinal "Thread" With and without olive^"^^^^^ Kato techniques7 Esophageal Replacement Colonic i n t e r p o s i t i ~ n ~ ~ , ~ ~ ~ . ~ ~ ~ Gastric tube e s ~ p h a g o p l a s t y ~ , ~ ~ Jejunal interpositiong3 Gastric t r a n s p ~ s i t i o n ~ ~ . ~ ~ ~
I
1094
PART
VI
THORAX
inflamed strictures of the esophagus, most of these strictures resolve with effective antireflw surgery followed by regular postoperative esophageal dilatation. A small percentage requires limited "sleeve" resection of the strictured area, but some fail to respond and require esophageal replacement.
Caustic Strictures Though uncommon in developed countries as a result of legislation mandating childproof containers for caustic substances, many children in developing countries continue to sustain caustic esophageal injuries. Most cases are mild and respond to repeated dilatation. Full-thickness injury to more than a very short segment of the esophagus invariably results in an intractable stricture that fails to respond to dilatation and usually requires substitution. Continuing with dilatation at regular intervals for longer than 6 to 12 months is unproductive. The need to resect the damaged esophagus continues to be disputed. The risk for malignant conditions and the ease with which esophagectomy can be performed in children favor resection and substitution rather than bypass procedures. Caustic strictures are discussed extensively in Chapter 68.
Miscellaneous Indications
TYPES OF ESOPHAGEAL REPLACEMENT Although the colon continues to be the most frequently used organ for esophageal substitution in children, dissatisfaction by some surgeons has led to the use of alternatives. The methods most commonly used are shown in Figure 69-1. The advantages and disadvantages of the various substitution procedures are outlined in Table 69-2. Several artificial prostheses have been used as substitutes for the esophagus; however, all of them have functioned for only very short periods.loo
ROUTE FOR POSITIONING THE ESOPHAGEAL SUBSTITUTE The posterior mediastinurn is the shortest distance between the cervical region and the abdomen for esophageal r e p l a ~ e m e n t .Colonic ~~ interpositions were originally placed subcutaneously on the anterior chest wall, but the cosmetic appearance of this method is unacceptable and it
Right Colon
The need for replacement because of bleeding esophageal Left varices is virtually obsolete as a result of the success of alternative techniques, particularly sclerotherapy and portosystemic shunts. Tumors of the esophagus may require resection of extensive length of the esophagus. Examples of such tumors in children are diffuse leiomyReversed gastric tube oma and inflammatory pseudotumor. The esophagus may be extensively damaged by prolonged impaction of foreign bodies, such as aluminum ring pull-tabs, which are radiolucent and may escape detection on conventional radiography. Other unusual indications for esophageal R... replacement include intractable achalasia, diffuse candidiasis in children with immune deficiency, ~ c l e r o d e r m a , ~ ~ Jejunum - Interposition and epidermolysis bullo~a.~R
CHARACTERISTICS OF AN IDEAL ESOPHAGEAL SUBSTITUTION 1. The substitute must function as an efficient conduit from mouth to stomach to satisfy the nutritional needs of the child. 2. Gastric acid reflux into the conduit must be minimal; if reflux does occur, the substitute should be resistant to gastric acid. 3. The substitute should not impair respiratory or cardiac function. 4. The operative technique should be technically unchallenging and adaptable to small children. 5. The conduit should not produce any external deformity. 6. The conduit must grow-with the child and continue to function into adult life.13
Free graft
Stomach
Methods of esophageal replacement.
CHAPTER
Method
Advantages
Disadvantages
Colon
Adequate length Reflux seldom occurs
Precarious blood supply Graft necrosis High incidence of leaks and strictures Multiple anastomoses Redundancy over the long term Slow transit of food
Gastric tube
Adequate length Good blood supply
Very long suture line High incidence of leaks and strictures Reflux leading to Barrett's syndrome
Size of conduit appropriate Rapid transit
Esophageal Replacement
1095
is thriving and weighs at least 5 kg. In the interim, it is important to stimulate the swallowing. reflex by offering. sham oral feedings during regular gastrostom; feedingsy Infants who achieve good sham feeding will undoubtedly rapidly accept oral nutrition when the esophageal substitute has been successfully connected. In all cases, adequate mechanical preparation of the intestine is essential because the organ that has been selected for esophageal replacement may be unsuitable and an alternative technique may be required. Excellent comprehensive reviews of the history of esophageal replacement have been documented by May and Samson in 196974and by Postlethwait in 1983.87
COLONIC INTERPOSITION
Jejunum
Appropriate size
Very precarious blood supply Retention of peristaltic activity Length can be a problem Three anastomoses
Colonic interposition continues to be the most widely used procedure for esophageal replacement in children. In adults with carcinoma of the esophagus, the currently preferred technique is gastric transposition, with colonic interposition being reserved as a secondary procedure.
Free jejunal graft
Appropriate size Good peristaltic activity
Specialized technique for microvascular anastomosis Prolonged operating time Precarious blood supply High failure rate
History
Stomach
Adequate length easily attained Excellent blood supply Single anastomosis Ease of procedure
Bulk of stomach in thorax Reflux common early on Poor gastric emptying Affects pulmonary function? Affects growth?
has been abandoned. The advantages and disadvantages of the other routes are outlined in Table 69-3.
TIMING Although esophageal replacement is possible in newborns, the procedure should generally be delayed until the infant
1
69
In 1911, Kelling58used a segment of transverse colon to bypass the esophagus. Because the mesentery was too short for the planned jejunal interposition, he based the colon on the left colic artery. However, the patient died before an attempt could be made to join the cervical esophagostomy to the upper end of the colon. In 1911, V~llietl2~ preserved the mesenteric pedicle to the right end of the colon transplant in a cadaver. In 1914, Von Hacker carried out the first successful colonic interposition in an adult.lZ4The first successful colonic bypass in a child was reported by Lundblad in 1921.68The patient underwent the procedure for an esophageal stricture at 3 years of age and lived until he was 37 years old, at which time he died accidentally. Ochsner and Owens79 reviewed the literature in 1934 and could find only 20 reported cases of colonic esophagoplasty. In 1951, Rudler and Monod-BrocagVescribed the retrosternal ileocolonic graft. In 1955, Dale and ShermanZ0described two infants with esophageal atresia who underwent
Route
Advantages
Disadvantages
Retrosternal
Ease of procedure Useful when the transpleural and mediastinal routes are inflamed or surgery has previously been performed
Longest route from neck to abdomen Angulation of the graft unavoidable Problems with access if cardiac surgery is required
Transpleural
Convenience and ease of the procedure
Displacement of the lung Requires thoracotomy
Posterior mediastinal
Most direct route Organ contained in the mediastinum Little or no lung compression Thoracotomy not always required
Mediastinum may be unavailable because of previous surgery, fibrosis, or inflammation
1
1096
PART
VI
THOK.\X
reconstruction of the esophagus with a right colonic retrogasti-ic anterior ~nediastinali~lterpositioilat 2 years of age. Four years later, Battersby and Moore") reported five cases of right colon replacemeilt for conge~litalatresia of the esophagus. The three children who u~lderwent substernal placement of the colon survi\red. They recommended delaying the procedure until the intint was at least 9 months of age. Major advances in use of the colon for esophageal replacement were documented by Shernlarl and Waterston ill 1957,1(Niby Waterston in 1961 and 1964,l?Qnd by Belsey in 1965.12 Waterston and Belsey were strong proponents of the transpleural route and use of the left colon supplied by the left colic vessels. In 1967, Othersen and ClatworthyH3 stated that the colon was the best organ for esophageal replacement in children and recommended delaying the operation until the child was 18 to 24 months old so that gravity in the erect position would assist in food passage through the colonic interposition. Freeman and Cass,'" in 1982, advocated placing the transposed colon in the route of the native esophagus in the posterior mediastinum and reported an impressively low rate of complications.
Surgical Technique Colonic interposition entails use of either the right colon based on the ileocolic vessels placed in the retrosternal position or the left colon based on the left colic vessels positioned in a retrohilar position in the left pleural cavity or in the posterior mediastinum (Fig. 69-2).
Right Colon Retrosternal Technique The abdomen is opened through either a midline upper abdominal incision or a transverse upper abdominal muscle-cutting incision that transects both rectus abdominis mt~scles.The entire colo11 must be mobililed and exposed to provide detailed and accurate assessrrlent of its blood supply. In a study of 600 specimens, Sonrleland et al.L()X reported that only 24% of specinlens showed the typical textbook picture of three vessels to the right side of the colon arising from the superior mesenteric artery. The middle colic artery was absent in 3.6% of cases. The marginal artery was occasionally absent. 111 individual children, the anatomy of the vascular supply determines the section of colon most appropriate for the interposition procedure. The blood supply for the right colonic interposition is based on the middle colic artery. However, if a segment of terminal ileum is to be used for the interposition,llVhe ileocolic vascular supply to the graft must be preserved if possible. The length of intestine to be used is carefully estimated, and bulldog clamps are placed across all vessels that require division. The clamps are left in position for at least 10 minutes to ensure that the blood supply is adequate, that the marginal vessels continue to pulsate, and that the color of the section of colon selected for the interposition remains normal. The blood supply can be further evaluated by removing the appendix and observing the flow of blood in the appendicular artery. If the blood supply seems to be satisfactory, the vessels that require division are carefully and securely ligated and divided. It is important to preclude hematoma formation
in the mesentery. The ileum is divided between the clamps, and the distal stump is closed in preparation for relocation into the neck. The transverse colon is then divided to the left of the middle colic artery, and intestinal continuity is restored by an end-to-end ileotransverse colostorny. A transverse cervical incision that encircles the previously constructed ceivical esophagostomy is made. The incision should extend to the midline of the neck appl-oximately 1 c ~ nabove the ~nanubriumsterni. The upper border and posterior surface of the manubrium are exposed by dividing the cenical f.ascia and the origin ofthe stel-nomastoid muscle. It rriay be necessary to enlarge the openii~ginto the retrostcrnal space by removing the upper part of the ~nanubrium,sternoclavicular joint, or both. 'The I-etrosternal tunnel is developed from above through a cervical incision in a plane directly posterior to the sternum and anterior to the thymus and pericardiurn, and the anterior attachinents of the diaphragm are divided fi-om below. The tunnel must be wide enough to accomnlodate at least two to three fingers. The stornach is then ~nobilizedto allow the colon and its vascular pedicle to pass behind the stomach, over the anterior surfice of the liver, and through the retrostel-nal tunnel into the neck. It is vital to ensure that there are no kinks or twists in the graft that may impair the blood supply. The distal end of the colonic interposition is anastornosed to the anterior wall of the stomach close to the lesser curvature. An antireflux submucosal gastric tunnel has been devised as a method of preventing reflux of gastric acid into the colon graft."' The proximal end of the graft, which will comprise the ascending colon or the terminal ileum, is anastomosed in end-toend fashion to the dis~alend of the cervical esophagus. During preparation of the esophagus for anastomosis, it is imperative to preserve the blood supply and to meticulously mobilize the full thickness of the esophagus. The length of the colonic interposition must be.just suf'ficier~tto bridge the gap between the esophagus and the stomach. Excess intestine should be resected before anastomosis while the blood supply to the remaining graft is preserved. Redundancy is a problem that increases with tirne and can lead to stasis. Pyloroplasty is generally recommended to prevent this complication.
Left Colon Transpleural Technique The left colon transpleural technique was originally described by Waterston.wtl In this method the left transverse colon based on the ascending branch of the left colic artely is placed isopelistaltically in the retrohilar position. In the original description, the entire procedure was performed through a left thoracic incision with access to the abdomen provided by detaching the diaphragm peripherally from the chest wall. An alternative approach is to use separate abdominal and thoracic incisions or a thoracoab dominal incision.l? The left colon graft is based on the ascending branch of the left colic artery. Intestinal continuity is restored by an end-ttrend colocolic anastomosis. The colon graft is passed in a retrogastric and retropancreatic direction and then through a separate lateral incision in the posterior diaphragm into the left pleural cavity. The colon is passed behind the hilum of the left lung and into
the neck by tu~inelingthrough Sihson's fijsc.i;i in a posterior tiil-ection to the s~ibclavianvcsscls and I;itel-;~lto the carotid sheath. The PI-oximalend oi'thc colonic interposition is istorno tor nosed in cnd-to-rid f'nshion to the c.c~.\ic.al esophagus, and the distal end is anastornosed cithcl. to the distal sturnp of esophagus (in rases of' csol)h;igc~;~l ;~t~.csi;~) or prefera1)ly to the l)ostc~.iorw;ill of' tlic. stom;lcli. Qloroplasty is again i.cc.oll~lncndcd.F~.cc.m;~n ;ind (hss"' ~nodifiedthe proccd~ll.c.1,y ~)l;~cing the c.olon in the postcriol- ~nediastin~um in tlic. site of'the nornial csol)ha;~t.lyonset, most are diagnosed in late childhood or c;~~.ly ;~dolcsc.cnce. Only a fi.w studies it,c.l~~de more tha11 ;I 1i;itited ntlrnber ()f cases,l".':'.'"*".l'~."li.l""an~ I;li.g(.s( Illrllti(.entcr set-ies in~olvcsonly 1 75 p;~tierlts.1 l X The ctioloastroenterol Nutr 1998;26:380. 98. Liebermann-Meffert D, Allgiiwer M, Srhmid P, Rlum AL: Muscular equivalent of the lower esophageal sphincter. Gastroenterology 1979;76:31 . 99. Lim HC, Nigro MA, Beierwaltes P, et 31: Nitrazepaminduced cricopharyngeal dysphagia, al~norrnalesophageal peristalsis and associated bronchospasn~:ProI)able cause of nitrazepanl-relatet1 sudden drath. Brain I)rv 1992; 14:309. 100. Liu HY" -
-
Helicobacter pylori Infection: In the past 3 decades, mortality rates related to gastric cancer, gastric ulcer, and duodenal ulcer have declined, whereas those of esophageal adenocarcinoma and GERD have risen.133Some studies suggest that H. pylori colonization may be protective against severe esophagitis and Barrett's esophagus.52,265 These epidemiologic data have led some to suggest that H. pylorishould not be eradicated in patients with GERD. However, H. pylori is a risk factor for the development of peptic ulcer and gastric cancer, which has caused many physicians to be uncomfortable with that recommendation. This issue remains under inve~tigation.g2,~~~J51 Pepsin, Ttypsin, and Bile Salts: Pepsin and trypsin are prote~lyticenzymes that have a traumatic effect on the esophageal mucosa. Pepsin causes its most significant damage at a pH of 2 to 3, whereas trypsin is most damaging at a pH between 5 and 8.Zo0243Bile salts increase the permeability of the esophageal mucosa to acid and are noxious to the esophageal mucosa in the presence of acid. Conjugated bile salts are injurious to the esophagus at an
Underlying Congenital Problems: Children with esophageal atresia are prone to pathologic GER.2"70,137,145,219,??3 In these cases, esophageal peristalsis is impaired and the LES is incompetent. The incidence of reflux in these children declines as the children grow, but complications of GERD mandate antireflux surgery in 10% to 30% of children after esophageal atresia repair.24,138,215 One of the common manifestations of GERD in children with esophageal atresia is recurrent esophageal anastornotic stenosis. Appropriate prophylactic medical treatment of reflux in these children may lead to diminished stricture formation. Children with congenital diaphragmatic hernia often have functional anatomic abnormalities of the esophagus leading to GER. The incidence of pathologic GER is reported to be greater than 20% in surviving infants. About 15%of children with congenital diaphragmatic hernia require an antireflux procedure.78,"5J24 Congenital abdominal wall defects such as gastroschisis and omphalocele are also associated with an increased incidence of GER, possibly because of increased intra-abdominal pressure.1gJ36
1124
PART
VI
THORAX
Neurologically Impaired Children: Neurologically impaired children are prone to the development of GER. The underlying cause is thought to be related to a foregut motility problem. Impaired esophageal motility and delayed gastric emptying are important factors contributing to reflux in these children.49922'
DIAGNOSIS There are few objective studies that compare the value of the various diagnostic techniques used for the diagnosis of GER in children. Tests for GER are individually useful in documenting different aspects of GER and are valuable only when used in the appropriate clinical context.
relation to the severity of the esophagitis.174 They also noted that some patients with esophagitis had pathologic duodenal-gastroesophageal reflux, but not pathologic reflux by pH probe analysis. Multiple intraluminal electrical impedance technologies with the capacity to detect all types of reflux (acid, nonacid, liquid, and air) have been developed over the last 2 decades. This technique is useful for investigating Belaji ~ . 2 ~et al. reported that 59% of nonacid r e f l u ~ . * 2 ~ . ' ~ GER events were not conventional acid reflux and were not detected by the pH probe studies.lVn infants, nonacid GER has been documented in association with respiratory symptoms such as apnea. Such findings have led investigators to hypothesize that apneic episodes in infants may be caused by a protective respiratory reflex. Further investirration will be recluired to determine the importance of impedance and other new technologies in identifying pathologic GERD in infants and children.l88,260 u
History and Physical Examination: The history and physical examination are the most important components of the evaluation of an infant or child with possible GERD. Documentation of the growth rate and identification of the primary symptoms, such as failure to thrive, primary aspiration, recurrent coughing, reactive airways disease, stridor, apnea, recurrent pneumonia, irritability, heartburn, abdominal pain, and dysphagia, are helpful in guiding the remainder of the patient's workup.209,2j0 Upper Gastrointestinal Contrast Series: An upper gastrointestinal contrast series is neither specific nor sensitive It does, however, provide a for the diagnosis of GER.1s47J87 detailed road map of the patient's anatomy to-rule out other causes of vomiting. Problems such as pyloric stenosis, malrotation, partial duodenal outlet obstruction, hiatal hernia, and esophageal stricture are readily seen. Esophageal pH Monitoring: Esophageal pH monitoring measures the duration and frequency of acid reflux episodes. It is most useful if used in conjunction with regular daily activities such as eating and sleeping. The presence of symptoms should be noted in parallel with the pH probe record. A reflux episode is defined as an esophageal pH of less than 4 for a period of 15 to 30 seconds. The percentage of total time that the esophageal pH is less than 4 is then converted into a reflux index, which reflects the cumulative exposure of the esophagus to acid.gVt should be remembered that acid reflux is more common in the first year of life and that adult indices are not applicable to these patients. In children, the upper limit of normal is a pH below 4 less than 5.5% of the time. In infants younger than 1 year, the normal value increases to 12%.31,7.5.20Y,2",248,266 Endoscopic and histopathologic confirmation of esophagitis shows a strong correlation with abnormal pH monitoring. Ninety-five percent of adults with biopsydocumented esophagitis will have an abnormal pH probe reading.2"1"z2'3 However, esophagitis is not the only significant symptom seen in children with pathologic GER.N,131,13pH probe monitoring does not detect nonacid reflux episodes. In some studies, the presence of duodenal contents in the esophagus has been confirmed by monitoring for the presence of bilirubin in the gastroesophageal refl~xate.~",84,1"~19"24' Ore1 and Markovic reported a study of 65 children with symptoms of GERD and noted that duodenal GER increased in
Endoscopy: Endoscopy and biopsy are useful for determining the presence and degree of esophagitis and the presence of other problems such as strictures, webs, or infections. There is a poor correlation between endoscopic appearance and histopathology, so esophageal biopsy is recommended at the time of endos~opy.2~J~~,207 The presence of intraepithelial eosinophils or neutrophils and increased morphometric measures of basal cell layer thickness and papillary height are valid indicators of reflux esophagitis.2"46,20Y Nuclear Scintigraphy: In nuclear scintigraphy, technetium-labeled formula or food is orally ingested, and patients are scanned for evidence of GER or aspiration. This technology can demonstrate nonacid reflux and can provide information relative to gastric emptying.l69,18j,218,232Lack of standardized techniques and the short duration of the study limit the value of this test.218 Esophageal Manometry: Esophageal manometry studies evaluate the activity of the lower and upper esophageal sphincters and monitor the organized contractile activity of the esophagus. The technique is not used for the diagnosis of GER, but helps the clinician better understand the g yis. useful in the differential underlying p a t h ~ ~ h ~ s i o l oIt diagnosis of primary and secondary esophageal motility alterations but is used infrequently to diagnose GER in the pediatric population.Y1."0."4 Other new technologies, including fiber-optic endoscopic evaluation of swallowing with sensory testing, are also being assessed for their value in the workup of GERD in children.143,233
EVALUATION OF PEDIATRIC PATIENTS WITH SUSPECTED GASTROESOPHAGEAL REFLUX DISEASE GERD in infants and children is multifaceted and complex. The appropriate steps in the evaluation of a child suspected of having GER are controversial. The workup must include a careful history and physical examination. An upper gastrointestinal study to look for anatomic abnormalities, a 24hour pH probe monitoring study, or an impedance study and, in some cases, endoscopy with
CHAPTER
biopsy of the distal esophageal mucosa are performed as a part of the workup. Please refer to Box 71-1 for the recommendations formulated by the Society of Pediatric Gastroenterology and Nutrition.209
Conservative Therapy Infants and children who have symptoms of GER can benefit from changes in lifestyle. Smaller and frequent feeding is encouraged in babies instead of larger feedings at infrequent intervals. Thickened feedings may be helpful
71
1125
Gastroesophageal Reflux Disease
in those with poor weight gain, and there is evidence to support a 1- to 2-week trial of hypoallergenic formula in Positioning formula-fed babies with vomiting.g7~209~2"~246.'4Y therapy is a widely adopted, but controversial part of antireflux therapy. Although esophageal pH monitoring has demonstrated that infants have significantly less GER in the prone position than in the supine position, prone positioning has been associated with a higher rate of sudden infant death syndrome (SIDS).7"161J84 In infants from birth to 12 months old with GERD, the risk for SIDS outweighs the benefits of prone sleeping. Therefore, the American Academy of Pediatrics recommends nonprone positioning during sleep.lz6Prone positioning is acceptable in an awake baby in the postprandial period. For older children,
Box 71-1 Evaluation o f Children for Gastroesolphageal Reflux Disease 1. Recurrent vomiting. Pediatric patients with recurrent vomiting should be evaluated with a detailed history and physical examination, with special attention paid to identify warning signals. These warning signals may be bilious or forceful vomiting, failure to thrive, gastrointestinal (GI) bleeding, fever, hepatosplenomegaly, signs of raised intracranial pressure, seizures, abdominal distention, diarrhea, constipation, feeding or respiratory problems, irritability, or genetic disorders. If none of these signs are present and the infant has a normal growth pattern, no diagnostic workup is necessary. Because vomiting in this group of patients will resolve by 12 months of age, conservative treatment, including supine positioning of the infant, a short trial of hypoallergenic formula, or thickening of feedings, may be recommended. If symptoms do not improve by 18 to 24 months of age, further evaluation with upper GI contrast studies should be considered. If an infant with recurring vomiting has additional symptoms, such as failure to thrive or irritability, or if the child is older than 2 years, an upper GI series, 24hour pH monitoring, and in selected cases, upper endoscopy with biopsy to rule out the presence of esophagitis may be performed. If the infant has failure to thrive despite adequate calorie intake, tests to include a complete blood count, electrolytes, bicarbonate, urea nitrogen, creatinine, alanine aminotransferase, ammonia, glucose, urine analysis, and urine ketones and reducing substances and a review of newborn screening tests must be performed. 2. Heartburn or chest pain. These patients are older children and adolescents, and initially, a change in lifestyle, avoidance of precipitating factors, and a 2- to 4week trial of histamine H p receptor antagonists (H2RAs) or proton pump inhibitors (PPIs) is recommended. If the symptoms do not resolve, an upper GI series to rule out esophageal motor disorders, such as achalasia, and upper endoscopy with biopsy to determine the presence and severity of esophagitis should be considered. 3. Esophagitis. This diagnosis can be confirmed with upper endoscopy and biopsy, and the initial treatment consists of lifestyle changes and H2RA or PPI therapy. In patients who do not respond to therapy, an incorrect diagnosis such as eosinophilic esopha&is or inadequate treatment should be considered. Esophageal pH monitoring is useful for determining the efficacy of the treatment being used. .
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&
4. Dysphagia or odynophapa. An upper GI study is recommended in children with difficult or painful swallowing and upper GI endoscopy with biopsy in those with suspected esophagitis. 5. Apnea or apparent life-threatening event (AI,TE). ALTE can be identified as an episode of apnea or change in color and muscle tone in an infant requiring intervention. The first event genereally occurs around the first 2 months of life and rarely after the age of 8 months. These babies carry a high risk for sudden death and have a prevalence of vomiting of 60% to 70% and abnormal esophageal pH monitoring of 40% to 80%. Despite reports that demonstrate gastroesophageal reflux (GER) as a potential cause of aprlea, investigations in unselected patients with ALTE have not demonstrated a relationship between esophageal acidification and apnea or bradycardia. If an infant's esophageal pH monitoring demonstrates gross emesis or oral regurgitation at the time of ALTE, this group of patients may benefit from antireflux therapy. In severe cases not responding to medical management, surgery may be considered. Caution is advised when diagnosing and treating GER as an underlying cause of ALTE. c e children with asthma and 6. Asthma. ~ h e ~ r e v a l e n of abnormal esophageal pH monitoring ranges between 25% and 75%. It is suggested that esophageal acid exposure in asthmatic patients may cause airway irritability and variable airway obstruction. Thus, esophageal pH monitoring plus atrial of vigorous medic4 therapy for GER is recommended for children with asthma who may have the following problems: GER disease, radiologic evidence of recurrent pneumonia, nocturnal asthma occurring more than once a week, need for a high or continuous dose of corticosteroids, and inability-to wean from medical therapy. 7. Recurrent pneumonia. Clinical studies have demonstrated that GER can cause recurrent pneumonia and lead to pulmonary fibrosis. Flexible bronchoscopy with pulmonary iavage fluid demonstrating a large percentageof lipid-laden macrophages and nuclear scintigraphy can be used to detect aspiration, but both test results lack specificity. Neurologically impaired children may have abnormal swallowing leading to aspiration. In such cases, videofluoroscopic swallowing studies or fiber-optic endoscopic swallowing evaluation may be helpful in making the diagnosis. -
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1126
PART
VI
THORAX
recommended conservative treatment includes weight loss if the patient is overweight and avoidance of large meals, caffeine, chocolate, and spicy
The goals of antireflux medical treatment are to control symptoms, prevent complications, and facilitate the healing of esophagitis. Acid suppressants and prokinetic agents are the two major pharmacotherapies that can be used to prevent the symptoms and damage caused by GER. Antacids neutralize gastric acid, whereas antisecretory agents, H2RAs and PPIs, reduce the secretion of gastric acid.
gastric emptying. Cisapride is a mixed serotonergic agent that reduces esophageal acid exposure. Studies have shown that cisapride improves symptom scores, esophagitis, and pulmonary function in patients with GER.6oZl7,247However, it has also been noted to potentially cause serious cardiac arrhythmias and has been withdrawn from the market in Meta-analysis and randomized conmany co~ntries.1~,6"7~ trolled trials have demonstrated no clinically important benefits of cisapride in children.13," Metoclopramide, an antidopaminergic agent, is reported to give equivocal results in some studies.149.'09 Its adverse effects. such as dyskinesia, may be irreversible. In conclusion, thk present evidence is not suff~cientto support the use of prokinetic therapy for GER, although it is widely used.
Histamine H2 Receptor An tagonists
Erythromycin
H2RAs decrease acid secretion by inhibiting the H2 receptor at the parietal cell of the stomach. Ranitidine at an oral dose of 5.0 mg/kg has been shown to control gastric pH for 9 to 10 hours in infants.152 Different randomized controlled trials in adults have demonstrated that cimetidine, ranitidine, and famotidine are effective in controlling symptoms and treating esophagitis.4832sG
Reports have suggested that erythromycin has prokinetic effects on the gastrointestinal tract at doses lower than antimicrobial levels, but no randomized controlled trials have been performed.62
Proton Pump Inhibitors
Endoluminal therapy for GERD in adults as an alternative to other surgical therapies has been a new development. Two techniques are currently under active investigation. Internal gastroplication involves the placement of sutures just below the esophageal-gastric junction by way of an endoscope.l"~Z04 The other endoluminal technique uses radiofrequency energy delivered to the distal LES tissues and gastric cardia. This technique, known as the Stretta procedure, decreases LES compliance and increases LES muscle mass, thereby limiting the TLESRs responsible for GERD.238It has shown positive clinical results in openlabel prospective clinical trials.77,'38 Islam and associates have reported the use of radiofrequency to treat recurrent GEKD in six children. The short-term follow-up results appear to be promising.l1'
Medical Therapy
PPIs bond and deactivate Hf,K+-ATPase, or proton pumps, by crossing parietal cell membranes and accumulating in secretory canaliculi.26Vhese drugs are most effective if they are administered half an hour before a meal.2I1 Some studies have demonstrated that omeprazole may be very effective in the treatment of esophagitis that has been refractory to different treatment regimens, , ~ ~drug , ~ most often reported is including H ~ R A S . ~The omeprazole at dosages of 0.5 to 3.3 mg/kg daily.57 There are potential concerns regarding prolonged use of PPIs in children and associated hypergastrinemia. Pathologists have described parietal cell hypertrophy and polyps in fundus biopsy samples from patients receiving long-term PPI treatment." Additionally, because gastrin is a trophic hormone, patients maintained on long-term PPI therapy may have the potential for the development of colon cancer if they are genetically susceptible to do so.36
Antacids and Surface Agents Antacids neutralize gastric acid and are preferred for the short-term relief of GER symptoms such as heartburn and esophagitis. Studies have shown that treatment with aluminum-containing antacids increases plasma aluminum levels in infants.'" Because other safe alternatives are available, chronic use is not recommended. Sucralfate is a surface agent that adheres to damaged mucosal lesions on the esophagus. However, there are not enough data to determine the safety and efficacy of sucralfate in children.Z0"
Prokinetic Agents In recent studies, TLESRs are considered the most important component of GER. Prokinetic agents increase LES pressure, enhance esophageal peristalsis, and accelerate
Endoscopic Treatment
Indications for Surgical Treatment Surgical management is indicated in children under the following circumstancesll7.lfl220g9223.249:
1. Failure of medical therapy. In children who have continuing symptoms such as persistent pulmonary symptoms, life-threatening events, vomiting with failure to thrive, unremitting heartburn, or an inability to wean from medical treatment despite optimal medical therapy, surgery should be considered. 2. Presence of an associated anatomic defect such as a hiatal hernia, malrotation, or diaphragmatic hernia. 3. Esophageal stricture secondary to GERD. 4. Post-esophageal atresia repair status with a recurrent stricture that does not respond to conservative medical treatment. 5. Neurologically impaired children who have diiiculty feeding and have serious reflux as an associated symptom.
CHAPTER
71
Gastroesophageal Keflux Disease
1127
Surgical Techniques The aim of surgical treatment in GER is to prevent episodes of reflux while avoiding complications such as dysphagia and an inability to burp and vomit. Many operative techniques have been described for children. The main techniques currently used for children include the complete-wrap Nissen fundoplication, the modified complete-wrap Nissen-Rossetti fundoplication, and partialwrap procedures, including the Thal-Ashcraft fundoplication, the Toupet fundoplication, and the Boix-Ochoa f~ndoplication."2,8',2~6,223,2~0 All these techniques attempt to achieve a physiologic high-pressure zone at the distal end of the esophagus that will prevent reflux. Over the last decade, all of these procedures have been performed via a laparoscopic approach. Long-term results after laparoscopic fundoplication seem to be similar to those after the open procedure, but the laparoscopic procedures are less invasive and appear to have fewer complications.158 a Nissen fundoplication. There are advocates for each of the techniques just mentioned. The authors prefer a floppy Nissen fundoplication under all circumstances when corto complete the wrap. Some surgeons also place four to recting GER. Other surgeons advocate for a complete-wrap fundoplication in neurologically impaired six sutures to attach the esophagus to the crura circumchildren and a partial-wrap fundoplication in neurologiferentially above the wrap to prevent herniation of the wrap or other intra-abdominal contents into the chest cally normal children with GER." Still other authors prefer a partial-wrap fundoplication in all patients." No (Fig. 71-3). The wrap is performed over an appropriately high-quality randomized studies have been conducted to sized bougie within the esophagus to prevent the credetermine which operation is best under what circumation of a tight wrap. Additionally, the fundoplication stances. The senior author has retrospectively reviewed the should be loose enough to allow a blunt-tipped clamp to results after partial-wrap Toupet fundoplication in neuropass between the fundal wrap and the esophagus conlogically normal patients and complete-wrap Nissen taining the b o ~ g i e . ~ ~ fundoplication in a similar population and found the recurrence rate to be almost twice as high with the partialThal-Ashcraf? Fundoplication wrap procedure."l This finding is consistent with results In this technique, at least 2.0 cm of the distal intrareported by Jobe and others, who also found a much abdominal portion of the esophagus is mobilized higher recurrence rate in adult patients after a partialer, pediatric surgery wrap p r ~ c e d u r e . ~ ~ W o w e vmany circumferentially. The crural defect is closed posteriorly groups have advocated the efficacy of partial-wrap procewith a figure-of-eight suture that also passes through the dures in children with acceptable recurrence rates.~z~44~54posterior esophageal wall. Anteriorly, the fundus is folded over the anterior surface of the intra-abdominal part of the esophagus and held in place with running or Open Operative Techniques interrupted nonabsorbable suture. The fundus is attached to the crura and to the esophagus to achieve a Nissen Fundoplication 270-degree anterior fundoplication. Some surgeons The operation is best performed through an upper midprefer interrupted sutures for this suture line, but most line or left subcostal incision. The left lobe of the liver is surgeons use a running suture. The anterior 270-degree mobilized, folded on itself, and retracted to the patient's surface of the intra-abdominal portion of the esophagus right. Three or more upper short gastric vessels are is wrapped by the fundus (Fig. 71-4) ."I6 divided to mobilize the fundus of the stomach. The anterior peritoneum over the gastroesophageal junction is Toupet Fundoplication incised transversely. The distal end of the esophagus is In the Toupet technique, the esophagus is dissected in mobilized circumferentially. Dissection is continued up the same manner as for a Nissen fundoplication. The into the thorax when needed to achieve at least a 3.0-cm length of the intra-abdominal portion of the esophagus. crura are approximated posteriorly to snug the hiatus. The vagus nerves are mobilized with the esophagus. A The fundus is mobilized either with or without division Penrose drain is often looped around the esophagus and of the short gastric vessels. The fundus is then pulled vagi to help mobilize the distal esophageal segment. The through the retroesophageal space and secured to the diaphragmatic crura are repaired posteriorly with nonleft and right crura with interrupted sutures. The most absorbable suture. The fundus is then fitted around the cephalad sutures of the wrap incorporate all three strucesophagus for 360 degrees. Usually, three to four intertures: fundus, crus, and esophagus. The wrap is anchored posteriorly to the crura with two or three sutures. rupted sutures are placed in the fundus and esophagus
1128
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VI
THORAX
a
.
-
Thal-Ashcraft fundoplication.
The fundus is sewn to the right and left lateral borders of the esophagus to create a 270-degree posterior wrap, with the anterior quadrant of the esophagus left free of the wrap (Fig. 71-5).258
Boix-Ochoa Technique In this technique, a 2.0- to 3.0-cm length of the intraabdominal portion of the esophagus is restored. The cmral defect is repaired and the cmra are sutured to the esophagus at the anterior and two lateral points. To restore the angle of His, a suture is passed through the fundus and the right rim of the hiatus. Multiple sutures are placed between the fundus and the anterior esophageal wall. The fundus is then tacked to the diaphragm with sutures that open the fundus like an umbrella (Fig. 71-6).sl
-
Boix-Ochoa fundoplication.
Laparoscopic Nissen Fundoplication Although all the aforementioned open techniques have been performed laparoscopically, the most commonly performed laparoscopic technique is the Nissen fundoplication. The laparoscopic approach has the technical advantages of enhanced visualization and magnification and is associated with less postoperative pain. For these reasons, laparoscopic fundoplication has become the treatment of choice in children with pathologic GER over the last decade. Safe and effective laparoscopic procedures in the treatment of GER in infants and children require advanced laparoscopic skills, as well as sophisticated electronic equipment and specialized laparoscopic instruments.
Positioning and Trocar Placement The patient is placed at the end of the operating table with the lower extremities taped in a cross-legged position or, in the case of older children (>30 kg), with the legs supported in stirrups. Proper padding must be used to prevent pressures sores or peripheral neuropathy. The bladder is emptied with a Credi maneuver in infants. Catheterization is not usually necessary in older children. After the anesthesiologist has secured the airway, an appropriately sized dilator is placed. Because dysphagia is a common early postoperative problem unless carefully avoided, the authors prefer large dilators to fully distend the esophagus and avoid the formation of a tight wrap. The patient is placed in a reverse Trendelenburg position with the left side raised slightly. This position uses gravity to pull the small bowel loops and the transverse colon away from the upper part of the abdomen and establish better exposure of the gastroesophageal junction. The operating surgeon is positioned at the end of the table. An open technique is used to insert the first trocar. The authors prefer an expandable 5-mm trocar through the deepest aspect of the umbilicus. This expandable trocar helps keep air from leaking through the trocar site during the operative procedure. A 30-degree, 4 or 5-mm scope is then passed through the trocar after the pneumoperitoneum has been developed. The other four
CHAPTER
71
Gastroesophageal Reflux Disease
1129
-- -
, -
Laparoscopic Nissen fundoplication: a plane is
developed between the right crus and the esophagus.
.
-
Trocar placement for laparoscopic Nissen
fundoplication.
trocars are placed under laparoscopic surveillance as indicated in Figure 71-7. The trocars should be secured to the abdominal wall to avoid slippage in or out during insertion or withdrawal of instruments during the procedure. Three-millimeter and 4 m m trocars are used for most children up into adolescence. A segmented, multiarticulated retractor is used to hold the left lobe of the liver away from the esophageal hiatus. Fundoplication is begun by dividing the gastrohepatic ligament. A hook cautery or scissors can be used for this purpose. Dissection is continued up to the right crus. The small vessels and the hepatic branches of the vagus nerve in the gastrohepatic ligament are divided. If the left hepatic artery is encountered in the gastrohepatic ligament, it should be preserved. A plane between the right crus and the esophagus is identified and enlarged (Fig. 71-8). The dissection is continued over the top of the esophagus while taking care to not injure the anterior vagus nerve, which is usually adherent to the esophageal muscle. A hook cautery is used to divide the short gastric vessels (Fig. 71-9). The dissection is continued proximally along the fundus to the esophagus. The left side of the esophagus is freed from the crura. This circumesophageal dissection is continued until the entire esophagus has been freed from the crura. The window behind the esophagus is enlarged. The intra-abdominal portion of the esophagus should be freed until a tension-free, 3.0-cm length of esophagus is developed. The crura are approximated posteriorly with interrupted nonabsorbable sutures. The most cephalad of the sutures should also pass through the posterior wall of the esophagus while avoiding injury to the posterior vagus. Three to five more
sutures are then applied between the esophagus and the crura to prevent potential herniation of the wrap into the chest (Fig. 71-10). Additionally, it should be noted that the longer the intra-abdominal esophagus, the less likely the patient will suffer from migration of the fundoplication wrap into the chest. The fundus is wrapped around the esophagus after pulling it through the retroesophageal window (Fig. 71-11). The wrap is secured in position with interrupted nonabsorbable sutures (Fig. 71-12). The length of the wrap should be around 2.0 cm in children and 1.5 cm in infants. Longer wraps are associated with dysphagia and an inability to burp and vomit. The abdomen is inspected for bleeding and visceral injury. The instruments and trocars are removed
.
-
Laparoscopic Nissen fundoplication: the short gastric
vessels are divided with a hook cautery.
1130
PART
.
VI
THORAX
1.aparoscopic Nissen fundoplication: the hiatus is
a
-
Laparoscopic Nissen fundoplication: the
closed posteriorly and the esophagus is attached to the crura with four to six sutures.
"floppy" fundoplication is secured to the esophaaus . . for a distance of 1.5 to 2.0 cm.
and the wounds closed according to the preference of the operating surgeon.
emptying showed marked improvement of their gastric emptying with fundoplication alone." Johnson et al. s u b sequently reported a small group of children with foregut autonomic dysfunction who did not show improvement of their gastric emptying after pyloroplasty alone.l18 Pyloroplasty or antroplasty to improve gastric emptying in children with gastrointestinal autonomic dysfunction remains controversial. It is likely that the fundoplication improves gastric emptying more than pyloroplasty does.
Pyloroplasty or Antroplasty The prevalence of foregut autonomic dysfunction is high in children with GER.49,227Approximately 50% of children with GER have delayed gastric emptying. Postfundoplication complications attributed to delayed gastric emptying include early satiety, gas bloating, and recurrent GER. Pediatric surgeons have often used pyloroplasty or a derivative pyloric operation with the intent to improve gastric emptymg after fundoplication, and multiple studies have shown improved gastric emptying after In 199'7, Brown et fundoplication and pyloric s~rgery.l~~,2~2 al. reported a study in which children with delayed gastric
.
-
Laparoscopic Nissen fundoplication: the fundus is
pulled through the retroesophageal window and evaluated for appropriate symmetry with the "shoeshine" maneuver.
Gastrostomy Gastrostomy is often performed in children with swallowing disorders, food refusal, chronic failure to thrive, and aspiration with swallowing. Obviously, patients with a short-term need for enteral feeding are benefited by nasogastric or nasoenteric tubes. However, patients with a long-term need for enteric feeding are best served by a gastrostomy or jejunostomy. Currently, there are multiple surgical options for enteral feeding devices, including open gastrostomy, percutaneous endoscopic gastrostomy, a gastrojejunostomytube through the gastrostomy, laparoscopic gastrostomy, lesser curvature gastrostomy, simple jejunostomy, and Roux-en-Yjejunostomy. It is controversial whether patients who need gastrostomy placement should undergo a workup for GER. Some authors believe that no workup is needed."".Their view is that either most patients with a gastrostomy will not vomit or the vomiting will resolve after gastrostomy feedings are initiated. This view is not shared by many pediatric surgeons who believe that a workup for GER should be performed before gastrostomy placement.flJ73 If significant reflux is identified, an antireflux procedure should be performed along with the gastrostomy. A third view is that patients with GER who need enteric feedings should have either a gastrojejunostomy or a jejunostomy tube placed. The disadvantage of this third view is that the patients must then be fed by drip methods, which is a much less attractive option for parents who are struggling
CHAPTER
to care for their child. Gastrojejunal tubes are frequently dislodged. Many patients live a long distance away from a medical facility for children, so dislodgement of the tube is a difficult logistic issue for them to cope with. Feeding into the stomach without an antireflux procedure also risks massive aspiration. In our experience, parental fatigue seems to be much greater as parents try to cope with the persistent vomiting and poor weight gain of their vomiting child. For these reasons, the authors prefer to mle out gross reflux before performing a gastrostomy. Patients with significant documented reflux or a predilection for postgastrostomy reflux, such as those with a large hiatal hernia or spasticity associated with increased intra-abdominal pressure, are treated by simultaneous gastrostomy and fundoplication. Richards et al. reported that two thirds of patients who gag and retch postoperatively can be identified preoperatively by a careful history. They characterized these patients as vomiters and not refluxers and advocated the avoidance of fundoplication in such patients.lg7On the other hand, Owings reviewed 138 neurologically impaired patients undergoing fundoplication. She found that 33% of these neurologically impaired patients were cured of their gagging and retching by fundoplication. Thirty-five percent did not retch either preoperatively or postoperatively. Twenty percent of the patients retched both preoperatively and postoperatively, and these symptoms developed postoperatively in 12% (Owings E, personal communication). Because two thirds of neurologically impaired patients do not have significant retching postoperatively, the authors do not withhold fundoplication from these patients. When a patient needs chronic enteral feeding, several gastrostomy options are most frequently used. Open gastrostomy can be performed with a variety of techniques. The classic technique is a Stamm gastrostomy, which is usually performed by way of a small 4cm midline incision located equidistant between the xiphoid and umbilicus.l2 The anterior wall of the stomach is identified and two purse-string sutures are placed. A tube is passed through the left upper quadrant in an appropriate position. A balloon or mushroom catheter is inserted into the stomach inside the purse-string sutures (Fig. 71-13). The purse-string sutures are tied snugly. The gastrostomy is tacked in two to four quadrants to the abdominal wall with absorbable sutures (Fig. 71-14). The gastrostomy tube is secured to the skin with a suture. The percutaneous endoscopic gastrostomy (PEG) technique was first described by Michael Gauderer, a pediatric surgeon. Excellent descriptions of the PEG PEG is technique are available in the literat~re.~~,~53'" a minimally invasive technique that usually requires a general anesthetic in the pediatric population. Its disadvantages include an inability to choose the precise position on the stomach wall to site the gastrostomy and the fact that it is a blind technique that can lead to penetration of the colon or liver. Another common method for placement of a gastrostomy tube or button is laparoscopic gastrostomy. It is a minimally invasive technique that requires a general anesthetic. However, it is versatile and can easily be performed with other laparoscopic techniques. It allows precise placement of the gastrostomy
71
Gastroesophageal Reflux Disease
1131
.
Stamm gastrostorny: one or two purse-string sutures are placed in the anterior wall of the stomach and tied snugly around the gastrostomy tube.
device at the chosen site on the stomach wall. Placement of a primary button is relatively easy with this technique. Two methods are commonly used to place a gastrostomy laparos~opically.2~~ The first method is the port site method in which a medial left upper quadrant port site is enlarged. The intra-abdominal stomach is grasped at the site of the intended gastrostomy site and pulled up through the abdominal wall. Two stabilizing sutures are then passed through the fascia, through the wall of the stomach, and back out through the fascia on the opposite side.
a
-
Stamm gastrostomy: the stomach is secured to
the abdominal wall around the gastrostomy site with three or four sutures.
1132
PART
VI
THORAX
.
Laparoscopic U-stitch gastrostomy: the stomach is grasped and held near the abdominal wall while two U-stitches are placed for countertraction of the anterior stomach wall. •
This stitch is repeated on the lower side of the gastrostomy wound. The stomach is pulled out through the enlarged port site and a purse-string suture applied. A hole is made in the stomach wall inside the purse-string suture. The button or catheter is inserted through the hole and the stomach is allowed to return to the abdominal cavity. The purse-string suture is tied snugly. The two stabilizing sutures are also tied snugly. The gastrostomy tube or button can be fixed externally with a suture, depending on the surgeon's preference. This port site technique is simple but has some drawbacks. The port site, which is enlarged, can break down and allow evisceration of the stomach wall through the skin site, particularly in thinwalled infants. The most common problem with this technique is that it is difficult to completely return the stomach wall back into the peritoneal cavity. The gastrostomy tract is lined with gastric mucosa, which has a greater tendency to leak and also creates a troublesome, nonclosing gastrocutaneous fistula when the gastrostomy tube or button is removed."" The other commonly used laparoscopic gastrostomy technique is the U-stitch technique. In this technique, a U-stitch is passed through the abdominal wall adjacent and medial to a left upper quadrant port site, through the stomach wall, and back out through the abdominal wall. A second U-stitch is passed parallel to the first about 1 cm apart (Fig. 71-15). A needle is passed through the trocar site and directly into the stomach, which has been inflated with air through a Levine tube placed by the anesthetist. The needle is passed into the inflated stomach through the port site inside the two U-stitches. A guidewire is passed through this needle into the stomach (Fig. 71-16). The tract is dilated over the guidewire up to
-
Laparoscopic U-stitch gastrostomy: a needle and
guidewire are passed through the port site into the inflated stomach. Dilators are passed over the guidewire up to a size 20 French.
a size 20 French. A 14French balloon button is passed over the guidewire into the stomach, with an &French dilator used to stiffen the stem of the button as it is passed into the stomach. The U-stitches are tied over the wings of the gastrostomy button or over bolsters if a gastrostomy tube is being placed (Fig. 71-17)."3 The primary disadvantage of this technique is that the stomach
a
-
Laparoscopic Ustitch gastrostomy: the U-stitches
are loosely tied over the wings of the gastrostomy button and removed on the second postoperative day.
CHAPTER
is not directly secured to the abdominal wall. However, after placing over 1000 gastrostomy buttons in this manner, lack of site fixation does not seem to be a major problem, very much like a PEG tube does not usually lead to local leakage of gastric contents into the peritoneal cavity.2j5
Complications of Antireflux Procedures Complications may be classified according to occurrence during surgery, early after surgery, or late. Complications during surgery include bleeding from the short gastric vessels, the spleen, or an aberrant left hepatic artery. In adult laparoscopic series, it has been reported that perforation of the esophagus or stomach occurs in about 1% of ~ ~have seen only one gastric perprimary p r o ~ e d u r e s . 2We foration and no esophageal perforations during primary fundoplication in over 1000 laparoscopic fundoplication procedures. Pneumothorax may occur with either open or laparoscopic techniques. The pneumothorax usually develops during dissection of the mediastinal esophagus in an effort to gain more esophageal length. The pneumothorax can be relieved by placing a small intravenous catheter in the ipsilateral chest and removing it at the end of the operation after the abdomen has been closed. Conversion rates from laparoscopic to open surgery should be less than 3% for primary operations. Many fundoplication patients experience early dysphagia when the wrap becomes edematous several days after completion of the surgical procedure. This dysphagia can be avoided by keeping the wrap loose and floppy, dividing the upper short gastric vessels, and placing the patient on a soft diet for 2 to 3 weeks postoperatively.10Y A tight hiatus can likewise cause dysphagia and must be carefully avoided. It is also important to not make the wrap too long. In the authors' experience, a wrap 3.0 cm in length is more likely to elicit dysphagia than a floppy 2.0-cm wrap. Patients with severe esophageal dysmotility can report dysphagia even with a loose wrap. Prokinetic agents may be helpful in treating this group of patients. Recurrent reflux is a common complication after fundoplication in children.82 It is often related to postoperative retching and gaggng (Ngerncham M, personal communication). It is important to recognize that postfundoplication retching is most often initiated by central nervous system abnormalities and is not primarily a gastrointestinal symptom. The most common cause of postoperative gagging is overfeeding of the patient. Zealous parents are thrilled to have a reliable mechanism to feed their semistarved child and often overfeed them. A careful history of the timing of the retching is essential in determining its underlying cause. Gagging and retching can be ameliorated by drip feedings, emptying the stomach of air before initiating feedings, treating constipation, and as previously mentioned, avoiding overfeeding of the patient. However, postfundoplication gagging and retching remain a major problem, especially in neurologically impaired children. Other postfundoplication complications include gasbloating syndrome and an inability to vomit. Most patients with a floppy Nissen fundoplication can burp and vomit within 6 months of the operative procedure (Owings E, personal communication). True gas-bloating syndrome is
71
Gastroesophageal Reflux Disease
1133
uncommon in these patients. It is usually seen in neurologically impaired patients who are aerophagic. More commonly, patients who seem bloated are constipated and have a distended, air-filled colon rather than air in their stomach. These gas-bloating symptoms can be ameliorated by treating their constipation with fiber and appropriate laxative admini~tration.~" Dumping syndrome can also follow the formation of an antireflux wrap. The fundoplication streamlines the stomach and decreases the size and reservoir function of the stomach. The addition of a pyloroplasty is associated with an even higher incidence of dumping. Patients with sweating and diarrhea after feeding should be managed by restriction of food intake, reduction in carbohydrate intake, and drip feedings.'" Small bowel obstruction is another complication that is relatively rare after laparoscopic fundoplication, but not uncommon in patients after open fundoplication. A rate of 2.6% has been reported after open surgery.82
Outcome and Results The success rates of open and laparoscopic antireflux procedures are excellent. In a multicenter review of more than 7000 children over a 20-year period, good to excellent results were achieved in 95% of neurologically normal children and 84.6% of neurologically impaired children with the use of open surgical techniques.82z1jg Similar success rates can be achieved with laparoscopic fundoplication. Chung and Georgeson reported their success with both laparoscopic Nissen and Toupet fundoplication. They showed that of patients undergoing laparoscopic Nissen fundoplication, 3.5% had recurrent symptoms at 2 years versus 6.1% of those undergoing Toupet fundoplication." The most common cause of fundoplication failure after laparoscopic repair is slippage of the wrap into the chest (Ngerncham M, personal communication). For this reason, great effort should be made to prevent slippage of the fundoplication wrap into the chest. A recent report assessing laparoscopic Thal antireflux procedures showed a silent reflux rate of 25% in symptom-free children.108 As mentioned earlier, partial-wrap fundoplications appear to be associated with a higher recurrence of GER than complete-wrap fundoplications. A common problem is knowing what to do with a child who has failed multiple fundoplications. Medical management of the reflux should be used to control the recurrent symptoms whenever possible. Radiofrequency ablation is another possibility, as suggested by Islam et al.112 If redo surgery is necessary, Roux-en-Y esophagojejunostomy has been reported to be effective, but this technique is associated with a high rate of serious complications.~%other possibility is to redo the fundoplication with a Collis-Nissen technique108 or hiatopIa~ty,~O thereby lengthening the intra-abdominal portion of the esophagus. No reliable resolution to the problem of recurrent reflux after fundoplication in children has been reported thus far. The authors prefer performing a redo Nissen fundoplication after the first recurrence, followed by a laparoscopic Collis-Nissen procedure for a second recurrence of reflux symptoms.
1134
PART
VI
THORAX
SUMMARY GER is a common disorder in children a n d often requires surgical correction. GER in infants a n d children is more complex than adult GER. Failure of medical management a n d a n inability to wean from antireflux medications are the most common indications for the surgical treatment of reflux. A complete-wrap fundoplication appears to have better outcomes t h a n partial-wrap fundoplication, although this contention is controversial. Postoperative retching a n d recurrent GER are the most common a n d vexing complications of antireflux surgery.
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Note: Page numbers followed by the letter f refer to figures and those followed by t refer to tables. Page numbers followed by the letter b indicate boxed material.
AaDo, (alveolar-arterial oxygen difference) in congenital diaphragmatic hernia, 938, 942-943 in respiratory failure, 135 Aarskog's syndrome, 1149 ABCDE sequence, for life support, 267-272, 268f, 270f-271f with burn patient, 385 Abdominal cocoon, 1365 Abdominal compartment syndrome hepatic hemangiomas with, 2102, 2106 in trauma patient, 302-303, 303f infantile hepatic hemangioendothelioma with, 495, 496 Abdominal packing, 301-302 Abdominal pain in intussusception, 13'24, 1325 in peptic ulcer disease, 1228-1229 multidetector computed tomography in, 35,35f Abdominal pressure. See Intra-abdominal pressure. Abdominal trauma, 295-313 appendicitis secondary to, 1502 compartment syndrome in, 302-303,303f diagnostic modalities in, 295-297, 296f gastrointestinal, 310, 3 11-312 in birth injury, 405, 405f in child abuse, 404 laparoscopic repair of, 297, 299, 300f, 313 role of pediatric surgeon in, 295, 313 seat-belt injuries in, 31 1, 31 1f intestinal stricture secondary to, 1365 to kidney, 317 to colon, 310-31 1 to diaphragm. See Diaphragm, trauma to. to kidney. See Kidney, trauma to. to liver. See Liver, trauma to. to pancreas. See Pancreas, trauma to. to small intestine, 310, 311, 311f to duodenum, 303-304, 304t, 305f-307f, 306307, 3061, 307t to spleen. See Spleen, trauma to. to stomach, 297, 310 to vasculature, 378 Abdominal wall defects of, 1157-1 167. See also Bladder exstrophy; Ectopia cordis; Gastroschisis; Omphalocele; Umbilical hernia. antenatal considerations in, 1161 associated conditions with, 1162, 1162t cryptorchidism as, 1162, 1167, 1195 clinical features of, 1161-1 163 complications of, 1166, 1167 congenital syndromes with, 1160-1 161 embryological basis of, 1158-1 160, 1159f
Abdominal wall (Continued) genetics of, 1160, 1161 historical perspective on, 1157 in prune-belly syndrome, 1158, 1781, 1781f-1783f, 1786 intestinal malrotation with, 1346 obstetric delivery with, 1161 outcome of, 1 1 6 6 1167 spectrum of, 1157-1158,1158f-1159f, 1158t treatment of, 1163-1 166, 1164f, 1166f umbilicoplasty in, 1153, 1154f, 1163, 1166 desmoid tumor of, in Gardner's syndrome, 1422 embryology of, 1158-1 159, 1159f hernia of, rectus block for repair of, 245,245f soft tissue sarcoma of, 550 as rhabdomyosarcoma, 534 transplantation of, after intestinal graft, 749 trauma to, by seat belt, 311, 311f, 346 Abdominoplasty for prune-belly syndrome, 1781, 1782f-1783f patch, 303, 303f ABI (ankle-brachial index), 377-378 Ablative instruments, 40-42 Abortion. See also Fetus, selective reduction of; Termination of pregnancy. spontaneous, 2061 Abscess (es) appendiceal, 1502, 1503 breast, 887, 888, 890 Brodie's, 2033, 2034f, 2035, 2037f cervical lymphadenitis with, 845, 845f crypt, in Hirschsprung's disease, 1529, 1529f epidural, 2009, 2010,2010f spinal, 2013 first branchial anomaly with, 867 hepatic, 1642-1644,1643f, 1645-1646,1646f intra-abdominal, in appendicitis, 1509 intracranial, 2008-2013, 2010f secondary to sinusitis, 819, 2009 lung, 1015-1017, 1017f mastoid, subperiosteal, 815 mediastinal, 1028 otitis media with, 815, 816 perianal, 1597-1598,1598f in Crohn's disease, 1458 perinephric, 324 periorbital subperiosteal, 819 periphlebitic, 2132 peritonsillar, 823, 2132 pharyngeal space, 2132 presacral, 1396 psoas, 2040 renal, 1745 retropharyngeal/parapharyngeal, 823, 823f mediastinitis secondary to, 1027 torticollis secondary to, 877 salivary gland, 837, 839 spinal epidural, 2013 Volume 1, pages 1-1140; Volume 2, pages 1141-21
Abscess(es) (Continued) splenic, 1694 in leukemia patient, 1644 subperiosteal, 2034f intracranial, 2010, 2010f periorbital, 819 thyroid, pyriform sinus tract with, 869f urachal, 1149 vitelline duct remnant with, 1148 Abuse. See Child abuse; Sexual abuse. Acardiac twinning, 82t, 85, 2080 Accelerated hyperfractionated radiation therapy, 429 Accidental injury. See Emergency management; Trauma. ACE (angiotensin-converting enzyme), 629 ACE (angiotensin-converting enzyme) inhibitors for heart failure, in neonate, 148, 150t nephrotoxicity of, 2120 Acetabular index, 2020, 2020f Acetaminophen, 237-238,238t for fever, in brain injury, 273 toxicity of, liver transplantation for, 733 Acetate, in parenteral nutrition, 206, 2061, 207 Acetic acid solution, for infected wounds, 352 Acetylcholinesterase, amniotic fluid, abdominal wall defects and, 1161 Acetylcholinesterase inhibitor, for Ogilvie's syndrome, 1496 Acetylcholinesterase staining, of rectal biopsy in Hirschsprung's disease, 1518, 1518f, 1526, 1527 in intestinal neuronal dysplasia, 1562, 1563f N-Acetylcysteine for inhalation injury, 395 for meconium ileus, 1296 for milk curd syndrome, 1365 Acetylhydrolase, necrotizing enterocolitis and, 104 Achordoma, 2102 Acid burns, 395-396 Acid ingestion. See Esophagus, caustic injury to. Acid-base balance. See also pH. carbon dioxide equilibrium and, 95, 121 in fetus, 95-96,96t in neonate, 95, 96, 96t parenteral nutrition and, 207, 208 pulmonary circulation and, 120 Acidosis. See alro Lactic acidosis; Metabolic acidosis; pH; Respiratory acidosis. in fetus, 96, 96t in malignant hyperthermia, 231, 232, 232t in neonate, 96, 96t postoperative, 99 in trauma patient, with severe bleeding, 300-301,902 oxyhemoglobin dissociation curve in, 121 pulmonary vasoconstriction caused by, 120
Acinic cell carcinoma, salivary gland, 840, 840f ACLS (Advanced Cardiac Life Support), 69 Acoustic neuroma, in neurofibromatosis type 2,679 Acquired immunodeficiency syndrome (AIDS). See also Human immunodeficiency virus (HIV) infection. blood transfusion and, 189 respiratory infections in, 1008, 1009 Acquired tolerance, 685-693, 685f-693f Acrosyndactyly, 2074, 2074f, 2075 ACTH (adrenocorticotropic hormone), 629, 633-634, 634f, 635, 637 Actinomycin (dactinomycin), 423t, 428-429 Actinomycosis cervicofacial, 848 in persistent thyroglossal duct, 870 osteomyelitis in, 2044 Activated partial thromboplastin time (APTT), 183,184t, 185, 186 Activated protein C resistance. See Protein C. Actuators, microelectromechanical, 57, 58 Acute phase proteins in sepsis, 171 interleukin-6 and, 165 sulfur amino acids in, 104 Acute respiratory distress syndrome (ARDS). See also Respiratory failure. anti-LPS monoclonal antibody and, 172 continuous venovenous hemofiltration for, 779 extracorporeal life support for, 141t lung transplant for survivor of, 769 mechanical ventilation for, 125, 127 pharmacologic adjuncts for, 127 Acute tubular necrosis after renal transplantation, 707, 710 burn-related, 384 Acyclovir after intestinal transplant, 750 for herpes simplex viral esophagitis, 1386 for post-transplant lymphoproliferative disease, 762 Addison's disease, 636637 Adenitis, cervical, 832. See also Cervical lymphadenopathy. Adenoid (pharyngeal tonsil) anatomy of, 822 EBV-related hypertrophy of, 828 middle ear effusion and, 815 sleep-disordered breathing and, 823-825, 824f Adenoid cystic carcinoma, pulmonary, 641 Adenoidectomy, 815, 824-825 Adenoma adrenal, 635 aldosterone-secreting, 636 bronchial, 641, 642f hepatocellular, 495, 498 islet cell, 1683 nipple, 888, 891 parathyroid, 858, 858f pituitary, 633, 634, 635 salivary gland, 826, 839, 839f Adenomatous polyps, 1414, 1417. See also Familial adenomatous polyposis. Adenopathy. See Lymphadenopathy. Adenosine, for supraventricular tachycardia, 151, 152t Adenoviruses as gene therapy vectors, 16, 17, 17t, 18 bronchiolitis caused by, 1004 ADH (antidiuretic hormone), in neonate, 93-94,94t
Adhesins, 158 Adhesion molecules in biliary atresia, 1611 in Hirschsprung's disease, 1525-1526 in inflammation, 159-160, 160f, 161, 165, 166 in neonate, 167 in SIRS, 168, 169, 169f in tumor invasion, 418 Adhesions abdominal. See also Intestinal obstruction, adhesions with. perihepatitis as cause of, 1645 prevention of, 1360 labial, 1903, 1942 Adipose tissue brown, 98,99, 100 inflammation of, in obesity, 1244 measurement of, 195 Adolescent patients. See also Bariatric surgery in adolescents. consent by, 258 renal transplant recipients, 711 Adrenal gland(s), 628-638 anatomy of, 628 birth injury to, 405 cortical insufficiency of, 63&637 in Allgrove's syndrome, 1113 embryology of, 628-629 fetal, 628, 630, 637 hemorrhage of infection-related, 637 neonatal, 630, 637 hyperaldosteronism and, 636 hyperplasia of ACTH oversecretion with, 635 congenital, 637, 1913, 1914t. See also Pseudohermaphroditism, female. hyperaldosteronism in, 636 nodular, 634f, 635 hypoplasia of, congenital, 637 imaging of, 629-630 incidental mass of, 637 neoplasms of cortical, 633-636, 634f, 636f medullary. See Neuroblastoma; Pheochromocytoma. physiology of, 629 Adrenal rests, 628-629 in enteric duplication cyst, 964 inguinal, 1189 Adrenalectomy, 637-638, 638f for adrenocortical tumors, 635 aldosterone-secreting, 636 for incidental mass, 637 for nodular hyperplasia, 635 laparoscopic, 637, 638 Adrenaline. See Epinephrine (adrenaline). a-Adrenergic blockers for hypertension, 2120 preoperative, for pheochromocytoma excision, 632 R-Adrenergic blockers. See Beta blockers. Adrenocorticotropic hormone (ACTH), 629, 633-634, 634f. 635,637 Adrenogenital syndrome, 637, 1913, 1914t. See also Pseudohermaphroditism, female. Adriamycin (doxorubicin), 424t, 426, 428-429 as terato-gen, esophageal atresia and, 1054, 1070 Advanced Cardiac Life Support (ACLS), 6 9 Advanced Trauma Life Support (ATLS),266 for thoracic trauma, 276-277 mannequin simulators for, 69 musculoskeletal injuries and, 339, 341 Volume 1, pages 1-1140; Volume 2, pages 1141-21
AESOP (Automatic Endoscopic System for Optimal Positioning), 49, 49t, 50 for cholecystectomy, 1639, 1640, 1640f Afibrinogenemia, congenital, 185 AFP. See Alpha fetoprotein (AFP). Afterload, 146, 147 Afterload-reducing agents, for heart failure, in neonate, 148, 150t, 151 Aganglionosis colonic. See Hirschspmng's disease. short-bowel syndrome secondary to, 1369, 1369f, 1540 small intestine, 1531, 1539-1540, 1542f-1543f vs. meconium ileus, 1293 AIDS (acquired immunodeficiency syndrome). See also Human immunodeficiency virus (HIV) infection. blood transfusion and, 189 respiratory infections in, 1008, 1009 Air embolus, pulmonary laceration with, 282 Air-leak syndrome extracorporeal life support for, 140t high-frequency ventilation and, 126 Airway. See also Aspiration, pulmonary; Larynx; Trachea. functional anatomy of, 983-984 inflammatory disease of, 830-831 inhalation injury to, 394-395 by ammonia fumes, 1084 trauma to, 275, 275t, 276, 277, 278, 282-283, 283f, 291 Airway management. See also Endotracheal intubation. in burn patient, 385 in trauma patient, 267, 268f, 272 in upper airway obstruction, 827-829 Airway obstruction. See also Respiratory distress. anesthesia-related, laryngospasm in, 223, 229,233 caustic ingestion with, 1084 clinical presentation of, 983 deep neck space infection with, 823 evaluation of, 983 facial deformities with, 806, 812 fetal, 82t, 85 foreign body. See Foreign body, airway. inhalation injury with, 395 ammonia fumes in, 1084 laryngeal anomalies with, 829-830, 829f-830f laryngoscopy with, 973 laryngotracheobronchitis with, 830 lymphatic malformation with, 2099, 2138, 2139 macroglossia with, 825 management of, 827-829 neonatal airway anatomy and, 983-984 sleep-related, 823-825, 824f obesity and, 1246, 1252 stenosis with. See Laryngotracheal stenosis; Subglottic stenosis; Tracheal stenosis. supraglottitis with, 830-831 third branchial cleft anomalies with, 868 tracheotomy for. See Tracheotomy (tracheostomy). tuberculosis with, 1003 tumors with, 644. See also Subglottic hemangioma. hemangioma as, 2103 in Hodgkin's disease, 576, 576f laryngeal, 831, 831f, 989-990, 989f teratoma as, 563, 564, 564f vascular compression with, 997-998, 1070. See also Trachea, compression of. vocal cord immobility with, 988-989
Airway pressure release ventilation, 123, 125 Airway resistance, 119-120 ALADIN syndrome, 1113 Alagille's syndrome, 732, 1613-1614 Albumin in fluid replacement, 226 for burn patient, 387, 388t in meconium, 1290-1291, 1292 intra-alveolar, for congenital diaphragmatic hernia, 945 serum calcium and, 209 nutritional status and, 195 serum-ascites gradient of, 1409 Alcohol. See Ethanol, injection of; Fetal alcohol syndrome. Aldosterone, 628, 629. See also Mineralocorticoids. excess of, 636 myocardial fibrosis caused by, 148 neonatal acid-base balance and, 96 Aldosteronoma, 636 Alemtuzamab (Campath) before transplantation, 693 for intestinal transplantation, 749 Alkali ingestion. See Esophagus, caustic injury to. Alkaline phosphatase placental, germ cell tumors and, 556 serum, osteogenic sarcoma and, 654 Alkalosis. See also Metabolic alkalosis. controlled, for brain injury, 273 hypertonic saline causing, 389 in fetus and neonate, 96t oxyhemoglobin dissociation curve in, 121 pulmonary vasodilation caused by, 120 Alkylating agents, 422, 42% Allantois, 1143, 1144f, 1145 cloaca and, 1566 Allen's test for radial artery catheter placement, 123 in hand trauma, 348 Allergic colitis, 1386 Allergy airway obstruction in, 828 fungal sinusitis in, 819 milk protein, 1386 Allgrove's syndrome, 1112-1 113 Alloderm, 390 Aloe vera, for first-degree burns, 385 Alosetron, for intestinal pseudo-obstruction, 1366 Alpha fetoprotein (AFP), 77 abdominal wall defects and, 1161 conditions with elevation of, 77, 555-556 germ cell tumors and, 555-556 ovarian, 595, 609 pineal, 673, 678 teratoma as cervicofacial, 564, 565 mediastinal, 565, 962 ovarian, 566 sacrococcygeal, 560,562 testicnlar, 567 testicular, 622, 623, 626 yolk sac tumor as, 567, 609, 622, 623,626 liver tumors and benign, 495-496,498, 499 malignant, 502, 503, 505, 510, 511 normal levels of, by age, 495, 495t, 555, 555f, 595t Sertoli-Leydig cell tumors and, 606 Aluminurn toxicity, 209 Alveolar dead space, 120. See also Dead space, pulmonary.
Alveolar proteinosis, extracorporeal life support for, 142 Alveolar rhabdomyosarcoma, genetics of, 415-416,417t, 419 Alveolar soft part sarcoma, 547 Alveolar-arterial oxygen difference (AaDo*) in congenital diaphragmatic hernia, 938, 942-943 in respiratory failure, 135 Amebiasis. See Entamoeba histolytica infection. Amelia, 2051f Amenorrhea, congenital anomalies with, 1568 vaginal agenesis as, 19361937 American Board of Surgery, 5 American Pediatric Surgical Association, 5 American Society of Anesthesiologists (ASA) fasting guidelines, 224, 224t monitoring standards, 234 patient status classification, 221-222 Amiloride, for adrenocortical hyperplasia, 636 Amino acids conditionally essential, 196, 196t, 204 essential, 196, 196t in enteral formulas, 1372 in neonatal diet, 101, 104, 108, 196 in breast milk, 202 in parenteral formulas, 204, 208 in parenteral formulas, 204, 208 for short-bowel syndrome, 212 hypercalciuria and, 209 Aminocaproic acid, during extracorporeal life support, 139 Aminophylline, necrotizing enterocolitis and, 1429 5-Aminosalicylic acid (ASA) compounds for Crohn's disease, 1455 for ulcerative colitis, 1465-1466 Amiodarone, for supraventricular tachycardia, 151, 152t, 153 Amniocentesis, 78 for diagnosis of cystic fibrosis, 1292, 1293 Arnnioreduction, for twin-twin transfusion syndrome, 82t, 85 Amniotic bands, 2075 fetoscopic intervention for, 78 Amniotic fluid. See also Oligohydramnios; Polyhydramnios. abdominal wall defects and, 1161 alpha fetoprotein in, 77 fetal fluid balance and, 92, 93f lung development and, 934,936 therapeutics delivered via, 81-82, 82t Amphotericin B for Aspergillus infection, 775, 1006 renal insufficiency secondary to, 779 Amputation, 2050-2059 congenital limb deficiency and, 2050-2054, 2051f-2055f, 2054t for purpura fulminans, 2058 for trauma, 345, 379, 2055, 2056t for tumors, 205G2058, 2056t, 2057f bone, 658,659,659f, 660,662,665, 666667 soft tissue sarcomas, 548 for vascular disease, 2058 overview of, in children, 2050 phantom phenomenon secondary to, 2058-2059 stump overgrowth secondary to, 2050, 2058 traumatic, 345, 2054-2055 replantation for, 352, 2055-2056 Anabolic steroids for chronic anemia, hepatocellular adenoma caused by, 498 for Fanconi's anemia, 179
Anal continence, 1591, 1592. Seealso Incontinence, fecal. Anal fissure, 1385, 1596-1597 constipation and, 1549, 1592, 1596, 1597 in Crohn's disease, 1458, 1465, 1597 sexual abuse as cause of, 1599 Analgesia. See Pain management. Analgesic Ladder, 236, 237f Anaphylaxis latex-induced, 232 thiopental-induced, 233 Anaplastic large cell lymphoma, 580, 582, 584 Anastomosis, virtual reality simulator for, 69 Anatomic dead space, 120 Anderson-Hynes pyeloplasty, 1734f Androblastoma, 606 Androgen insensitivity, 1914t, 19161917, 1919-1920 inguinal canal in, 1174, 1188-1 189 Androgens. See also Intersex abnormalities; Testosterone. adrenal synthesis of, 629, 1916f, 1916t breast hypoplasia and, 887 cryptorchidism and, 1197, 1198 epididymal development and, 1195 for aplastic anemia, hepatocellular adenoma associated with, 495 from ovarian tumors, 594, 595t, 604, 606, 607, 612 testicular descent and, 1193-1 194, 1194f Anemia, 178-182, 179f. See alsoAplastic anemia; Hemolytic anemias; Iron-deficiency anemia. birth injury as cause of, 405 indwelling arterial lines and, 123 postoperative apnea associated with, 223 Anencephaly, 1987,1990 Anesthesia complications of, 231-232, 232t gastrointestinal motility and, 1361 during extracorporeal life support, 138-139 epidural, 247-249, 247f, 248t fluid management with, 225-226 for diaphragmatic hernia repair, 942 for fetal surgery, 79 for fracture reduction, of hand, 352 for inguinal hernia repair, 244, 1175-1 176 in neonate hypothermia associated with, 99 physiology of, 221, 222f, 222t, 228 infiltration, 243, 244 inhalation, 227-229, 227t, 228f dose versus age, =1,222f, 228 laryngospasm associated with, 223, 229 malignant hyperthermia associated with, 231-232, 2321 intramuscular induction for, ketamine in, 239 intravenous agents in, 221, 222f, 232-233, 233f ketamine as, 238t, 239 local anesthetics for, 243, 243t metabolism of children and, 21 1, =1, 222f, 222t, 228 monitoring of, 233-235, 234f mortality associated with, 222-223 neuraxial, 243, 247-249,247f, 248t neuromuscular blocking agents with, 229-231,2301 monitoring of, 235 patient preparation programs for, 223 pediatric anesthesiologists for, 221, 222-223 physical status classification for, 221-222 physiology of, 221, 222f, 222t, 228 premedication for, 221, 224-225 preoperative evaluation for, 223
Volume 1, pages 1-1 140; Volume 2, pages 1141-2146.
Anesthesia (Continued) preoperative fluid restrictions for, 223-224, 224t. 225 regional, 243-249, 245f-247f intravenous, 244 risk of, 221-223 topical, 243, 244, 244t Aneuploidy. SPPPloidy, of cancer cells. Aneurysm (s) congenital, 21 11, 21 12f in connective tissue disorders, 2114, 2114f mycotic, 2115-2116, 2116f traumatic, 21 1 4 2 115. See also Pseudoaneurysm. intracranial, 366 venous, 2 126,2129 Aneurysmal bone cyst, 652f, 654,655f, 659 Angioblastoma of Nagakawa. See Tufted angioma. Angiofibrorna, juvenile nasopharyngeal, 821 Angiogenesis biology of, 418 corticosteroid inhibition of, 2104 in cancer, 419 in neuroblastoma, 473, 474, 475, 486 inhibition of, 422, 426427 by fenretinide, 484 in engineered tissi~es,22, 25 in hemangioma, 2095, 2104 in pathologic processes, 418-419 Angiography. SPPalso Compnted tomographic angiography; Magnetic resonance angiography (MRA). in portal hypertension, 1657 of liver tumors benign, 496, 497, 498 malignant, 504 of pulmonary embolism, 2132 of renal artery stenosis, 21 19, 21 19f, 2120 of trauma, 377 aortic, 278, 287, 290 catheter-related, 380 fracture-related, 342 renal, 319, 322, 324 upper extremity, 379 of vascular anomalies, 2103 arteriovenous malformation as, 21 13 Angioma, 546, 2094 tufted, 2094, 2098 Angiomyolipoma, renal, 1709 Angioplasty for central venous obstruction, 2124 for renal artery stenosis, 2120 for subclavian-axillaryvein thrombosis, 2131 Angiosarconla breast, 892 hepatic, 505 secondary to radiation, 497 Angiotensin, 629 Angiotensin receptor blockers, for heart failure, in neonate, 150t Angiotensin-converting enzyme (ACE), 629 Angiotensin-converting enzyme (ACE) inhibitors for heart failure, in neonate, 148, 150t nephrotoxicity of, 2120 Angle of His, 1122-1 123 Aniridia, 420-421, 446, 447, 451 Ankle fracture of, physeal, 342 tumor resection in, 666 Ankle-brachial index (ABI), 377-378 Ankyloglossia, 825, 825f Annular pancreas, 1260, 1261, 1261t, 1262, 1262f, 1263-1264, 1266, 1671 pancreatitis associated with, 1674, 1675, 1675f
Anoplasty, for perineal fistula, 1569, 1571 Anorectal achalasia, 1531 Anorectal atresia, Hirschsprung's disease with, 1528 Anorectal malformations, 15661588. See also Anus, imperforate. as imperforate anus without fistula, 1566, 1569, 1569f, 1571, 1571f-1572f, 1577-1578 associated anomalies with, 1567-1568, 1567f hypospadias as, 1567, 1894 spinal, 1810 classification of, 1566, 1566t clinical findings in, 1569, 1569f-1572f, 1571 colostography of, 1573-1574, 1573f-1574f, 1586 colostomy for, 1484, 1484f, 1485, 1485t, 1488, 1573 closure of, 1584 complications of, 1573, 1586 decision making for, 1569-1571, 1569f, 157lf, 1586 permanent, 1587 embryological basis of, 15661567 historical perspective on, 1566 incidence of, 1566 initial management of, 1569-1574, 1569f, 1571f, 1573f-1574f outcomes with, 1585-1588, 1586t, 15871, 1588t pathophysiology of, 1568-1569 reconstruction for, 1574-1585 as reoperation, 1588 basic principles of, 1574 complications of, 1585-1588 rectal prolapse as, 1586, 1596 female, 1578-1584, 1579f-1581f, 1583f-1585f, 1947-1949, 1948f in cloacal exstrophy, 1865-1866 limited anorectoplasty in, 1573 male, 1574-1578, 1575f-1578f postoperative care for, 1584-1585, 1584t teratoma with, 557, 559, 560, 564 Anorectal manometry, 15161517, 1517f, 1531 after pull-through, for Hirschsprung's disease, 1542, 1546 in constipation, 1593, 1594 in fecal soiling without constipation, 1595 in intestinal neuronal dysplasia, 1562, 1594 Anorectal myectomy, 1531, 1543-1544, 1544f-1545f Anorectal venous malformation, 2107 Anorectoplasty, posterior sagittal basic principles of, 1574 complications of, 1585-1588 in females, 1578-1582, 1579f-1581f, 1948-1949, 1948f in males, 1574-1578, 1575f-1578f limited, 1573 postoperative care with, 1584-1585, 1584t Anoxic brain damage, cerebral palsy and, 405 Antacids for gastroesophageal reflux, 1126 for peptic ulcer disease, 1229, 1230 prophylactic, stress ulcers and, 1231 Antegrade enema, 1483f, 1485 for incontinence, 1834, 1834f in cloacal exstrophy, 1866 Antegrade pyelography, of megaureter, 1772 Anthracycline, 423t-424t Antibiotic lock technique, 209-210 Antibiotic prophylaxis in heart transplantation, 761 in lung transplantation, 771, 775 to prevent necrotizing enterocolitis, 1445
Volume 1, pages 1-1140; Volume 2, pages 1141-2146
Antibiotic therapy for appendicitis, 1506, 1509 for burns intravenous, 394 topical, 383, 389-390, 389t, 396 for catheter-related infection, with parenteral nutrition, 209-2 10 for fracture, open, 344 for gastritis and peptic ulcer, 1230, 1230t for intracranial infection, 2012 for lung infection. SeeLung(s), infections of. for lymphadenitis, acute, 845 for musculoskeletal infection, 2044, 2045t for necrotizing cnterocolitis, 1438, 1439 for osteomyelitis, acute, 2037-2039, 2038t for otitis media, 815, 816 for peritonsillar cellulitis, 823 for pharyngotonsillitis, 8= for retropharyngeal/parapharyngeal infection, 823 for sepsis, 172, 173 for septic arthritis, 2040, 2041 t for urinary tract infection, 1745-1747, 1747t in Crohn's disease, 1456 in cystic fibrosis, 1011 in short-bowel syndrome, 1373-1374 Antibiotics, antitumor, 422, 423t-424t Antibodies. Set also Immunoglobulin (s); Monoclonal antibodies. for immunosuppression, with transplant heart, 761, 761f islet cell, 724, 726 liver, 738t, 739 lung, 770-771, 771t pancreas, 720 renal, 707,708-709 radiolabeled, to detect metastases, 47 Antibody-dependent cell-mediated cytotoxicity, 163 Anticardiolipin antibody, 187, 2121-2122, 2130 Anti-CD3 antibodies. See OKT3 (muromonabCD3). Anticholinergic agents for bladder dysfunction, 1824 in dysfunctional elimination syndrome, 1812 in nocturnal enuresis, 1815 in overactive bladder syndrome, 1814 neuropathic, 1809, 1810, 1810f, 1811 with posterior urethral valves, 1812 preoperative, 224, 231 with ketamine, 239 Anticholinesterase agents, with neuromuscular blockade, 231 Anticonvulsants, for head injury patients, 273, 366367 Antidiuretic hormone (ADH), in neonate, 93-94,94t Antigen matching, 695 Antihistamines for anaphylaxis, 232, 233 for transfusion reactions, 189, 190 Antilymphocyte antibodies, in transplantation. SPPalso OKT3 (muromonab-CD3); Thymoglobulin. heart, 76lf intestinal, 750 liver, 738t renal, 707, 708, 710, 712 Antimetabolites, 422, 423t Antimicrobials, topical, for bums, 383, 389-390, 389t, 396 Antioxidants for burns, 384 for systemic inflammatory response syndrome, 173 vitamins as, 198
Antiphospholipid antibodies, 2121-2122 venous thrombosis and, 187,2130 Antiplasmin, 186 Antisialagogues, preoperative, 224 Antithrombin 111, 184t, 186-187 deficiency of, 187,2130,2131 Antithymocyte globulin (ATG), 707. See also Thymoglobulin. in heart transplantation, 761, 761f in intestinal transplantation, 749 in lung transplantation, 770, 771, 771t, 774 a,-Antitrypsin as inhibitor of fibrinolysis, 186 deficiency of, 1606 in stool, protein malabsorption and, 213 Antivenin, 353 Antral atresia, 1232, 12321, 1233f Antrectomy, for stress ulcers, 1231, 1232 Antrochoanal polyp, 818 Antroplasty, gastric emptying and, 1130 ~ Anorectal entries. Anus. S P al,so abscess adjacent to, 1597-1598, 1598f in Crohn's disease, 1458 anatomy of, 1590-1591, 1590f Crohn's disease in region of, 1454, 1457, 1458, 1459, 1460, 1598 dilation program for postoperative, 1584, 15841, 1586 with fissure, 1597 embryology of, 1566-1567 fissure of. .Yep Anal fissure. fistula in, 1597, 1598, 1598f. See also Anorectal malformations. imperforate. See also Anorectal malformations. bladder exstrophy with, 1842, 1843f in prune-belly syndrome, 1783, 1786 urinary tract abnormalities with, 1822, 1823f 1824 with sacral agenesis, 1822 without fistula, 1566, 1569, 1569f, 1571, 1571f-1572f, 1577-1578 internal sphincter achalasia of, 1594 n~alpositioned constipation secondary to, 1593 measurement of, 1593 rhabdomyosarcoma of, 535 sexual abuse and, 1599 sphincter mechanism of, 1568, 1590-1592 trauma to, 312, 404, 1599 Anxiety, patient pain management and, 236,274 preoperative, 22 1, 223, 224 with burns, 394 Aorta. Ser also Great vessels, anomalies of. acute obstruction of, catheter-related, 380 adrenal rests along, 628, 631 arteritis of, 21 17 coarctation of, 1961-1964, 196'Lf-1963f subisthmic, 2120 traumatic, 277-278, 287 with ventricular septa1 defect, 153 midaortic syndrome of, 21 18, 21 19, 2120, 2121 robotic anastomosis of, ovine, 55, 56t trauma to, 276,277-278, 279,287-288, 287t, 288f-289f, 290, 31 1, 378 epidemiology of, 275, 275t, 276 seat belt causing, 346 Aortic aneurysm abdominal, congenital, 21 11 mycotic, 21 15, 2116, 2116f Aortic arch(es), 861, 862f anomalies of, 1980, 1980f-1981f, 1982 airway obstruction by, 997,998 Aortic graft, vs. engineered tissue, 21
Aortic valve congenital stenosis of, 86 endocarditis of, 21 15-21 16 Aortograph, of trauma, 278,287, 290 Aortopexy, for tracheomalacia, 998, 1070 APC (adenomatous polyposis coli) gene, 421, 519, 1420, 1421 Apert's syndrome, 22, 797-798, 797f, 799f, 800, 2074, 2074f Aphthous stomatitis, in ulcerative colitis, 1465 Aphthous ulcer, in Crohn's disease, 1453, 1454 Aplasia cutis congenita, 2063 Aplastic anemia, 179 amegakaryocytic thrombocytopenia with, 182 androgen therapy for, hepatocellular adenoma associated with, 495 in copper deficiency, 199 Apnea. See also Respiratory distress. during sleep, 823-825, 824f obesity and, 1246, 1252 gastroesophageal reflux with, 1124, 1125b mida~olamsedation and, 224 of prematurity, xanthines for, 1429 postoperative, 223 reflex, 997-998 tracheomalacia with spells of, 1070 Apnea index, 823 Apoptosis, 414 cytotoxic T lymphocytes and, 163 Hirschsprung's disease and, 1526 in tumors, 419, 426 neuroblastoma as, 475, 486, 487 Wilms' tumor as, 459 necrotizing enterocolitis and, 1433 radiation damage and, 43 Appendectomy, 1505-1509, 1507f-1508f complications of, 1509 adhesive bowel obstruction as, 1358, 1509 for spontaneous bacterial peritonitis, 1477 in Ladd procedure, 1352, 1354 in reduction of intussusception, 1333, 1336 laparoscopic, 1506, 1508, 1508f normal appendix found at, 1504, 1505, 1506, 1508 ulcerative colitis and, 1466 Appendicitis, 1501-1509 chronic, 1502 complications of, 1509 diagnosis of, 1503-1505 multidetector computed tomography in, 35,35f differential diagnosis of, 1505, 1505t vs. Meckel's diverticulum, 1309, 1505 epidemiology of, 1501-1502 gangrenous, 1502 historical perspective on, 1501 in cystic fibrosis, 1299, 1502 in Hirschsprung's disease, 1502, 1530 misdiagnosis of, 1502, 1503, 1504, 1509 outcomes of, 1509 pathophysiology of, 1502-1503 perforated, 1502, 1503, 1506, 1508-1509 hepatic abscess in, 1642-1643 in Hirschsprung's disease, 1530 preoperative pain management in, 236 presentation of, 1502-1503 recurrent, 1502, 1509 simple, 1502 spectrum of, 1502 spontaneous resolution of, 1502, 1503, 1506 treatment of, 1505-1509, 1507f-1508f. See also Appendectomy. unusual locations of, 1501 Appendicostomy, 14801, 1483, 1484, 1485 after anorectal malformation repair, 1587 urinary diversion concomitant with, 1796 Volume 1, pages 1-1140; Volume 2, pages 1141-21
Appendicovesicostomy, 1795, 1797, 1797f, 1798, 1832, 1833f robot-assisted, 53, 54t, 55 Appendix anatomical variations of, 1348, 1501 anatomy of, 1501 carcinoid tumors of, 518, 518f, 1502, 1505 embryology of, 1501 function of, 1501 histology of, in Hirschsprung's disease, 1530, 1531 in inguinal hernia, 1188 umbilical fistula to, 1146, 1149 Appendix testis. Sre Hydatid of Morgagni. Apple-peel intestinal atresia, 1276, 1276f, 1282, 1283 Aprotinin, for postoperative bleeding, after lung transplant, 772 Apt test, 1385 APTT (activated partial thromboplastin time), 183, 184t, 185, 186 APUD (amine precursor uptake and decarboxylation) tumors carcinoid. See Carcinoid tumors. neuroblastoma as, 470 Aqueductal stenosis, 82t, 85, 1995f, 2001 Arachidonic acid, 197, 197f Arbaprostil, peptic ulcers and, 1230 ARDS. See Acute respiratory distress syndrome (ARDS). Arginine, 196 necrotizing enterocolitis and, 1431 Argon beam coagulator, 41 Arrhenoblastoma, 606 Arrhythmias, cardiac extracorporeal life support for, 142 in congenital heart disease, with pulmonary hypertension, 766 in malignant hyperthermia, 231, 2321 in trauma patient, 272 myocardial contusion and, 285, 286 inhalation anesthetics and, 228, 228f, 229 neonatal, 151, 152t, 153 uncontrollable, transplantation for, 756 Arterial catheter, 123. See also Umbilical arteries, catheterization of. complications of, 380, 2058, 21 16 intraoperative, 235 Arterial disorders, classification of, 21 11, 21 12t. See also specijc. disordms. Arterial embolism, 21 15-21 17, 21 15t Arterial grafts, tissue-engineered, 24 Arterial occlusion. See also Ischemia. amputation secondary to, 2058 clinical manifestations of, 21 16 syndromes associated with, 21 17-2122, 2118f-2119f, 2118t Arterial switch operation, 1975, 1976f myocardial infarction secondary to, 38 Arterial thrombosis, 21 15-21 17, 2115t. See also Thrombosis. Arteriography. See Angiography. Arteriovenous fistula arteriovenous malformation with, 2100, 2101,2113 in Parkes-Weber syndrome, 2129 iatrogenic, 380 portal hypertension caused by, 1654 post-traumatic penile, 331 renal, 319, 324 Arteriovenous malformation (AVM), 2112-2114, 2113f classification of, 21 12 clinical features of, 2100, 2100f, 21 12-21 13 familial, 2096
Arteriovenous malformation (Continued) hepatic, 495, 497, 2102, 2112 histopathology of, 2095 in hereditary hemorrhagic telangiectasia, 2101 intracranial, 21 11, 21 13 radiosurgery for, 45, 46 management of, 2107,2113-2114 oral and pharyngeal, 826 spinal cord, 21 11 staging of, 2100 vs. hemangiopericytoma, 546 Arteritis aneurysms in, 21 15 etiologies of, 21 17 fibromuscular hyperplasia as, 2118, 2119 in Kawasaki disease, 848, 2117 stroke secondary to, 21 17 Takayasu's, 21 17, 2120 Arthralgia in Crohn's disease, 1454 in ulcerative colitis, 1464 Arthritis gonococcal, 2040,2044 in Crohn's disease, 1454 Lyme, 2044 septic, 2033,2034f, 2039-2041,2040t, 2041t Arthrodesis, after tumor resection, 666 Arthrography, 342 Arthrogryposis multiplex congenita, 1194, 2074-2075 Arthroscopy, 342 Artificial erection, 1887, 1891 Artificial sphincter, urinary, 1831, 1831f Arytenoid lateralization, 989 Arytenoidectomy, partial, 989 Arytenoidopexy, 989 ASA. See American Society of Anesthesiologists (ASA); 5-Aminosalicylic acid (ASA) compounds. Ascariasis, 1365 Ascites, 1407-141 1. See also Intraperitoneal fluid. after portoenterostomy, 1612 anatomy and pathophysiology of, 1407-1408 biliary, 1409-1410, 1409t, 1615 causes of, 1407t chylous, 1409t, 1410-1411, 2107,2140 clinical features of, 1408 diagnosis of, 1408-1409, 1408f, 1409t vs. omental cyst, 1402 hepatocellular, 1407t, 1408f, 1409, 1409t laparoscopic evaluation of, 440 necrotizing enterocolitis with, 1437, 1439, 1440 portal hypertension with, 1656, 1658 after shunt operation, 1663 primary peritonitis with, 1475, 1476 urinary, 1409t, 1411 prenatal, 1817 Asia, pediatric surgery in, 9-10 ~ A p a r a g i n a s e424t , Aspergillus infection in cancer patient, 1006, 1006f in HIV-infected patient, 1010 in transplant patient bone marrow, 781 liver, 740t lung, 775 Asphyxia at birth, gastrointestinal perforation secondary to, 1235 traumatic, 276, 291, 291f Asphyxiating thoracic dystrophy, 915-917,917f
Aspiration, pulmonary. See also Pneumonia, aspiration. anesthesia-related, preoperative fasting and, 224, 224t, 225 enteral feeding and, 203 esophageal atresia with, 1015, 1057, 1058 extracorporeal life support for, 141t gastroesophageal reflux and, 1125b laryngotracheoesophageal cleft and, 995 lung transplant for fibrosis secondary to, 767 tracheoesophageal fistula with, 1016 Aspirin anemia associated with, 180 bleeding time and, 183 for arteritis, 2117 gastroschisis and, 1160 peptic ulcers associated with, 1228 platelet function and, 183, 190 Reye's syndrome and, 238 Asplenia, 1693 Assist mode, in mechanical ventilation, 124 Asthma anesthesia-related laryngospasm and, 223 bronchiectasis in, 1013 extracorporeal life support for, 142 gastroesophageal reflux and, 1125b mechanical ventilation for, 127 misdiagnosis of, in airway obstruction, 983 obesity-related, 1246 recurrent pneumonia associated with, 1011 Astrocytoma, 671, 671t, 673 anaplastic, 678 cerebellar, 674, 674f cervicomedullary, 676 hypothalamic/chiasmatic, 676677,676s low-grade supratentorial, 677, 677f malignant supratentorial, 678 pineal region, 678 Ataxia brain tumor with, 672 cerebellar, neuroblastoma with, 469 Ataxia telangiectasia, alpha fetoprotein in, 555 Atelectasis esophageal atresia with, 1056 liquid ventilation and, 126 mechanical ventilation and, 123, 125, 126, 127, 128 mechanism of, 119 post-traumatic bronchial injury and, 283 postoperative, 291 pulmonary tumors with, 644 adenoma as, 641 rhabdomyosarcoma as, 644f ATG. See Antithymocyte globulin (ATG). ATGAM (equine antithymocyte globulin), 707 Athetoid cerebral palsy, nutritional support in, 214, 214t Atlantoaxial subluxation, torticollis secondary to, 368, 875t, 877, 877f ATLS. See Advanced Trauma Life Support (ATLS). Atracurium, 230t Atrial flutter after lung transplantation, 773 in neonate, 153 Atrial natriuretic peptide, postnatal surge in, 93 Atrial septal defect, 1964-1966, 1964f-1966f traumatic, 285, 286 Atrial septostomy during extracorporeal life support, 138 for primary pulmonary hypertension, 766 Atrioventricular nodal reentry, 151 Atrioventricular node, fetal, immune destruction of, 151 Volume 1, pages 1-1 140; Volume 2, pages 1141-21
Atrioventricular septal defect, 153, 1968-1971, 1969f-1971f Atropine for bradycardia, in propofol anesthesia, 233 for trauma patient, during intubation, 267 to prevent sialorrhea, with ketamine, 239 ~ t y ~ i cteratoid/rhahdoid al tumors, 671, 678, 679 Audiometry, 814 Auditory canal, external, 813, 814 embryology of, 865f first branchial anomaly and, 814, 862, 867-868,867f-868f laceration of, 817 Aural atresia, 814 Auricle (pinna) anatomy of, 813 displacement of, in mastoiditis, 815, 816f embryology of, 814 fabrication of, 791 preauricular cysts and, 871 trauma to, 816 Autonomic nerve tumor, gastrointestinal (GANT) , 516 Avalvulia, 2127 Avascular necrosis, femoral head fracture-related, 345 hip dysplasia and, 2021, 2022, 2023 Avastin. See Bevacirumab (Avastin). AVM. See Arteriovenous malformation (AVM). AWU mnemonic, for neurologic evaluation, 272 Axilla, lymphatic malformation in, 2099, 2099f Axillary vein, thrombosis of, 2131-2132 Azathioprine, 686,687-689, 687f, 689f, 708 for Crohn's disease, 1455 for ulcerative colitis, 1466 in heart transplantation, 760,76Ot, 761,761f in lung transplantation, 770, 771, 771t
B lymphocytes, 163, 165, 166. See also Lymphocytes. development of, 581, 581f Hodgkin's disease and, 575 in neonates, 167-168 Bacille Calmette-GuCrin, HIV infection and, 1009 Bacitracin, for burns, SNt, 390, 396 Backboard, pediatric, 346, 346f, 356 Backwash ileitis, 1463, 1471 Bacteria intestinal. See Intestine, bacteria in. toxins of, 158-159. See also Lipopolysaccharide (LPS, endotoxin). in necrotizing enterocolitis, 1436 virulence of, 158-159 in neonatal sepsis, 170 Bactroban (mupirocin), 3891 Bag-mask ventilation, of trauma patient, 267 Ballard score, 89, 90f Bands, in sepsis, 168, 171 Bannayan-Riley-Ruvalcaba syndrome, 2102 Barbiturates. See also Thiopental. highdose, in brain injury, 364 Bardet-Biedl syndrome, 1936 Bariatric surgery in adolescents. See also Obesity. compliance following, 12461248, 1247t, 1253 complications of, 1248, 1250, 1251, 1252 ethical considerations in, 260-261 outcomes of, 1242-1243, 1252-1253,1253t patient selection for, 213, 1250-1252, 1251f, 1251t
INDEX Bariatric surgery in adolescents (Continued) procedures for, 1248, 1248t, 1249f, 1250 regionalization of, 1242, 1252, 1253 robotic systems and, 52 surgeon training for, 1248 team approach to, 1243,1247, 1251,1253 Barium contrast. See also Barium enema; Esophagography; Upper gastrointestinal contrast series. contraindicated, in necrotizing enterocolitis, 1437 Barium enema. See also Enema, contrast. in appendicitis, 1504 in constipation, 1593-1594 in Hirschspmng's disease, 1515, 1516f, 1549 in intestinal neuronal dysplasia, 1562 in intussusception, 1326-1327, 1327f, 1328-1329,1329f-1330f perforation secondary to, 1328, 1329, 1334, 1334f in neonatal intestinal obstruction, 1271-1272, 1273f-1275f, 1274 with meconium ileus, 1292 Barlow maneuver, 2019, 2020,2021 Barotrauma, 123, 124, 128 after inhalation injury, 395 high-frequency ventilation and, 126 in bronchopulmonary dysplasia patient, 123 in extracorporeal support patient, 138 inverse ratio ventilation and, 125 pneumoperitoneum secondary to, 1437 ventilator settings and, 127, 128 Barrett's esophagus adenocarcinoma and, 517 after caustic injury, 108G1087 after esophageal atresia repair, 517, 1069 bile reflux and, 1039 congenital diaphragmatic hernia and, 944 in remnant, after colonic interposition, 1097 Basal cell carcinoma, sebaceous nevus progressing to, 2064 Basal cell nevus syndrome, ovarian fibromas in, 593, 605 Basal metabolic rate, 98. See also Resting energy expenditure (REE). Basiliximab (Simulect), 707, 738t, 770-771,771 t Bastionelli maneuver, 1178 Battle's sign, 366, 817 Bcl-2 protein fanlily in Hirschsprung's disease, 1526 in neuroblastoma, 475, 486 in Wilms' tumor, 459 Bear claw deformity, in Crohn's disease, 1454, 1454f Becker's nevus, of breast, 886 Beck's triad, 286 Beckwith-Wiedemann syndrome abdominal wall defects in, 1151, 1160, 1167 adrenocortical carcinoma in, 633 genetics of, 447 hepatoblastoma in, 449, 502 hyperinsulinemia in, 1680, 1681, 1682t nephrogenic rests in, 451 neuroblastoma in, 467 rhabdomyosarcoma in, 525 Wilms' tumor in, 446,447, 449, 461 Bell-clapper testis, 1205, 1207 Benchekroun procedure, 1833 Benzodiazepines for burn patient, 394, 394t for intubation, in trauma patient, 267 ketamine with, 239 opioids with, 240 preoperative, 224 Bernard-Soulier syndrome, 183, 190
Beta blockers for burn patient, 392-393, 393f for hypertension, 2120 for hyperthyroid symptoms, 853 for portal hypertension, 1658 in neonate for heart failure, 148, 150t for supraventricular tachycardia, 151, 1521, 153 preoperative, for pheochromocytoma excision, 632 Beta cell adenoma, 1683, 1685 Beta cell carcinoma, 1685 Betaprost, for pulmonary vascular disease, 766 Bevacizumab (Avastin), 426 Bianchi intestinal lengthening procedure, 1377-1378, 1377f with resection of duplication, 1395 Bicarbonate for acidosis, 96 for burn patient, 389, 396 for uric acid calculi, 1751 in local anesthetic, 244 in short-bowel syndrome, 213 parenteral nutrition and, 207 Bidirectional Glenn anastomosis, 1977 Bier block, 244 Bifid renal system, 1758, 1761. See also Duplex collecting system. Bifid sternum, 914915,914t, 915f-916f Bile. See also Cholestasis. in short-bowel syndrome, 1370, 1373 Bile acid binder, for short-bowel syndrome, 213 Bile acids, serum, 1606 Bile duct(s) adenocarcinoma in, 1420 common anomalies of pancreatic part of, 1672 perforation of, 1409-1410, 16141615 injury to, 303, 304f endoscopic treatment of, 301, 303, 304f paucity of, 1613-1614 Bile reflux, into esophagus, 1039, 1123, 1124 Bile salts, for liver dysfunction, in short-bowel syndrome, 1373 Bilhaut-Cloquet procedure, 2075 Biliary ascites, 1409-1410, 1409t, 1615 Biliary atresia, 1603-1613 associated anomalies with, 1604 classification of, 1603-1604, 1604f clinical presentation of, 1605 complications of, 1611-1613 liver abscess as, 1643 diagnosis of, 1605-1607, 1606t differential diagnosis of, 1603, 1605 etiology of, 1604 historical perspective on, 1603 incidence of, 1603 intrahepatic, 1613 nutritional complications of, 1611 nutritional support in, 212, 212t, 1611 jejunal feeding for, 1481-1482 vitamin E in, 198 outcomes with, 1610-1611 pathology of, 1604-1605, 1605f portosystemic shunt in, 1659 treatment of, 1603, 1607-1610, 1608f-1609f, 1609t liver transplantation in, 732, 732f, 739, 1608, 1609, 1610, 1612, 1613 Biliary carcinoma in choledochal cyst, 1622, 1630-1631 molecular biology of, 1631 Biliary dyskinesia, 1635, 1636, 1642 in cystic fibrosis, 1299 Volume 1, pages 1-1140; Volume 2, pages 1141-2146.
vii
Biliary hypoplasia, 1605, 1608f, 1613-1614 Biliary tumors, rhabdomyosarcoma as, 535 Biliopancreatic diversion, 1248, 1248t, 1250 Bilirubin, serum, in parenteral nutrition patient, 209 Billroth I procedure, for spontaneous gastric perforation, 1236 Billroth I1 procedure, for stress ulcers, 1231 Biobrane dressing, 390, 390f, 396 Bioluminescent imaging, 38-40 Biopsy, 437-442 bone, 655-656,655f intestinal, in graft-versus-host disease, 780 laparoscopic, 439-440 liver. See Liver, biopsy of. lung. See Lung, biopsy of. needle, 438-439,439f, 439t laparoscopically directed, 440 of fetal tissues, 78 open incisional, 442 of soft tissue sarcoma, 548 overview of, 437 robot-assisted, .53, 54t salivary gland, 837 specimen handling for, 437-438 stereotactic, of brain tumors, 673 thoracoscopic, 439, 440-442, 441f, 977-980 Bioreactors, 21-22, 23, 27 Birth injuries, 404-405, 405f diaphragmatic eventration in, 937, 946 retinal hemorrhage in, 402 to nose, 820 Birth weight, 89, 90, 9lf. See also Gestational age; Low-birth-weight infant. growth rate and, 194 obesity risk and, 1245 Bishop-Koop procedure, 1297-1298, 1297f, 1299, 1300 Bismuth, for Helicobacterpylori infection, 1386 Bisphosphonates, for malignant bone tumors, 657 Bite injuries, 352-353 BK virus infection, after renal transplant, 712 Bladder anatomical relationships of, 327 calculi in, 1748, 1750, 1752, 1753 urinary diversion and, 1800, 1801 capacity of age and, 320, 1824 measurement of, 1824 diverticulum(a) of, 1820, 1821f posterior urethral valves and, 1811, 1811f vs. ureterocele, 1763-1764, 1764f inguinal hernia sac with, 1188 pressure in, 1817-1818. See also Urodynamic evaluation. prune-belly syndrome and, 1783, 1783f-1784f, 1784 trauma to, 327-329, 328f at bladder neck, 331 diagnostic evaluation of, 319-320 grading of, 320, 321t iatrogenic, 327, 3'28 pelvic fracture with, 318, 320, 327, 328, 328f tumors of exstrophy and, 1858 neuroblastoma as, primary, 468 rhabdomyosarcoma as, 532,533, 1949 ureterocele and, 1763-1764, 1764f valve, 1818, 1818f
viii
INDEX
Bladder augmentation or replacement, 1795-1797, 1796f, 1798-1799, 1799f, 1824-1828. See also Urinary diversion (s). after bladder exstrophy repair, 1858 artificial sphincter with, 1831, 1831f autoaugmentation for, 1827, 1829f, 1835 before renal transplantation, 1835 choice of donor site in, 1825 complications of, 1799-1801, 1835-1837 continent channel for use with, 1797-1798, 1797f-1798f, 1832-1833, 1832f-1833f. See also Mitrofanoff procedure. fecal incontinence and, 1833-1834, 1834f for cloacal exstrophy, 1863 for dysfunctional elimination syndrome, 1812 for neuropathic bladder, 1809, 1810f gastric segment for, 1797, 1827, 1827f complications of, 183G1837 ileocecal, 1797, 1799, 1799f, 1825-1826,1837 indications for, 1818-1819, 1822, 1824 large bowel for, 1797, 18261827 philosophy of, 1824 physiologic considerations in, 1824-1825, 1825f small bowel for, 17961797, 1825, 1826f 1827f ureter for, 1825, 1827-1828, 1828f, 1835 with posterior urethral valves, 1812 Bladder base reconstruction, for ureterocele, 1767 Bladder dysfunction, 1805-1815, 1817-1818, 1818f. See also Bladder outlet obstruction; Urodynamic evaluation. assessment of, 1805-1807, 1805t, 1806f-1808f in dysfunctional elimination syndrome, 1812-1813, 1812f-1814f in nocturnal enuresis, 18141815 in overactive bladder syndrome, 1813-1814 neuropathic. See Neuropathic bladder. renal disease contributing to, 1818 renal transplantation and, 700, 701, 705-706 Bladder exstrophy, 1841-1 859 anatomic variants of, 1842, 1843f-1844f, 1846 clinical presentation of, 1842-1845, 1844f cloacal exstrophy and, 1158, 1158t. 1160, 116'2 covered, 1846 cryptorchidism associated with, 1195 diagnostic studies in, 1847 duplicate, 1843f, 1846 embryogenesis of, 1841-1842, 1842f genital defects in, 1845, 1845f-1846f historical perspective on, 1841 incidence of, 1841 prenatal diagnosis of, 18461847 rectal prolapse associated with, 1596, 1845 treatment of, 1847-1859 approaches in, 1847, 1847f bladder neck reconstruction in, 1852-1853, 1853f complications of, 1858 epispadias repair in, 1851-1852, 1851f-1852f Kelly repair in, 1853-1855, 1854f-1855f single-stage, 1855-1857, 1856f-1857f staged recoristruction in, 1847-1851, 1847f-1850f summary of, 1858-1859 urinary diversion in, 1847, 1857 umbilicus and, 1149, 1153
Bladder neck reconstruction, 1828-1832, 1830f-1831f in bladder exstrophy, 1852-1853, 1853f, 1858 in cloacal exstrophy, 1863 Bladder neck-rectal fistula, 1570f anorectoplasty for, 1577, 1577f-1578f Bladder outlet obstruction, 1818. See also Bladder dysfunction; Urethra, obstruction of; Urethral valves. causes of, 1811 diverticula and, 1820, 1821f in prune-belly syndrome, 1783, 1784 megaureter caused by, 1772 Bladder outlet resistance, 1817 artificial sphincter for, 1831, 1831f procedures for correction of, 1828-1832, 1830f-1831f Blalock-Taussig shunt, modified, 1972, 1977 Blastoma, pulmonary, 641-642, 643f, 6431 Bleeding. See Coagulation; Hemorrhage. Bleeding time, 183, 184t Bleomycin, for lymphangioma, 2139 Blepharoptosis, congenital, 2070-2071, 2070f Block vertebra, 2026f, 2027 Blocksom vesicostomy, 1792, 1792f Blood gases, arterial extracorporeal life support and, 135, 138 in burn patient, 386 in congenital diaphragmatic hernia, 938, 939-940,942-943,945 in malignant hyperthermia, 232 in trauma patient, 269 with thoracic injury, 277 measurement of arterial catheter for, 123 intraoperative, 235 microelectromechanical analyzer for, 58 vs. transcutaneous gas tensions, 122 neonatal acid-base imbalance and, 96 pulmonary circulation and, 120 weaning from ventilator and, 128 Blood pressure. See also Hypertension. as afterload, 146, 147 children's maintenance of, in hypovolemia, 319 hypocalcemia and, with fresh frozen plasma transfusion, 227 measurement of arterial catheter for, 123 microelectromechanical sensors for, 58 Blood transfusion. See Transfusion therapy. Blood volume. See also Hypovolemia. burns and, 384, 385,388,389 estimation of lost volume, 226 hematocrit and, 226, 226t maintenance of, central catheter and, 236 normal, 187,226 Blood-brain barrier post-traumatic edema and, 356 tumors causing breakdown of, 672 Blood-spinal cord barrier, post-traumatic edema and, 356 Blood-testis barrier, 1185, 1207 Blue rubber bleb nevus syndrome, 2102-2103, 2107 Boari flap, 327 Bochdalek hernia. See Diaphragmatic hernia, congenital (CDH). Body composition, measurement of, 195 in obese patients, 1252 Body mass index (BMI), 213, 1244-1245, 1244f, 1246, 1251f, 1252 definition of, 1243 Boerhaave's syndrome, 1047 Boix-Ochoa fundoplication, 1127, 1128, 1128f
Volume 1, pages 1-1140; Volume 2, pages 1141-2146
BOLD (blood oxygen level-dependent) imaging, 37 Bone biopsy of, 653,655-656, 655f hyperostosis of, in melorheostosis, 21 14 immature, 337-339, 338f-341f infection of. See also Osteomyelitis. tuberculous, 2042, 2044 lymphangiectasia of, 2140 maturation of, nutritional status and, 195 mineral density of bariatric surgery and, 1250, 1252 measurement of, 195 parenteral nutrition and, 207, 209 tissue-engineered, 22-23, 23f trauma to. See Fracture (s); Musculoskeletal trauma. Bone cement, 661 Bone cyst(s), 650, 650t aneurysmal, 652f, 654, 655f, 659 fracture secondary to, 651, 651f, 658 locations of, in relation to physis, 652f, 654 treatment of, 658 unicameral. See Unicameral bone cyst. Bone disease Gorham-Stout syndrome as, 2099 metabolic, in parenteral nutrition patients, 209 Bone graft after resection, of benign tumor, 661 distraction osteogenesis prior to, 22 for cleft anomaly, 806, 809 Bone marrow, lymphocyte origin in, 581 Bone marrow failure, 178-180, 179f amegakaryocytic thrombocytopenia in, 182 Bone marrow transplantation, 431-432, 779-782. See also Stem cell transplantation. complications of, 780-782, 780f lymphoproliferative disease as, 584-585 pulmonary infection as, 100G1008 veno-occlusive disease as, 431-432, 780-781, 1654 cytomegalovirus-safe blood products and, 188 for acquired aplastic anemia, 179 for Diamond-Blackfan anemia, 180 for Fanconi's anemia, 179 for neuroblastoma, 479-480, 481, 483-484, 485,486 immunological principles of, 685, 687, 688f, 689, 690f-691f, 691,692 in utero, 83t, 86 lung transplant subsequent to, 768 overview of, 779 types of, 779 vascular access for harvest in, 779 Bone metastasizing renal tumor of childhood, 450 Bone scan of osteomyelitis, 2035, 2042 of rib fractures, in child abuse, 278 of tumors, for staging, 655 Bone transport, 663,664f Bone tumors, 649-667 age of child and, 650t, 653,664-665 benign, 649,650,650t fracture through, 650, 651, 651f giant cell, 652, 653 irradiation contraindicated for, 656 locations of, 651, 652f metastases from, 652 radiography of; 654 reconstruction after resection of, 661 site of, 652 staging of, 659
Bone tumors (Continued) treatment of, 658, 659 biopsy of, 653,655-656,655f chemotherapy for, 656657,661 in metastatic disease, 666667 clinical presentation of, 653-654 commonly occurring, 649, 650t. See also specific tumors. cryotherapy for, 657-658, 660f diagnosis of, 649, 653-654 fracture associated with, 650-651, 651f at joint, 652 in telangiectatic osteogenic sarcoma, 652 through osteogenic sarcoma, 656 genetics of, 653, 653f growth and, 663, 663f, 665 incidence of, 649,650t local recurrence of, malignant, 661 locations of, in relation to physis, 651, 652f magnetic resonance imaging of, 654 malignant histologic types of, 6501, 652-653 metastasis(es) from management with, 6 6 6 6 6 7 staging and, 654-655 to lung, 645-646,645t, 666 with benign tumors, 652 minimally invasive treatment of, 658 multiplicity of, 651-652 radiation therapy for, 656, 657, 657f, 659 reconstruction after resection of, 657-658, 661-664, 662f-665f metastases and, 666667 site and, 665-666 resection of, 657-658 adjuvants in, 659 biopsy and, 655-656 compartments for, 654, 658-659,659f of benign lesions, 659, 660f of malignant lesions, 659-661, 660f-661f role of pediatric surgeon for, 649 sites of, 652 reconstruction and, 665-666 size of, 650-65 1 staging of, 654-655 Bone's criteria, 170 BOOP (bronchiolitis obliterans organizing pneumonia), 781 Bosentan, for pulmonary vascular disease, 766 Botulinum toxin for anal sphincter hypertonicity, 1530, 1543f for esophageal achalasia, 1114 Bovie. .Yep Electrocautery. Bowel. See Colon; Duodenum; Intestine; Small intestine. Bowel vaginoplasty, 1937,1939-1941,1940f BPI (bactericidal permeability-increasing) protein, 172, 173 Brachial plexus, birth injury to, 404-405 Brachydactyly, 2075 Brachytherapy, 430 for bone tumors, 659 Bracka buccal graft hypospadias repair, 18861887, 1889f-189Of, 1891, 1893, 1894, 1895 Bradykinin antagonists, for burns, 384 Brain. S ~al.~o P Central nervous system; Cerebral entries. arteriovenous malformation in, 2111,2113 infections of, suppurative, 2008-2013, 2010f-2011f positron emission tomography of, 38 stereotactic radiosurgery of, 43,44-47, 45f-46f
Brain injury, traumatic, 357-367 basic concepts for management of, 356 birth-related, 405 coagulopathy in, 273-274, 363 complications of, early, 365-367 contusion as, 356, 357-358, 358f, 365 delayed deterioration in, 365 early management of, 269,272-273,356 in "minor" injury, 365 in severe injury, 363-365, 364f-365f, 364t surgical, 364-365 epidemiology of, 357 evidence-based recommendations for, 355 in child abuse, 357, 361-362, 363,401-402, 401t, 402f outcomes with, 367 seizures secondary to, 366 in traumatic asphyxia, 291, 291f initial assessment in, 362-363, 362f outcomes after, 367 penetrating gunshot, 361 low-velocity, 358, 359f surgery for, 364 vascular injury in, 366 prevention of, 357 primary vs. secondary, 272-273,355-356 transport in, 356-357 types of, 357-362,358f-361f Brain tumors, 671-679. See also Pineal gland, tumors in region of. age at presentation with, 671, 671t clinical features of, 671-672 genetics of, 679 histologic classification of, 671 imaging of, 672-673 in Turcot's syndrome, 1422 incidence of, 671 location of, relative to tentorium, 671, 671t metastatic, 679 radiosurgery for, 45, 4 6 4 7 radiotherapy for, 46, 673 specific iypes of, 674-679, 674f-678f germinoma, 556,563,678 neuroblastoma metastatic, 469 primary, 468 teratoma, 557, 558, 563, 671t, 678 surgical intervention for, 673-674 torticollis secondary to, 877 Brainstem contusion of, 359 herniation of, in child abuse, 401 tumors of glioma as, 673, 675f, 676, 679 surgery for, 674 Branchial anomalies coexisting thyroglossal duct cyst with, 870 embryogenesis of, 861-865,862f, 863t, 864f-865f epidemiology of, 865-866 first, 814,861,862, 865, 867-868,867f-868f as parotid masses, 837-838 vs. preauricular cyst, 871 piriform sinus, 861, 863, 868-869, 869f second, 826, 861,862-863,865-867,866f thymic cyst as, 865, 872 vs. cervicofacial teratoma, 564 Branchial arch syndrome, first and second, 788-789 Branchio-oculofacial syndrome, 866 Breast (s), 885-892. See also Gynecomastia. absence of, congenital, 886, 2066 in Poland's syndrome, 886, 907, 908f, 912, 2071 rolume 1, pages 1-1140; Volume 2, pages 1141-2146.
Breast(s) (Continued) accessory, 886, 886f asymmetry of, 8 8 6 8 8 7 congenital anomalies of, 886-887, 886f-887f, 2064, 2066, 2067f-2069f, 2068-2070 development of normal, 885,885t, 888, 2064 premature, 885 ovarian tumors with, 594, 604 discharge from, 888, 888f. 890, 891 enlargement of, 887,887t, 888 fibrocystic changes in, 891 hypoplasia of, 8 8 6 8 8 7 in Poland's syndrome, 907, 912 iatrogenic injury to, neonatal, 886, 886f infections of, 887, 888, 890 masses in, 888-892, 889f, 889t, 891t pain in, 891 trauma to, 891 tuberous, 2066,2068f Breast cancer. See also Phyllodes tumor. genetics of, 593-594,892 in children, 891-892 in Klinefelter's syndrome, 2068 juvenile papillomatosis and, 891 maternal, rhabdomyosarcoma associated with, 525 Breast-feeding, 202. See also Milk, human. biliary atresia and, 212 breast reduction surgery and, 887 childhood obesity and, 1245 intestinal flora and, 1433, 1445 inverted nipples and, 886 milk allergy and, 1386 silicone implants and, 1111 Breath hydrogen test in chronic intestinal pseudo-obstruction, 1549 in necrotizing enterocolitis, 1435 Brodie's abscess, 2033, 2034f, 2035, 2037f Bronchial adenoma, 641, 642f Bronchial arteries, embolization of, 1014, 1015f Bronchiectasis, 1012-1014, 1013f in atypical mycobacterial infection, 1004 in tuberculosis, 1003, 1013 lymphedema associated with, 2141 Bronchioalveolar carcinoma, 641, 642t Bronchiolitis, 1004-1005, 1004f Bronchiolitis obliterans biopsy of, 1024f lung transplant for, 768 secondary to lung transplant, 768, 773-774, 774f, 775, 776 Bronchiolitis obliterans organizing pneumonia (BOOP),781 Bronchioloalveolar carcinoma, 957 Bronchogenic carcinoma, 641, 642 Bronchogenic cyst, 641, 642t, 955, 963-964, 963f-964f. See also Bronchopulmonary foregut malformation. lung abscess associated with, 1015 thoracoscopic excision of, 977 Bronchography, of distal bronchial injury, 283 Bronchopleural fistula, thoracoscopy and, 980 Bronchopulmonary dysplasia, 128, 135 barotrauma in patient with, 958 lung transplantation and, 769 vitamin A for, 198 vitamin E for, 198 Bronchopulmonary foregut malformation. See also Bronchogenic cyst. computed tomography of, 35 Bronchopulmonary sequestration, 955, 956, 957-958,958f
Bronchoscopy, 974-977 after lung transplant, for biopsy, 771 for foreign body removal, 974, 975-976, 975f, 977, 1012, 1014, 1015 history of, 971 in bronchiectasis, 1014 in chronic lung infection, 1014 in inhalation injury, 395 in thoracic trauma, 278, 283, 291 indications for, 974 instrumentation for, 974975,974f-975f, 975t in esophagoscopy, 1044 of lung abscess, 1016, 1017 of tumors, 644 virtual reality simulator for, 69 Bronchus(i) inflammation of, in laryngotracheobronchitis, 830 mainsten) atresia of, 958 stricture of, post-traumatic, 283 trauma to, 276, 277, 282-283, 283f epidemiology of, 275, 275t Brooke formula, 388t Broviac-type catheter, 203, 209 Brown adipose tissue, 98, 99, 100 Brown-Skquard syndrome, 368 Buccal graft hypospadias repair, 18861887, 188%-1890f, 1891, 1894, 1895 Buccal mucosal vaginoplasty, 1939 Bucket-handle fractures, 403 Budd-Chiari syndrome, 1654, 1656, 1660 Budesonide, for Crohn's disease, 1455 Bupivacaine, 243, 243t caudal, 248 epidural infusion of, 248t Rurkholdm'a c~pacia,766, 1011 Burkitt's lymphoma, 580-581 clinical presentation of, 583-584, 584f growth rate of, 583 histology of, 582, 582f intestinal involvement of, 1364 treatment of, 585-586, 588 Burn centers, 389,389t Burns, 383-397 analgesia for, 394, 394t antibiotics for, intravenous, 394 antimicrobials for, topical, 383, 389-390, 389t, 396 causes of, 383 chemical, 385, 395-396. .Yep also Esophagus, caustic ir?ju~yto. child abuse as cause of; 383, 383f, 403 complement activation by, 164 degree of, 385, 385f depth of, 384, 385-386, 385f. dressings for, 389, 390, 390f electrical, 383, 385, 396 amputation secondary to, 2058 epidemiology of, 383 escharotomy for, 385, 386, 386f excision and grafting for, 385, 389, 390-391, 391f, 39'2, 394 extracorpo1-eal life support for, 142 first aid for, 385, 386 first-degree, 385, 385f, 389 flnid resuscitation for, 385, 386-389, 388t with chemical burn, 395 with inhalation injury, 395 historical perspective on, 383 hypermetabolic response in, 391-393, 392f-393f infectious complications of, 385, 390, 394 inhalation injrny in, 386, 394-395 major, definition of, 389t ~nannequinsimulation of, 69-70
Burns (Continued) nutrition for, 393, 393t outpatient, 396 pathophysiology of, 384-385, 384f rehabilitation with, 39G397 scar formation secondary to, 397 sedatives and anxiolytics for, 394, 394t size of, 386, 387f-388f, 387t stress ulcers secondary to, 1226, 1231 transfer to burn center for, 389, 38% Busulfan, 42% Butterfly vertebra, 2027f N-Butyl-cyanoacrylate, as scleroagent, 2129
CA-125, ovarian tumors and, 602, 606 Caffeine fibrocystic breasts and, 891 gastroesophageal reflux and, 1126 Cajal, interstitial cells of Hirschsprung's disease and, 1527 mesenchymopathies of, 1547, 1548 Calcineurin inhibitors. See Cyclosporine; Tacrolimus. Calcitonin gene-related peptide, testicular descent and, 1174, 1194, 1194f Calcium. See also Hypercalcemia; Hypocalcemia. deficiency of, after massive enterectomy, 1372 heart muscle and, 147 in p a r e n t e d nutrition, 206t, 207, 208, 209 serum, in neonate, 95 supplementation with gastrointestinal polyps and, 1422 hyperosmolar, bowel mucosa and, 1429 Calcium channel blockers contraindicated in neonate, 147, 153 for esophageal achalasia, 1113-1 114 for Raynaud's syndrome, 2121 Caliceal diverticulum, 1713 infected, horseshoe kidney with, 1719 Caloric requirements, 195, 1951, 196, 225 in burn patient, 393, 393t neonatal, 96, 97-99, 98f Calorimetry, 195, 196, 210, 212 Camey enterocystoplasty, 1825, 1826f Campath. See Alemtuzamab (Campath). Camptodactyly, 2074 Camptothecins, 422, 424t, 429 Canadian pediatric surgery, 5, 6 Cancer. See also Angiogenesis; Chemotherapy, cancer; Oncogenes; Radiation therapy; Tumor suppressor genes; speczjir organ or tumor type. after renal transplantation, 712-713 chromosomal abnormalities in, 415-416, 416f, 417t, 418, 420-421 diagnostic methods for, 419, 420t clinical trials in, 426, 432 epidemiology of, 41 1-412, 41% genetic screening and, 421 hereditary disorders associated with, 420-42 1,446 histopathologic stages of, 418 history of pediatric oncology, 411, 412 hypercalcemia in, 857 immunotherapy for, 427 for nenroblastoma, 427, 485 invasive stage of, 418,419 lung infections in patient with, 1005-1008, 1006f-1007f metastasis of, 418, 419
Volume 1, pages 1-1 140; Volume 2, pages 1141-2146.
Cancer (Continued) molecular biology of, 412-419, 413f, 415t, 416f, 417t molecular diagnostics in, 419-420, 420t, 437-438 open biopsy and, 442 normal cell physiology and, 412-414, 413f ploidy in, 415, 438 risk-stratified treatment for, 425, 437, 442 stem cell transplantation for, 431-432. See also Bone marrow transplantation. in utero, 83t, 86 stereotactic radiosurgery for, 43, 44-47, 45f-46f extracranial, 43, 46, 47 in children, 4 6 4 7 targeted therapy for, 425-426 transfusion in patient with, 188 of platelets, 190 Candida infection catheter-related, 210 in immunocompromised patient, 1006, 1007 as hepatic or splenic abscess, 1644 colonic obstruction caused by, 1495 in necrotizing enterocolitis, 1436 of burns, 389, 390 parastomal, 1488 transplantation and liver, 740t lung, 771, 775 Cantrell. .Yep Pentalogy of Cantrell. Cantwell-Ransley epispadias repair, 1851-1852, 1851f, 1858 Capillary hemangioma, 2094, 2096 Capillary leak syndrome, 168, 17'2 Capillary malformation (port-wine stain), 2063, 2095, 2096, 2098, 2098f lumbosacral, 2102 management of, 2106 vs. hemangioma, 2097 with pyogenic granuloma, 2097 Capillary refill time, 348 Capillary-arteriovenous malformation, 2101 Capillary-lymphatic-venolismalformation. See Klippel-Trenaunay syndrome. Capillary-venous malformation, 2101 Capnography, 234235, 234f Capnometry, 122 Carbohydrate. See al.~oGlucose (dextrose). malabsorption of, 203, 213 metabolism of, in neonate, 100-102, 101t, 104 postoperative, 107, 107f, 108 nutritional requirements for, 195, 196-197 Carbon dioxide acid-base regulation and, 95, 121 arterial cerebral blood flow and, 139 congenital diaphragmatic hernia and, 938,939-940,942,943,945 extracorporeal support and, 138, 139 in trauma patient, 269 measurement of, 122, 123 mechanical ventilation and, 127, 128 caprlography of, 234-235, 234f end-tidal in trauma patient, 267, 277 malignant hyperthermia and, 231, 232 measurement of, 122,234235,234f extracorporeal removal of, 126 Carbonic anhydrase, 95 in erythrocytes, 121 in proximal tubules, 96 mafenide acetate as inhibitor of, 389
Carboplatin, 423t Carboxyhemoglobin, 122 Carcinoembryonic antigen (CEA), in colorectal carcinoma, 521 Carcinoid syndrome, pulmonary tumor with, 641 Carcinoid tumors gastrointestinal, 518, 518f in appendix, 518, 518f, 1502, 1505 in Meckel's diverticulum, 1311 pulmonary, 518,641 renal, in horseshoe kidney, 1718-1719 Cardiac. See also Heart. Cardiac arrest anesthesia-related, 222, 223, 227, 229 extracorporeal life support and, 135, 138, 141t, 142 in child abuse, with brain injury, 401 traumatic, 266, 277, 285 Cardiac arrhythmias. See Arrhythmias, cardiac. Cardiac catheteri~ation,21 16 Cardiac defects. Sef Heart disease, congenital. Cardiac failure. See Congestive heart failure. Cardiac output, 146-147, 147f measurement of, 123 mixed venous oxygen saturation and, 122,123 Cardiac surgery. See also Heart disease, congenital. extracorporeal life support following, 141, 141t mediastinitis secondary to, 1028 Cardiac tamponade, 277, 278, 285, 286,287f amebic abscess as cause of, 1646 chylous, 1027 during extracorporeal life support, 140 penetrating injury with, 291 vs. tension pneuniothorax, 280 Cardiogenic shock extracorporeal life support and, 135, 142 inotropic agents for, 150t, 151 Cardiomyopathy congestive, in neonate, 148, 151 extracorporeal life support for, 141t transplantation for, 754, 755, 755f, 756, 760, 762, 763 Cardiopulmonary bypass. See also Extracorporeal life support (ECLS). for aorta repair, with traumatic rupture, 290 Cardiovascular disorders. See also Heart disease, congenital. multidetector computed tomography of, 35 neonatal arrhythmias as, 151, 152t, 153 congenital heart disease as, 153 congestive heart failure as, 148, 150t, 151 renal trans~lantas risk factor for. 713 ~ardiovasculsrphysiology, neonatal, 146-147, 147f Cardioversion, 151 Carney's triad, 515-516 Carnitine, in parenteral nutrition solution, 208 Caroli's disease, 1623, 1626, 16'29, 1630 liver transplantation for, 732 Carotid artery injury to, 378, 380 during birth, 405 pseudoaneurysm of, after craniopharyngioma surgery, 677 Carpenter's syndrome, 798 Cartilage articular, 337, 338f injury to, 341, 342 repair of, 22 tissue-engineered, 22, 23, 23f
Cartilaginous tumors. See also specific tumors. commonly occurring, 650t MRI of, 654 sites of, 652 in relation to physis, 651, 652f size of, 650 wide resection of, 650, 651f CAS (computer-assisted surgery), 42 Caspases, 414, 426 in neuroblastoma, 475, 486 Caspofungin, 1007 Casting of fracture, 339f, 342, 344 Castleman's disease, 848 Catecholamines adrenal synthesis of, 628, 629 halothane interactions with, 228 in burn patients, 391-392 in neonate in perinatal period, 101, 102, 103 in postoperative period, 101, 106, 107, 107f, 108 inflammation and, 166 neuroblastoma as source of, 468, 469, 470 pheochromocytoma and, 631, 632,635 Catheterizable channels, continent, 1797-1 798, 1797f-1798f, 1832-1833, 1832f-1833f. See also Mitrofanoff procedure. Catheterization. See also Arterial catheter; Urinary catheterization; Vascular access; Venous catheter. virtual reality simulator for, 69 Cat-scratch disease, 832, 847, 847f, 1644-1645 Cauda equina syndrome, neuroblastoma with, 469 Caudal block, 247-248, 247f after sevoflurane anesthesia, 229 vs. penile block, 246, 1893 Cauliflower ear, 816 Cavernous hemangioma, 2094,2096,2099 Cavernous lymphangioma, 2138 Cavitation ultrasound aspirator, 41 CD3. See OKT3 (muromonab-CD3). CD20. See Rituximab (anti-CD20 monoclonal antibody). CD34+-selected peripheral blood stem cells, in neuroblastoma, 484 CD44, in neuroblastoma, 474, 486 CDH. See Diaphragmatic hernia, congenital (CDH). CEA (carcinoembryonic antigen), in colorectal carcinoma, 521 Cecostomy, 1483,1485 continent, 1834, 1834f Cecum, volvulus of, 1350, 1356, 1363, 1364, 1498 Celecoxib, in cancer chemotherapy, 426 Celiac disease, esophageal dysmotility in, 1112 Cell cycle, 412-413, 413f cancer chemotherapy and, 422,425 malignant transformation and, 413,417,418 radiation damage and, 43, 44 CellCept. See Mycophenolate mofetil (CellCept). Cellulitis lymphatic malformation with, 2106, 2107, 2138 lymphedema with, 2142 orbital, 818-819 peritonsillar, 822-823 retropharyngeal/parapharyngeal, 823 Cellulose, for adhesion prevention, 1360 Cement, bone, 661 Central core disease, malignant hyperthermia in, 231
Volume 1, pages 1-1140; Volume 2, pages 1141-21
Central hypoventilation syndrome (Ondine's curse) esophageal dysmotility in, 1112 genetic mutation in, 1523 Hirschsprung's disease with, 1528 neuroblastoma associated with, 467 Central nervous system. See also Brain; Spinal cord. cysts in, with gastrointestinal mucosa, 1393 germinoma of, 556,567 infections of, suppurative, 2008-2013, 2010f-2011f sarcoma of, 546 teratoma of, 557 Central pontine myelinolysis, 389 Central venous catheter, 194, 203, 204. See alto Venous catheter. caval thrombosis secondary to, 2130 deep venous thrombosis secondary to, 2131 in bone marrow transplantation, 779 in emergency trauma management, 270 infection associated with, 209-210, 2132 intraoperative, 235 technical complications of, 210 CEP-751, antitumor activity of, 426 Cephalohematoma, subgaleal, in birth injury, 405 Cerebellar ataxia, neuroblastoma with, 469 Cerebellum herniation of, brain tumor with, 672, 674f tumors of astrocytoma as, 674, 674f surgery for, 674 Cerebral contusion, 356, 357-358, 358f, 365 Cerebral edema, post-traumatic, 356, 357, 36Of, 362, 365 Cerebral palsy cryptorchidism in, 1196, 1198-1 199 difficult delivery and, 405 neuropathic bladder in, 1810-181 1 nutritional support in, 214, 214t Cerebral perfusion pressure, in trauma patient, 272, 273, 356, 363 Cerebrocostomandibular syndrome, 917-918 Cerebrospinal fluid (CSF). See also Hydrocephalus; Intracranial pressure (ICP) . head trauma and drainage of, 364, 364t leak of, 358,363,366 ear trauma with, 817 neonatal sepsis and, 171, 173 physiology of, 1996 rhinorrhea of, nasal encephalocele with, 820 tumor markers in with germinoma, 556,678 with pineal tumors, 673, 678 Cerebrovascular injuries, 366 Cerumen, 813, 814 Cervical lymphadenopathy, 844-848, 845f-847s anatomy of, 844,844f-845f atypical mycobacteria in, 1003, 1004 general approach to, 832, 844 in lymphoma, 827,833,848 in pharyngotonsillitis, 822, 823 in thyroid carcinoma, 848, 851, 854, 855, 856,857 Cervical spine. See a130 Spine. hemivertebrae in, torticollis secondary to, 877 lymphangiectasia of bone in, 2140 pseudosubluxation of, 346,369 trauma to, 267, 346, 346f 356, 368, 369-370 as birth injury, 405
xii
INDEX
Cervical vascular injuries, 378 Cervicofacial teratoma, 563-565, 563f-564f Cervicomedullary astrocytoma, 676 Cervix, adenocarcinoma of, 1951-1952 Cesarean delivery. Set a1.w EXIT (ex utero intrapartum treatment). abdominal wall defects and, 1161, 1165 after hysterotomy, for fetal surgery, 79, 80 defects managed by, 78t, 81 for teratoma cervicofacial, 564 sacrococcygeal, 560 CFTR (cystic fibrosis transmembrane conductance regulator), 12, 12f Chagas' disease, megaesophagus in, 1112 Chamberlain procedure, 577, 586f, 587 CHAOS (congenital high airway obstruction syndrome), 868 CHARGE association, 1055 Chkdiak-Higashi syndrome, ovarian tumors in, 593, 606 Chemical burns, 385,395-396 Chemoemboli~ation,of liver tumors, 511, 733 Chemosis, 819 Chemotaxins, 160, 161, 165 Chemotherapy, cancer. See also sperzfic cancer: adjuvant, 421 common agents for, 422, 423t-424t complications of hemorrhagic cystitis as, 781-782 lung infections as, 1005-1008, 1006f-1007f thyroid carcinoma as, 855 veno-occlusive disease as, 1654 principles of, 421-422, 425 radiation therapy with, 428-429 risk stratification for, 425, 437 stem cell transplantation following, 431, 779 targeted, 425-426 Chest. See also Mediastinum. evaluation of, with multidetector computed tomography, 35 rhabdomyosarcoma of, 534-535 Chest injury. Set Thoracic trauma. Chest pain, in esophageal disorders, 1125b Chest radiography in airway obstruction, 828 of burn patient, 386 of trauma, 278, 280, 280f-284f, 281, 282, 286f-288f, 292 penetrating, 291 to aorta, 287-288, 287t, 288f to diaphragm, 284, 284f, 285t, 312-313 Chest tube after core needle biopsy, 439 for chylothorax, 1027 for pneumothorax in neonate, 1021-1 023, 1022f in older child, 1023, 1023t in trauma patient, 280, 280f-281f, 281, 282 spontaneous, 1021 in trauma patient, 269, 270f, 279, 292 placement of, 269, 270f with airway injury, 283, 283f with hemothorax, 281, 282 with pleural effusion, 282 with pneumothorax, 280, 280f-281f, 281, 282 removal of, topical anesthesia for, 244 Chest wall congenital deformities of, 894-918 depression in. Set Pectus excavatum. diaphragmatic hernia with, 944 in diffuse skeletal disorders, 915-918, 917f918f in Poland's syndrome. See Poland's syndrome.
Chest wall (Continued) multidetector computed tomography of, 35 protrusion in. See Pectus carinatum. sternal, 912-915, 913f-916f, 914t soft tissue sarcoma of, 550 as rhabdomyosarcoma, 534535 trauma to, 269, 275, 279 Chiari malformation prenatal treatment and, 84 vocal cord immobility caused by, 988 Chiari I1 malformation, 1992-1993, 2066f Child abuse, 400-404, 402f-403f. See also Sexual abuse. burns in, 383,383f, 403 chylothorax in, 1025 chylous ascites in, 1410 emergency management in, 265 epidemiology of, 400 fractures in, 347,40lt, 402-403 rib, 278, 279, 403, 404 head injury in, 357, 361-362, 363, 401-402,401t outcomes with, 367,402 seizures secondary to, 366 legal aspects of, 400 ophthalmologic evaluation in, 363 pancreatitis in, acute, 1673 presentation of, 400-401,401t primary peritonitis secondary to, 1475 rectal injury in, 312 vaginal injury in, 312 Child-Pugh score, 1658, 1664, 1664f Children's Oncology Group (COG), 432,445 Chimeric proteins. See Fusion genes and proteins. Chlamydia pneumoniae, 1002-1003 Chlamydza trachomatis, perihepatitis caused by, 1645 Chloral hydrate, for burn patientq, 394t Chloride in fluid therapy, 225 in parenteral nutrition, 206, 206t, 207, 208 Choanal atresia, 819, 819f Choking, in esophageal motor disorders, 1110 Cholangiocarcinoma, 505 Cholangiography in biliary atresia, 1607 in biliary hypoplasia, 1607, 1608f in inspissated bile syndrome, 1614, 1614f of choledochal cyst, 1625-1626, 1625f with pancreas divisum, 1677, 1677f of choledocholithiasis, 1638-1639, 1638t, 1639f, 1642 Cholangitis after portoenterostomy, 1609, 1611-1612, 1613 cholelithiasis with, 1637 sclerosing in ulcerative colitis, 1464, 1464f liver transplantation for, 732 Cholecystectomy, 1637-1642, 1638f-1641f, 1638t, 1642t for biliary dyskinesia, 1636, 1642 for gallbladder polyps, 1636-1637 for hydrops of gallbladder, 1636 in hemolytic anemias, 181, 182, 1635-1636, 1641 in short-bowel syndrome, prophylactic, 1371 robot-assisted, 53, 54t, 1639, 1640f simulation software for laparoscopy in, 68 Cholecystitis acalculous, 1635, 1636, 1637 calculous, 1637. See also Cholelithiasis. Cholecystokinin, for liver dysfunction, in short-bowel syndrome, 1373 iolume 1, pages 1-1140; Volume 2, pages 1141-21
Cholecystolithotomy, 1637 Choledochal cyst, 1620-1631 anatomic classification of, 1620, 1621f carcinoma arising in, 1622, 1630-1631 clinical presentation of, 1624-1625, 1625f diagnosis of, 1625-1626 etiology of, 1622-1623, 1623f historical perspective on, 1620 intrahepatic, 1620, 1629 liver abscess secondary to, 1643 liver transplantation and, 7% pancreatitis and, 1624, 1625, 1631, 1672-1673, 1677, 1677f pathology of, 1620-1622 prenatal diagnosis of, 1623-1624, l623f surgical management of, 1626-1629, 1627f-1628f outcomes of, 1629-1631 timing of, 1624 Choledochocele, 1620, 1621, 1621f etiology of, 1623 surgical treatment of, 1628-1 629 Choledocholithiasis, 1638-1639, 1638f; 1638t, 164'2 pancreatitis associated with, 1672, 1674, 1675 Cholelithiasis, 1635-1636, 1637 after ileal resection, 1371, 1635, 1636 complications of, 1637 in bone marrow transplant patients, 780, 1642 in cystic fibrosis, 1299, 1635 in hemolytic anemias, 181, 182, 1635-1636, 1637, 1641, 1642, 1673, 1693, 1698 nonsurgical treatment of, 1637 pancreatitis and, 1637, 1642, 1672, 1673 parenteral nutrition and, 209, 1635, 1636, 1637, 1673 surgical treatment of, 1637-1642, 1638f-1641f, 1638t, 1642t Cholestasis in chronic graft-versus-host disease, 782 in necrotizing enterocolitis, 1443 liver transplantation for, 732-733, 732f parenteral nutrition and, 196, 204, 206, 209, 1373 stoma for bile drainage in, 1482 surgical lesions with, in intbncy, 1603, 1613-1615, 1614f. Set ~ L Y OBiliary atresia; Choledochal cyst. Cholesteatoma, of middle ear, 816 Cholestyramine for diarrhea, in short-bowel syndrome, 1373 for short-bowel syndrome, 213 Choline magnesium tl-isalicylate, 238, 238t Cholylsarcosine, 1373 Chondroblastoma, 652, 652f, 654, 659, 665 Chondrocytes, in tissue engineering, 22, 23f Chondrogladiolar deformity, 904, 905,905f Chondroma periosteal, 659 pulmonary, 515-516 Chondromanubrial deformity, 904, 005, 906f, 907 Chondromyxoid fibroma, 652f Chondrosarcoma, 652,653 cryotherapy for, 660f glucose intolerance with, 654 in hereditary multiple exostoses, 651 in Maffucci syndrome, 2129 resection of, 651f Chordae tendineae, injury to, 286, 286f.
I
! ! I I
I I
!
Chordee epispadias with, 1858 hypospadias with, 1870, 1879, 1880, 1887, 1890f curvature repair in, 1887-1888, 1891, 1891f-1892f, 1895 preservation of urethral plate and, 1884, 1885f, 1886 sex assignment surgery and, 1927, 1929f penile torsion with, 1907 urethral duplication with, 1904 Chorioangiopagus, 85 Choriocarcinoma, 555, 556 extragonadal, 568 hepatic, 505 pineal region, 678 ovarian, 594t, 595, 595t, 607, 609 testicular, 622 Chorionic villus sampling, 78 Choristoma, 826 Choroid plexus tumors, 671, 678-679 sarcomas, 546 Chromaffin cells, 628, 629 Chromium, 198t, 199,206 Chromosomal abnormalities fetal karyotyping and, 78 in cancer, 415-416,416f, 417t, 418, 420-421 diagnostic methods for, 419, 420t Chronic granulomatous disease, liver abscesses in, 1643, 1643f Chyle, composition of, 1026, 2141 Chylothorax, 1024-1027, 1025f, 2140-2141. See also Thoracic duct. thoracoscopic treatment of, 977, 980 traumatic, 290, 10241025, 1026, 1027 in birth injury, 405, 1026 Chylous ascites, 1409t, 1410-141 1, 2107, 2140 Chyluria, 2140 CIC (clean intermittent catheterization), 1824. Set also Continent catheterizable channels; Urinary diversion (s). in dysfunctional elimination syndrome, 1812 with neuropathic bladder, 1808, 1809, 1810, 1810f, 1811 with posterior urethral valves, 1812 Cidofovir, for laryngeal papilloma, 990 Cimetidine for gastroesophageal reflux, 1126 for peptic ulcer disease, 1229, 1230 unilateral thelarche caused by, 888 Circumcision, 1905-1906 complications of, 331, 1905, 1906, 1906f in chronic graft-versus-host disease, 782 penile block for, 246-247, 247f topical anesthesia for, 244 urinary tract infection and, 1741, 1905 Cirrhosis biliary atresia with, 1605, 1610, 1611 biliary hypoplasia with, 1614 choledochal cyst with, 1622 hepatocellular carcinoma and, 502, 503 in cystic fibrosis, 766 liver transplantation for, 732-733 portal hypertension with, 1652, 1656, 1657, 1658, 1661, 1665 primary peritonitis with, 1475, 1476 transjugular portosystemic shunt in, 1387 with esophageal varices, 1387 Cisapride for adhesion prevention, 1360 for chronic intestinal pseudo-obstruction, 1549 for gastroesophageal reflux, 1126 for postoperative ileus, 1361 Cisatracurium, 230t Cisplatin, 423t, 428
Cisterna chyli, 1025, 1025f, 1026 embryology of, 2137, 2138f Citrate toxicity, 188, 227, 273 Citrulline, dependency on parenteral nutrition and, 1371 Clam cystoplasty, 1824, 1825, 1826f Clavicular fracture in birth injury, 404 in child abuse, 403 Clear cell sarcoma of kidney, 450, 454, 454t, 455,460, 461 Cleft anomalies, 788-792, 788f-792f. See also Craniofacial anomalies. adenotonsillar hypertrophy in, 824 classification of, 788, 788f middle ear effusions associated with, 815 of lip and palate, 803-812, 2062 associated anomalies with, 811-812 embryology of, 803 ethnic differences in, 803 etiology of, 805 genetic counseling about, 806, 806t orthodontic appliances for, 806 prenatal repair of, 83t, 86 submucous, 812 surgical correction of, 805-809,807f-810f revisions of, 809-811,811f teratoma with, 557 variations in, 803, 804f unusual, 803,805,805f Cleft hand, 2073 Clefts, branchial, 861, 862f, 863t. See also Branchial anomalies. Clinical Risk Index for Babies (CRIB), 91 Clinical trials, 259 for cancer, 426,432 Clinodactyly, 2074 Cloaca embryology of, 1566-1567 persistent, 1566, 1566t, 1571, 1571f-1572f, 1945, 1947, 1947f cutaneous vesicostomy with, 1791-1792 in prune-belly syndrome, 1786 postoperative care with, 1584, 1585 reconstruction for, 1578, 1579f-1581f, 1580-1582, 1583, 1584, 1947-1949, 1948f urologic problems secondary to, 1585, 1588, 1588t Cloacal exstrophy, 1149, 1158, 1158t, 1160, 1162, 1842, 1843f, 1859-1865, 1860f-1863f, 1862t continent urinary reservoir for, 1798 sex assignment surgery in, 261 Clonal exhaustion-deletion, 691-693, 6935 696 Clonidine caudal, 248 epidural infusion of, 248, 248t with sevoflurane anesthesia, 229 Closing capacity, 118f, 119, 128 Closing membrane, 861, 863 Clostridium difJicilecolitis, 1387 in bone marrow transplant patient, 780 Clostridium species, necrotizing enterocolitis and, 1433,1436 Clotting factors. See Coagulation factors. Cloverleaf skull, 798, 798f Clubfoot, 2024-2025, 2024f Clubhand, 2073 CMV. See Cytomegalovirus (CMV) infection. Coagulation, tests of, 183, 184t, 185 Coagulation cascade, 184f Coagulation disorders, 183, 185-187, 185t thrombosis in, 2130 trauma patient with, 274
Coagulation factors, 184f deficiencies of, 183,185-186, 185t blood loss with, 226 in head trauma, 274 natural anticoagulants and, 186-187 synthesis of, 186 tests of, 183, 184t, 185 Coagulopathy. See also Thrombocytopenia. in systemic inflammatory response syndrome, 172 in trauma patient, 273-274 brain injury and, 273-274, 363 with severe bleeding, 300-301, 302 mesenteric venous thrombosis in, 2130 neuroblastoma with, 469, 481, 482 renal vein thrombosis in, 1754 Cocaine necrotizing enterocolitis and, 1429-1430 tetracaine with, 244, 244t Coccidioides infection, 1010 osteomyelitis in, 2044, 2045f Cochlea anatomy of, 813 dysplasia of, 814 temporal bone fracture and, 817 Cochlear implant, 814-815 Cockett's syndrome, 2127 Cocoon, abdominal, 1365 Codeine, 240, 240t for diarrhea, 1373 Codman's triangle, 654 COG (Children's Oncology Group), 432, 445 Cohen cross-trigonal ureteral reimplantation, 1748f Cold, common, 818 Colectomy for Crohn's colitis, 1457-1458, 1459 for familial adenomatous polyposis, 1421-1422 for ulcerative colitis, 1464, 1466, 1467, 1468, 1469 history of, 1462-1463 Colitis. See also Enterocolitis; Necrotizing enterocolitis, neonatal; Ulcerative colitis. allergic, 1386 amebic, liver abscess secondary to, 1645 Crohn's. 1457-1458. 1459 ileoanal pouch in, 1457, 1458, 1471 eosinophilic, 1599 indeterminate, 1457, 1466-1467 infectious bloody diarrhea in, 1387 Clostridium difficik in, 780, 1387 pseudomembranous, in Hirschsprung's disease, 1529 Collagen. See also Connective tissue disorders. in burn dressing, 390 Collis-Nissen fundoplication, 1069, 1133 Coloanal venous malformation, 2107 Colon atresia and congenital stenosis of, 1275, 1493-1 495, 1494f vs. Hirschsprung's disease, 1519 with Hirschsprung's disease, 1493, 1495, 1528 duplications of, 1391, 1395-1397, 1396f-1397f malrotatjon of. See nLso Intestinal rotation and fixation. in prune-belly syndrome, 1786 nutrient absorption by, 137'2
Volume 1, pages 1-1140; Volume 2, pages 1141-2 146.
xiv
INDEX
Colon (Continued) obstruction of, 1363-1366, 1493-1498, 1494f-1495f, 1497f-1499f. See also Hirschsprung's disease; Intestinal obstruction; Intussusception; Meconium ileus. in reverse rotation, 1348, 1349f, 1356 polyps of. See Polyp(s), gastrointestinal. segmental dilatation of, congenital, 1498 stricture(s) of, 1364, 1495-1496, 1495f in cystic fibrosis, 1300 postoperative, in Hirschsprung's disease, 1546 stromal tumors of, 515 tissue-engineered, 25, 25f, 26 transit time in, studies of, 1594 trauma to, 310-31 1 varices of, 1655 vascular malformations in, 1598 volvulus of, 1363-1364, 1498, 1499f Colon conduit, 1793-1794 Colon interposition esophageal, 1095-1097, 1096f, 1098t for caustic strictures, 1088-1089, 1089f, 1089t for short-bowel syndrome, 1376, 1376f Colonic manometry, 1595 Colonic neobladder, 1827 Colorectal carcinoma, 518-522, 519t, 52Of-521f, 1364, 1496 colonic obstruction by, 1364, 1496 familial adenomatous polyposis and, 421, 519, 1419-1420, 1421 hereditary nonpolyposis, 520 in Crohn's disease, 519-520, 1459-1460 in ulcerative colitis, 519, 1459-1460, 1464, 1464f in urinary diversion, 520, 1837 juvenile polyposis and, 1417 Colostogram, of anorectal malformation, 1573-1574, 1573f-1574f, 1586 Colostomy. See also Enterostoma(s). choices for, 1482f, 1484f, 1485, 1485t complications of, 1489-1490, 1489f, 1489t parastomal hernia as, 1363, 1489 for anorectal malformations. See Anorectal malformations, colostomy for. for refractory constipation, 1595 in chronic intestinal pseudo-obstruction, 1549 in Crohn's disease, 1458 in Hirschsprung's disease, 1485, 1488, 1489f leveling, 1530, 1533 indications for, 1483-1484, 1483f stoma care in, 1488 takedown of, 1488-1489 technical aspects of, 1488 Coma, 272. See also Consciousness. emergency management with, 272 in diffuse axonal injury, 359 Combretastatin, 426 Common cold, 818 Commotio cordis, 276, 285 Compartment syndrome abdominal hepatic hemangiomas with, 2102, 2106 in trauma patient, 302-303, 303f infantile hepatic hemangioendothelioma with, 495, 496 in burned extremities, 386 in musculoskeletal trauma, 344-345, 349 in vascular trauma, 379, 381 Complement system, 164-165, 164f in neonate, 168, 170 macrophage activation and, 161 phagocytosis and, 160, 163
Computed tomographic angiography of cerebral trauma, penetrating, 358,366 of renal trauma, 319 of vascular trauma, 377, 378f aortic, 288, 290 iatrogenic, 380 Computed tomographic cystography, of bladder trauma, 320 Computed tomography (CT), 3 4 3 6 as virtual reality data source, 63, 64f, 67-68 for needle biopsy, 438, 439 for thoracoscopic biopsy, 441, 441f in image-guided radiation therapy, 429, 430 in image-guided surgery, 42 in PET/CT scanning, 38, 39f multidetector, 35, 35f of appendicitis, 1504 of fetus, 77 of salivary glands, 836 of trauma abdominal, 295-296, 296f, 297, 311-312 to bladder, 319, 320 to duodenum, 304,305t, 306,306t to kidney, 319, 320, 323, 324, 325 to pancreas, 308, 308f, 308t, 309, 3091, 310 to ureter, 320, 326 brain for initial assessment, 362-363, 362f, 365, 366, 367 in child abuse. 402 type of injury And, 357, 358, 358f-361f, 359, 361 musculoskeletal, 342 spinal, 368, 369 thoracic, 278, 281, 283 to aorta, 288, 289f, 290 to diaphragm, 284-285 to pericardium, 287 of tumors bone, for staging, 655 brain, 672 three-dimensional, 34, 35-36, 36f for preoperative planning, 67-68,68f Computer-assisted surgery ( C A ), 42 Concussion, cerebral, 357, 359, 365, 367 Condyloma acuminata, 1599 Conformal radiation therapy, 429 Congenital adrenal hyperplasia, 637, 1913, 1914t. See also Pseudohermaphroditism, female. Congenital heart disease. See Heart disease, congenital. Congestive heart failure after heart transplant, 762 anthracycline therapy and, in Wilms' tumor patients, 461 arteriovenous malformation with, 2100, 2107,2112,2113 in Parkes-Weber syndrome, 2129 benign liver tumors with, 495, 496, 497 bronchopulmonary sequestration with, 957 causes of, 150t extracorporeal life support for, 134135, 140, 141, 141t, 142 in neonate, 148, 150t, 151, 153 in pulmonary vascular disease, 766 medications for, 150t renal artery stenosis with, 2118, 2120 transplantation for, 756 traumatic, 278 tumor-related with cardiac teratoma, 565 with hemangioma, 2097, 2102, 2105f, 2106 Volume 1, pages 1-1 140; Volume 2, pages 1141-21
Conjoined twins, 2079-2091 anesthetic management for, 2085 classification of, 2080, 2081f, 2081t clinical experience with, 2090-2091 embryogenesis of, 2080 ethical issues regarding, 2083-2084 heteropagus (parasitic), 2079, 2080, 2091 hindgut duplications in, 1396 historical perspective on, 2079 incidence of, 2079 obstetric management of, 2080-2082 organ system reconstruction in abdominal wall, 2089 central nervous system, 2086 gastrointestinal system, 2086-2087 genitourinary system, 2087, 2088f, 2089 heart, 2087 liver and pancreaticobiliary system, 2086 skeletal system, 2089 skin, 2083, 2084f, 2085 prenatal diagnosis of, 2080, 2081f preoperative diagnostic studies of, 2082-2083,2082t, 2083f preoperative planning for, 2085 survival of, prior to separation, 2079-2080 timing for separation of, 2084-2085 Connective tissue. See Soft tissue(s). Connective tissue disorders. See also Ehlers-Danlos syndrome; Marfan's syndrome. arterial disease in, 21 14, 21 14f inguinal hernia in, 1188 maternal, neonatal heart block and, 151 Consciousness. See also Coma. traumatic brain injury and, 359, 362, 363 Consent, 258, 259 for sex assignment surgery, 261-262 Constipation, 1592-1595 acute, 1592 anorectal malformations and, after repair, 1569, 1586, 1586t, 1587 chronic, 1592-1595, 1593t sphincter hypertrophy in, 1813 definition of, 1592 diet and, 1592, 1594 functional, 1592, 1593t idiopathic, 1549-1550, 1549t, 1550f, 1550t, 1594-1595 vs. appendicitis, 1505 vs. Hirschsprung's disease, 1516f, 1519, 1549-1550, 1550t in Hirschsprung's disease at presentation, 1593, 1594 postoperative, 1541-1542, 1543f, 1545, 1546 ultrashort, 1531 in intestinal neuronal dysplasia, 1561, 1562, 1563 voiding dysfunction secondary to, 1813, 1813f, 1814 Continence. See also Incontinence. fecal, 1591, 1592 Continent catheterizable channels, 1797-1798, 1797f-1798f, 1832-1833, 1832f-1833f. See also Mitrofanoff procedure. Continent stomas, 1488 appendicostomy as, 1587 Continent urinary reservoirs, 1791, 1795, 1798-1799,1799f, 1826 Continuous positive airway pressure (CPAP), 125 Contractility, cardiac, 146, 147 inotropic agents and, 148, 150t, 151
Contrast studies. See also Barium contrast; Enema; Esophagography; Upper gastrointestinal contrast series. BOLD functional MRI, 37 in necrotizing enterocolitis, 1437-1438 ultrasound, 33-34, 34f Copper, 198t, 199,206 Cor pulmonale, laryngomalacia with, 986 Cord blood, endogenous opioids in, 105 Core needle biopsy, 438-439,439f, 439t laparoscopically directed, 440 thoracoscopically directed, 980 Cornelia de Lange syndrome, 1111,1498 Corner fractures, 403 Coronary artery aneurysms, 21 15 Coronary artery disease, in graft, 754, 762,763 Corpus callosotomy, 2007 Corpus luteum cysts, 601 Corticosteroid therapy antenatal, congenital diaphragmatic hernia and, 939 calcium losses caused by, 207 cancer chemotherapy with, 424t for Addison's disease, 637 for airway obstruction, 828, 830 for anaphylaxis in latex sensitivity, 232 thiopental-induced, 233 for arteritis, 21 17 for biliary atresia, postoperative, 1609-1610, 1609t for bone cyst, unicameral, 658 for bronchiolitis obliterans organizing pneumonia, 781 for congenital adrenal hyperplasia, 1920-1921 for congenital diaphragmatic hernia, 939, 945 for Crohn's disease, 1455, 1458 for Diamond-Blackfan anemia, 180 for esophageal injury, caustic, 1083, 1085, 1086, 1088 for hemangioendothelioma, hepatic, 496 for hemangioma, 2104, 2104f subglottic, 994, 995 vaginal, 1951 for idiopathic (immune) thrombocytopenic purpura, 183,1693 for intussusception, 1323, 1327-1328 for pulmonary fibrosis, 767-768 for transfusion reactions, 189, 190 for ulcerative colitis, 1464, 1466, 1467 in acute respiratory distress syndrome, 127 in brain injury, 363 in brain surgery, 674 in septic shock, 173 in spinal cord injury, 370 in transplantation, 686, 687-688, 687f, 708 diabetes secondary to, 724 heart, 760, 760t, 761 intestinal, 749, 750 liver, 737, 738t, 739 lung, 769,771, 771t pancreas, 721 renal, 495, 708, 710 maternal fetal hydrops and, 83 fetal lungs and, 117 necrotizing enterocolitis and, 1444 neonatal, hyperglycemia and, 102 peptic ulcer disease caused by, 1226, 1228, 1229 Pneumocystis pneumonia and, 1007, 1008
Corticotropin-releasing hormone (CRH), 629, 633,635,637 Cortisol, 628, 629. See also Glucocorticoids. elevation of in burn patients, 391-392, 393 in Cushing's syndrome, 633-635, 634f postoperative, 106, 107 Cotton-Myer subglottic stenosis grading system, 991,99lf, 993 Cough, 827,828,829,830,831 chylothorax caused by, 1025 Counseling. See Genetic counseling; Prenatal counseling. Cowper's duct cyst, 1819, 1820f, 1903 CPAP (continuous positive airway pressure), 125 Cranial defects, tissue-engineered repair of, 22,23 Cranial neuropathy brainstem glioma presenting as, 676 branchial anomaly with, 866 traumatic, 363 after basilar skull fracture, 366 Cranial suspensory ligament, 1193,1194f Craniectomy strip, 795-796 therapeutic decompressive, 365 Craniofacial anomalies. See also Cleft anomalies. distraction osteogenesis for, 2063 middle ear effusions associated with, 815 reconstruction for, 787-800 computer-assisted planning for, 67-68, 68f for clefts, 788-792, 788f-792f for craniosynostosis nonsyndromic, 793-796, 793f-795f syndromic, 793,796800,796f-800f history of, 787 principles of, 787-788, 788f sleep apnea in, 824, 825 vs. positional deformations, 794 Craniopharyngioma, 677, 677f Craniosynostosis nonsyndromic, 793-796, 793f-795f syndromic, 793, 796800, 796f-800f Creactive protein, 171 Cremasteric contraction reflex, 1196 testicular torsion and, 1205 CRH (corticotropin-releasing hormone), 629, 633,635,637 CRIB (Clinical Risk Index for Babies), 91 Cricoid cartilage, 984 Cricoid split anterior, 992, 992t posterior, 989 Cricopharyngeal disorders, 1110 Cricopharyngeus, birth injury to, 405 Cricothyrotomy, 828 in trauma patient, 267 Cricotracheal resection, 992, 992f-993f, 993-994 Crohn's colitis, 1457-1458, 1459 Crohn's disease, 1453-1460 anal fissure in, 1458, 1465, 1597 appendicitis in, 1505 clinical features of, 1454, 1454t bloody diarrhea as, 1387 colon carcinoma in, 519-520, 1459-1460 diagnosis of, 1454-1455, 1455f epidemiology of, 1453 etiology of, 1453 Meckel's diverticulum in, 1305 medical treatment of, 1455-1456 pancreatitis in, 1672 pathology of, 1454, 1454f Volume 1, pages 1-1140; Volume 2, pages 1141-21
Crohn's disease (Continued) perianal, 1454,1457,1458, 1459, 1460 fistula in, 1598 surgical treatment of, 1456-1458, 1456t, 1457f outcomes of, 1458-1459, 1458f-1459f, 1459t vs. indeterminate colitis, 1457, 1466-1467 Crossed renal ectopia, 1717, 1719-1720, 1720f Crossmatching for transplantation, 695-696 intestinal, 747 renal, 702 Cross-trigonal ureteral reimplantation, 1748f for megaureter, 1775 Croup, 828, 830-831 Crouzon's syndrome, 22, 796-797, 796f Crush injuries, of skull, 361, 361f Cryoablation, of liver tumors, 51 1 Cryoprecipitate for head trauma patient, with coagulopathy, 274 for von Willebrand's disease, 183 Cryotherapy, 41-42 for bone tumors, 657-658,659, 660f Cryptococcus infection, 1010 Cryptorchidism, 1193-1205 acquired, 1196, 1197, 1200, 1203, 1205 associated abnormalities with, 1194-1 195 abdominal wall defects as, 1162, 1167, 1195 imperforate anus as, 1567 inguinal hernia as, 1198, 1199, 1200, 1204, 1205 myelodysplasia as, 1806 prune-belly syndrome as, 1195, 1781, 1785 scrota1 ectopia as, 1907-1908 testicular-epididymal fusion as, 1163 classification of position in, 1195-1 196, 1195f complications of, 1197-1 199, 1197f diagnosis of, 1199 embryology of, 1174, 1194 iatrogenic, 1184 in cystic fibrosis, 1300 incidence of, 1196-1 197 splenogonadal fusion presenting as, 1189 torsion in patient with, 1198, 1205 trauma to inguinal testis in, 1198-1 199 treatment of, 1200, 1201f-1202f, 1203 complications of, 1203-1204, 1204t fertility after, 1204, 1204t hormonal, 1200 laparoscopic, 1203 tumors associated with, 622, 1198, 1205 germinoma as, 567 CSF. See Cerebrospinal fluid (CSF). CT. See Computed tomography (CT). Curling's ulcer, 1226 Currant jelly stool, intussusception with, 1314f, 1317,1317f, 1324, 1386 Currarino's triad, 560, 560f, 1396, 1528, 1567 Cushing's disease, 634, 634f, 635 Cushing's syndrome, 633-635,634f Cushing's ulcer, 1226, 1227, 1231 CyberKnife, 46, 46f, 47, 49, 49t Cyclin-dependent kinases, 413, 425 Cyclins, 413 Cyclooxygenase, necrotizing enterocolitis and, 1432 Cyclophosphamide, 422, 423t, 425,428 Cyclosporine for Crohn's disease, 1456 for ulcerative colitis, 1466 in transplantation heart, 754, 760, 760t, 761f liver, 689, 689f, 737, 738t, 739 lung, 770, 771, 771t, 775
xvi
INDEX
Cyclosporine (Continued) pancreatic, 721 renal, 707-708 mechanism of action, 707-708, 738t side effects of, 708, 737, 738t, 739 renal insufficiency as, 779 Cylindroma, pulmonary, 641 Cystadenocarcinoma, pancreatic, 1684 Cystadenoma ovarian, 593, 1418 pancreatic, 1683, 1684 Cyst(s) and cystic lesions bile duct. See Choledochal cyst. bone. See Bone cyst(s). central nervous system, gastrointestinal mucosa in, 1393 Cowper's duct, 1819, 1820f, 1903 dermoid oral, 826 ovarian, 61 1f duplication. See Duplication(s), alimentary tract. epidermoid. See Epidermoid cyst(s). Gartner's duct, 1902-1903, 1950-1951 hepatic, nonparasitic, 499 laryngeal, 830 leptomeningeal, enlarging, 366 lymphatic, 2101. Y . ep also Cystic hygroma. mediastinal, 955, 959-966, 960t, 961f-966f, 1393 mesenteric. See Mesenteric and omental cysts. neck. See Neck, cysts and sinuses of. oral, 826 ovarian. See Ovarian cysts. pancreatic. See Pancreas, cysts associated with. paraurethral, female, 1902-1903, 1950-1951, 1951f pericardial, 963, 1393 pharyngeal, 826 preauricular, 871 pulmonary. See Lung(s), cystic lesions of. renal. See Kidney (s), cystic disease of. retroareolar, 890-891 salivary gland, %6, 826f, 838, 838f sebaceous, in Gardner's syndrome, 1422 splenic, 1692-1693, 1697, 1698 thymic, 865, 872, 955,960t, 961,962f umbilical, 1146, 1147f, 1148, 1307f umbilical cord, 1307f, 1310 urachal, 1148-1149, 1148f Cysteine, in parenteral solution, 207, 208 Cystic adenomatoid malformation, congenital, 641, 642t, 955, 956, 957 lung abscess associated with, 1015 pneumatocele associated with, 1016f prenatal treatment of, a t , 83 Cystic fibrosis appendicitis in, 1299, 1502 bronchiectasis in, 1013, 1013f, 1014 cholelithiasis in, 1299, 1635 clinical presentation of, 1010 colonic fibrosis in, long-segment, 1498 colonic obstruction in, 1498, 1498f cryptorchidism in, 1300 diagnosis of, 1010, 1292, 1293 etiology of, 1010 genetics of, 12, 12f, 1289-1290 hemoptysis in, 1014, 1015f hydrocele in, 1300 hypersplenism in, 1697 inguinal hernia in, 1188, 1300 intussusception in, 1320 jejunoileal atresia in, 1274, 1282 jejunostomy in, 1481, 1483f lung infections in, 1003, 1010-1011
Cystic fibrosis (Continued) lung transplant for, 765-766, 773, 775, 1011 meconium ileus in. See Meconium ileus. meconium plug syndrome in, 1294 nasal polyps in, 818 pancreatitis in, 1673 pediatric surgeon's involvement in, 1011 pneumothorax in, 1021 portal hypertension in, 766 portosystemic shunt for, 1659, 1660f primary peritonitis in, 1476 rectal prolapse in, 1299, 1595-1596 vas deferens abnormalities in, 1188 vitamin E in, 198 Cystic hygroma, 826, 1400, 2138, 2139, 2139f, 2140. See also Lymphatic malformations. mediastinal, 966, 2139, 2139f terminology for, 2098, 2138 vs. cervicofacial teratoma, 564 Cystic nephroma, 1712-1713,1712f Cystitis, hemorrhagic, after bone marrow transplantation, 781-782 Cystography of bladder injury, 319-320 of megaureter, 1772 Cystolitholapaxy, 1752, 1753 Cystoplasty. See Bladder augmentation or replacement. Cystosarcoma phyllodes, of breast, 890, 892 Cystoscopy before gender assignment surgery, 1921-1922, 1922f fetal, 78 Cystourethrography. Seevoiding cystourethrography. Cytarabine, 423t Cytogenetics. See Chromosomal abnormalities. Cytokines. See also Interleukin entries. in Crohn's disease, 1453 in host defense, 159, 160, 161, 163, 165-166 in necrotizing enterocolitis, 1430-1432, 14301, 1433, 1434 in neonatal sepsis, 170-171 in stress response, 105-106 in systemic inflammatory response syndrome, 168-169, 169f, 170, 172, 173 recombinant, in cancer therapy, 427 Cytomegalovirus (CMV) infection esophageal, 1386 in cancer patient, 1007 in HIV-infected patient, 1009-1010 in transfused lymphocytes, 188, 189 sialadenitis caused by, 837 transplantation and heart, 757, 761, 762 intestinal, 747, 750, 751 liver, 739, 740t lung, 775 renal, 712 Cytotoxic crossmatching, 747 Cytotrophoblasts, 568, 609
da Vinci Surgical System, 49-53, 49t, 51f, 52t clinical applications of, 53, 54t, 55 conclusions on, 55, 57 experimental applications of, 55, 56t to neck lesions, 867 for splenectomy, 1696 Dacarbazine, 423t Volume 1, pages 1-1 140; Volume 2, pages 1141-214
Daclizumab (Zenapax),707 in transplantation intestinal, 749 islet cell, 724 liver, 738t lung, 770-771, 771t renal, 707, 708 Dactinomycin. SeeActinomycin (dactinomycin). DAI (diffuse axonal injury), 273, 357, 358, 359, 360f, 361 in shaken baby syndrome, 401 Dakin solution, 389t, 390 Dal-Pont osteotomy of mandible, simulation of, 68 Damage-control strategy for abdominal trauma, 301-302, 301t for thoracic trauma, 279 Dantrolene, for malignant hyperthermia, 231, 232, 232t Data Knife, 57, 57f DataGlove, 66, 66f Daunomycin, 423t DDAW (desmopressin). See also Vasopressin. for nocturnal enuresis, 1814, 1815 for syndrome of inappropriate ADH secretion, 94 D-dimer assay, 184t in disseminated intravascular coagulation, 186 de Quervain's thyroiditis, 852 Dead space, pulmonary, 118t, 120 capnographic tracing and, 234f high-frequency ventilation and, 125 weaning from ventilator and, 128 Decerebrate posturing, 272, 359 Decompressive craniectomy, therapeutic, 365 Decorticate posturing, 272 Decortication, for empyema, 1018 Deep venous thrombosis (DVT) complications of, 2132-2133, 2133t in iliac compression syndrome, 2127 in ventilated patient, 128-129 lower extremity, 2131, 2132 mesenteric venous thrombosis and, 2130 upper extremity, 2131-2132 Defecation. See also Constipation; Feces; Incontinence, fecal. functional disorders of, 1549-1550, 1549t, 1550f, 1550t, 1592, 1593t, 1595 in newborn, 1515, 1519, 1592 normal frequency of, 1549, 1592 physiology of, 1568-1569, 1591-1592 Defensins, 161, 167 Deflux. See Dextranomer-hyaluronic acid copolymer (Deflux). Demyelinating syndromes, 1523 Dendritic cells, immunotherapy and, for neuroblastoma, 485 Denys-Drash syndrome, 421, 446, 447, 461 Depsipeptide, 426 Dermal sinus tract, 1994 Dermal substitutes, synthetic, 390 Dermoid cyst cervical, 865, 870-871 mediastinal, 962 nasopharyngeal, 826 oral, 826 Dermoid sinus nasal, 819-820, 820f suprapubic, 1149 Dermoid tumor, ovarian, 611f Desflurane, 222t, 227t, 229 Desmoid tumor, abdominal, in Gardner's syndrome, 1422 Desmoid-type fibromatosis, 542
Desmoplastic infantile ganglioglioma, 671 Desmoplastic small round cell tumor, 544t, 547 ovarian involvement by, 615 Desmopressin (DDAW). See also Vasopressin. for nocturnal enuresis, 1814, 1815 for syndrome of inappropriate ADH secretion, 94 Detrusorrhaphy, extravesical, 1749f Detrusor-sphincter dyssynergy, 1807, 1808f, 1809, 1817,1818 in myelodysplasia, 1821-1822, 1822f Developmental disabilities, nutritional support in, 214,214t Dexamethasone. See also Corticosteroid therapy. for meningitis, 173 maternal, necrotizing enterocolitis and, 1444 Dexamethasone suppression test, 634f, 635 Dextran as plasma substitute, 188 for adhesion prevention, 1360 Dextranomer-hyaluronic acid copolymer (Deflux), 1748,1766,1767,1776 Dextrose. See Glucose (dextrose). Diabetes mellitus. See also Insulin; Islet cell transplantation; Pancreas, transplantation of. Haemophilus vaccine and, 1002 in cystic fibrosis, lung transplantation and, 766,775 in neonate, 10'2 management of, complications and, 717 maternal arterial thrombosis and, 21 15 childhood obesity and, 1245 neonatal hypoglycemia and, 102 polysplenia syndrome and, 1604 sacral agenesis and, 1810, 1822, 2029 small left colon syndrome and, 1496, 1497f, 1498 post-transplant, 708, 724, 775 type 2 bariatric surgery and, 1252 in children, 1246 inflammation and, 1244 type 1, arterial occlusion in, 2121 Dialysis, renal acquired renal cystic disease and, 1713 parenteral amino acids and, 204 peritoneal. See Peritoneal dialysis. transplantation and, 700, 701, 710, 713 vascular access for, 700, 701-702 in bone marrow transplant patient, 779 Diamond anastomosis, duodenal, 1264, 1265, 1265f Diamond-Blackfan anemia, 179, 180 Diapedesis, 159, 160, 168 Diaphragm embryology of, 933, 1107-1108 erosion of, by amebic abscess, 1646 eventration of, 935,937, 946 in children's breathing, 276 trauma to, 269 abdominal injury with, 312-313 epidemiology of, 275, 275t, 292 laparoscopic repair of, 297, 313 thoracic injury with, 276, 278, 284-285, 284f, 285t Diaphragmatic hernia. See also Pulmonary hypoplasia. congenital (CDH), 83-84,931-945 associated anomalies with, 932-933 bronchopulmonary sequestration as, 958 hypoplastic left heart syndrome as, 153
Diaphragmatic hernia (Continued) malrotation as, 1346 pectus anomalies as, 894, 944 scoliosis as, 944 diagnosis of postnatal, 93&937 prenatal, 936, 936f, 937, 938-939 differential diagnosis of, 937 embryology of, 933-934,935 epidemiology of, 932 esophageal dysmotility associated with, 1112 gastroesophageal reflux and, 142,944, 944f, 1123 genetics of, 932 historical perspective on, 931-932,932f molecular biology of, 934 outcomes with, 943-944,944f pathology of, 934936, 934f-935f prognostic factors in, 937-938 pulmonary hypertension and, 123,935 treatment of, 938-945 ECLS in, 135, 139, 140, 140t, 142 ECMO in, 83, 127, 767,932f, 938, 939, 940,942-944,945,945f fetal, 259, 939, 944-945 for recurrent defects, 942 future, 944945,945f liquid ventilation in, 126-127, 945, 945f lung transplant in, 767, 945 postoperative, 942 preoperative, 939-940 surgical, 940-942,941f ventilator in, 938, 939-940, 942, 943 gastric volvulus associated with, 1234, 1234t, 1235 of Morgagni, 937,945-946 robot-assisted repair of, 53, 54t thoracoscopic closure of, 977 Diaphyseal aclasis, 651 Diaphyseal fractures, 342 Diaphysis, 337, 338f tumors in relation to, 652f, 654 Diarrhea after bone marrow transplantation, 780 bloody, 1387 in short-bowel syndrome, 1372, 1373 tumor-associated, with neuroblastic tumors, 469,486 Diastematomyelia, 1994, 2027, 2102 Diatrizoate enema for meconium ileus, 1275, 1289, 1292, 1295-1296 for milk curd syndrome, 1365 Diazepam, for burn patients, 394, 394t Diazoxide, for persistent hyperinsulinemic hypoglycemia in infancy, 1681, 1683 Diencephalic syndrome, 676 Diffuse axonal injury (DAI), 273, 357, 358, 359,36Of, 361 in shaken baby syndrome, 401 Diffuse brain injury, 357, 358-359, 361 early management of, 364, 365 initial CT findings in, 359, 360f, 361, 362, 362f, 364f subdural hematoma with, 359, 364, 364f Diffuse intrinsic pontine glioma, 676 Diffuse large cell lymphomas, 580, 582, 583, 583f Diffusion capacity, 118t, 120 DiGeorge syndrome, heart defects in, 153 Digital ischemia syndrome, 381 Digoxin, for heart failure in neonate, 148, 150t, 151 with supraventricular tachycardia, 151 Diphallia, 1907, 1907f Volume 1, pages 1-1140; Volume 2, pages 1141-2146
Diphenoxylate, 1373, 1466 2,3-Diphosphoglycerate, 121 Disabled children gastroesophageal reflux in, 214, 1121, 1126, 1127, 1131 nutritional support for, 214, 214t Disappearing bone disease, 2099 Discitis, 2042 Dismembered pyeloplasty, 1734-1 736, 1734f Disseminated intravascular coagulation causes of, 186 diagnosis of, 186 in head injury, 273-274 in liver failure, 186 in neonatal sepsis, streptococcal, 170 purpura fulminans secondary to, 2058 treatment of, 186 Distal intestinal obstruction syndrome, 1291, 1299 after lung transplant, 773 Distraction osteogenesis during chemotherapy, 663 of facial bones, 2063 prior to bone grafting, 22 Diuretic renography, 1729, 1729f, 1733, 1737 with megaureter, 1771-1772 Diuretics calcium losses caused by, 207, 209 for ascites, 1409 for heart failure, in neonate, 148, 150t for hypertension, 2120 Diverticulosis, small-bowel, multiple atresias with, 1276 Diving reflex, 1235, 1433 DNA cancer chemotherapy and, 422,423t-424t cell cycle and, 412-413, 413f DNA content (ploidy), 415, 438 DNA damage by ionizing radiation, 43-44 by nitric oxide, 161-162 DNA index, 415 DNA microarrays, 40, 419, 420, 425 DNA repair genes, mutations of, 421 DNET (dysembryoplastic neuroepithelial tumor), 671, 677-678, 678f Dobutamine, for heart failure, 150t, 151 Docetaxel, 4241 Donnai-Barrow syndrome, 1160-1 161 Donut sign, of intussusception, 1326, 1326f Dopamine adrenal synthesis of, 629 for brain injury, 273 for heart failure, 150t, 151 neonatal acid-base balance and, 96 Doppler ultrasound imaging, 32, 34 for needle biopsy, 438 of amniotic flow, 936 of arterial occlusion, 21 16 of arteriovenous fistula, penile, 331 of burned extremity, 386 of hand circulation, 348 of hepatic artery, after Kasai procedure, 1611 of intestinal malrotation, 1350, 1351f of renal allograft, 70&707 of salivary glands, 836, 836f of tumors, hepatic, 504 of vascular injury, 377 Dor fundoplication, robot-assisted, 53, 54t Dorsal lumbotomy approach, 1735, 1736, 1736f Double aortic arch, airway obstruction by, 997,998 Double bubble sign, of duodenal obstruction in atresia or stenosis, 1262, 1262f in volvulus, 1350, 1351f
xviii
INDEX
Double minutes, 417 Double wall sign, of pneumoperitoneum, 1437 Down syndrome (trisomy 21) adenotonsillar hypertrophy in, 824 anorectal malformations in, 1566, 1571 duodenal atresia in, 1260, 1261t, 1269 esophageal dysmotility in, 1111, 1113 heart defects in, 153 Hirschsprung's disease in, 1528, 1529, 1545 leukemia in, 420 macroglossia in, 825 middle ear effusion in, 815 nutritional support in, 214, 214t Doxorubicin. See Adriamycin (doxorubicin) . Dressings for burns, 389, 390, 390f outpatient, 396 for soft tissue wounds, 352 Drooping flower sign, 1764, 1765f, 1949, 1950f Drop mets, 673, 675 Dropped lung, 283 Drotrecogin alfa, for sepsis, 173 Drug delivery systems, microelectromechanical, 58 Dual energy x-ray absorptiometry, 195 Duchenne's muscular dystrophy, malignant hyperthermia in, 231 Ductus arteriosus closure of, 148,935, 1959 fetal, 148, 149f afterload and, 147 indomethacin and, 79 indomethacin and, 79,238 maintaining patency of, 153, 756, 943 patent, 1959-1961, 1960f-1961f afterload and, 147 arterial catheterization with, 123, 235-236 congenital diaphragmatic hernia with, 148 historical perspective on, 4 in Down syndrome, 153 pulmonary hypertension with, 123 robot-assisted ligation of, 54t, 55 thoracoscopic occlusion of, 977 Ductus venosus, 148 Duhamel operation, 1532f, 1536, 1538, 1539, 1539f-154Of, 1542 complications of, 1546-1547 redo of, 1545f Duodenal atresia and stenosis, 1260-1267, 1261f-1265f, 1261t imperforate anus with, 1567 jejunal feeding in, 1481 iejunoileal atresias with, 1270, 1276 malrotation with, 1262, 1263, 1346 pyloric web with, 1233 Duodenal duplication, 1391, 1392f, 1393-1394, 1394f Duodenal intubation, for diagnosing biliary atresia, 1607 Duodenal switch, biliopancreatic diversion with, 1248, 1248t, 1250 Duodenal ulcer. See Peptic ulcer disease. Duodenostomy, cyst, 1626, 1627f, 1629 Duodenum adenocarcinoma of, 1421 biopsy of, in thrombocytopenic patients, 780 obstruction of. See abo Duodenal atresia and stenosis. by congenital bands. See Ladd's bands. by preduodenal portal vein, 2126 polyps in, 1420, 1421, 1422 trauma to, 303-304, 304t, 305f-307f, 306-307, 306t, 307t
Duplex collecting system. See also Ureteral duplication. definition of, 1758 Gartner's duct cyst with, 1950 megaureter associated with, 1771 partial nephroureterectomy with, 1767 terminology for, 1758 ureteropelvic obstruction with, 1761, 1761f, 1762, 1767 urinary tract infection with, 1743, 1744f vesicoureteral reflux with, 1760, 1761, 1762, 1762f-1763f, 1763, 1765-1 766, 1766, 1767, 1768 Duplex exstrophy, 1842, 1843f Duplication(s), alimentary tract, 1389-1397 appendiceal, 1501 associated anomalies with, 1389, 1390 clinical manifestations of, 1390-1391 definition of, 1389 diagnosis of, 1391-1392,1391f-1392f vs. mesenteric cyst, 1400, 1402 duodenal, 1391, 1392f, 1393-1394,1394f esophageal associations of, 964-965, 965f-966f, 1392, 1393, 1393f etiology of, 1389-1390 foregut. See also Bronchogenic cyst. abdominal, 1393-1394, 1394f thoracic and thoracoabdominal, 955, 959, 960,963-966,963f-966f, 1393, 1393f thoracoscopic biopsy of, 977 gastric, 1391, 1393-1394, 1678 gastric mucosa in, heterotopic, 1308, 1387, 1389, 1390, 1391, 1392, 1393, 1394, 1395, 1396 hemorrhage associated with, 1386, 1387 hindgut, 1391, 1392, 1395-1397, 1396f-1397f, 1498 intestinal obstruction with, 1366, 1391, 1395 intussusception with, 1319, 1321, 1366, 1391, 1392, 1395 locations of, 1389, 1389t pancreatic involvement by, 1391, 1392f, 1394, 1678 pyloric, 1234 pyloroduodenal cyst as, 1232 small intestine, 1390, 1391, 1391f-1392f, 1392,13941395, 1395f Duplication (s), genitourinary. See also Duplex collecting system; Ureteral duplication. colorectal duplications with, 1396 in bladder exstrophy, 1843f, 1846 of horseshoe kidney, 1717 penile, 1904, 1907, 1907f urethral, 1819,1820f-1821f, 1904-1905, 1904f uterine, 1943-1944,1943f-1944f vaginal, 1943-1944, 1943f-1944f Dura mater closure of, after brain tumor surgery, 674 sarcomas of, 546 DuraGen, 674 DVT. See Deep venous thrombosis (DVT) . Dyschezia, infant, 1549, 1549t Dyschondroplasia, in Maffucci syndrome, 2129 Dysembryoplastic neuroepithelial tumor (DNET), 671, 677-678,678f Dysfibrinogenemias, 185 Dysfunctional elimination syndrome, 1812-1813, 1812f-1814f Dysgerminoma, 554,567. See also Germinoma. biologic markers associated with, 556, 594t, 595 gonadoblastoma coexisting with, 613 in mixed germ cell tumors, 568
Volume 1, pages 1-1140; Volume 2, pages 1141-2146.
Dysmotility, gastrointestinal. See Enteric nervous system; Esophageal dysmotility; Gastric emptying; Intestinal dysmotility; Intestinal pseudo-obstruction. Dysphagia. See also Swallowing. after esophageal atresia repair, 1070-1071, 1111 evaluation of, 1125b esophagoscopy in, 1040 in esophageal achalasia, 1113, 1114 Dystocia sternomastoid tumor and, 875 teratoma causing cervicofacial, 564 sacrococcygeal, 559:560
Ear, 813-817 anatomy of, 813 branchial anomalies associated with, 867-868,867f vs. preauricular cyst, 871 cholesteatoma in, 816 congenital anomalies of, 814 embryology of, 814, 863, 863t, 864f examination of, 814-81 5 infection of, 815-816, 816f tissue-engineered, 22 trauma to, 81G817, 817f tumors of, 817 Ear tags, 789, 789f, 814 Ebstein's anomaly of tricuspid valve, 151 EBV. See Epstein-Barr virus (EBV) infection. ECF (extracellular fluid) in fetus and neonate, 91-92,93, 94,95 third-space loss and, 226 Echinococcal infection liver abscesses in, 1646, 1646f pulmonary, 1005, 1005f Echocardiography antenatal, omphalocele and, 1161 in chest trauma, 278, 285, 286, 290, 291 in pectus excavatum, 898 Eclampsia, sacrococcygeal teratoma and, 85 ECLS. See Extracorporeal life support (ECLS) ECMO. See Extracorporeal membrane oxygenation (ECMO). Ectopia cordis, 912-914, 1157-1158, 1158f, 1158t, 1162 embryogenesis of, 1160 outcome of, 912,913,914,1167 prenatal diagnosis of, 1161 treatment of, 912-914,913f-914f, 1165 Edema cerebral, post-traumatic, 356, 357, 360f, 362, 365 lower extremity. See also Lymphedema. causes of, 2141 pulmonary. See Pulmonary edema. EDNRB. See Endothelin-B receptor (EDNRB). Edrophonium, with neuromuscular blockade, 230 Effort thrombosis, 2131-2132 EGF. See Epidermal growth factor (EGF). Ehlers-Danlos syndrome arterial degeneration in, 21 14, 21 14f inguinal hernia in, 1188 Eisenmenger's syndrome, 766, 770 Ekehorn's rectosacropexy, 1596 ELA-Max, 244,244t
Elbow injury to fracture in, 342f posterior fat pad sign in, 341, 341f ultrasonography of, 342 reconstruction of, after tumor resection, 665 Electrical burns, 383, 385, 396 amputation secondary to, 2058 Electrocardiogram, in trauma patient, 272 with thoracic injury, 278, 285, 286 Electrocautery, 40-41 Electroencephalography (EEG) in seizure evaluation, 2003, 2004, 2005 intracranial, 2005 Electrogastrography, 1548 Electrolytes. See also Fluid management or resuscitation. in burn patient, 388-389 in fluid therapy, 225 intraoperative, 226 in neonate, 91-96, 93f, 94t, 96t in parenteral nutrition patient disturbances, 208-209 requirements, 206-207, 206t Electrosurgery, 40-41 Elephantiasis, 2099 ELSO (Extracorporeal Life Support Organization), 134, 136, 137, 140-141, 140t, 141t Embolism arterial, 2115-2117, 2115t pulmonary, 2132-2133 in ventilated patient, 129 septic, jugular thrombophlebitis with, 2132 venous. Y . ep Thromboembolism, venous. Embolization bronchial artery, 1014, 1015f in abdominal trauma for hepatic hemorrhage, 301, 301f for renal injury, 319, 324 for splenic injury, 297 for splenic pseudoaneurysm, 299, 299f of aneurysm, congenital, 21 11 of liver tumors, benign, 496, 497 hemangioma as, 2106 of nasopharyngeal angiofibroma, 821 of vascular anomalies, 2103 arteriovenous malformation as, 2107, 2113,2114 Embolosclerotherapy, of arteriovenous fistula, in Parkes-Weber syndrome, 2129 Embryology alimentary tract duplications and, 1389-1390 bladder exstrophy and, 1841-1842, 1842f choledochal cyst and, 1622-1623 cloaca1 exstrophy and, 1862 colonic atresia and, 1493-1494 duodenal atresia or stenosis and, 1260 gastroesophageal reflux and, 1120-1121 germ cell tumors and, 554 Hirschsprung's disease and, 1523-1526, 1524f-1525f inguinal hernia and, 1173-1 174 Meckel's diverticulum and, 1304 mesenteric-omental cysts and, 1399-1400 of abdominal wall, 1158-1 159, 1159f of adrenal glands, 628-629 of anus and rectum, 1566-1567 of appendix, 1501 of biliary system, 1604 of breast, 885, 2064 of central nervous system, 1987, 1988-1990, 1988f-1989f of cleft lip and palate, 803 of cloaca, 1842, 1842f
Embryology (Continued) of diaphragm, 933, 1107-1 108 of ear, 814 of enteric nervous system, 1523-1525, 15245 1560 of esophagus, 1107-1 108 of female genital tract, 1935-1936 of foregut, 1053-1054,1071,1107 of hand, 2071 of intestinal rotation and fixation, 1342-1346, 1343f-1347f of kidney, 1705, 1715, 1716f, 17241725 of lungs, 1 1 4 116, 115f, 933-934 congenital diaphragmatic hernia and, 934,935 of lymphatic system, 2137, 2138f of male genitalia, 1871-1874, 1872f-1874f of mediastinal masses, 955 of neck, 861-865,862f, 863t, 864f-865f of nose, 818 of pancreas, 1671-1672 of parathyroid glands, 850 of portal vein, 1651-1652 of salivary glands, 835 of skin, muscle, connective tissue, and tendons, 2061-2062 of spleen, 1691 of testicular descent, 1174,1193-1 194, 1194f of thoracic duct, 1025 of thyroid glands, 850 of twinning, 2080 of umbilicus and related structures, 1143, 1144f, 1145, 1145t, 1304 of ureter and ureteral anomalies, 1758-1 761, 1759f-1760f of venous system, central, 2124, 2125f sexual differentiation in, 1911-1913, 1912f ureteropelvic junction obstruction and, 17241725 Embryonal brain tumors, 671, 671t Embryonal carcinoma, 555 biologic markers associated with, 556, 594t, 595 extragonadal, 567 in sacrococcygeal teratoma, 559 pineal region, 678 in mixed germ cell tumors, 568 ovarian, 5941,607,609 Embryonal sarcoma, undifferentiated, hepatic, 505 Emergency management, 265-274. See also Trauma. ABCDE in, 266-272,268f, 270f-271f coagulopathy and, 273-274 for burns, 385, 386 pain management in, 274 peaks of mortality and, 265-266 prehospital, 266 primary survey in, 266-272, 268f, 270f-271f resuscitation phase in, 267, 272-273, 277 secondary survey in, 267 signs of successful resuscitation in, 269 EMLA (eutectic mixture of local anesthetics), 244, 244t Emphysema acquired lobar, in viral bronchiolitis, 1004, 1004f congenital lobar, 955,958-959,959f pulmonary interstitial, barotrauma-related, 128 Empyema, 1017-1018, 1019f-1020f pleural debridement for, 977, 978,980 Volume 1, pages 1-1 140; Volume 2, pages 1141-2
Encephalocele capillary malformation overlying, 2098 nasal, 820 nasopharyngeal, 826 Encephalopathy, portal hypertension with, 1655, 1656, 1658,1659,1661, 1664, 1665, 2126 Enchondroma, location of, in relation to physis, 652f Enchondromatosis, 651-652. See also Maffucci syndrome; Ollier's disease. ovarian tumors associated with, 593, 606 Encopresis, 1549, 1549t, 1592, 1595 vs. ultrashort Hirschsprung's disease, 1531 End ureterostomy, 1792, 1793f End-diastolic volume. See Preload. Endocarditis, bacterial, embolic complications of, 2115-2116, 2116f Endocatch 11,1695, 1695f, 1696 Endodermal sinus tumor. SeeYolk sac (endodermal sinus) tumor. Endometriosis, 601-602 magnetic resonance imaging of, 597 sarcomas arisitlg from, 614-61 5 Endophthalmitis, pyogenic liver abscess with, 1644 Endopyelotomy, 1719, 1736, 1737 Endoscopic retrograde cholangiopancreatography (ERCP) in ascariasis, 1365 in choledocholithiasis, 1638, 1638f, 1642 in infants, 1607 in pancreatitis, 1674, 1675, 1677f of biliary duct injury, 303, 304f of ductal anomalies, 1625 of pancreas divisum, 1676 of pancreatic injury, 308, 309, 309f, 310 of pancreatic pseudocyst, 1678 Endoscopy. See also Bronchoscopy; Esophagoscopy; Laparoscopy; Laryngoscopy; Thoracoscopy. colonoscopy, 1465 fetal, 78, 79-80, 79t, 81f, 83, 84, 85 for biopsy, 439-442, 441f for gastrostomy tube placement, 199, 1042-1043 for urethral alignment, after injury, 330 history of, 971 microelectromechanical devices and, 57 robotic systems and, 48, 49, 50, 53 training simulations for, 61, 68-69, 69f, 70 virtual, with 3-D CT, 35-36, 36f Endothelial cells cytokines secreted by, 165 in angiogenesis, 418, 419 cancer chemotherapy and, 422,426 in systemic inflammatory response syndrome, 168, 169f, 172, 173 in tissue engineering, 22, 23, 24, 27, 27f neutt-ophils and, 159-160, 167 Endothelin-3. 1521. 1522-1523. 1523t. 1525 Endothelin-1, in hepatopulmonary syndrome, 1656 Endothelin converting enzyme-1, 1521, 1523, 1523t Endothelin-B receptor (EDNRB) Hirschsprung's disease and, 1521, 1522-1523, 15231, 1526 intestinal neuronal dysplasia and, 1560 Endotoxin. See Lipopolysaccharide (LPS, endotoxin). Endotracheal intubation. See also Extubation. complications of, 128, 129 esophageal, 1047, 1048. 1049 gastric perforation as, 1235, 1236
Endotracheal intubation (Continued) long-term, 983,984,990-991,996 for upper airway obstruction, 828 in burn patient, 385 in inhalation injury, 395 in trauma patient, 266, 267, 268f, 269, 272 with brain injury, 356, 364 with spinal injury, 356, 370 with thoracic injury, 277 Endotracheal tube, 127 removal of, 128 selection of, 267, 828 End-stage liver disease (ESLD) in biliary atresia, 1611, 1612, 1613 transplantation for, 731, 732-733, 734 with intestinal transplant, 745 End-stage renal disease (ESRD), transplantation for, 699, 700, 701, 702, 710, 711, 713 Enema an tegrade for bowel management, 1483f, 1485 for cloaca1 exstrophy, 1866 for incontinence, 1834, 1834f contrast. See (also Barium enema; Diatrizoate enema. in distal intestinal obstruction, 1494 in Hirschspmng's disease, 1515-1516, 1516f vs. idiopathic constipation, 1549 with total colonic aganglionosis, 1531, 1531f in meconium plug syndrome, 1496, 1497f for bowel management after anorectal malformation repair, 1587 antegrade, 1483f, 1485 in intestinal neuronal dysplasia, 1562, 1563 for constipation, 1550, 1550f, 1594 acute, 1592 Energy metabolism, 195-196, 195t in cerebral palsy, 214 in neonate, 96-99, Y8f postoperative, 105, 105f, 107, 108, 212 protein metabolism and, 104, 108 with biliary atresia, 212 obesity and, 1243, 1245 postoperative, 195-196, 210-21 1 in critically ill patient, 212 in neonate, 105, 105f, 107, 108 Enflurane, 228,228f gastric emptying and, 1361 Enprostil, peptic ulcers and, 1230 Entamoeba histolytica infection in graft-versus-host disease, 780 liver abscess in, 1645-1646 Enteral nutrition, 199, 200t, 201t, 202-203 See also Formula(s);Gastrostomy. for biliary atresia, 212 for burn patient, 386, 393 for Crohn's disease, 1456 for failure to thrive, 213-214 for short-bowel syndrome, 203, 212-213 for surgical patient, 21 1 nasogastric, 199, 203 Enteric nervous system aganglionosis and, 1527-1528, 1527f anal sphincter and, 1591 disorders of, 1547, 1548 embryology of, 1523-1525, 1524f, 1560 ganglion cell density of, 1561 hyperganglionosis and. See Intestinal neuronal dysplasia. physiology of, 1527, 1527f postnatal development of, 1561 Enteritis, infectious, after intestinal transplant, 750
Enterocolitis, 780. See also Hirschsprung's disease, enterocolitis of; Necrotizing enterocolitis, neonatal. in graft-versus-host disease, 780 methicillin-resistant S. aureus in, 1495 Enterocystoplasty. See Bladder augmentation or replacement. Enteroenterostomy, robotic, porcine, 55, 56t Enterostoma(s), 1479-1490. See also Appendicostomy; Colostomy; Gastrostomy; Ileostomy; Jejunostomy. care of, 1488 choices for, 14841485, 1484f, 1485t closure of, 1488-1 489 complications of, 1489-1490, 1489f, 1489t parastomal hernia as, 1363, 1489 continent, 1488 historical perspective on, 1479 in chronic intestinal pseudo-obstruction, 1549 in Crohn's disease, 1457, 1458, 1459 in Hirschsprung's disease, total colonic, 1531 in necrotizing enterocolitis, 1440, 1441-1442, 1482,1483f in ulcerative colitis, 1467, 1468, 1470f, 1471, 1482-1483 indications for, 1480-1484, 1483f-1484f quality of life and, 1479-1480 sites for, 1486, 1486f-1487f, 1488 umbilical, 1153, 1484f, 1486 technical aspects of, 1485-1486, 1486f-1487f, 1488 types of, 1480, 1480f-1482f, 1480t, 1481t Enuresis. See also Incontinence, urinary. airway obstruction and, 824 nocturnal, 18141815 Envenomation injuries, 352-353 Eosinophilic esophagitis, 1112, 1112f, 1125b Eosinophilic granuloma, temporal bone involvement of, 817 Eosinophilic proctocolitis, 1599 Ependymoma, 671, 671t, 675-676,675f in Turcot's syndrome, 1422 Epidermal growth factor (EGF), in gastrointestinal tract, 1430, 1430t Epidermal growth factor receptor (EGFR), 414,419, 425 in germ cell tumors, testicular, 556 Epidermoid carcinoma, salivary gland, 827 Epidermoid cyst(s) cervical, 869 hepatic, 499 in Gardner's syndrome, 1422 testicular, 622, 623 Epidermolysis bullosa, pyloric atresia associated with, 1233 Epididymis rupture of, 331 undescended testis and fusion with, 1199 separation from, 1195 Epididymitis, 1205-1 206, 1206t ectopic ureter with, 1763 Epidural abscess, 2009, 2010, 2010f spinal, 2013 Epidural anesthesia, 247-249, 247f, 248t postoperative ileus and, 1361 Epidural catheter, 248-249, 248t Epidural hematoma, 273, 358, 359, 364365, 365f Epiglottitis, 830 Epilepsy surgery, 2002-2008, 2003f. See also Seizures.
Volume 1, pages 1-1140; IJolume 2, pages 1141-21
Epinephrine (adrenaline) adrenal synthesis of, 628, 629 arrhythmias associated with, inhalation anesthetics and, 228, 228f, 229 for anaphylaxis latex-induced, 232 thiopental-induced, 233 for bronchospasm, in inhalation injury, 395 postoperative levels of, 106, 107, 107f racemic, in airway obstruction, 828, 830 Epiphysiodesis contralateral to tumor resection, 663 with vascular malformations, 2108 Epiphysis, 337, 338f fracture of in birth injury, 404 in child abuse, 403 injury to, ultrasonography of, 342 tumors in, 652f, 654 Epipodophyllotoxins, 422, 424t Epispadias, 1842, 1843f repair of, 1851-1852, 1851f-1852f complications of, 1858 Epistaxis, 820-821 Epithelioid sarcoma, 549f-550f Epstein-Barr virus (EBV) infection Hodgkin's disease and, 575 in HW-infected patient, 837 lymphoid interstitial pneumonitis and, 1008, 1009f leiomyosarcoma and, 543 mononucleosis in, 822, 837, 848 neuroblastoma therapy and, 484 transplantation and heart, 757 intestinal, 750-751 liver, 739, 740t lymphoproliferative disorder and, 585, 712, 739, 740t, 750-751, 774 Epulis, 825-826, 825f ERBBP proto-oncogene, 417,425 Erb's palsy, 404-405 diaphragmatic eventration in, 946 ERCP. See Endoscopic retrograde cholangiopancreatography (ERCP). Erectile dysfunction postoperative ileoanal pouch procedure and, 1470 in Hirschsprung's disease, 1546 post-traumatic, 330, 331 Erection artificial, 1887, 1891 prevented by penile block, 1893 Ergotamine, maternal use of, intestinal atresia and, 1269 Erythema nodosum, in ulcerative colitis, 1464, 1464f Erythroblastopenia of childhood, transient, 179-180 Erythrocytes (RBCs) 2,3-diphosphoglycerate in, 121 enzymes in carbonic anhydrase, 121 deficiencies of, 182 glutathione peroxidase, 199 transketolase, in thiamine deficiency, 198 mean corpuscular volume of, 178, 179f transfusion of, 187-189, 190 during extracorporeal life support, 138 for anemia, 180 hematocrit and, 187, 188, 226, 2'26t in sickle cell disease, 181 in B-thalassemia, 182 in traumatic emergency, 271
Erythromycin for gastroesophageal reflux, 1126 for intestinal pseudo-obstruction, 1366, 1549 postoperative ileus and, 1361 Erythropoietin, 1430-1431, 1430t Eschar, 384, 385, 386, 389 excision of, 385, 389, 390-391 microorganisms in, 394 Escharotomy, 385, 386, 386f Exherichia coli human milk and, 202 in neonatal sepsis, 170, 172 ESLD. See End-stage liver disease (ESLD). Esmolol, in neonate, for supraventricular tachycardia, 151, 152t, 153 Esophageal achalasia, 1112-1 114, 1113f-1114f, 1125b. Seealso Esophageal dysmotility. gastric adenocarcinoma with, 518 Esophageal atresia. See also Tracheoesophageal fistula. aspiration associated with, 1015, 1057, 1058 associated anomalies with, 1054-1056, 1055t anorectal, 1569 classification of, 1052-1053, 1053f, 1053t, 1056, 1056t clinical presentation of, 10561057 complications after repair of, 1067-1071, 1068f, 1070f anastomotic stricture as, 1041-1042, 1041f, 1045, 1068, 1068f, 1069 after circular myotomy, 1064 suture material and, 1061 Barrett's esophagus as, 517, 1069 motor disturbances as, 1111 diagnosis of, 1056-1058,1057f-1058f vs. pyloric atresia, 1232 epidemiology of, 1054 gastroesophageal reflux in after repair, 1068, 1069, 1070, 1071, 1111, 1123 preoperative, 1058, 1111, 1123 historical background of, 1051-1053, 1052f operative repair of by replacement. See Esophageal replacement. esophagoscopy of anastomosis in, 1041-1042, 1041f-1042f thoracoscopic, 977, 1061, 1062f with distal fistula, 1059-1061, 1059f-1060f, 1062f with long gap, 1061, 1063-1065, 1063f-1064f, 1093, 1093t with upper-pouch fistula, 10661067 without fistula, 1065-1066 outcomes with, 1067 pathogenesis of, 1053-1054 preoperative treatment of, 1058, 1058f Esophageal dysmotility, 1107-1 114 after caustic injury, 1086 after esophageal atresia repair, 1070-1071 anatomical basis of, 1107-1 108 aspiration secondary to, 1015 evaluation of, 1038-1039, 1109-1 110, 1109f-1110f, 1125b overview of, 1107 physiological basis of, 1108-1 109 specific disorders of, 1110-1 114, 111If-1 114f Esophageal manometry, 1038-1039 after atresia repair, 1069 in motility disorders, 1109-1 110, 1109f-Illof, 1111, l l l l f achalasia as, 1113, 1113f-1114f gastroesophageal reflux and, 1124
Esophageal overdrive pacing, 153 Esophageal replacement, 1093-1 104 colonic inteiposition for, 1095-1097, 1096f, 1098t for caustic strictures, 1088-1089, 1089f, 1089t, 1097 for esophageal atresia, 1065 for achalasia, 1114 for atresia, 1065, 1093, 1093t gastric transposition for, 1065, 1101, 1102f, 1103-1104, 1103t gastric tube for, 1065, 1098, 1099f-1100f, 1100, llOOt ideal substitute for, 1094 indications for, 1093-1094 jejunal interposition for, 1065, 1100-1 101, IlOlt routes for positioning of, 1094-1095, 1095t summary of methods for, 1094,1094f, 1095t timing of, 1095 Esophageal stricture after transection, for varices, 1663 anastomotic, 1041-1042,1041f, 1045, 1061, 1064, 1068, 1068f, 1069 caustic, 1082, 1083, 1085, 1085f-1086f complications of, 1085-1087, 1087f, 1088t esophageal replacement for, 1088-1089, 1089f, 1089t, 1094, 1097, 1103 outcomes of, 1087-1089, 1089f, 1089t congenital, 1071-1072, 1072f gastroesophageal reflux and, 1123, 1126 peptic, 1093-1094 Esophageal transection, for varices, 1662-1663 Esophageal varices. SeeVarices. Esophagitis after esophageal replacement, 5 17 bleeding in, 1386 diagnosis of, 1124-1 125, 1125b dysmotility with, 1112, 1113 eosinophilic, 1112, 1112f, 1125b esophagoscopy in, 1039-1040, 1041 reflux. See also Gastroesophageal reflux disease (GERD). bile reflux in, 1039, 1123, 1124 biopsy in, 1124 esophagoscopy in, 1039-1040 factors affecting, 1122, 1123 medical therapy for, 1123, 1126 pH monitoring in, 1039, 1069, 1124 Esophagoesophagostomy, 1059-1061, 1060f, 1062f robotic, porcine, 55, 56t Esophagography, 1038-1039, 1041 of atresia, 1057, 1057f-1058f of caustic injury, 1084, 1085f of congenital stenosis, 1071, 1072f of esophageal achalasia, 1113, 1113f of perforation, 1048, 1049 of tracheoesophageal fistula, 1057, 1058f Esophagojejunostomy, Roux-en-Y, after failed fundoplication, 1133 Esophagoscopy, 1038, 1039-1045, 1040f-1042f in eosinophilic esophagitis, 1112, 1112f in gastroesophageal reflux, 1039-1040, 1040f, 1124, 1125b in motility disorders, 1109, 1113 of caustic injury, 1084, 1084t, 1086, 1088 Esophagus acid clearance from, 1122 anatomy of, 1108 autonomic innervation of, 1107, 1108 biopsy of, 1038, 1039, 1124, 1125b caustic injury to, 1082-1089 carcinoma secondary to, 517, 1086 Volume 1, pages 1-1140; Volume 2, pages 1141-21
Esophagus (Continued) clinical presentation of, 1083-1084 diagnosis of, 1040-1041, 1084t dysmotility secondary to, 1112 epidemiology of, 1082 esophageal replacement for, 1088-1089, 1089f, 1089t, 1094, 1097, 1103 management of, 1082, 1084-1086 outcomes of, 1086-1089, 1088t, 1089f, 1089t pathophysiology of, 1083 perforation in, 1047, 1083, 1084, 1087, 1087f, 1088 substances involved in, 1082-1083, 1083t, 1088t compression of, by vascular anomalies, 1978, 1979 congenital anomalies of. See also Esophageal atresia; Tracheoesophageal fistula. endoscopy of, 1041 laryngotracheoesophageal cleft as, 995-996, 1072-1074, 1073f-1074f true congenital stenosis as, 1071-1072, 1072f dilatation of, 1041-1042, 1045 for anastomotic stricture, 1068, 1071-1072 for caustic stricture, 1068, 1082, 1085-1086, 1087, 1087f, 1088 duplications associated with, 964-965, 965f-966f, 1392, 1393, 1393f embryology of, 1107-1108 evaluation of, 1038-1039. See alto Esophagoscopy. foreign body in, 1043, 1044, 1045 after atresia repair, 1068, 1069 congenital stenosis with, 1071 esophageal replacement for injury caused by, 1094 perforation by, 1047, 1050 motility of, 1108-1 109, 1122 methods for evaluation of, 1038-1039, 1109-1110, 1109f-1110f motor disorders of. See Esophageal dysmotility. obstruction of, by teratoma, 563, 564 perforation of, 1041, 1045, 1047-1050, 1048f-1049f caustic, 1047, 1083, 1084, 1087, 1087f, 1088 pseudodiverticulum of, 1048, 1050, 1064 rupture of, spontaneous, 1047, 1048-1049 stenosis of, congenital, 1071-1072, 1072f tissue-engineered, 25, 25f, 26 trauma to, 277,279,283-284,291, 1041, 1047-1050 epidemiology of, 275, 275t, 276 iatrogenic, 1041, 1045, 1047-1050, 1049f in birth injury, 405 mediastinitis secondary to, 1027, 1028 tumors of, 515, 517, 1069 after caustic injury, 517, 1086 esophageal replacement after resection of, 1094 ESRD (end-stage renal disease), transplantation for, 699, 700, 701, 702, 710, 711, 713 Estrogen exposure esophageal atresia and, 1054 hepatocellular adenoma secondary to, 498 Estrogen secretion by adrenocortical tumors, 635 by ovarian lesions, 594, 595t, 600, 604, 606, 609 ESWL (extracorporeal shock wave lithotripsy), 1748, 1751, 1752
xxii
INDEX
Ethanol, injection of in complex vascular malformation, 2129 in liver tumors, 51 1 in lymphatic malformation, 2107 Ethics, 257-262 decision making in, 258 of bariatric surgery, 260-261 of gene therapy, 18 of innovation and research, 258-260 of living donor lung transplantation, 776 of renal transplantation, 695 of separating conjoined twins, 2083-2084 of sex assignment surgery, 261-262 of stem cell use, in tissue engineering, 28 of treating congenital anomalies, 1260 principles of, in pediatric surgery, 257-258 Ethylenediaminetetraacetic acid, hypocalcemia associated with, 273 Etoposide, 424t. 428 Euglobulin lysis time, 184t Europe, pediatric surgery in, 7 Eustachian tube, 813, 815 branchial anomaly associated with, 868 cholesteatoma and, 816 embryology of, 863 Eustachian valve, 148 persistent, 2 124 Everolimus, 708 Ewing's family tumors, 652-653. See also Ewing's sarcoma; Primitive neuroectodermal tumors (PNETs). Ewing's sarcoma, 652-653 biopsy of, 655 chemotherapy for, 6 5 6 6 5 7 epidemiology of, 654, 664 genetics of, 415, 416, 417t, 419 lactate dehydrogenase and, 654 locations of, in relation to physis, 652f, 654 pulmonary metastases from, 645 radiation therapy for, 657 resection and reconstruction for, 662f, 664f staging of, 654, 655 EXIT (ex utero intrapartum treatment), 781, 82t, 85 for cenicofacial teratoma, 564 for cystic lung lesions, 956 Exomphalos. See Omphalocele; Umbilical hernia. Exostoses, multiple hereditary, 651 Expiratory reserve volume, 118, 118f Exposure, of trauma patient, 272 Exstrophy complex, 1842, 1843f urethral duplication in, 1904 Extracellular fluid (ECF) in fetus and neonate, 91-92, 93, 94, 95 third-space loss and, 226 Extracellular matrix bacterial adherence to, 158 in tissue engineering, 21, 22 of cardiac valves, 23 invasive cancer and, 418 Extracorporeal carbon dioxide removal, 126 Extracorporeal life support (ECLS), 126, 134-142. See also Extracorporeal membrane oxygenation (ECMO). circuit for, 136137, 136f, 137t, 142 complications of, 139-140 configurations for, 135-136, 136f contraindications to, relative, 135 cost of, 142 discontinuation of, 139 for primary pulmonary hypertension, 127 future of, 142 historical background of, 134 indications for, 134-135
Extracorporeal life support (ECLS) (Continued) operative procedures during, 138-139 patient management in, 137-139, 138f purpose of, 134 results of, 134, 140-142, 140t, 141t Extracorporeal Life Support Organization (ELSO), 134, 136,137, 140-141, 140t, 141t Extracorporeal membrane oxygenation (ECMO), 134. See also Extracorporeal life support (ECLS). after bone marrow transplantation, 779 contraindications to, intracranial hemorrhage as, 135 during resection of sacrococcygeal teratoma, 562 ex utero intrapartum initiation of, 85 for heart transplant candidate, 756, 757 in congenital diaphragmatic hernia, 83, 127, 767,9325 938,939,940, 942-944,945,945f in congestive heart failure, 151 liquid ventilation with, 127, 945, 945f lung transplant for patient on, 768 vascular complications of, 380 vs. high-frequency ventilation, 126, 141 Extracorporeal shock wave lithotripsy (ESWL), 1748, 1751, 1752 Extremity(ies). See also Amputation; Ischemia; Limb deficiency, congenital; Limb length inequality. tumors of, 20562058,2056t, 2057f. See also Bone tumors. nonrhabdomyosarcomatous sarcomas, 548-550,549f-550f rhabdomyosarcoma, 535-536, 549 vascular trauma to, 348, 351, 378-380, 379t venous thrombosis in, 2131-2132. See also Deep venous thrombosis (DVT). Extubation failure of, anterior cricoid split for, 992,992t laryngotracheal reconstruction and, 993 Eye (s). See also Visual abnormalities. endophthalmitis of, pyogenic liver abscess with, 1644 trauma to, 272 uveitis of, in ulcerative colitis, 1465 Eyelid, congenital drooping of, 2070-2071, 2070f
Facial anomalies. See Cleft anomalies; Craniofacial anomalies. Facial hypoplasia, torticollis as cause of, 878, 878f, 879 Facial nerve anatomy of, 813,814 parotid gland and, 835, 836, 837 surgical exposure and, 867-868,868f first branchial anomalies and, 862, 867-868, 868f neuroma of, 817 paralysis of during parotid surgery, 867 otitis media with, 815-816 temporal bone fracture with, 817, 817f Factor V Leiden mutations, 187, 2130 Factor VII, recombinant for biopsy-related hemorrhage, 442 for massive hemorrhage, 301 for variceal bleeding, 1658 Volume 1, pages 1-1140; Volume 2, pages 1141-21
Failure to thrive nutritional support for, 213-214 sodium depletion causing, 213 Falciform ligament, nonfixation of, 1362-1363, 1363f Fallopian tube in inguinal hernia, 1178-1 179, 1179f, 1186, 1187 in hermaphrodite, 1189 salpingitis of, acute, with perihepatitis, 1645 salpingo-oophorectomy of, robot-assisted, 54t Familial adenomatous polyposis, 421, 519, 1419-1422, 1420f hepatoblastoma in, 421, 502 Familial Mediterranean fever, 1477 Familial polyposis ileoanal pouch procedure in, 1421, 1472 ileostomy in, 1483, 148G1485, 1486 Famotidine for gastroesophageal reflux, 1126 for peptic ulcer disease, 1230 Fanconi's anemia, 179, 182 Farnesyl transferase inhibitors, 425 Fascia iliaca block, 246, 246f Fascial sling, for bladder outlet, 1831, 1831f Fasciotomy for snakebite, 353 in lower extremity trauma, 379 in upper extremity trauma, 351 of burned extremity, 386 in electrical burn, 396 FAST (focused abdominal sonography for trauma), 296297. 296f echocardiography in conjunction with, 286 gastrointestinal trauma and, 311, 312 renal trauma and, 319 Fasting euglycemia during, 225 preoperative, 223-224, 224t, 225 fluid deficit caused by, 225 Fat (s) body composition of, 195 in chyle, 1026 in enteral formulas, 200t, 201t, 202 for short-bowel syndrome, 212-213 intestinal adaptation and, 1370 in parenteral formulas, 204-206, 208 peroxidation of, 108 malabsorption of, 213 metabolism of carnitine and, 208 in neonate, 100, 101, 102-104, 103f postoperative, 106, 107-108 nutritional requirement for, 195, 197, 197f Fatty acids deficiencies of, in biliary atresia, 212 omega-3, for Crohn's disease, 1456 requirements for, 197, 197f Fawn tail, 2102 Fc receptors, 163, 164 FDG (fluorodeoxyglucose). See Positron emission tomography (PET). Fear. See Anxiety, patient. Fecal pigment, spectroscopy of, 1607 Fecalith, in appendicitis, 1502, 1504 Fecaloma, 1593, 1594 Feces. See also Defecation; Incontinence, fecal. formation of, 1568 in failure to thrive, 213 in short-bowel syndrome, 213 unabsorbed carbohydrates in, 203 Feet. See Foot (feet).
Female genital tract. See also Cloaca; Ovary(ies); Uterus; Vagina. embryology of, 1935-1936 Feminizing tumors, adrenocortical, 635 Femoral artery, iatrogenic injury to, 378f, 380 Femoral cutaneous nerve, lateral, fascia iliaca block and, 246, 246f Femoral deficiency, 2050-2051,2052f-2053f Femoral head, avascular necrosis of fracture-related, 345 hip dysplasia and, 2021, 2022, 2023 Femoral hernia, 1175, 1185, 1188 Femoral neck, fracture of, 345,345f Femoral nerve, fascia iliaca block and, 246, 246f Femoral shortening osteotomy, 2022, 2022f Femur. See (~1.50Femoral head; Femoral neck. fracture (s) of fixation of, 343f growth disturbances secondary to, 339, 341f in birth injury, 404 in child abuse, 403 reconstruction of, after tumor resection, 666,667 Fenretinide (4HPR), for neuroblastoma, 484 Fentanyl, 240, 241, 241t, 242 caudal, 248 during extracorporeal life support, 138-139 epidural infusion of, 248, 24% in neonate, operative stress and, 106, 211 in patient-controlled analgesia, 243, 243t inhalation anesthetics with, 229 transdermal, 242 Ferric gluconate, 207 Ferritin, serum, in neuroblastoma, 470,487 Ferrous sulfate, peptic ulcers associated with, 1228 Fetal alcohol syndrome neuroblastoma in, 467 rhabdomyosarcoma in, 525 Fetal hydantoin syndrome, 467 Fetal interventions. See also Prenatal diagnosis; Shunt, thoracoamniotic; Stem cells. fetoscopic, 78, 79-80, 79t, 81f, 83, 84, 85 tracheal occlusion as, 259 for congenital diaphragmatic hernia, 259, 939 for cystic mediastinal lesion, 960, 965 for enteric cyst, thoracic, 1393 for gastroschisis, 1161 for lung mass, 956, 956f for myelomeningocele, 83t, 84-85, 1991-1992, 1992f, 2062 for posterior urethral valves, 82t, 83, 1899-1900 for teratoma mediastinal, 565 sacrococcygeal, 82t, 85, 559 historical perspectives on, 6, 78, 79t management of mother and fetus in, 78-79 medical, 81-82, 82t open technique of, 78, 80f percutaneous, 78, 80,83,85,86 problems amenable to, 33, 78, 78t, 82-86, 82t-83t risks of, 79-80 robotic, in animal models, 48, 55, 56t Fetus. See also Embryology; Prenatal diagnosis. acid-base balance in, 95-96, 96t alpha fetoprotein in, 77, 555 biochemical screening and, 77 cardiovascular physiology of, 146, 147-148, 149f, 935 cell sampling from, 77, 78, 86 fluid balance in, 91-92, 93f
Fetus ( Continued) healing without scarring in, 86-87 hepatic tumors in hemangioendothelioma as, 496 mesenchymal hamartoma as, 497 imaging of with computed tomography, 77 with MRI, 37, 77 with ultrasound, 32-33, 77, 78 lung development in, 114117, 115f-116f medical treatment of, 81-82,82t. See also Fetal interventions. metabolism in, 97, 100, 101 neuroblastoma in, 467 renal function in, 93 selective reduction of, 82t, 85 small intestinal development in, 1370 stem cell transplantation in, 82, 83t, 86, 87 tissue engineering for, 28, 78 water content of, 91,98 Fetus in fetu, 558, 2080 intrahepatic, 499 retroperitoneal, 558, 558f Fiber, dietary constipation and, 1592, 1594 gastrointestinal polyps and, 1422 Fibrin casts, in inhalation injury, 395 Fibrin degradation products, 184t, 186 Fibrin sealant for adhesion prevention, 1360 for airway injury, 283, 283f for biopsy-related hemorrhage, 442 for lymph leak, 1411 for lymphangioma, 2139 in perianal Crohn's disease, 1458 Fibrinogen, 186 congenital deficiency or defect of, 185 Fibrinolysis, 186 Fibrinolytic therapy. See Thrombolytic (fibrinolytic) therapy. Fibroadenoma, of breast, 889-890,889f Fibroblast growth factor, basic (bFGF) hemangioma and, 2095,2104 Wilms' tumor and, 448, 460 Fibroblasts cytokines secreted by, 165 on synthetic dressing, 390 Fibroma (s) chondromyxoid, 652f in Gardner's syndrome, 1422 non-ossifying, 652, 652f, 654 ovarian, 593, 605-606 Fibromatosis(es), 542 Fibromuscular hyperplasia, 21 17-21 18, 21 19, 2119f, 2120-2121 Fibronectin aganglionosis and, 1525 bacterial adherence to, 158, 168 Fibroproliferative lung disease, pre-ECLS mechanical ventilation and, 135 Fibrosarcoma breast, 892 in Gardner's syndrome, 1422 infantile, 542, 543, 544t, 546 vs. lymphatic malformation, 2099 ovarian, 593, 615 pulmonary, 546 tracheal, 546 Fibrous dysplasia, 654 in Gardner's syndrome, 1422 resection of, 659 Fibrous hamartoma of infancy, 542 Fibular deficiency, 2051, 2053f, 2054, 2054t femoral deficiency with, 2050-2051 Fimbriae, 158 Iolume 1, pages 1-1 140; Volume 2, pages 1141-2
Fine-needle aspiration biopsy, 438 in lymphadenitis, 845, 846, 847 needle tract tumor recurrence and, 439 of thyroid nodule, 8 5 4 8 5 5 salivary gland, 837 Finger, tissue-engineered, 23, 23f, 82 Finite element models, in simulation, 61, 64 First and second branchial arch syndrome, 788-789. See also Branchial anomalies. FISH (fluorescence in situ hybridization), 419, 425,437,438 Fish oil, for Crohn's disease, 1456 Fistula(s) anal, 1597, 1598, 1598f anorectal anomalies with. See Anorectal malformations. arteriovenous. See Arteriovenous fistula. in Crohn's disease, 1454, 1456, 1457, 1458 neck. See Neck, cysts and sinuses of. omphaloileal, 1304, 1307f, 1310-131 1, 1311f superior rresical, 1842, 1843f, 1846 thoracic duct, 1026, 1027 urethrocutaneous, 1890f, 1894, 1894f Fitz-Hugh-Curtis syndrome, 1645 Five Ps in compartment syndrome, 344 in ischemia, 348 FK-506. See Tacrolimus. Flail chest, 269, 277, 279 in cerebrocostomandibular syndrome, 918 Flap procedures, for ureteropelvic junction obstruction, 1734, 1734f-1735f, 1735 Flap tissue transfer, 2063 Flap valve, 1797, 1797f, 1832, 1832f. See also Mitrofanoff procedure. Flatfoot deformity, 2024 Flavopiridol, 425 Fletcher factor, deficiency of, 185-186 Flexor digitorum, test of, 350, 351f Florida pouch, 1826 Flow cytometry, 415, 437 Fluid balance in fetus, 91-92, 93f in neonate, 91-96,94t, 96t preoperative fasting and, 225 third-space loss and, 226 Fluid management or resuscitation for burn patient, 385,386389, 388t with chemical burn, 395 with inhalation injury, 395 for critically ill infants, 225 for pheochromocytoma patient, 632 for premature infants, =5 for renal transplant patient, 704, 705, 706 for sepsis or SIRS, 17'2 for trauma, 271-272 to brain, 356, 363, 364, 364t, 365 in gastrointestinal hemorrhage, 1384 in hypertrophic pyloric stenosis, 1218 in short-bowel syndrome, 1372, 1373 intraoperative, 225-226 maintenance, 196, 225 parenteral nutrition and, 206 preoperative restriction in, 223-224, 224t, 225 Fluorescence in situ hybridization (FISH), 419, 425,437,438 Fluorodeoxyglucose (FDG). See Positron emission tomography (PET). &Fluorodopamine, 630 5-Fluorouracil, 423t, 428 Focal brain injury, 357-358,358f-359f, 366
xxiv
INDEX
Focal nodular hyperplasia (FNH), 495, 498-499, 499f Focal segmental glomerular sclerosis (FSGS), 699, 700, 701, 710, 711 Foley Y-V-plasty, 1734f, 1735 Folic acid, 1250 neuroblastoma and, 487 supplementation of after bariatric surgery, 1250 during pregnancy, 805, 1808,1988,1990 Follicular cysts, ovarian, 600-601, 600f, 602 Fontan procedure, 1975, 1977-1978, 1978f Foot (feet) ablation of, 2051, 2054 bone tumor in, 666 congenital anomalies of, 2023-2025, 2023f-2024f puncture of, with osteomyelitis, 2042, 2043f Football sign, of pneumoperitoneum, 1437 Foramen cecum, 850,865,866f Foramen ovale, 120, 148, 149f closure of, 148, 935 patent in congenital diaphragmatic hernia, 148 in neonate referred for cardiac transplant, 756 Forearm, reconstruction of, after tumor resection, 665 Foregut cyst duplication. See Duplication(s), alimentary tract, foregut. in floor of mouth, 826 Foreign body airway abscess secondary to, 1015 bronchiectasis secondary to, 1013, 1014 bronchoscopic removal of, 974,975-976, 975f, 977, 1012, 1014, 1015 pneumonia caused by, 1011, 1012 esophageal. See Esophagus, foreign body in. in appendix, 1502 in Meckel's diverticulum, 1311 intestinal obstruction caused by, 1364 nasal, 821 soft tissue injury caused by, 351, 352 Foreskin phimosis of, 1905 preservation of, in hypospadias repair, 1884, 1885f Formula(s) enteral, 200t, 201t, 202-203 for burn patients, 393 hyperosmolar, 1428-1429 hypoallergenic, 1125, 1372 intestinal flora and, 1433 necrotizing enterocolitis and, 202, 1428-1429,1432, 1433,1434, 1435, 1439, 1444, 1445 parenteral, 204-206 low-fat, 1410 Fourth ventricle area postrema of, 672 trapping of, 2001-2002 tumors in, 674, 675, 675f Fowler-Stephens orchidopexy, 1203 in prune-belly syndrome, 1785 Fractionated radiosurgery, 4 4 4 5 , 46 Fractionated radiotherapy, 44, 4 6 4 7 , 429 Fracture (s). See also Musculoskeletal trauma. birth injury with, 404 child abuse with, 347, 401t, 402-403 rib fractures in, 278, 279 deformities secondary to, 339, 341f, 342 evaluation of, 339, 341-342, 341f physical findings in, 349
Fracture(s) (Continued) femoral neck, 345, 345f growth disturbances secondary to, 339, 342, 344 hand, 349-350,351-352 healing of, 338-339, 340f-341f, 342 lymphangiectasia as cause of, 2140 management of definitive, 342, 342f-343f, 344 immediate, 342 mechanics of, 337 nasal, 820 open, 344 of hand, 349-350 pelvic, urinary tract injuries with, 318, 327, 328, 328f, 329, 330-331 periosteum and, 337, 338, 339f, 342, 345 physeal, 337-338, 339, 339f imaging of, 341f, 342 management of, 342,343f, 344 premature closure caused by, 345 rib. See Rib(s), fracture of. skull, brain injury with, 357, 358, 358f-359f, 363,364 spinal, 345-346, 346f temporal bone, 816817, 817f tumor-related, 650-651, 651f atjoint, 652 telangiectatic osteogenic sarcoma with, 652 through osteogenic sarcoma, 656 types of, 337, 338f unicameral bone cyst with, 651, 651f, 658 vascular trauma with, 342, 344, 345 in extremities, 378-380, 379t Frank-Starling relation, 147, 147f FRC. See Functional residual capacity (FRC). Free flaps, 352 Free radicals. See Oxygen free radicals. Fresh frozen plasma citrate in, hypocalcemia caused by, 227 during extracorporeal life support, 138 for disseminated intravascular coagulation, 186 for head trauma patient, with coagulopathy, 274 for massive blood loss, 226 for neonatal sepsis, 173 Fryns' syndrome, 1161 FSGS (focal segmental glomerular sclerosis), 699, 700, 701, 710, 711 Functional residual capacity (FRC) , 118, 118f, 119 in congenital diaphragmatic hernia, 938 low, in children, 276 mechanical ventilation and, 125, 128 Fundoplication, 1127-1 130, 1127f-1130f after esophageal repair for achalasia, 1114 for atresia, 1065, 1069, 1111 for congenital stenosis, 1072 complications of, 1133 gastrostomy with, 199, 1131 laparoscopic, 1127, 1128-1 130, 1129f-113Of, 1133 outcomes of, 1133 pyloroplasty and, 1130, 1133 robot-assisted, 53, 54t Fungal infection catheter-related, 210 hepatic, 1644 in necrotizing enterocolitis, 1435-1436, 1438 in transplant patient bone marrow, 781 heart, 761
Fungal infection (Continued) liver, 737, 739, 740t lung, 775 mediastinal, 1028 of burns, 389, 390, 394 pulmonary bronchiectasis and, 1013 in cancer patient, 1006-1007, 1006f in HIV-infected patient, 1010 sinusitis as, 819 Ft~rlowpalate repair, 809, 810f Furosemide. See also Diuretic renography. for heart failure, in neonate, 148, 150t Fusion genes and proteins, 415, 416, 419,427 fine-needle aspiration biopsy and, 438
Gabexate mesylate, 1673 Galactorrhea, 888, 888f juvenile hypothyroidism with, 601 Galactosemia, soy formulas in, 200t, 202 Galeazzi's sign, 2019 Gallbladder. See also Cholecystectomy; Cholecystitis; Cholelithiasis. absent, 1237 hydrops of, 1636, 21 15 polyps of, 1636-1637 Gallium 67 scan, in non-Hodgkin's lymphoma, 585 Gallstones. See Cholelithiasis. Gamma cell tumor, 1685 Gamma globulin for neonatal sepsis, 173 prophylactic, for low-birth-weight infants, 173 Gamma Knife, 45, 45f Ganciclovir after heart transplant, 762 after intestinal transplant, 750, 751 after lung transplant, 775 for cytomegalovirus esophagitis, 1386 Gangliocytoma, 671 Ganglioglioma, 671, 677, 677f Ganglion cell tumors, of brain, 671 Ganglion cells in neuroblastoma, 472, 473 intestinal. See also Aganglionosis; Hirschsprung's disease; Intestinal neuronal dysplasia. staining of, 1562, 1562f-1563f stem cells for, 1526 Ganglioneuroblastoma diarrhea associated with, 469, 486 horseshoe kidney with, 1719 neuroblastoma maturing to, 473 pathology and histology of, 472, 472t, 473,473f Ganglioneuroma diarrhea associated with, 469,486 neuroblastoma maturing to, 468,473,483,487 pathology and histology of, 472, 472t, 473,473f Gangrene. See also Ischemic necrosis, gastrointestinal. extremity amputation secondary to, 2058 arterial thrombosis and, 21 15, 21 16 intestinal adhesive obstruction with, 1359, 1360 appendicitis with, 1502 intussusception with, 1314f, 1317, 1333 necrotizing enterocolitis with, 1439, 1440 umbilical, 1146 vasospasm causing, 380, 381, 2121
Volume 1, pages 1-1140; Volume 2, pages 1141-2146.
GANT (gastrointestinal autonomic nerve tumor), 516 GAP (glans approximation procedure), 1880, 1882, 1883f Gardner's syndrome, 519, 1420, 1422 Gartner's duct cyst, 1902-1903, 1950-1951 Gas exchange, pulmonary, 120-121, 121f Gastrectomy, partial for spontaneous perforation, 1236 for stress ulcers, 1231-1232 Gastric. See also Stomach. Gastric acid. See also pH, esophageal monitoring of. gastroesophageal reflux and, 1123,1126 hypersecretion of, after massive enterectomy, 1372, 1373 in preterm infant, 1226, 1428, 1433 ulcers and, 1225, 1225t, 12261228, 1229, 1230, 1231 Gastric band, laparoscopic adjustable, 260, 1242-1243, 1248, 1248t, 1250 Gastric cancer. See Stomach, tumors of. Gastric dilatation, in spinal injury, 369 Gastric duplication, 1391, 1393-1394, 1678 Gastric emptying gastroesophageal reflux and, 1123, 1124 inhalant anesthetics and, 1361 prokinetic agents and, 1126 pyloroplasty and, 1130, 1133 Gastric emptying study before enteral feeding, 199 with suspected gastroesophageal reflux, 1124 Gastric mucosa, ectopic, 1307-1308, 1308f, 138G1387 in duplications, 1308, 1387,1389,1390, 1391, 1392, 1393, 1394, 1395,1396, 1678 Gastric outlet obstruction. See also Pyloric stenosis, hypertrophic. by foreign body, 1364 congenital, 1232-1234, 1232f-1233f, 1232t duplication presenting as, 1391, 1394 in peptic ulcer disease, 1230 Gastric perforation, spontaneous, in newborn, 1235-1236, 1236f Gastric transposition, for esophageal replacement, 1065, 1101, 1102f, 1103-1104, 1103t Gastric tube. See also Nasogastric tube. esophageal injury caused by, 405 in trauma patient, 272 Gastric tube esophagoplasty, 1065, 1098, 1099f-llOOf, 1100, ll00t Gastric ulcer. See Peptic ulcer disease. Gastric varices, 1654, 1657, 1659, 1662, 1663-1664. See also Varices. Gastrin, maternal, neonatal ulcers and, 1230 Gastrinoma, 1231, 1685 Gastritis bleeding in, 1385, 1386 causes of, 1225t, 1386 clinical presentation of, 12281 epidemiology of, 1226 Helzcobacter pylon' in, 1227, 1229 stress, in neonate, 1385 Gastrocystoplasty, 1797, 1827, 1827f before renal transplantation, 1835 complications of, 18361837 Gastroduodenoscopy with duodenal obstruction, 1263 with gastroesophageal reflux, 1039-1040,1040f Gastroduodenostomy, for gastric perforation, 1236 Gastroenteritis, acute, vs. appendicitis, 1505 Gastroesophageal junction, esophagoscopy of, 1038
Gastroesophageal reflux, normal physiologic, 1108-1109, 1124 Gastroesophageal reflux disease (GERD), 1120-1 134. See also Esophagitis; Fundoplication. after lung transplant, 772-773 bleeding in, 1386 clinical features of, 1121 congenital diaphragmatic hernia with, 142, 944,944f, 1123 congenital esophageal stenosis and, 1071, 1072 definition of, 1121 diagnosis of, 1120,1124-1125, 1125b esophagoscopy in, 1039-1040,1040f, 1124 manometry in, 1039, 1069, 1124 embryological basis of, 1120-1 121 enteral feeding and, 199, 203, 1130-1131 esophageal atresia and after repair, 1068, 1069, 1070, 1071, 1111 before repair, 1058, 1111 esophageal cancer secondary to, 517 esophageal dysmotility in, 1112 esophageal injury and caustic, 1086, 1088 peptic, 1093-1094 gastroschisis with, 1123, 1162 gastrostomy and, 199, 1130-1 131 historical perspective on, 1120 in disabled children, 214, 1121, 1126, 1127, 1131 laryngeal stenosis with, 991 laryngomalacia with, 829, 986 laryngotracheoesophageal cleft with, 995 microgastria with, 1237-1238 omphalocele with, 1162 pathophysiology of, 1121-1124, 1121f-1122f primary, 1112 respiratory complications of, 1124, 1125b aspiration as, 1015 esophageal pH monitoring and, 1039 robotic surgery for, 53 spasmodic croup in, 830 summary of, 1134 treatment of, 1125-1133 conservative, 1125-1 126 endoluminal, 1126 medical, 1126 surgical, 1126-1 133, 1127f-1132f Gastrografin. See Diatrizoate enema. Gastroileal pouch, 1799 Gastrointestinal autonomic nerve tumor (GANT), 516 Gastrointestinal hemorrhage. See Hemorrhage, gastrointestinal. Gastrointestinal motility. See Enteric nervous system; Esophageal dysmotility; Gastric emptying; Intestinal dysmotility; Intestinal pseudoobstruction. Gastrointestinal stromal tumors (GISTS), 515-517,5171 Gastrointestinal tumors, 515-522 carcinoid, 518, 518f clinical presentation of, 515 colorectal adenocarcinoma, 518-522, 5191, 520f-521f in familial adenomatous polyposis, 421 esophageal, 517 gastric, 515, 517-518 incidence of, 515 stromal, 515-517, 517t Gastrojejunal tube, 1484 dume 1, pages 1-1140; Volume 2, pages 1141-2
Gastrojejnnostomy for stress ulcers, 1231 intnssusception around tube in, 1322 Gastropexy, for congenital esophageal stenosis, 1072 Gastroplasty, vertical banded, 1248, 12481 Gastroplication, endoscopic, 1126 Gastroschisis, 1157, 1158, 1158f, 1158t, 1160, 1160f associated conditions with, 1162, 1162t cryptorchidism as, 1195 intestinal atresia as, 1270, 1271, 1277, 1281, 1282,1283 clinical features of, 1162 complications of, 1166, 1167 short-bowel syndrome as, 1369, 1369f gastroesophageal reflux associated with, 1123,1162 genetics of, 1161 incidence of, 1I62 obstetric delivery with, 1161 outcome of, 1 1 6 6 1167 prenatal diagnosis of, 1161 prenatal treatment of, 831, 86 rotational abnormality in, 1346 treatment of, 1165, 1164f, 1165-1 166,1166f enterostomy in, 1484f, 1486 umbilicoplasty after repair of, 1153, 1154f Gastroscope, flexible video, for esophagoscopy, 1043-1 044 Gastrostomy, 199 endoscopic, 199, 1042-1043 gastric perforation in placement of, 1236 gastroesophageal reflux and, 199, 1130-1131 in cricopharyngeal disorders, 1110 in esophageal atresia, 1061, 1065 in short-bowel syndrome, 1372 intnssnsception around tube in, 1322 robot-assisted, 53 techniques of, 1131-1133,1131f-1132f, 1480t Gaucher's disease, 1693, 1697 GD2 ganglioside, in neuroblastoma, 427, 474, 485 GDNF (glial cell line-derived neurotrophic factor), 1521-1522, 1522f, 1523t, 1524,1525, 1705 Gefitinib (Iressa), 425 Gemcitabine, 428 Gene amplification, 417, 419, 420t, 426 Gene chips, 40 Gene expression radiolabeled probes of, 38 RNA microarrays and, 419-420 Gene therapy, 15-18, 16f, 17t anticancer, 427 for hepatocellular carcinoma, 510 with angiogenesis inhibitors, 475 fetal, 82 for cystic fibrosis, 1011 for Hirschsprung's disease, 1526 liver shortage and, 740 Genetic counseling, 1 4 1 5 about cleft lip and palate, 806, 806t about Hirschsprung's disease, 1523 Genetic testing cancer and, 421 guidelines for, 594 prenatal, 1 4 1 5 , 78 Genetics. See also Cancer, molecular biology of. molecular, 11-15, 12f, 13t of inflammatory response, 166, 169 of obesity, 1243 Genioplasty, osseous, 789, 790f, 800
xxvi
INDEX
Genitalia ambiguous. See also Intersex abnormalities; Sex assignment. hypospadias with, 1870, 1894, 1919 burns to, 403 lymphedema of, 2144 trauma to, 312, 331, 404 Genitourinary anomalies. See also Bladder exstrophy; Cloaca1 exstrophy; Duplication (s), genitourinary; Intersex abnormalities; Urethra, anomalies of. anorectal malformations with, 1567 imperforate anus as, 1822, 1823f, 1824 hindgut duplications associated with, 1396 rhabdomyosarcoma with, 524 sacrococcygeal teratoma with, 557, 559 urinary tract infection and, 1742 Wilms' tumor with, 446 Genitourinary trauma, 312, 317-331 anatomic considerations in, 317-318, 327 clinical features of, 318 diagnostic evaluation of, 318-320 epidemiology of, 317 grading of, 320, 321, 321f, 321t, 323, 325, 329,330 iatrogenic, 317, 326, 327, 328, 329, 331 in child abuse, 312, 401t, 404 mechanisms of injury in, 317 to bladder, 318,319-320,321t, 327-329,328f to bladder neck, 331 to external genitalia, 312, 331, 404 to kidney. See Kidney, trauma to. to ureter, 320, 321t, 326327 to urethra, 312, 318, 320, 321t, 329-331, 329f, 1901-1902 Genitourinary tumors. See also specific organ or tumor type.
rhabdomyosarcoma as, 532-534 Genomic imprinting, 446, 447 GERD. See Gastroesophageal reflux disease (GERD). Germ cell tumors biologic markers of, 555-556 cytogenetics of, 556557, 596 embryology of, 554 extragonadal. See also Teratoma. choriocarcinoma as, 568 cytogenetics of, 557 embryonal carcinoma as, 567 future perspectives on, 569 germinoma as, 563,567-568 gonadoblastoma as, 568 mediastinal, 557, 565, 567, 568, 959, 960t, 961,96lf, 962-963 mixed, 567,568-569 pineal. Seepineal gland, tumors in region of. polyembryoma as, 568 prognosis of, 554 staging of, 555, 555t treatment for, overview of, 569 yolk sac tumor as, 559, 561, 562, 567 histologic types of, 55+555 ovarian. See Ovarian tumors, germ cell. overview of, 554 risk stratification of, 569 sites of, 554 testicular. See Testicular tumors. Germ cells, cryptorchidism and, 1198 Germinoma, 567 extragonadal, 567-568 intracranial, 556, 563, 678 ovarian, 567, 607, 608f. See also Dysgerminoma. testicular, 567. See also Seminoma.
Gershoni-Baruch syndrome, 1160 Gestational age, 89,90, 90f-9lf. See also Birth weight. necrotizing enterocolitis and, 1428 neonatal mortality and, 90, 92f total body water and, 92 GFR (glomerular filtration rate) in fetus, 93 in neonate, 93, 94 Giant cell rich osteogenic sarcoma, 652 Giant cell tumor, of bone, 652,653,654,659 Giantcell arteritis, 21 17 Gingivostomatitis, herpetic, 822 GISTS (gastrointestinal stromal tumors), 515-517,517t Glans approximation procedure (GAP), 1880, 1882, 1883f Glansplasty, meatal advancement (MAGPI), 1880-1882, 1881f-1882f Glanzmann's thrombasthenia, 183, 190 Glasgow Coma Scale, in traumatic brain injury, 362, 367 Glaucoma, in Sturge-Weber syndrome, 2098 Gleevec. See ST1571 (Gleevec). Glenn anastomosis, bidirectional, 1977 Glial cell line-derived neurotrophic factor (GDNF), 1521-1522, 1522f, 1523t, 1524,1525,1705 Glioblastoma, 678 in Turcot's syndrome, 1422 Glioma, 671 brainstem, 673, 675f, 676 gefitinib for, 425 nasal, 820 Gliomatosis peritonei, ovarian teratoma with, 610,611 Glomangiomatosis, 2100 Glomerular filtration rate (GFR) in fetus, 93 in neonate, 93, 94 Glomus tympanicum tumor, 817 Glomuvenous malformations, familial, 2100 Glossoptosis, 803, 812, 825 glossopexy for, 1070 Glottis, laryngoscopic evaluation of, 973,983 Glucagon in burn patients, 391-392 in perinatal period, 100, 101, 103 in reduction of intussusception, 1330 postoperative stress and, 107 small left colon syndrome and, 1498 Glucagon-like peptide-2, for short-bowel syndrome, 1374 Glucocorticoids. See also Corticosteroid therapy; Cortisol. adrenal synthesis of, 628, 629 inflammation and, 166 insufficiency of, 636637 Gluconeogenesis, 197 cortisol and, 629 in neonate, 100, 101, 102, 103 postoperative, 106, 107 Glucose (dextrose) in fluid therapy, 225 for burn patient, 387, 388t in parenteral formulas, 204, 206, 208,210 intraoperative administration of, 225 nutritional requirement for, 196197 Glucose intolerance, obesity and, 1246 Glucose metabolism in neonate, 100-102, lOlt postoperative, 106, 107, 107f, 108 postoperative, 106, 107, 107f )lume 1, pages 1-1140; Volume 2, pages 1141-2146.
Glucose polymer, in enteral formulas, 202 Glutamine for short-bowel syndrome, 1374 in parenteral feeding, of neonates, 104, 196 y-Glutamyl transpeptidase, 1606 Glutathione peroxidase, 199 Glyceryl trinitrate, for anal fissures, 1597 Glycogen, storage of, 97 in neonate, 197 in perinatal period, 100-101 Glycogen storage disease, type I focal nodular hyperplasia in, 495 hepatocellular adenoma in, 495, 498 Glycogenolysis, 197 in neonate, 100-101 postoperative, 107 Glycopyrrolate, to prevent sialorrhea, with ketamine, 239 Glypican-3, in Wilms' tumor, 448 Goiter, 850, 851-853, 852t Goldenhar's syndrome, esophageal dysmotility in, 1112 Goldie-Coldman model, 422, 657 Goldstein test, 1181 Gonadal dysgenesis, 1912f, 1915t, 1917 diagnosis of, 1918t, 1919t, 1920 gonadoblastoma in, 568, 1920 ovarian, 612-613 testicular, 624 mixed, 1912f, 1915t, 1917, 1921, 1922, 1930 diagnosis of, 1918t, 1920 gonadectomy in, 624, 1920 Gonadoblastoma, 1920 extragonadal, 568 ovarian, 568,595t, 612-613 robot-assisted oophorectomy for, 53 testicular, 624 Gonadotropins. See also Human chorionic gonadotropin (hCG). cryptorchidism and, 1197 ovarian tumors and, 595t, 607 Gonococcal infection as arthritis, 2040, 2044 as perihepatitis, 1645 as peritonitis, 1477 GorhamStout syndrome, 2099 Graft-versus-host-disease bone marrow transplantation with, 431, 432, 779, 780, 782 chronic, 782 cytomegalovirus infection associated with, 1007 immunological basis of, 685, 689, 692 lymphoproliferative disease associated with, 584 transfusion-related, 188, 189, 190, 782 Granulocyte colony-stimulating factor for bone marrow transplant patient, 781 with typhlitis, 780 for hypersplenism, 1664 with chemotherapy, for lymphoma, 588 Granulocytic sarcoma, ovarian, 615 Granuloma(s) eosinophilic, temporal bone involvement of, 817 in chronic granulomatous disease, liver abscesses with, 1643, 1643f in Crohn's disease, 1454, 1455 pulmonary plasma cell, 640-641 vs. metastasis, 441, 441f pyogenic, vs. hemangioma, 2097 suprastomal, with tracheotomy, 986 umbilical, 1143, 1146
Granulosa-theca cell tumors, 593, 594, 595t, 604-605,605f in Peutzjeghers syndrome, 1418 Graves' disease, 851, 852-854 Great vessels, anomalies of. See also Aorta; Ductus arteriosus. pulmonary slings, 1978-1980, 1978t, 1982-1983, 1983f, 1984 airway obstruction by, 997,998 transposition of great arteries, 151, 1973-1975, 1974f, 1976f-1977f vascular rings, 1978-1984, 19781, 1979f-1983f robot-assisted division of, 54t, 55 Greater saphenous vein cutdown of, in trauma patient, 269-270, 271f duplication of, varicosity and, 2130 Growth malnutrition and, 195 normal, 194 of premature infant, 90, 91f, 97, 194 Growth factor receptors, 413f, 414,415 Growth factors hypertrophic pyloric stenosis and, 1216 lung development and, 117 congenital diaphragmatic hernia and, 945 malignant transformation and, 414, 415 necrotizing enterocolitis and, 1430-1431, 1430t signal transduction and, 413, 413f Wilms' tumor and, 459-460 Growth failure, in Crohn's disease, 1454, 1456 Growth hormone for burn patients, 391, 392, 392f, 393 for renal transplant patients, 713 for short-bowel syndrome, 1374 Growth plate. See Physis. Growth retardation in ulcerative colitis, 1464, 1465, 1466 intrauterine (IUGR), 89-90 hypoglycemia and, lOlt Gunshot wounds, to brain, 361 Gustilo classification, of open fractures, 344 Gynecomastia, 892,892f, 2066,2068-2070, 2069f adrenocortical tumors with, 635 Sertoli cell tumor with, 622, 624
HAART (highly active antiretroviral therapy), 1008, 1009 Haemophilus injluenzae infection, 1002 type B (HIB), 1002 acute lymphadenitis in, 845 osteomyelitis in, 2033-2034, 2037, 2038, 2038t septic arthritis in, 2040, 2041t supraglottitis in, 830-831 Haemophilus parainjluenzae peritonitis, 1477 Hageman factor, deficiency of, 185-186 Hairy nevus, giant, 2063-2064,2065f Halothane, 222, 222t, 227, 227t, 228, 228f, 229 gastric emptymg and, 1361 Hamartoma(s) breast, 886,891 fibrous, of infancy, 542 gastric polyps as, 1421 hepatic in tuberous sclerosis, 495, 498 mesenchymal, 495,496,497-498,497f-498f malignant tr-ansformation of, 505 vs. nonparasitic cyst, 499
Hamartoma(s) (Continued) in tuberous sclerosis, 1709 intestinal polyps as, 1364, 1414, 1415 in Peutzjeghers syndrome, 1417, 1418, 1418f lipofibromatous, of median nerve, 2075 lymphangioma as, 2137 pancreatic, 1684 pulmonary, 641 splenic, 1697 umbilical, 1149 Hand(s) bone tumor in, 665 congenital anomalies of, 2071, 2073-2075, 2073t, 2074f in Poland's syndrome, 907,908f, 2071, 2074 embryology of, 2071 ischemic necrosis of, radial artery catheter causing, 123 trauma to, 348-352,349f-351f Hand-foot syndromes, 181 Hand-foot-and-mouth disease, 822 Handicapped children. See Disabled children. Haptic feedback, 48,60-61, 6667,66f, 68 Harlequin eye sign, in coronal synostosis, 794 Harmonic scalpel, 41 for liver resection, 507, 508 for splenectomy, 1694, 1695-1696, 1695f partial, 1697 for splenic cyst excision, 1692-1693 Harmonic ultrasound imaging, 34, 34f Harrison's grooves, 904 Hartmann's pouch, for Crohn's disease, 1457-1458, 1459 Hashimoto's thyroiditis, 852 hCG. See Human chorionic gonadotropin (hCG). Head and neck masses. See also Neck. fine-needle aspiration biopsy of, 438 rhabdomyosarcoma as, 531-532 teratoma as, 563-565, 563f-564f Head circumference, normal, 195 Head trauma. See also Brain injury, traumatic; Skull fracture. early complications of, 365-367 epidemiology of, 357 outcomes with, 367 resuscitation in, 269 temporal bone fracture in, 81G817, 817f Hearing loss, 814-815,816, 817 Heart. See also Cardiac entries; Pericardial entries; Valves, cardiac. bacterial endocarditis of, 21 15-21 16, 21 16f ectopic. See Ectopia cordis. imaging of, ultrasound, contrast-enhanced, 33-34, 34f trauma to, 279, 285-287, 286f-287f epidemiology of, 275, 275t, 276, 292 initial resuscitation with, 277 penetrating, 291 presentation of, 276,277, 278 tumors of rhabdomyosarcoma as, 535 teratoma as, 557,558,565-566 Heart block, in neonate, 151 Heart disease, congenital. See also Great vessels, anomalies of; Valvular disorders, cardiac. associated anomalies with asplenia as, 1693 chest wall deformities as, 895, 904905 diaphragmatic hernia as, 932,933 esophageal atresia as, 1055 imperforate anus as, 1567 olume 1, pages 1-1 140; Volume 2, pages 1141-21
Heart disease (Contznued) atrial septal defect, 1 9 6 4 1966, 1964f-1966f atrioventricular septal defect, 153, 1968-1971, 1969f-1971f congestive heart failure in, 148, 150t, 151 heart block in, 151 hypoplastic left heart syndrome, 1975, 1977-1978, 1977f-197% in utero tolerance of, 148 neonatal management of, 153 neuroblastoma in situ in, 467 prenatal correction of, 82t, 85-86 tetralogy of Fallot, 153, 1971-1973, 1972f-1974f transplantation for heart, 754-755, 755f, 762,763 lung, 766767 ventricular septal defect, 153, 19661968, 1967f-1968f in tetralogy of Fallot, 1971, 197'2, 1972f-1973f omphalocele with, 1163 with transposition of great arteries, 1975 Heart failure. See Congestive heart failure; Right-sided heart failure. Heart rate, 146 in trauma patient, 267 Heart transplantation, 754-763 ABO-incompatihle, 757 combined with lung transplant, 767 complications of, 761-762, 761t mediastinitis as, 1028 contraindications to, 756 donor evaluation for, 757 extracorporeal life support as bridge to, 141, 756, 757 for hypoplastic left heart syndrome, 153, 754-755, 756, 757, 758, 759f, 762 for teratoma, resectable, 566 history of, 685, 686t, 688-689, 754, 754f immu~osuppressionfor, 754, 760-761,76Ot, 761f indications for, 754755, 755f operative techniques in, 757-760, 758f-759f organ allocation for, 757 organ procurement for, 757 postoperative management in, 760 preoperative evaluation for, 755-756, 756t preoperative management in, 75G757 results of, 762-763, 762f ventricular assist device as bridge to, 151, 756, 757 Heartburn. See Gastroesophageal reflux disease (GERD). Height, normal growth and, 195 Heineke-Mikulicz strictureplasty, 1457, 1457f Helicobacter pylori infection diagnosis of, 1229 gastroesophageaI reflux disease and, I123 in heterotopic mucosa, in Meckel's diverticulum, 1307 peptic ulcer disease and, 1226, 1227, 1227t, 1228, 1229, 1386 primary gastritis and, 1386 Heliox, 828 Helium dilution test, 118 Heller myotomy, 1114 robot-assisted, 53, 54t Hemagglutinin, 158 Hemangioendothelioma infantile hepatic, 495, 496497, 496f, 2112 transplantation for, 733 kaposiform, 2094, 2097-2098, 2097f, 2105 salivary gland, 839
xxviii
INDEX
Hemangioma (Continued) associated anomalies with, 2096, 2102 arteriovenous malformation as, 21 13 breast, 888-889, 889f cavernous, 2094,2096, 2099 clinical features of, 209S2097, 2096f-2097f congenital noninvoluting, 2097 rapidly involuting, 2097, 2097f, 2102, 2106 cutaneous hepatic hemangioendothelioma with, 495,496 subglottic hemangioma with, 830, 994 differential diagnosis of, 2097, 2102 gastrointestinal bleeding caused by, 1387 obstruction caused by, 1364 head and neck, 826,2096f, 2104 bifid sternum with, 914 hepatic, 497, 2102, 2105f, 2106 focal nodular hyperplasia with, 498 in Maffucci's syndrome granulosa cell tumors with, 593 of hand, 652 management of, 2103-2106,2104f-2106f with corticosteroids, 2104, 2104f for subglottic lesion, 994, 995 for vaginal lesion, 1951 with interferon-a, 21042105 for mediastinal lesion, 966 for subglottic and tracheal lesions, 994, 995 for vaginal lesion, 1951 mediastinal, 966 ovarian, 614 pathogenesis of, 2095 radiologic characteristics of, 2103 salivary gland, 835, 836, 836f, 838-839 splenic, 1697 subglottic, 828,830,830f, 99&995,994f, 2103 tracheal, 994995 ulceration of, 2103 vaginal, 1951 visceral, 2102 Hemangiopericytoma, 542, 546 Hematemesis in child, 1387 in infant, 1386 in newborn, 13841385 varices as cause of, 16541655, 1657 Hematocele, 331 Hematochezia, 1386 anal fissure with, 1596, 1597 eosinophilic proctocolitis with, 1599 rectal ulcer with, 1599 Hematocrit, blood products and, 187, 188, 226, 226t Hematoma bladder, 328, 329 duodenal, 3 0 4 , 3 0 4 ~305f, 306,306t secondary to biopsy, 780 gastrointestinal, 310 hepatic abscess secondary to, 1643 in birth trauma, 405, 405f iatrogenic, femoral catheterization and, 380 in birth injury, 404, 405, 405f in vascular injury, 377 intracranial, 266, 272, 273, 357, 358, 359, 359f in birth injury, 405 in child abuse, 401 in "minor" injury, 365 surgery for, 364365, 365f nasal, septal, 820
Hematoma (Continued) penile, 331 secondary to nerve block, 246, 247 perinephric, 322 pulmonary, 281 renal, 323 retroperitoneal, 322, 323 scrotal, 331 upper extremity, 379 Hematoma block, for fracture reduction, of hand, 352 Hematopoietic growth factors, recombinant, for anemia, 179 Hematopoietic stem cell transplantation. See Stem cell transplantation. Hematuria evaluation of, multidetector computed tomography in, 35 in hemorrhagic cystitis, 781-782 urinary tract trauma with, 318-319, 320 renal, 319,320-321,323, 324 ureteral, 326 urethral, 329 Hematuria-dysuria syndrome, 1797, 1800, 1836 Hemi-Fontan procedure, 1977, 1977f, 1978 Hemihypertrophy adrenocortical tumors with, 633 hepatoblastoma with, 502 vascular malformations with, 2101, 2101f, 2107-2108, 2112, 2114 Wilms' tumor with, 446, 449 Hemi-Kock pouch, 1833 Hemimelia, 2051f Heminephroureterectomy, robot-assisted, 53, 54t Hemisacrum, 1567, 1572 Hemiscrotectomy, orchiectomy with, for germ cell tumor, 623 Hemivagina(s), 1568, 1571, 1582, 1583, 1583f, 1585f Hemivertebra(e), 2027,2027f-2029f anorectal malformations with, 1567, 1569 in spondylothoracic dysplasia, 917, 918f neurenteric cyst with, 965 torticollis secondary to, 877 Hemoglobin fetal in Diamond-Blackfan anemia, 179 oxygen saturation and, 122 oxyhemoglobin dissociation curve and, I21 nitric oxide and, 161, 162 oxyhemoglobin dissociation curve and, 121, 121f Hemoglobin concentration, mixed venous oxygen saturation and, 122, 123 Hemoglobin saturation, 118t monitoring of, 121-123 Hemoglobinopathies. See Hemolytic anemias. Hemolymphangioma, 2138 Hemolysis during extracorporeal life support, 140 in transfusion reactions, 189 Hemolytic anemias, 181-182. See also Sickle cell disease; Spherocytosis, hereditary; Thalassemia(s). cholecystectomy in, 1635-1636, 1641 cholelithiasis in, 181, 182, 1635-1636, 1637, 1641,1642,1673,1693, 1698 splenectomy in. See Splenectomy, in hemolytic anemias. Hemolytic-uremic syndrome colonic stricture in, 1495 renal graft loss in, 71 1
Volume 1, pages 1-1 140; Volume 2, pages 1141-2146
Hernoperitoneum adrenal hemorrhage with, in neonate, 637 FAST sonography of, 297 Hemophilia, 185 gene therapy for, 18 trauma patient with, 274 Hemopneumothorax, 269,272 epidemiology of, 275t Hemoptysis, 1014, 1015f Hemorrhage. See also Hematoma; Vascular trauma. adrenal infection-related, 637 neonatal, 630, 637 after open biopsy, 442 anemia secondary to, 180-181 estimation of blood loss in, 226 extracorporeal life support with extracranial, 140 intracranial, 135, 136, 137, 139 gastrointestinal, 1383-1387 common causes of, 13841387, 1385t diagnostic algorithms for, 1383f-1384f esophagoscopy in, 1041 in blue rubber bleb nevus syndrome, 2103,2107 in necrotizing enterocolitis, 1435, 1439 in peptic ulcer disease, 1229, 1230, 1231 initial management of, 1383-1384 juvenile polyps with, 1387, 1415, 1416 lymphoid polyps with, 1419 Meckel's diverticulum with, 130S1309, 1308f-1309f portal hypertension with, 1654-1655, 1657, 1658. See also Varices. rectal. See Rectal bleeding. stress ulcers with, 1231 submucosal, 1364 vascular malformations with, 1598 hepatic during resection, 508 in birth injury, 405 in coagulation disorders, 183, 185-186, 185t in trauma patient, 272, 377 abdominal injury and, 299,300-302, 300f-301f, 301t brain injury and, 358-359, 358f-361f, 361, 365, 366 hand injury and, 348 renal injury and, 324 thoracic injury and, 280f, 281-282,291 intracranial. See also Intraventricular hemorrhage. brain tumor with, 672, 673, 679 in birth injury, 405 in child abuse, 401 intraperitoneal, ruptured hepatocellular adenoma with, 498 intraventricular as birth injury, 405 in premature infants, vitamin E and, 198 traumatic, 359, 360f, 361, 362 massive, recombinant factor VII for, 301 platelet transfusion for, 190 portal hypertension with, 1654-1656, 1657 pulmonary, 1014, 1015f after lung transplant, 772 in pulmonary vascular disease, 766 retinal, in child abuse, 361 Hemorrhagic cystitis, after bone marrow transplantation, 781-782 Hemorrhagic disease of the newborn, 1384 Hemorrhagic shock, nitric oxide synthase and, 169
INDEX Hemorrhoids, 1598-1599, 1599f in ulcerative colitis, 1465 Hemosiderosis, transfusional, 180 Hemostatic instruments, 40-41 Hemothorax, 269, 276, 277, 278, 280f, 281 epidemiology of, 275, 275t, 276 traumatic, 282 Henderson-Hasselbalch equation, 95, 118t, 121 HenochSchonlein purpura intussusception in, 1320, 1327-1328 renal graft loss in, 711 subrnucosal hemorrhage in, 1364 Heparin antithrombin I11 and, 187 during extracorporeal life support, 138, 139, 140 for disseminated intravascular coagulation, 186 for inhalation injury, 395 for pulmonary embolism, 2132 for venous thrombosis, 187 renal vein, 1754, 1754t in parenteral nutrition solution, 207 prophylactic for liver transplant patient, 737 for spinal injury patient, 370 Hepatic veno-occlusive disease, 431-432, 780-781,1654 Hepaticojejunostomy, robotic, porcine, 55, 56t Hepatitis bacterial, 1644 cirrhosis secondary to, 733 Hepatitis B hepatocellular carcinoma and, 503 transfusion-acquired, 189 Hepatitis C, transfusion-acquired, 189 Hepatobiliary scintigraphy. See Radionuclide studies, hepatobiliary. Hepatoblastoma, 502-511, 502t, 505f, 505t, 509f, 511t. See also Liver, tumors of. biopsy of, hemorrhage secondary to, 442 etiology of, 502 glypican9 in, 448 in Beckwith-Wiedemann syndrome, 449,502 in familial adenomatous polyposis, 421,502 laparoscopic visualization of, 440 transplantation for, 733 vs. hemangioendothelioma, 496 Hepatocellular adenoma, 495, 498 Hepatocellular ascites, 1407t, 1408f, 1409, 1409t Hepatocellular carcinoma, 502-51 1, 502t, 505t, 51 1t. See also Liver, tumors of. arising in hepatocellular adenoma, 498 transplantation for, 733 vs. focal nodular hyperplasia, 498 Hepatocytes injury to, portal hypertension caused by, 1652-1653,1653t necrosis of, in posthepatic portal hypertension, 1653-1654 tissue engineering with, 26-27 Hepatopulmonary syndrome, 1656 Herceptin. See Trastuzumab (Herceptin). Hermaphroditism, 1915t, 1917 diagnosis of, 1918t, 1920 inguinal contents of, 1188-1 189 management of, 1921, 1922, 1926, 1930
Hernia. See Abdominal wall, hernia of; Diaphragmatic hernia; Femoral hernia; Inguinal hernia; Internal hernia; Intestinal obstruction, hernias with; Parastomal hernia; Umbilical cord hernia; Umbilical hernia. Herniography, 1175, 1187 Herpangina, 822 Herpes simplex virus (HSV) as gene therapy vector, 17, 17t esophagitis caused by, 1386 gingivostomatitis caused by, 822 liver transplantation and, 740t Heterotaxia, intestinal malrotation in, 1346, 1348, 1350, 1354f High-frequency oscillatory ventilation (HFOV), 125,126,141 Highfrequency ventilation (HFV), 125-126 Hilar twist, for lung trauma, 277, 279 Hilgenreiner's line, 2020, 2020f Hill gastropexy, for congenital esophageal stenosis, 1072 Hinman syndrome, 1812-1813, 1812f Hip, developmental dysplasia of, 2018-2023, 2019f-2023f, 2020t Hirschspmng's disease, 1514-1547 acquired, 1530 animal models of, 1520,1526 appendicitis in, 1502, 1530 associated anomalies with, 1528 colonic atresia as, 1493, 1495, 1528 imperforate anus as, 1567 in Waardenburg's syndrome, 1522 neuronal dysplasia as, 1560, 1561 clinical presentation of, 1515 constipation in, 1593, 1594 diagnosis of, 1515-1519, 1516f-1518f differential diagnosis of, 1519, 1519t vs. idiopathic constipation, 1516f, 1519, 1549-1550, 1550t vs. intestinal neuronal dysplasia, 1562 vs. meconium ileus, 1293-1294, 1295f embryogenesis of, 1523-1526, 1524f-1525f enterocolitis of, 1515, 1516, 1516f, 1528-1530, 1529f-1530f colostomy in, 1533 in Down syndrome patients, 1528 recurrent, 1541-1542, 1543f, 1544, 1545, 1546 esophageal dysmotility in, 1112 genetic counseling and, 1523 genetics and molecular biology of, 13, 13t, 14, 1519-1523, 1519f-1522f, 1523t historical perspectives on, 4, 5, 1514, 1532, 1532f ileoanal pouch for, 1469 in adolescents and adults, 1515, 1530-1531 in premature infants, 1532 in small intestine, 1531, 1539-1540, 1542f-1543f incidence of, 1514 neuroblastoma associated with, 467 outcomes with, 1545-1547 pathology of, 1526-1527, 1526t in appendix, 1530, 1531 pathophysiology of, 1527-1528, 1527f postoperative stooling problems in, 1541-1542, 1543f, 1544 intestinal neuronal dysplasia with, 1561 quality of life in, 1547 rectal biopsy in, 1517-1519, 1517f-1518f, 1532-1533, 1533f after pull-through, 1542, 1543f segmental, 1530 Volume 1, pages 1-1 140; Volume 2, pages 1141-21
xxix
Hirschsprung's disease (Continued) small intestine, 1531, 1539-1540, 1542f-1543f stem cell research for, 1526 surgical techniques in, 1532-1544 anorectal myectomy, 1531, 1543-1544, 1544f-1545f colostomy, 1485, 1488, 1489f leveling, 1530, 1533 complications of, 1529, 1530, 1545-1547 Duhamel operation, 1532f, 1536, 1538, 1539, 1539f-154Of, 1542 complications of, 1546-1547 redo of, 1545f endorectal pull-through, 1534, 1535f-1537f, 1536 historically common, 1532, 1532f in extended small intestinal disease, 1539-1540, 1542f-1543f in right-sided disease, 1538, 1542f in total colonic disease, 1538-1539 rectal biopsy, 1517-1519, 1532-1533, 1533f redo pull-through, 1544, 1545f workup for, 1543f Swenson procedure, 1532, 1532f, 1538, 1540, 1541f complications of, 1546 redo of, 1545f total colonic, 1531-1532, 1531f genetics of, 1519-1520, 1519f intestinal transplant for, 1540 outcome with, 154G1547 pathology of, 1526t in appendix, 1530, 1531 surgical techniques in, 1538-1539 ultrashort, 1528, 1531, 1543-1544, 1544f-1545f Histamine, tissue injury and, 106 Histamine H2 receptor antagonists for gastroesophageal reflux, 1122, 1125b, 1126 for peptic ulcer disease, 1229, 1230 in parenteral nutrition solution, 207 in short-bowel syndrome, 1372, 1373 in Zollinger-Ellison syndrome, 1231 prophylactic, stress ulcers and, 1231 Histidine-tryptophan-ketoglutarate solution, 735 Histiocytic necrotizing lymphadenitis, 848 Histiocytosis X. See Langerhans cell histiocytosis. Histone deacetylase inhibitors, 426 Histoplasmosis bronchiectasis and, 1013 in HIV-infected patient, 1010 mediastinitis in, 1028 History of pediatric surgery, 3-10, 3f-5f, 8b, 9f-10f HIV. See Human immunodeficiency virus ( H N ) infection. HLA (human leukocyte antigen) bone marrow transplantation and, 685, 779 in cystic fibrosis, 12 organ transplantation and, 691,695,696 heart, 757 intestinal, 747 lung, 774, 776 pancreatic, 723 renal, 702, 703 Hodgkin's disease, 57.5-580. See also Lymphoma. clinical presentation of, 575-576, 576f cervical lymphadenopathy in, 833, 848 diagnosis of, 576, 576f, 577 vs. thyroglossal duct cyst, 870
Hodgkin's disease (Continued) epidemiology of, 575 histologic subtpes of, 576, 576f historical perspective on, 575 in mediastinum, 576, 576f, 577, 960t outcome with, 580 prognostic factors in, 580 splenectomy in, 577-578,579-580, 1697 staging of, 576-577, 577t complications of, 579 treatment of, 577-578,578t complications of, 575, 578-580 for recurrent disease, 580 for refractory disease, 580 osteogenic sarcoma secondary to, 653 Holt-Oram syndrome, 2073 Homeobox genes hypospadias and, 1876 intestinal neuronal dysplasia and, 1560 Homocysteine, thrombosis and, 187, 2130 Homovanillic acid, urinary, neuroblastoma and, 468,470,483, 487 Hormone-sensitive lipase, in neonate, 102, 103 Horner's syndrome brachial plexus injury with, 405 first rib fracture with, 279 neuroblastoma with, 468, 479 spinal cord injury with, 368 Horseshoe kidney, 171G1719, 1718f-1719f Wilms' tumor with, 457,458f Hox. See Homeobox genes. 4HPR (fenretinide), for neuroblastoma, 484 H-probe, 58 HPV. See Human papillomavirus (HPV). HSV. See Herpes simplex virus (HSV). Human chorionic gonadotropin (hCG), cryptorchidism and, 1197, 1200 0-Human chorionic gonadotropin (PhCG) , from germ cell tumors, 555, 556, 595 choriocarcinoma as, 568,609,622 pineal, 673, 678 polyembryoma as, 568, 609 precocious pseudopuberty and, 594 seminoma as, 622 teratoma as intracranial, 563 mediastinal, 565, 962 ovarian, 566 sacrococcygeal, 560 testicular, 567 Human immunodeficiency virus (HIV) infection. See also Acquired immunodeficiency syndrome (AIDS). acute, 832 blood transfusion and, 189 Candida in, colonic obstruction caused by, 1495 Epstein-Barr virus infection in, 837 ieiomyosarcoma in, 543 lung infections in, 1008-1010, 1009f lymphadenopathy in, 848 salivary gland cysts in, 838 Human leukocyte antigen. See HLA (human leukocyte antigen). Human papillomavirus (HPV), papillomas caused by laryngeal, 831, 989-990, 989f perianal, 1599 pharyngeal, 826 Humerus, fracture of in birth injury, 404 in child abuse, 403 vascular injury in, 342
Hunter-Hurler syndrome, inguinal hernia in, 1188 Hiirthle cell carcinoma, 854 Hyaline membrane disease extracorporeal life support for, 140t high-frequency ventilation for, 126 Hyaluronan, Wilms' tumor and, 448,459-460 Hyaluronic acid, serum, in biliary atresia, 1611 Hyaluronic acid membrane, abdominal adhesions and, 1360 Hydatid disease hepatic, 1646, 1646f pulmonary, 1005,1005f Hydatid of Morgagni, 1205, 1206 Hydranencephaly, 1997,1997f Hydrocele abdominoscrotal, 1189 acute, 1189 testicular torsion with, 1206 after hernia repair, 1184, 1187 congenital, 1189 embryogenesis of, 1173,1173f, 1174 herniography of, 1175 in cystic fibrosis, 1300 traumatic, 331 tumor with, 622 teratoma as, 567 ventriculoperitoneal shunt and, 1187 vs. inguinal hernia, 1173f, 1189 Hydrocephalus, 1995-2002. See also Intracranial pressure (ICP). brain tumor with, 672,673,674 cerebellar astrocytoma as, 674, 674f craniopharyngioma as, 677, 677f medulloblastoma as, 675 of choroid plexus, 678 of pineal region, 678 tectal glioma as, 676 teratoma as, 563 clinical features of, 1997 etiology of, 1995f, 199G1997, 1997f management of, 1998-2002 myelomeningocele with, 84, 1993 outcome and prognosis with, 2002 pathophysiology of, 1995-1996 radiologic features of, 1997-1998 vocal cord immobility caused by, 988 Hydrochlorothiazide, for hypertension, 2120 Hydrocodone, 240,240t Hydrocolpos, malformations with, 1568, 1571, 1572, 1579f, 1582 cutaneous vesicostomy and, 1791-1792 imperforate hymen as, 1902, 1941, 1950 vaginal agenesis as, 1936, 1937 Hydrofluoric acid burns, 396 Hydrogen, bacterial production of in chronic intestinal pseudo-obstruction, 1549 in necrotizing enterocolitis, 1435, 1436 Hydrogen peroxide in phagolysosome, 160 reperfusion injury and, 158 Hydrometrocolpos imperforate hymen with, 1902, 1941 in McKusick-Kaufman syndrome, 1936 Hydromorphone, 241, 241t, 242 caudal, 248 epidural infusion of, 248, 248t in patient-controlled analgesia, 243, 243t Hydronephrosis. See also Hydroureteronephrosis; Ureteropelvic junction (UPJ) obstruction. definition of, 1723 diagnostic evaluation of, 1727-1732, 1728f-1732f, 1743, 1743f, 1745 olume 1, pages 1-1140; Volume 2, pages 1141-2146.
Hydronephrosis (Continued) differential diagnosis of, 1727, 1727t management of, 1733. See also Pyeloplasty. megaureter with, 1771, 1772 multicystic dysplastic kidney and, 1710-1711,17lOf, 1725, 1727 persistent cloaca with, 1791 prenatal diagnosis of, 1723, 1725, 1726f grading of, 1725, 1725t prenatal counseling and, 1725-1726 renal development and, 1725-1726 spontaneous resolution of, 1733 urethral obstruction causing, 82t, 83 ureteral anomalies with, 1763, 1764f-1765f urinary tract infection and, 1743 Hydrops fetalis chylothorax with, 1026 cystic lung mass with, 955-956, 956f, 957, 958 cystic mediastinal lesion with, 960, 965 heart block causing, 151 teratoma causing mediastinal, 565 sacrococcygeal, 559, 560 thoracic duplications with, 1391 treatment of, 82t, 83, 83t, 85 Hydrops of gallbladder, 1636,2115 Hydroureteronephrosis. See also Hydronephrosis. in bladder exstrophy, 1842 in male fetus, with posterior urethral valves, 1819 in prune-belly syndrome, 1781, 1784 in spinal dysraphism, 1808 Hydroxyapatite-coated implants, 59 Hydroxyl radical, 160, 162, 167 5-Hydroxytryptamine, tissue injury and, 106 Hymen, imperforate, 1902, 1941, 1941f, 1942, 1950, 1951f Hyoid bone abscess above, 867 anatomy of, 827 dermoid cyst adjacent to, 871 thyroglossal duct cyst and, 864, 865f, 869, 870 Hypaque. See Diatrizoate enema. Hyperacute rejection, 695-696 renal, 702 Hyperaldosteronism, 636 Hyperammonemia after urinary tract reconstruction, 1836 parenteral amino acids and, 204 portal hypertension with, 1655 Hyperbaric oxygen, for necrotizing fasciitis, 1146 Hyperbilirubinemia. See alsoJaundice. during extracorporeal life support, 140 in acute liver failure, 733 intravenous fat emulsions and, 206 neonatal, 1606 self-limited, 1603 Hypercalcemia differential diagnosis of, 857, 857t familial hypocalciuric, 857 in hyperparathyroidism, 857, 858, 858f in hypervitaminosis D, 198 in neonate, 95 Hypercapnia, permissive, 128 in congenital diaphragmatic hernia, 940 Hypercarbia extracorporeal life support and, 139 in respiratory failure, 127 Hypercoagulable state. See Coagulopathy. Hyperfractionated radiation therapy, 429
Hyperglycemia in central nervous system injury, 356, 363 in parenteral nutrition patients, 208, 209 intraoperative, 225 neonatal, 102, 197 postoperative, 106, 107, 107f in critically ill patient, 211-212 Hyperinsulinism, 102, 1679-1683, 1679t, 1681f, 1682t, 1683f Hyperkalemia aldosterone production and, 629 in malignant hyperthermia, 231, 232,232t in neonate, 95 in parenteral nutrition patients, 209 succinylcholine causing, 267 Hyperlipidemia, familial, 2130 Hypermagnesernia, in parenteral nutrition patients, 209 Hypermetabolic response, in burn patient, 391-393, 392f-393f Hypernatremia in burn patient, 389 in neonate, 94, 94t Hyperoxaluria after massive enterectomy, 1372 renal graft loss in, 71 1 Hyperparathyroidism, 857, 858, 858f Hyperphosphatemia, in parenteral nutrition patients, 209 Hypersplenism after portoenterostomy, 1612 partial splenectomy for, 1697 portal hypertension with, 1653, 1655, 1661-1662,1663, 1664-1665 Hypertelorism, 792, 792f, 800 in Crouzon's syndrome, 797 Hypertension. See also Blood pressure. controlled, for brain injury, 273 hyperaldosteronism with, 636 in renal transplant patient, 706, 713 incidence of, in children, 2118 intracranial, decompressive laparotomy for, 303 malignant, 21 18, 2120 neuroblastoma with, 468 pheochromoc~omawith, 630,631,631f, 632 portal. See Portal hypertension. pulmonary. See Pulmonary hypertension. renovascular. See Renovascular hypertension. sleep apnea and, 1246 ureteral abnormalities and, 1762 Hyperthermia after traumatic brain injury, 273, 356 for germ cell tumors, 569 malignant, 231-232,232t oxyhemoglobin dissociation curve in, 121 Hyperthyroidism, 852-854, 853t Hypertonic saline resuscitation, for burninduced shock, 389 Hypertriglyceridemia, in parenteral nutrition patients, 208, 210 Hyperventilation, controlled, for brain injury, 269, 272, 273, 363, 364, 364t Hyperviscosity syndrome, 21 15 Hypervolemia, serum sodium and, in neonate, 94, 94t Hypocalcemia in citrate toxicity, 188, 227, 273 in malnourished patient, albumin and, 209 in neonate, 95 Hypocarbia, for head trauma patient, 269, 272, 273 Hypoganglionosis, 1594. See also Aganglionosis Hypoglossal nerve, branchial anomalies and, 862.866
Hypoglycemia. See also Hyperinsulinism. differential diagnosis of, 1680-1681, 1681f in neonate, 101-102, lOlt during fluid therapy, 225 in Addison's disease, 637 in burn patient, prevention of, 387 in neonate, 100,101-102, 101t, 103, 197 on parenteral formula, 204 with sepsis, 170 in parenteral nutrition patients, 204, 208 Hypogonadism, gynecomastia with, 892 Hypokalemia in hyperaldosteronism, 636 in neonate, 94 in refeeding syndrome, 208 neuroblastic tumors with, 469 Hypomagnesemia in neonate, 95 in refeeding syndrome, 208 Hyponatremia fluid therapy and, 226 in burn patient, 388-389 in brain-injured patient, 364, 365 in burn patient, 388-389,390, 393 in neonate, 94, 94t renin and, 629 Hypoparathyroidism, secondary to thyroid surgery,856 Hypopharynx, 822 Hypophosphatemia in premature infants, 207 in refeeding syndrome, 208 Hypoplastic anemia, congenital, 179, 180 Hypoplastic left heart syndrome, 1975, 1977-1978, 1977f-1978f transplantation for, 153, 754, 756, 757, 758, 759f, 762 Hypopnea, 823-824 Hypospadias, 1870-1895 ambiguous genitalia with, 1870, 1894, 1919, 1921 anatomy of, 1877-1880, 1877f-1879f associated anomalies with, 1875 anorectal, 1567, 1894 fistula as, 1894, 1905 penile torsion as, 1907 scrotal, 1907-1908 chordee in, 1870, 1879, 1880, 1887, 1890f presenration of urethral plate and, 1884, 1885f, 1886 repair of, 1887-1888, 1891, 1891f-1892f classification of, 1870-1871, 1870f-1871f embryogenesis of, 1872,1916 etiology of, 1875-1877 historical perspective on, 1871 incidence of, 1870, 1874-1875 repair of, 1880-1895 age for, 1893 algorithm for, 1880f anesthesia for, 246247, 247f, 1893 anterior, 1880-1884, 1881f-1885f complications of, 1890f, 1893-1894, 1894f for curvature, 1887-1888, 1891, 1891f-1892f, 1895 in sex assignment surgery, 1927-1928, 1929f-1930f phases of, 1880 posterior, 1884-1887, 1885f-1890f results of, 18941895 summary of, 1895 technical considerations in, 1892-1893 two-stage, 18861887, 1889f with multiple failures, 1890f, 1891-1892 Volume 1, pages 1-1 140; Volume 2, pages 1141-2
Hypotension during anesthesia inhalation agents and, 227, 229 intravenous agents and, 233 escharotomy-related, 386 extracorporeal life support and, 135, 142 in sepsis or SIRS, 170, 172 in trauma patient, 377 pericardial tamponade and, 286 shock with, 319, 378 with abdominal injury, 378 with brain injury, 355 with spinal injury, 355, 368, 370 Hypothalamic-pituitary-adrenal axis, 629 Hypothalamus, glioma of astrocytoma as, 676-677,676f genetics of, 679 Hypothermia coagulopathy in, 301 extracorporeal life support for, 142 in neonate during surgery, 99 with sepsis, 170 in trauma patient, 272, 273 with severe bleeding, 300-301, 302 oxyhemoglobin dissociation curve in, 121 Hypothyroidism, 851 alpha fetoprotein in, 555 breast hypoplasia in, 887 galactorrhea in, 888 hepatic hemangiomas with, 2102, 2106 in Hashimoto's thyroiditis, 852 infantile hepatic hemangioendothelioma with, 496 ovarian cysts in, 601 premature thelarche in, 885 weaning from ventilator and, 128 Hypoventilation. See Central hypoventilation syndrome (Ondine's curse). Hypovolemia. See also Blood volume. children's maintenance of blood pressure in, 319 in burn patient, 388 in trauma patient, 271 plasma substitutes and, 188 serum sodium and, in neonate, 94,94t Hypovolemic shock, 180 vs. neurogenic shock, 368 Hypoxemia in respiratory failure, 127 inverse ratio ventilation for, 125 pulmonary vasoconstriction caused by, 120 Hypoxia children's predisposition to, 276 extracorporeal life support and, 139, 140 in central nervous system injury, 355, 357 in neonate gastrointestinal perforation secondary to, 1235 necrotizing enterocolitis and, 1433 tissue, in systemic inflammatory response syndrome, 169-170, 172
Ibuprofen, 238,238t ICAM-1 (intercellular adhesion molecule-I) , 159, 173 in biliary atresia, 1611 in Hirschsprung's disease, 1526 ICF (intracellular fluid) in fetus and neonate, 91-92,93 third-space loss and, 226 ICP. See Intracranial pressure (ICP).
xxxii
INDEX
Idiopathic (immune) thrombocytopenic purpura, 182-183 accessory spleens and, 1692 splenectomy in, 183, 1693, 1696, 1698 Ifosfamide, 423t, 428 Ig. See Immunoglobulin(s). IGF. See Insulin-like growth factor entries. IGF binding protein 1, in hyperinsulinism, 1680 IL. See Interleukin entries. Ileal atresia. SeeJejunoileal atresia and stenosis. Ileal channel, continent catheterizable, 1798, 1798f Ileal conduit, incontinent, 1793-1794, 1793f Ileal interposition, for ureteral injury, 327 Ileoanal pouch procedure, 14661469, 1468f-1471f complications of, 1470-1471 Crohn's colitis and, 1457, 1458, 1471 history of, 1462-1463 in familial polyposis, 1421, 1472 outcomes of, 1469-1470 stapled anastomosis in, 1472 stoma site for, 1487f Ileocecal cystoplasty, 1797 Ileocecal reservoir, 1799, 1799f Ileocecal valve, in short-bowel syndrome, 1371f, 1372, 1373, 1375 Ileocystoplasty, 1796-1797, 1825, 1826f Ileorectal anastomosis in Crohn's disease, 1457, 1457f, 1458, 1459 in ulcerative colitis, 1467 Ileostomy. See also Enterostoma(s). choices for, 1482f-1483f, 1484-1485 complications of, 1489-1490, 1489t in chronic intestinal pseudoubstruction, 1549 in Crohn's disease, 1457, 1459 in necrotizing enterocolitis, 1482, 1483f, 1484, 1486 in ulcerative colitis, 1467, 1482-1483, 1484-1485 after pouch removal, 1471 stoma site in, 1486, 1487f technique of, 1468, 1470f indications for, 1482-1483 sites for, 1486, 1486f stoma care in, 1488 technical aspects of, 1486, 1486f-1487f Ileovesicostomy, 17941795,1832-1833 Ileum duplications of, 1390, 1391, 1391f-1392f, 1392, 1394-1395, 1395f, 1397 Hirschsprung's disease in, 1531, 1540, 1542f-1543f lymphoid hyperplasia of, 1418, 1419f mesenteric cyst of, 1366, 1402 resection of, consequences of, 1371-1372, 1373, 1837 Ileus. See also Meconium ileus. functional, microcolon in, 1519 postoperative, 1360-1 361 enteral feedings and, 199, 202, 1361 renal trauma with, 324 Iliac vein(s), compression of, 2127, 2128f, 2141 Ilioinguinal-iliohypogastricblock, 245-246, 245f Iloprost, for pulmonary vascular disease, 766 Image. See also Three-dimensional images. modes of manipulation and, 31-32, YLt, 40 Image-guided biopsy, 438,439-442 Image-guided radiation therapy, 429-430 Image-guided radiosurgery, 43, 44-47, 45f-46f Image-guided surgery, 42-43
Imatinib for gastrointestinal stromal tumors, 516 neuroblastoma and, 475 Imipramine, for nocturnal enuresis, 1815 Immune response cortisol and, 629 Hirschsprung's disease and, 1526, 1528 in gastric and duodenal epithelium, 1227 postoperative stress and, 106 preterm gastrointestinal tract and, 1432, 1434 Immunoblastic lymphoma, 583 Immunocompromised patient. See also Human immunodeficiency virus (HIV) infection; Immunosuppression; Severe combined immune deficiency (SCID). atypical mycobacterial infection in, 846, 1003 fungal sinusitis in, 819 Hodgkin's disease in, 576 lung infections in, 1001 in cancer, 1005-1008, 1006f-1007f in cystic fibrosis, 1010-1011 in HIV infection, 1008-1010, 1009f thoracoscopic biopsy in, 977 transfusion in, 188, 189 Immunoglobulin (s), 163-164. See also Antibodies. in human milk, 104, 168, 202 in neonate, 167-168,170 opsonization by, 160, 160f, 163, 164 oral administration of, necrotizing enterocolitis and, 1444 Immunoglobulin A, 157, 157f, 163, 164 in Hirschsprung's disease, 1528 in neonate, 168, 170, 1444 Immunoglobulin A nephropathy, renal graft loss in, 71 1 Immunoglobulin E, 163, 164, 166 Immunoglobulin G, 163, 164, 166 bacterial defense against, 159 fetal heart block caused by, 151 for immune thrombocytopenic purpura, 1693 in neonate, 167-168, 170, 1444 Immunoglobulin M, 163-164 in neonate, 167, 168, 170 lymphomas with expression of, 581, 581f, 582-583 Immunoglobulin superfamily, adhesion molecules of, 159 Immunosuppression. See also Immunocompromised patient. for Crohn's disease, 1455-1456 for transplantation bone marrow, 779 heart, 754, 760-761, 760t, 761f intestinal, 742-743, 749 islet cell, 724-725, 726, 727 liver, 737, 738t, 739, 740-741 lung, 770-771, 771t, 774 pancreas, 720-721,722-723 principles of, 685,686-689, 687f, 690-693, 690f, 693f, 695,696 renal, 707-709,711, 712-713 for ulcerative colitis, 1466 lymphoproliferative disease secondary to, 584-585, 712, 739, 750-751, 774 Immunotherapy, cancer, 427 for neuroblastoma, 427, 485 Impedance measurement of body composition, 195 of gastroesophageal reflux, 1124 Impedance pneumography, 122 Imprinting, genomic, 446, 447
olume 1, pages 1-1 140; Volume 2, pages 1141-2146
IMV (intermittent mandatory ventilation), 123, 124, 128 In situ hybridization, 419, 420t Incontinence child abuse and, 404 fecal. See also Defecation; Soiling, fecal. anal manometry and, 1542 anorectal malformations and, 1569, 1586-1588, 1587t antegrade enema for, 1834, 1834f functional, 1549, 1549t, 1592, 1595 in Hirschsprung's disease, after surgery, 1545-1546, 1547 sacral defects with, 1567, 1573 urinary tract reconstruction and, 1833 urinary. See also Bladder dysfunction; Enuresis. bladder outlet resistance and, 1817, 1828-1832, 1830f-1831f dysfunctional elimination syndrome with, 1813 ectopic ureter with, in female, 1762, 1763, 1767-1768,1903 endoscopic injection for, 1747-1748, 1749f-1750f in Hirschsprung's disease, after surgery, 1546 neuropathic bladder with, 1809, 1810, 1811 posterior urethral valves with, 1812 spinal cord tethering with, 1810 urethral injury with, 330, 331 Indiana pouch, 1799, 1799f, 1826, 1833 Indomethacin ductus arteriosus and fetal, 79 for medical closure, 238, 1429 gastrointestinal perforation and, 1235, 1237,1429 necrotizing enterocolitis and, 1429 Infant. See Neonate(s); Premature infant. Infantile hepatic hemangioendothelioma, 495, 496-497,496f transplantation for, 733 Infection. See also Abscess(es) ; Sepsis. barriers to, 157-158, 157f burns and, 385, 390 fungal. See Fungal infection. host defense against, 159-168 humoral factors in, 163-166, 164f lymphocytes in, 162-163 monocytes-macrophages in, 161-1 62 neonatal, 166168 neutrophils in, 159-161, 160f hyperglycemia in, in neonate, 102 in necrotizing enterocolitis, 1435-1436 in parenteral nutrition patient, 209-210, 211 in transplant patient bone marrow, 780, 781 heart, 761, 762, 763 intestinal, 750-751 liver, 739, 740t lung, 771, 774-775 renal, 71 1-712 intraspinal, 2013 of bone. See Osteomyelitis. of brain, 2008-2013, 2010f-201 If of breast, 887, 888, 890 of fracture, open, 344 of liver, 1642-1646, 1642t, 1643f, 1646f of lung. See Lung(s), infections of. of mediastinum, 1027-1 028 from descending neck infection, 823, 1027
Infection (Continued) of middle ear and mastoid, 815-816, 816f of umbilicus, 1146, 1149, 1150 of upper respiratory tract. See also Sore throat. piriform sinus and, 868 Infection control, necrotizing enterocolitis and, 1444 Inferior petrosal sinus sampling, 634f, 635 Inferior vena cava. SerVena cava. Infertility feniale appendicitis and, 1509 bladder exstrophy and, 1858 v~ginalagenesis and, 1937 vaginal septum and, 1943 mal,: bladder exstrophy and, 1858 cryptorchidism and, 1198, 1199 after orchidopexy, 1203, 1204, 1204t in prune-belly syndrome, 1785 cystic fibrosis with, 1300 Fiodgkin's disease therapy and, 579 nguinal hernia repair and, 1185-1 186, 1187 ~esticulartorsion and, 1207 testicular tumors and, 626 varicocele and, 1207, 1208, 1209 Infiltration anesthesia, 243, 244 Inflammation. See also Infection; SIRS (systemic inflammatory response syndrome). bacterial lipid A and, 159 cortisol and, 629 cytokines and, 106, 159, 160, 161, 165-166 in necrotizing enterocolitis, 1430, 1430t, 1431-1432, 1433, 1434 genetic differences in, 166, 169 in burn patient, 384-385, 392 in inhalation injury, 395 in neonate, 167 postoperative, 105 macrophages in, 161-162 neutrophils in, 159-161, 160f obesity-induced, 1243-1244 summary of, 168 Inflammatory adhesions, 1361 Inflammatory bowel disease. See also Crohn's disease; Ulcerative colitis. bloody diarrhea in, 1387 colorectal carcinoma associated with, 519-520 I multidetector computed tomography in, 35 Inflammatory myofibroblastic tumor. See Inflammatory pseudotumor. Inflammatory polyps, gastrointestinal, 1364, 1387, 1414-1416, 1415f Inflammatory pseudotumor gastrointestinal, 1364-1 365 hepatic, 499 pulmonary, 640-641 Inflicted injuries. See Child abuse. Infliximab for Crohn's disease, 1456, 1458 for ulcerative colitis, 1466 Influenza, 1004 Information-guided therapy, 42-43 Informed consent, 258,259 for sex assignment surgery, 261-262 Inguinal hernia, 1172-1 189 bladder exstrophy with, 1844 clinical features of, 1174 contralateral exploration with, 1180-1 182 cryptorchidism with, 1198, 1199, 1200, 1204,1205
Inguinal hernia (Continued) direct, 1185, 1188 embryogenesis of, 1173-1 174 epidemiology of, 1173 examination for, 1174-1 175, 1175f factors contributing to, 1174, 11741 herniography of, 1175,1187 in connective tissue disorders, 1188 in cystic fibrosis patient, 1188, 1300 in intersex patient, 1188-1 189 in premature infant, 1173, 1176, 1185, 1186,1187 incarcerated, 1174, 1182-1 184, 1182f-1183f in premature infants, 1187 mortality associated with, 1186 ovary in, 1184, 1186 testicular atrophy secondary to, 1186 indirect, 1173, 1174 mortality associated with, 1186 peritoneal dialysis and, 1187 recurrent, 1184-1185, 1187, 1188 repair of, 1175-1 182 adrenal rests found in, 1189 anesthesia for, 244, 245-246, 245f, 1175-1176 complications of, 1 1 8 4 1186 historical development of, 1172-1 173 laparoscopic, 1179-1 180, 1180f complications of, 118G1187 open technique of in females, 1178-1179, 1179f in males, 117G1178, 1177f-1178f pain control following, 1176 same-day, 1176 timing of, 1176 sliding, 1187-1 188 fallopian tube in, 1178-1 179, 1179f, 1187 ultrasonography of, 1175, 1176f, 1181 with strangulation, 1182 ventriculoperitoneal shunt and, 1185, 1187 vs. hydrocele, 1173f, 1189 Inhalation injury, 386, 394395 by ammonia fumes, 1084 Inhibin, granulosa-theca cell tumors and, 604 Injury. See Emergency management; Trauma. Innominate artery compression of, 996, 996f erosion of, by tracheotomy tube, 986 tracheal compression by, 996,996f, 997, 998, 1979, 1982, 1982f Innovation. See Technological innovation. Inotropic agents, for heart failure, in neonate, 148, 150t, 151 Inotropy. See Contractility, cardiac. Inspiratory capacity, 118, 118f Inspiratory reserve volume, 118, 118f Inspissated bile syndrome, 1614, 1614f Insulin. See also Diabetes mellitus; Hyperinsulinism; Islet cell transplantation; Pancreas, transplantation of. chromium and, 199 cortisol and, 629 for burn patient, 391, 392, 393 in perinatal period, 100, 101, 102, 103 in postoperative period, 106, 107 micropumps for, 58 parenteral nutrition and, 207, 208 Insulin resistance, 1244, 1245, 1246 Insulin-like growth factor-1 (IGF-1) in biliary atresia, 1611 in burn patient, 391, 392 in tumor growth, 419, 426 receptor for, 414
Insulin-like growth factor-2 (IGF-2) Beckwith-Wiedemann syndrome and, 525 hepatoblastoma and, 502 rhabdomyosarcoma and, 525 Wilms' tumor and, 447 Insulin-like growth factor 3, testicular descent and, 1193, 1194f, 1912 Insulinoma, 1683, 1685 Integra, 390 Integrin receptors, 158, 160 Integrins, 159, 161, 166, 167, 173 invasive cancer and, 418 Intensity-modulated radiation therapy, 429430 Intensive care unit neuromuscular syndrome, 231 Interceed. See Cellulose. Intercellular adhesion molecule-1 (ICAM-l), 159,173 in biliary atresia, 1611 in Hirschsprung's disease, 1526 Intercostal nerve block, for rib fractures, 279 Interferon-a as angiogenesis inhibitor, 426 for hemangoendothelioma, hepatic, 496-497 for hemangioma, 21042105 mediastinal, 966 subglottic and tracheal, 994, 995 vaginal. 1951 for Gtestinal lymphangiectasia, 2140 for laryngeal papilloma, 990 ~nterferon-7,1 a , - l 6 1 , 163, 166 in neonate, 167, 168 in systemic inflammatory response syndrome, 169 tumor cells and, 426 Interleukin-1 (IL-1) corticosteroids and, 1455 in neonate, 167 in sepsis, 170-171 postoperative, 106 inflammation and, 159, 161, 165, 166, 1430t in systemic inflammatory response syndrome, 168-169, 170, 172 Interleukin-2 (IL-2), 166 for neuroblastoma, 427, 485 gastrointestinal, 1430t in neonate, 167 Interleukin-2 (IL-2) receptor antagonists. See also Cyclosporine. in transplantation heart, 761, 761f intestinal, 749 islet cell, 726 liver, 738t lung, 770-771,771t renal, 707, 709 Interleukin-4 (IL-4), gastrointestinal, 1430t, 1431 Interleukin3 (IL-5), in ulcerative colitis, 1463 Interleukin-6 (IL-6) in neonate in sepsis, 170-171 postoperative, 106 inflammation and, 165 in systemic inflammatory response syndrome, 168, 170, 171, 172 Interleukin-8 (11,-8) in inhalation injury, 395 in necrotizing enterocolitis, 1431 inflammation and, 160, 165 in systemic inflammatory response syndrome, 168, 169, 170 Interleukin-10 (IL-lo), necrotizing enterocolitis and, 1430t, 1431
Volume 1, pages 1-1140; Volume 2, pages 1141-2146.
xxxiv
INDEX
Interleukin-1 1 (IL-1l ) , necrotizing enterocolitis and, 1430t, 1431 Interleukin-12 (IL-12), 166 in cancer chemotherapy, 426 for neuroblastoma, 485 in necrotizing enterocolitis, 1432 Intermittent mandatory ventilation (IMV), 123, 124, 128 Internal hernia, 1348-1349, 1349f, 1350, 1354, 1356, 1361-1363, 1362f-1363f Intersex abnormalities, 1911-1932. See also Sex assignment. carcinoma in situ in germ cells of, 1198 classification of, 1913, 1914t-1915t, 1916-1917 diagnosis of, 1917-1920, 1918t, 1919t embryological basis of, 1911-1913, 1912f ethics of surgery for, 261-262 gonadoblastoma in, 624, 1920 inguinal hernia in, 1188-1 189 medical management of, 1920-1921 surgical reconstruction in, 1921-1931 for female assignment, 1922-1926, 1923f-1928f for male assignment, 192G1931, 1929f-1932f preparation for, 1921-1922, 1922f Intestinal adaptation, 743-744, 1369-1370, 1372, 1373, 1374 isolated liver graft for, 745 Intestinal atresia and stenosis abdominal wall defects with, 1162, 1164, 1166, 1167 classification of, 1275-1276, 1276f colonic, 1275, 1493-1495, 1494f duodenal, 1260-1267,1261f-1265f, 1261t jejunoileal atresias with, 1270, 1276 pyloric web with, 1233 duplication associated with, 1395 etiological theories of, 1390 Hirschsprung's disease with, 1528 intussusception associated with, 1270, 1272, 1274f, 1316 jejunoileal. SerJejunoileal atresia and stenosis. rectal, 1578 short-bowel syndrome secondary to, 1369, 1369f Intestinal dysmotility, 1547-1549, 1547f. See also Constipation; Enteric nervous system; Hirschsprung's disease; Ileus; Intestinal neuronal dysplasia; Intestinal pseudo-obstruction. after resection, 1370 colonic obstruction in, 1496 in pseudo-obstruction, 1366, 1547 multivisceral graft for, 745 opioids and, 1360-1361 rectosigmoid, in anorectal malformations, 1569 Intestinal exstrophy, 1862-1863, 1863f, 1864, 18641, 1865-1866, 1865f Intestinal failure, 743, 744, 745 Intestinal infarction. See also Ischemic necrosis, gastrointestinal. in inguinal hernia, 1184, 1186 mesenteric or omental cyst with, 1401 Intestinal lengthening procedures, 1377-1379, 1377f-1379f with resection of duplication, 1395 Intestinal neuronal dysplasia, 1496, 1547, 1560-1563, 1562f-1563f after pull-through, for Hirschsprung's disease, 1542, 1544 anorectal manometry in, 1562, 1594
Intestinal obstruction. See also Colon, obstruction of; Enema; Internal hernia; Intestinal atresia and stenosis; Intestinal dysmotility; Intestinal rotation and fixation; Intussusception; Meconium ileus; Volvulus. adhesions with in familial Mediterranean fever, 1477 inflammatory, 1361 postoperative, 1358-1360, 1359f-1360f after appendectomy, 1358, 1509 causes of, 1358 miscellaneous, 1364-1366, 1498 congenital bands with. SeeLadd's bands. Crohn's disease with, 1456-1457 duplications with, 1366, 1391, 1395 gastrointestinal tumors with, 515 colorectal carcinoma as, 521, 521f hernias with, 1361-1363 inguinal, 1174, 1182 internal, 1348-1349, 1349f, 1350, 1354, 1356,1361-1363,1362f-1363f Meckel's diverticulum and, 1306, 1308f, 1309, 1310-1311,1310f mesenteric or omental cyst with, 1401, 1401f, 1402 postoperative adhesive, 1358-1 360, 1359f-1360f after lung transplant, 773 intussusception with, 1321-1322, 1321f, 1356, 1361 vs. ileus, 1360 vitelline duct remnants and, 1148, 1309, 1310f Intestinal perforation in appendicitis, 1502, 1503, 1506, 1508-1509 in colonic atresia, 1494 in Crohn's disease, 1456, 1457 in Hirschsprung's disease, 1515, 1529 in neonate, 1236-1237 meconium ileus with, 1291, 1296, 1298, 1298f necrotizing enterocolitis with, 1437, 1439, 1440 in small left colon syndrome, 1498 intussusception with, 1317-1318, 1328, 1329,1330,1334, 1335-1336 Meckel's diverticulum with, 1309, 1311f radiographic diagnosis of, 1359 seat-belt trauma with, 1365 Intestinal pseudo-obstruction, 1366, 1366t chronic, 1111-1 112, 1356, 1496, 1523, 1547-1549 vs. segmental volvulus, 1498 Intestinal rotation and fixation, 1342-1356 disorders of. See also Volvulus. asplenia with, 1693 asymptomatic, 1348 classification of, 1346-1347, 1346f-1347f clinical manifestations of, 1347-1350, 1347f, 1349f, 1385 duodenal atresia with, 1262, 1263, 1346 historical perspective on, 4, 5, 1341 in prune-belly syndrome, 1786 jejunoileal atresia and, 1270, 1272, 1274, 1283, 1346 mesocolic hernia as, 1348-1349, 1349f, 1350,1356,1361, 1362f radiologic diagnosis of, 1350, 1350f-1354f, 1385-1386 reversed, 1346, 1348, 1349f, 1356 terminology for, 1346 treatment of, 1352-1354, 1355f, 1356 laparoscopic, 1354
Volume 1, pages 1-1140; Volume 2, pages 1141-2146
Intestinal rotation and fixation (Continued) normal, 1342-1346, 1343f-1347f fixation in, 1346, 1346f radiographic appearance of, 1350, 1350f Intestinal stricture (s) in Crohn's disease, 1457, 1459 in necrotizing enterocolitis, 1442-1443 post-traumatic, 1365 Intestinal transplantation, 742-752 complications of, 749-751, 750f donor selection for, 745, 747, 747f future prospects for, 752 graft options in, 745, 746f history of, 693, 742-743, 742t, 743t immunosuppression for, 742-743, 749 in chronic intestinal pseudo-obstruction, 1549 in Hirschsprung's disease, 1540 in short-bowel syndrome, 1373, 1379 after failed lengthening procedure, 1378 in jejunoileal atresia, 1283 indications for, 743t, 744 operative procedures in, 747-749,747f-748f outcomes of, 751-752, 751f postoperative management in, 749 recipient selection for, 743-745, 743t, 745t rejection in, 749-750, 750f Intestinal valves, construction of, 1375, 1375f Intestine. See also Colon; Small intestine. bacteria in as probiotics, 1444-1445 necrotizing enterocolitis and, 1433, 1434, 1444-1445 overgrowth of diagnosis of, 1549 in short-bowel syndrome, 1373-1374 barriers to infection in, 157, 157f, 158 herniated through diaphragm, 284-285, 284f tissue-engineered, 22, 24-26, 25f trauma to, 310-311, 311f diagnostic modalities in, 296, 297, 31 1-312 laparoscopic repair of, 297 vascular malformations in, 1598 Intestinocystoplasty, 1791 Intra-abdominal pressure cryptorchidism and, 1195 gastroesophageal reflux and, 1123 hydrocele and, 1187 inguinal hernia and, 1186, 1187 measurement of, 302-303 Intracellular fluid (ICF) in fetus and neonate, 91-92, 93 third-space loss and, 226 Intracranial pressure (ICP). See also Cerebrospinal fluid (CSF); Hydrocephalus. brain tumor and, 672 teratoma as, 563 craniosynostosis and, 795, 798 in trauma patient, 269, 272, 273, 356 management of, 363, 364, 364t, 365 monitoring of, 363, 364, 365 refractory elevation of, 364, 364t decompressive laparotomy for, 303 outcomes with, 367 with diffuse injury, 357 with gunshot wound, 361 with intracerebral hematoma, 358 monitoring of in shunt patient, 2001 in trauma patient, 363, 364, 365 Intraosseous vascular access in burn patient, 386 in trauma patient, 269,270-271
Intraperitoneal fluid. See also Ascites. FAST ultrasonography for detection of, 319 intestinal trauma and, 312 Intrauterine growth retardation (IUGR), 89-90 hypoglycemia and, 101t Intravascular oxygenation, 126 Intravenous pyelography ( I W ) in trauma patient, 319, 323, 326 of ureteral duplication, 1761, 1762f Intravenous urography ( N U ) in ureteropelvic junction obstruction, 1727 with ureteral anomalies, 1763, 1763f, 1764, 1765f Intraventricular hemorrhage as birth injury, 405 in premature infants, vitamin E and, 198 traumatic, 359, 360f, 361, 362 Introitus, masses of, 1949-1951, 1949f-1951f Intubation. S P Endotracheal ~ intubation; Endotracheal tube. Intussusception, 1313-1337 classification of, 1318-1323,1318f, 1320-1322f currantjelly stool in, 1314f, 1317, 1317f, 1324,1386 diagnosis of clinical, 1316f, 1323-13'25 radiologic, 1325-1327, 1325f-1327f, 1364 duplication as cause of, 1319, 1321, 1366, 1391, 1392, 1395 epidemiology of, 1316-1317 future expectations for, 1337 historical perspective on, 1313-1314 in cystic fibrosis, 1299 in diffuse juvenile polyposis infancy, 1416 intentional, for short-bowel syndrome, 1375, 1375f intrauterine, intestinal atresia with, 1270, 1272, 1274f, 1316 Meckel's diverticulum with, 1309, 1311, 1319, 1335 outcomes of, 13361337 overview of, 1314-1315, 1314f-1315f, 1386 pathogenesis of, 1315t, 1318-1323,1318f, 1320f-1322f, 1364, 1366 pathologic anatomy of, 1314f, 1317-1318 postoperative, 1321-1322, 1321f, 1361 after 1,add procedure, 1356 recurrent, 1318f, 1320, 1322-1323, 1323f, 1332, 1336 research update on, 1315t, 1316t, 1337 spontaneous reduction of, 1319 treatment of, 1327-1335 medical, 1323, 1327-1328, 1330 operative, 1328f, 133'2-1335, 1333f-1334f complications of, 1336 laparoscopic, 1335 overview of, 1327 radiologic, 1327f, 1328-1332, 1329f-1332f complications of, 1335-1336 delayed repeat enema in, 1327f, 1331, 1336 with pathologic lead point, 1321, 1321f, 1335 Invasins, 158 Inverse ratio ventilation, 125 Iodomethyl-1-19-norcholesterol (NP-59), 630, 635 Iowa (Kimura) intestinal lengthening procedure, 1378-1 379, 1378f Iressa. See Gefitinib (Iressa). Irinotecan, 424t, 429 Iron deficiency, esophageal replacement and, 1104 Iron dextran, in parenteral nutrition solution, 207, 208t
Iron overload, from transfusion, in Pthalassemia, 495 Irondeficiency anemia, 180-181 gastrointestinal tumors with, 516 in parenteral nutrition patients, 207 postoperative apnea and, 223 Ischemia. See also Arterial occlusion. amputation secondary to, 2058 bowel, mesenteric venous thrombosis with, 2130 five Ps in, 348 in arterial occlusion, 2116-2117 in central nervous system injury, 356, 357 in upper extremity trauma, 348, 351, 379-380 in vascular injury, 377, 378-380,379t iatrogenic, 380, 381 Ischemia-reperfusion injury. See Reperfusion injury. Ischemic necrosis, gastrointestinal. See also Gangrene; Intestinal infarction; Necrotizing enterocolitis, neonatal. adhesive obstruction with, 1359 gastric perforation in, 1235-1237 intussusception with, 1318, 1326, 13341335,1336 malrotation with, 1354, 1356 mesenteric venous thrombosis with, 2130 thrombotic, in infant, 2115 Islet cell adenoma, 1683, 1685 Islet cell carcinoma, 1685 Islet cell transplantation, 717, 723-727, 724f-725f Isochromosome, definition of, 596 Isodisomy, uniparental, 447 Isoflurane, 222f, 222t, 227t, 228, 228f, 229 Isosulfan blue, lymph node drainage and, with soft tissue sarcomas, 549, 549f Isotretinoin. See 13-cisRetinoic acid. IUGR (intrauterine growth retardation), 89-90 hypoglycemia and, lOlt I W (intravenous pyelography) in trauma patient, 319, 323, 326 of ureteral duplication, 1761, 1762f N U (intravenous urography) in ureteropelvic junction obstruction, 1727 with ureteral anomalies, 1763, 1763f, 1764, 1765f
Jaffe-Campanacci syndrome, 652, 654 Jarcho-Levin syndrome, 917, 918f Jaundice. See also Hyperbilirubinemia. diagnostic evaluation in, 1605-1607, 1606t in cholelithiasis, 1636, 1637, 1642 in chronic graft-versus-host disease, 782 in hypertrophic pyloric stenosis, 1216, 1218 in jejunoileal atresia, 1271, 1271t in parenteral nutrition patient, 209 liver transplantation and, 732, 733, 739 neonatal, self-limited, 1603 portal hypertension with, 1656 surgical lesions with, in infancy, 1603, 1613-1615, 1614f. See also Biliary atresia; Choledochal cyst. Jejunal interposition, for esophageal replacement, 1065, 1100-1101,1101t Jejunectomy, consequences of, 1371, 1371f, 1372 Jejunoileal atresia and stenosis, 1269-1284 classification of, 1275-1276, 1276f clinical presentation of, 1271, 1271t colonic atresia with, 1493
Jejunoileal atresia and stenosis (Continued) diagnosis of, 1271-1272, 1272f-1274f differential diagnosis of, 1272, 1274-1 275, 1275f vs. meconium ileus, 1293 etiology of, 1270 Hirschsprung's disease with, 1528 historical understanding of, 1269, 1270 incidence of, 1269 jejunal feeding in, 1481 malrotation with, 1270, 1272, 1274, 1283, 1346 meconium ileus associated with, 1271, 1271t, 1274-1275, 1275f, 1282, 1293, 1294f morbidity and mortality in, 1282-1284,1283t treatment of, 1276-1281, 1278f-1281f postoperative care in, 1282 Jejunostomy. See also Enterostoma(s). choices for, 1480f-1481f, 1480t, 1484 choledochal cyst excision with, 16261631, 1627f-1628f gastroesophageal reflnx and, 1130-1 131 in chronic intestinal pseudo-obstruction, 1549 in necrotizing enterocolitis, 1441 indications for, 1480-1482, 1483f nutrition and, 199, 202, 203 technical aspects of, 1485-1486 Jejunum, Hirschsprung's disease in, 1531, 1540 Jeune's disease, acquired, 901 Jeune's syndrome, 915-917,917f Joint (s) bone tumor and reconstruction ofjoint, 662, 662f-665f retention ofjoint, 660, 661f cartilaginous lesions about, 652, 652f Crohn's disease and, 1454 infection in, 2033,2034f, 2039-2041, 2040t, 2041t gonococcal, 2040, 2044 in Lyme disease, 2044 tuberculous, 2042, 2044 trauma to, 34'2, 344 ligament injury in, 350 ulcerative colitis and, 1464 Jugular vein injury to, 378, 380 internal aneurysm of, 2129 thrombophlebitis of, 2132 thrombosis of, infected, 823 Juvenile nasopharyngeal angiofibroma, 821 Juvenile papillomatosis, of breast, 891 Juvenile polyps bleeding with, 1387, 1415, 1416 classification of, 1414 in polyposis syndromes, 1414, 14161417, 1417f colon carcinoma in, 519 intestinal obstruction caused by, 1364 isolated, 1414-1416, 1415f
Volume 1, pages 1-1140; Volume 2, pages 1141-2146.
Kaposiform hemangioendothelioma, 2094, 2097-2098,2097f, 2105 salivary gland, 839 Karyotyping. See also Chromosomal abnormalities. fetal, 78 of tumors, 419, 420t Kasabach-Merritt syndrome, 495, 496, 826 kaposiform hemangioendothelioma with, 2097-2098,2097f, 2105
xxxvi
INDEX
Kasai procedure. See Portoenterostomy. Kawasaki disease, 848, 21 15, 21 17 hydrops of gallbladder in, 1636,2115 Kelly technique, for bladder exstrophy, 1853-1855, 1854f-1855f Keratinocytes, cultured, for burn patient, 391 Ketamine, 238t, 239 caudal, 248 for burn patients, 394, 394t Ketoconazole, in burn patients, 393 Ketone bodies, in neonate, 97, 100, 102, 103-104, 103f surgery and, 107-108 Ketorolac, 238-239,238t with sevoflurane anesthesia, 229 17-Ketosteroids, 595t, 624 Ketotic hypoglycemia, 1680-1681, 1681f Kidney (s). See also Renal entries. bladder dysfunction and, 1817-1818, 1818f, 1819 in myelodysplasia, 1821, 1821f congenital anomalies of, 1705-1706, 1715-1720, 1717f-1720f. Seealso Duplication(s), genitourinary; Renal dysplasia. anorectal malformations with, 1567 duplications as, 1743, 1744f, 1758 extrarenal pelvis as, 1728, 1728f in prune-belly syndrome, 1781, 1783, 1783f, 1786, 1789 trauma in setting of, 318 crossed ectopia of, 1717, 1719-1720, 1720f cystic disease of, 17061713 acquired, 1713 benign multilocular, 1712-1713, 1712f caliceal diverticulum as, 1713 classification of, 1706, 1706t in tuberous sclerosis, 1709 in von Hippel-Iindau disease, 1709-1710 multicystic dysplastic kidney as, 1705, 1706, 1710-1711, 1710f-1711f, 1725, 1727, 1762 polycystic. See Polycystic kidney disease. simple cyst as, 1713, 1713f ectopic, 1715-1716, 1717f-1718f with ureterocele, 1762, 1763 embryology of, l705,1715,1716f, 172G1725 horseshoe, 17161719, 1718f-1719f Wilms' tumor with, 457, 458f pelvic, 1715, 1717f-1718f thoracic, 1715-1716, 1717f trauma to, 320-326 algorithm for management of, 322f anatomic considerations in, 317-318 clinical features of, 318 complications of, 324 diagnostic evaluation in, 318-319, 320 epidemiology of, 317 grading of, 320,321,321f; 321t, 323,325 mechanisms of, 317 penetrating, 323 vascular, 322, 323-324, 325f tumor lysis syndrome and, 588 tumors of. See also Wilms' tumor. clear cell sarcoma as, 450, 454, 4 5 4 ~ 455, 460,461 in horseshoe kidney, 1718-1719 rhabdoid, 450, 451f, 460 synovial sarcoma, primary, 546 Kidney stones. See Urolithiasis. Kikuchi's disease, 848 Kimura (Iowa) intestinal lengthening procedure, 1378-1379, 1378f Kimura patch procedure, 1540, 1542f, 1547 King-Denborough syndrome, malignant hyperthermia in, 231
Kininogen, high-molecular-weight, 186 kit gene and kit protein germ cell tumors and, 554, 556 in cerebrospinal fluid, 556 in gastrointestinal stromal tumors, 516, 517t Kleeblattschadel malformation, 798, 798f Klinefelter's syndrome germ cell tumors in, 420 mediastinal teratoma as, 565 gynecomastia in, 892, 2068 Klippel-Feil syndrome, 2027, 2064, 2071 Klippel-Trenaunay syndrome, 2098,2101, 2101f, 2114, 2128-2129, 2129f Klumpke's palsy, 405 Knee congenital dislocation of, 2025-2026, 2026f reconstruction of, after tumor resection, 662f-6635 666 Kock pouch, 1467,1799,1800, 1824, 1825, 1827f, 1833 Kropp procedure, 1829,1830f, 1831 Krukenberg procedure, 2073 Kumar clamp technique, 1639, 1639f Kyphosis, congenital, 2026f, 2027, 2028-2029, 2029f
L Labia, lymphedema of, 2144 Labial adhesions (fusion), 1903, 1942 kaboratory studies in child abuse, 401t of ascitic fluid, 1408-1409, 1409t of burn patient, 386 of parenteral nutrition patient, 210, 21 1t of trauma patient, 272 Laceration Of canal, external, 817 pericardial, thoracoscopy of, 287 pulmonary, air embolus and, 282 repair of, topical anesthesia for, 244 soft tissue, 352 Lactase deficiency, 197, 202 Lactate, postoperative levels of, 106 Lactate dehydrogenase (LDH) ~ w ifamily ~ ~tumor ' ~ and, 654 germ cell tumors and, 556, 565, 568, 595, 607 in pleural fluid, with empyema, 1018, 1019f neuroblastoma and, 470, 487 non-Hodgkin's lymphoma and, 589 Lactated Ringer's solution for resuscitation of burn patient, 386, 387, 388t, 389 of trauma patient, 271 intraoperative, 225-226 Lactic acidosis in short.bowel syndrome, 1372, 1378 in thiamine deficiency, 206 Lactose, 197, 202 Lactose intolerance, after bowel resection, 1282 Ladd procedure, 1352, 1353-1354, 1355f, 1356 adhesive obstruction secondary to, 1359f Ladd's bands, 1261, 1262, 1348, 134gf, 1362, 1362f division of, 1352, 1353-1354, 1355f radiographic appearance and, 1350, 1353f Laminin, aganglionosis and, 1525 Langerhans cell histiocytosis, 833 diagnostic features of, 544t radiation therapy for, 657 Langerhans cells, 2062 Lansoprazole, for peptic ulcer disease, 1229 Lap Band. See Gastric band, laparoscopic adjustable.
Volume 1, pages 1-1140; Volume 2, pages 1141-2146.
Laparoscopy. See also Endoscopy; Minimal access surgery; Robotic surgery; specific procedure. diagnostic, 439-440 in abdominal trauma, 297 for diaphragmatic injury, 297, 313 for splenic pseudocyst, 299, 300f of ovarian lesions, 599-600, 599f, 601, 602, 613 operative stress and, 107 postoperative ileus and, 1361 simulation of, 60, 61, 68-69, 69f Lap-belt injuries. See Seat-belt injuries. Large cell lymphomas, 582, 583,583f, 584 Laryngeal atresia, 987 Laryngeal cleft, 995-996, 995f Laryngeal mask airway, 973,976 Laryngeal nerve recurrent, risk to in lung transplantation, 772 in piriform sinus surgery, 869, 869f in total thyroidectomy, 856 superior branchial arches and, 862, 863 risk to, in piriform sinus surgery, 869, 869f Laryngeal webs, 987-988, Y87f, 989,990 Laryngocele, 830 Laryngoesophageal cleft, 972,973 Laryngomalacia, 829, 829f, 984,986987, 987f laryngoscopy of, 973,973f Laryngoscopy, 971-973,972f-973f in airway obstruction, 983 Laryngospasm inhalation anesthesia and, 223, 229 thiopental induction and, 233 Laryngotracheal stenosis, 990-994, 991t, 992f-993f, 992t. See also Subglottic stenosis; Tracheal stenosis. Laryngotracheobronchitis, 828, 830 Laryngotracheoesophageal cleft, 995-996, 1072-1074, 1073f-1074f Laryngotracheoplasty, posterior graft, 989 Larynx. See also Airway; Vocal cords. anatomy of, 267,827,983-984 congenital anomalies of, 829-830, 829f-830f functions of, 827, 983 inflammatory disease of, 830-831 neoplasms of, 831,83lf, 989,989f trauma to during intubation, 129 vocal cord paralysis secondary to, 988 Laser ablation for vocal cord immobility, 989 in subglottic stenosis, 991-992 of capillary malformation, 2106 of esophageal lesions, 1043 of subglottic hemangioma, 994-995, 2105 Lasers, surgical, 41 Lasix renography. See Diuretic renography. Latex sensitivity, 232 bladder augmentation and, 1796 Laxative therapy, 1550, 1550f, 1592, 1594 for anal fissure, 1597 for intestinal neuronal dysplasia, 1562 LBP ( l i ~ o ~ o l ~ s a c c h a rbinding ide protein), 168, 169f, 172 LDH. See Lactate dehydrogenase (LDH). Leadbetter-Politano ureteral reimplantation, 1748f LeFort procedures, 798-799,800,800f after cleft repair, 811 Leg length. See Limb length inequality. Leiomyoma, ovarian, 614, 615
Leiomyosarcoma breast, 892 gastric, 515 intestinal, 1364 ovarian, 615 soft tissue, 543 Lemierre's syndrome, 823 Length, body, 194, 195 Leptomeninges cyst of, enlarging, 366 sarcomas of, 546 vascular anomaly of, 2098 LET (linear energy transfer), 43, 44 Leucovorin, 422 Leukemia acute lymphoblastic, torticollis in, 877 acute myelogenous, ovarian granulocytic sarcoma in, 615 arterial thrombosis in, 2115 fungal abscesses in, 1644 gene therapy as cause of, 15, 18 ovarian involvement by, 615 Poland's syndrome with, 907 testicular involvement by, 625 Leukocyte adhesion deficiency, 160, 161 delayed cord separation in, 1146 Leukocyte chimerism, 685-686, 687, 689, 690f, 691, 692f, 695 Leukocyte count in appendicitis, 1504 in neonatal sepsis, 171 Leukocyte scan in appendicitis, 1504 in musculoskeletal infection, 2035 Leukocyte-reduced blood products, 188, 189. 190 Leukocytes, in postoperative stress response, 106 Leukodystrophy, central dysmyelinating, 1523 Levobupivacaine, 243, 243t epidural infusion of, 248t Leydig cell tumor ovarian, 606-607 testicular, 622, 623t, 624 Leydig cells chemotherapy resistance of, 626 in cryptorchidism, 1197, 1198 LHR (lung-to-head ratio), 77, 83, 84,937 Lich-Gregoir procedure, modification of, 1749f Lidocaine epidural infusion of, 248t for fracture reduction, of hand, 352 for local anesthesia, 243, 243t in topical anesthetics, 244, 244t Life support. See ABCDE sequence; Advanced Trauma Life Support (ATLS); Extracorporeal life support (ECLS) Li-Fraumeni syndrome, 418, 421 nonrhabdomyosarcomatous soft tissue sarcomas in, 543 osteogenic sarcoma in, 653, 653f, 654 rhabdomyosarcoma in, 524525 I.igament(s), trauma to, 351 in hand, 350 Ligament of Treitj. in atypical malrotation, 1350, 1352f normal intestinal fixation and, 1346, 1346f, 1350, 1352f LigaSure vessel sealing device, 1696 Light index, 1020 Limb deficiency, congenital, 2050-2054, 2051f-2055f, 2054t. See also Foot (feet) ; Hand (s). phantom pain in, 2058
Limb hypertrophy. See Hemihypertrophy. Limb ischemia. See Ischemia. Limb length inequality after fracture, 339 after osteomyelitis, 2039 after septic arthritis, 2041 hip dysplasia with, 2019 iatrogenic vascular injury with, 380 multiple enchondromatoses with, 651,654 multiple hereditary exostoses with, 654 vascular malformations with, 2101, 2101f, 2107-2108, 2112, 2114, 2128, 2129f Linear accelerator for radiosurgery, 45-46,46f, 47 for radiotherapy, 44 Lingual thyroid, 826, 850, 864, 870, 871f Linoleic acid, 197 in biliary atresia, 212 Lip. See also Cleft anomalies. fistulas (pits) in, 805, 811-812 herpetic gingivostomatitis of, 822 pleomorphic adenoma of, 816 Lipid. See Fat(s). Lipid A, 158-159, 168. See also Lipopolysaccharide (LPS, endotoxin). sepsis therapies derived from, 172, 173 Lipid cell tumor. See Steroid cell tumor. Lipid emulsion, intravenous, 204-206 hypertriglyceridemia and, 208 iron dextran and, 207 Lipofibroma, of breast, 891 Lipoma(s) in Gardner's syndrome, 1422 intraspinal, 1594, 1806f, 1809f, 1810, 1822, 1993-1994,2027,2102 Lipopolysaccharide (LPS, endotoxin), 158-159, 161, 164, 165 absorption of, in preterm intestine, 1433 burns and, 384 in systemic inflammatory response syndrome, 168, 169f, 172, 173 necrotizing enterocolitis and, 1432, 1433, 1435 Lipopolysaccharide-binding protein (LBP), 168,169f, 172 Lipoprotein (a), thrombosis and, 187 Lipoprotein lipase heparin as cofactor of, 207 in neonate, 102, 103, 103f in systemic inflammatory response syndrome, 170 Lipoprotein X, 1606 Liposarcoma, 547 of breast, 892 Liquid ventilation, 126127,945, 945f Listeria monocytogenes, in neonatal sepsis, 170, 172 Lithotripsy, extracorporeal shock wave (ESWL), 1748,1751, 1752 Little's area, 818, 820 Liver anatomy of, segmental, 507-508,507f-508f, 734,734f arteriovenous malformation in, 495, 497, 2102 biopsy of, 440 biliary atresia and, 1606 biliary hypoplasia and, 1613, 1614 in portal hypertension, 1657 of tumors, 504 hemorrhage secondary to, 442 cyst of, nonparasitic, 499 fibrosis of, 1652-1653,1656, 1657, 1659 in polycystic kidney disease, 1707, 1709 Volume 1, pages 1-1140; Volume 2, pages 1141-21
Liver (C;ontinued) hematoma of abscess secondary to, 1643 in birth trauma, 405, 405f herniation of, fetal, 83, 84 infections of, 1642-1646,1642t, 1643f, 1646f of burn patient, fat deposition in, 392, 393 regeneration of, after resection, 26, 509 resections of ex vivo, 508 hemostasis in, 508 regeneration following, 26, 509 segmental anatomy and, 507-508, 507f-508f technique of, 507-509 tissueungineered, 22, 26-27 trauma to abscess secondary to, 1643 biliary duct injury in, 303, 304f cysts secondary to, 499 complications of, 299, 299f-300f imaging of, 295, 296f laparoscopic repair of, 297 nonoperative treatment of, 295, 297-298, 297t, 298t, 299,300 operative intervention for, 298, 300-302, 300f-301f, 301t tumors of, 502-51 1. See also Hepatoblastoma; Hepatocellular carcinoma. ablative therapies for, 51 1 adjuvant therapy for, 509-510,510f algorithm for diagnosis and treatment of, 503f benign, 495-499, 496f-499f hemangioma as, 497, 498, 2102, 2105f, 2106 incidence of, 505t biopsy of, 504 hemorrhage secondary to, 442 carcinoid, 518 clinical presentation of, 503 differential diagnosis of, 504-505 abscess in, 1644 epidemiology of, 502-503,502t, 505t follow-up of, 51 1 genetics and molecular biology of, 502 histology of, 505, 505f imaging of, 504, 504f laboratory studies with, 503 prognosis of, 51 1 radiation therapy for, 510 staging of, 505-506, 505t, 506f surgery for, 506-509 teratoma as, 496, 499, 505, 557 transplantation for, 509, 509f, 733, 739-740 Liver disease. See alto Cholestasis. clotting factor deficiencies in, 186 hepatocellular carcinoma and, 502 in short-bowel syndrome, 1373 metabolic, transplantation for, 733 obesity-related, 1246 portal hypertension caused by, 1652-1653, 1653t primary peritonitis in, 1475, 1476 trauma patient with, 274 Liver failure acute, transplantation for, 732, 733, 734 disseminated intravascular coagulation in, 186 extracorporeal support in, 26-27 in parenteral nutrition patient, 209, 744, 745 parenteral amino acids and, 204 Liver function tests, in biliary atresia, 1606, 1611
xxxviii INDEX Liver transplantation, 731-741 anatomical basis of, 734, 734f cell replacement as, 26 combined with intestinal transplant, 742, 744, 745,746f-747f, 748-749, 750 in Hirschsprung's disease, 1540 combined with lung transplant, 766 complications of acute pancreatitis as, 1673 infectious, 737, 739, 740t, 1643 portal hypertension as, 1653, 1654, 1654f technical, 737 donor operation for, 734735, 735f extracorporeal support prior to, 2 6 2 7 history of, 685, 686, 686f, 686t, 688-689, 6885 693,731 immunosuppression for, 737, 738t, 739, 740-741 indications for, 732-733, 732f absent portal vein as, 2126 a,-antitrypsin deficiency as, 1606 biliary atresia as, 732, 732f, 739, 1608, 1609, 1610, 1612, 1613 biliary hypoplasia as, 1614 hepatopulmonary syndrome as, 1656 total parenteral nutrition and, 1373 tumors as, 509,509f, 733, 739-740 veno-occlusive disease as, 781 organ allocation for, 731, 733-734, 740 organ preservation for, 694, 694f, 695, 734-735 outcome of, 739-741 postoperative care in, 737 rejection in, 739 renal transplantation with, for oxalosis, 71 1 transplantation operation in, 735-736, 736f Lizard bites, 353 Lobectomy, pulmonary fetal, 82t, 83 for abscess, 1017 for bronchiectasis, 1014 thoracoscopic, 977 Local anesthetics, 243, 24% for epidural infusion, 248, 248t for fracture reduction, of hand, 352 for wound repair, in soft tissue injury, 352 topical formulations of, 244, 244t Long QT syndrome, ventricular tachycardia in, 153 Loop diuretics, calcium losses caused by, 207 Loop ureterostomy, 1792, 1793f Loopography, 1573-1574, 1573f-1574f Loperamide, 1373, 1466 Lorazepam, for burn patients, 394, 394t Lordosis, congenital, 2026f, 2027 Loss of hetero~ygosity(LOH), in Wilms' tumor, 446,447,448, 459 Low-birth-weight infant, 89, 90, 9lf. See also Premature infant. growth rate in, 194 hepatoblastoma in, 502 necrotizing enterocolitis in, 1427, 1428, 1429 neonatal hyperglycemia in, 102 neonatal infection in, 170, 173 obesity risk in, 1245 parenteral nutrition for, 204, 206 respiratory quotient of, 97 LPS. See Lipopolysaccharide (LPS, endotoxin). Luciferase, 38, 39 Lumbar spine. See also Spine. trauma to, 346, 368 in seat belt injury, 311, 346f, 368
Lung(s). See also Pulmonary entries; Respiratory entries. abscess of, 1015-1017, 1017f biopsy of after lung transplant, 771 core needle, 439 in bone marrow transplant patient, 781 in HIV-infected patient, 1008, 1010 open, 1023-1024, 1024f thoracoscopic, 440-442,44lf, 977-980 cystic lesions of, 955-959, 956f, 958f-959f. See also Bronchogenic cyst; Cystic adenomatoid malformation, congenital. malignancy in, 641, 642, 642t, 643t, 644, 957 vs. pneumatocele, 1015 development of, 114-1 17,115f-116f, 933-934 congenital diaphragmatic hernia and, 934,935 hemorrhage in, 1014, 1015f after lung transplant, 772 in pulmonary vascular disease, 766 infections of. See also Pneumonia. barriers to, 157 bronchiectasis secondary to, 1012-1014, 1013f echinococcal, 1005, 1005f epidemiology of, 1001 in immunocompromised patient, 1001 with cancer, 1005-1008, 1006f-1007f with cystic fibrosis, 1010-1011 with HIV infection, 1008-1010, 1009f open biopsy of, 1023-1024, 1024f viral bronchiolitis as, 1004-1005, 1004f inhalation injury to, 394-395 lymphangiectasia in, 2140 physiology of, 117-121, 118f-119f, 118t, 121f trauma to, 269, 272, 276, 277, 279, 281-283, 282f-283f computed tomography of, 278 epidemiology of, 275, 275t tumors of, 640-646 benign, 640-641,64Ot, 644 malignant, 640, 640t, 641-642, 642f-644f, 644 carcinoid, 518, 641 cystic malformations with, 641, 642, 642t, 643t, 644,957 fibrosarcoma as, 518 rhabdomyosarcoma as, 535,536, 642, 643t, 644f metastatic, 640, 644-646, 645t from benign bone lesions, 652 from osteosarcoma, 645-646,645t, 666 from rhabdomyosarcoma, 526, 536, 645 from thyroid carcinoma, 855,856857 from Wilms' tumor, 448-449, 455, 645 thoracoscopy of, 440,441f thoracoscopy of, 440-442 volumes of, 118, 118f Lung transplantation, 765-776 complications of, 771-775, 773f-774f contraindications to, 768-769, 769t extracorporeal life support following, 142 for congenital diaphragmatic hernia, 767, 945 for cystic fibrosis, 765-766, 773, 775, 1011 future considerations in, 776 history of, 685, 686t, 693, 765 immunosuppression for, 770-771,771 t, 774 indications for, 765-768, 765t living donor, 770, 776 lung growth and function after, 775-776
Volume 1, pages 1-1140; Volume 2, pages 1141-2146.
Lung transplantation (Continued) operative technique in, 770 organ procurement for, 769-770 post-transplant surveillance with, 771 retransplantation for failure of, 768, 774 survival after, 775, 775f Lung-to-head ratio (LHR), 77, 83, 84, 937 Lupus anticoagulant, 187, 2130 Lupus erythematosus antiphospholipid antibodies in, 2121 esophageal dysmotility in, 1111 maternal, neonatal heart block and, 151 Luteinized thecoma, 595t, 605 Luteinizing hormone after orchiectomy or oophorectomy, 556 cryptorchidism and, 1197 Luteinizing hormone-releasing hormone, for cryptorchidism, 1200 Luteoma, stromal, 606 Lyme arthritis, 2044 Lymph, abdominal, 1407 Lymph node metastases, detection of isosulfan blue in, 549, 549f nanoparticles for, 59 radiolabeled antibodies for, 47 Lymph nodes, cervical, anatomy of, 844, 844f-845f Lymphadenectomy, iliac and retroperitoneal, robot-assisted, 53 Lymphadenitis cervical. See Cervical lymphadenopathy. mesenteric, 1505 Lymphadenopathy cervical. See Cervical lymphadenopathy. in cat-scratch disease, 16441645 mediastinal, 1027, 1028 Lymphangiectasia, 2137, 2140, 2141 Lymphangiography contrast, of lymphatic malformation, 2107 radionuclide in chylothorax, 1027 in chylous ascites, 2140 of lymphatic obstruction, 2140 of lymphedema, 2141,2142 Lymphangioma, 2137-2140,2138f-2139f. See also Lymphatic malformations. breast, 888-889 chylothorax associated with, 1025, 1025f, 1027 chylous ascites associated with, 1410 classification of, 2138 OK432 treatment for, 1404,2107, 2139 pathogenesis of, 2137 terminology for, 2098 vs. mesenteric-omental cyst, 1399 Lymphangiosarcoma, 2137,2142 Lymphangitis, 2138, 2141, 2142 Lymphatic hypoplasia, 2101 Lymphatic malformations, 2098-2099, 2099f. See also Cystic hygroma; Lymphangioma. chylothorax secondary to, 1027, 2140-2141 chylous ascites associated with, 1410, 2107, 2140 head and neck, 826 histopathology of, 2095 in complex-combined malformation, 2101, 2101f intestinal obstruction by, 1365-1366 lymphangiectasia as, 2137, 2140, 2141 lymphedema caused by, 2141 management of, 21062107 with OK-432, 1404, 2107 mediastinal, 2099, 2099f, 2107
Lymphatic malformations (Continued) mesenteric or omental cyst as, 1366 pathophysiology of, 2137 radiologic characteristics of, 2103 salivary gland, 835, 838, 839 vs. hemangioma, 2097 Lymphatic obstruction chylous ascites associated with, 1410 intestinal, 2140 lymphatic malformations secondary to, 2137 lymphedema caused by, 2141 pulmonary, 2140 Lymphatic system anatomical organization of, 2137 embryology of, 2137,2138f interstitial fluid and, 2137 Lymphedema, 2099,2137,2140,2141-2144, 2141f, 2143f-2144f upper extremity, 2141,2144 Lymphoblastic lymphoma, 580, 581-582, 583, 583f clinical presentation of, 584, 584f treatment of, 587,588t Lymphocele, after renal transplantation, 707 Lymphocytes, 161, 162-163, 165. See also B lymphocytes; T lymphocytes. development of, 581,581f-582f immunosuppressive agents and, 707, 708 in chyle, 1026, 1027 in Crohn's disease, 1453, 1455, 1456 in human milk, 202 in ulcerative colitis, 1463, 1466 transfused in immunodeficient patient, 189 in late let concentrate. 190 ~ym~h'ocytic interstitial pnkumonitis, 1008, 1009f Lymphocytic thyroiditis, chronic, 852 Lymphoid hyperplasia intestinal polyps as, 1414, 1418-1419, 1419f intussusception caused by, 1319, 1327-1328 Lymphoid polyps, 1418-1419, 1419f Lymphoma. See also Hodgkin's disease; NonHodgkin's lymphoma. in oral cavity and pharynx, 827 intestinal obstruction in, 1364 intussusception with, 1320, 1321 mediastinal lesions in, 959, 960t, 961 thoracoscopic biopsy of, 977 Lymphoproliferative disease, immunosuppression and in neuroblastoma, 484 post-transplant, 584-585, 712, 739, 750-751, 762,774 Lymphosarcoma, ileal, 1335 Lynch syndrome, 520 Lysosomes, 158, 160, 161
MAC (minimum alveolar concentration), 222f, 222t, 228 MACE procedure, 1595 Macroglossia, 825 lymphatic malformation with, 2099 Macrophages, 161-162, 163, 164, 165, 166 bacterial evasion of, 159 in burn patient, 384 in obesity, 1244 in systemic inflammatory response syndrome, 168, 169, 169f, 172 neonatal, 167 Macrostomia, 789, 789f
Mafenide acetate (Sulfamylon), 383, 389-390, 389t Maffucci syndrome, 652, 2128, 2129 ovarian tumors in, 593, 615 Magnesium failure to thrive and, 214 serum, in neonate, 95 short-bowel syndrome and, 1372 Magnetic resonance angiography (MRA) in portal hypertension, 1657 of conjoined twins, 2082, 2083, 2085 of hepatic tumors, 504, 504f of trauma, 377 catheter-related, 380 cerebral, 358, 366 Magnetic resonance cholangiopancreatography in biliary atresia, 1607 in pancreatitis, 1674, 1675, 1676f of ductal anomalies, 1625,1626 of pancreas divisum, 1676, 1676f of pancreatic trauma, 309 Magnetic resonance imaging (MRI), 36-37 as virtual reality data source, 63, 64f, 67-68 fetal, 37, 77 of cervicofacial teratoma, 564 of congenital diaphragmatic hernia, 936 of conjoined twins, 2080 of cystic lung lesion, 957 of esophageal atresia, 1056 of intestinal atresia, 1271 of sacrococcygeal teratoma, 559,560f functional, 37 brain tumors and, 673,677 in image-guided radiation therapy, 429, 430 in image-guided surgery, 42 intraoperative, for brain tumor resection, 673 molecular imaging with, 40 of pelvic lesions, 597 of salivary glands, 836 of trauma cerebral, 358, 359, 361, 363 musculoskeletal, 342 spinal, 346, 346f, 369 thoracic, 278, 285 of tumors brain, 672-673 hepatic, 504, 504f ultrafast, 3 6 3 7 Magnetic resonance spectroscopy, 547 Magnetic resonance urography (MRU), 1730, 1731f Magnetic resonance venography (MRV), 2126,2127,2128f MAGPI (meatal advancement glansplasty) , 1880-1882, 1881f-1882f Maintenance fluid requirement (MFR), =5 Mainz pouch, 1826 Major histocompatibility complex (MHC), 161, 163, 165, 166, 167 Malabsorption in cystic fibrosis, 1299 in short-bowel syndrome, 1371-1372, 1373 lymphangiectasia with, 2140 secondary to necrotizing enterocolitis, 1443 secondary to urinary tract reconstruction, 1837 Malussaiafurfur infection, catheter-related, 210 Malignant fibrous histiocytoma, 541, 542, 543 of breast, 892 of lung, 641 Malignant hyperthermia, 231-232,232t Malignant melanoma of soft parts, 547 Mallory-Weiss tear, 1041
Volume 1, pages 1-1140; Volume 2, pages 1141-2146.
Malnutrition assessment of, 194-195 failure to thrive in, 213-214 in burn patients, 393 in surgical patients, 21 1 Malone procedure, 1587 Malrotation. See also Intestinal rotation and fixation; Volvulus. asymptomatic, 1348 atypical, 1346, 1350, 1352f, 1354, 1356 definition of, 1346 Mammary duct ectasia, 888 Mandatory minute ventilation, 123, 125 Mandible hypoplasia of, 789, 789f distraction osteogenesis for, 2063 in Pierre Robin sequence, 803, 812 osteotomy of, simulation of, 68, 68f overgrowth of, lymphatic malformation with, 2099 Mandibulofacial dysostosis, 789, 79Of-79lf, 791 Manganese, 198t, 199, 206 Mangled Extremity Severity Score (MESS), 345, 379,379t, 2055, 2056t Mannitol for brain injury, 273, 364 for electrical burns, 396 Mannose receptors, 158 Mannose-binding lectin, in cystic fibrosis, 12 Manomeq. See Anorectal manometry; Colonic manometry; Esophageal manometry. Mapleson D system, 234f Marfan's syndrome arterial degeneration in, 21 14 with traumatic aortic dissection, 287 bronchiectasis in, 1013 inguinal hernia in, 1188 pectus excavatum in, 894, 899 Marijuana gynecomastia caused by, 892 macromastia caused by, 887 Masculinization. SeeVirilization. Mask airway, laryngeal, 973, 976 Mask ventilation, of trauma patient, 267, 269 Mastitis, neonatal, 887 Mastoid, 813 cholesteatoma extending to, 816 temporal bone fracture and, 816,817 Mastoidectomy, 815 Mastoiditis acute, 815-816,816f intracranial abscess secondary to, 2009,2010 Mathieu procedure, 1880, 1882-1883, I884f, 1893,1894 Matrix metalloproteinases, 418 angiogenesis and, 2095, 2104 Mayer-Rokitansky-Kiister-Hauser syndrome, 19361937 May-Thurner syndrome, 2127 McBurney's point, 1501, 1502, 1503, 1506 McCune-Albright syndrome, 593 McGoon index, modified, 998 McIndoe procedure, 1937-1938, 1938f McKusick-Kaufman syndrome, 1936 MCP-1 (monocyte chemotactic protein l ) , 160, 161, 165 MDCT (multidetector computed tomography), 35,35f Measles virus, Crohn's disease and, 1453 Mechanical ventilation, 123-1 29 breath phases in, 123-124 classification of ventilators for, 124 complications of, 123, 125, 126, 128-129
Mechanical ventilation (Continued) airway obstruction as, 983, 990 diaphragmatic eventration as, 946 control mode in, 124 extreme alternatives to, 126127. See also Extracorporeal life support (ECLS). goals of, 123 historical perspective on, 123 in brain injury, 363, 364t in congenital diaphragmatic hernia, 938, 939-940,942,943 in emergency management, 267,269 in neonate, neurodevelopmental impairment and, 140 in sepsis or SIRS, 172 in spinal cord injury, 370 investigational adjuncts to, 127 management of respiratory failure with, 127-129 modes of, 124-126 neuromuscular blocking agents for, 229 prior to extracorporeal life support, 135 pulmonary compliance and, 119, 119f, 124, 125, 127, 128 tidal volume and, 120, 124, 125, 126, 128 initial setting for, 127 time constants and, 120, 127 tracheotomy for, 984 weaning from, 124, 125, 127, 128 opioids and, 242 with extracorporeal life support, 138 Meckel's diverticulum, 1145t, 1147f, 1148, 1304-1311 anatomic variants of, 1307f anomalies associated with, 1305 anomalies related to, 1304, 1307f clinical manifestations of, 13061311 hemorrhage as, 13861387 intnssusception as, 1309, 1319, 1321, 1335 ectopic gastric mucosa in, 1386 embryogenesis of, 1304, 1305f-1306f incidence of, 1304 incidentally discovered, 1304, 1305-1306 inflammatory pseudotumor of, 1365 technetium 99m scan of, 1308, 1308f, 1386 vs. appendicitis, 1309, 1505 vs. ileal duplication, 1392 Meckel's scan. See Radionuclide studies, of gastric mucosa. Meconium . albumin concentration in, 1290-1291, 1292 passage of normal, 1592 with anorectal malformation, 1569, 1571 Meconium aspiration syndrome extracorporeal life support for, 140, 140t mechanical ventilation for, 127 Meconium cyst, 1291, 1296, 1298, 1298f Meconium ileus, 1289-1 300 adolescent patient with, 1498, 1498f clinical presentation of, 1291, 129lf complicated, 1275f. 1291, 1298, 1298f complications of, 1299-1300 diagnostic evaluation of, 1291-1293, 1291f-1293f differential diagnosis of, 1293-1 294, 1294f-1295f genetics of, 1289-1290 historical perspective on, 1289 jejunoileal atresia with, 1271, 1271t, 12741275, 1275f, 1282,1293, 1294f management of nonoperative, 12941296 operative, 12961298, 1296f-1297f postoperative, 1298-1 299
Meconium ileus (Continued) necrotizing enterocolitis in, after hyperosmolar enema, 1429 pathogenesis of, 1290-1291 results of treatment for, 1300, 1300f short-bowel syndrome secondary to, 1369 without cystic fibrosis, 1294, 1299 Meconium ileus equivalent, 1291, 1299, 1300 Meconium peritonitis, 1291, 1296, 1298 jejunoileal atresia with, 1271, 12735 1274, 1282,1283 Meconium plug syndrome, 1294, 1295f, 1299, 1369, 1496, 1497f with Hirschsprung's disease, 1519 Meconium staining, gastroschisis and, 1160 Median nerve lipofibromatous hamartoma of, 2075 macrodactyly and, 2075 test of, 348-349,349f Median sternotomy, mediastinal infection secondary to, 1028 Mediastinal tumors cystic, 959-961, 960t, 961f, 962-963 germ cell, 557, 565, 567, 568, 959, 960t, 961,96lf, 962-963 lymphoma as, 581,583,584,584f, 586587, 586f, 588,959,960t, 961 in Hodgkin's disease, 576, 576f, 577,960t thoracoscopic biopsy of, 977 Mediastinitis, 1027-1028 from descending neck infection, 823, 1027 Mediastinotomy. See Chamberlain procedure. Mediastinnm anatomic subdivisions of, 959 branchial anomaly in, 869 chyle in. See Chylothorax. cystic lesions of, 955,959-966,96Ot, 961f-966f lymphatic malformation as, 2099, 2099f, 2107 enteric duplications in, 1393 thoracic trauma and, 269, 276, 278, 280 with aortic rupture, 288 thoracoscopic biopsy in, 441, 977, 980 thoracoscopic inspection of, 440 Mediterranean fever, familial, 1477 Medium-chain triglycerides, 202, 212-213 for chylous ascites, 1410 Medulla oblongata. See also Brainstem. tumor of, vomiting associated with, 672 Medulloblastoma, 674-675, 6755 679 in Turcot's syndrome, 1422 Medulloepithelioma, 671 Megacolon, toxic, 1463, 1464, 1464f, 1466 Megacystis-microcolon-intestinal hypoperistalsis syndrome, 1496, 1548-1549 Megaesophagus, 1112, 1113 microgastria with, 1237 Megalourethra, 1905, 1905f Megaureter, 1771-1780 assessment of, 1771-1772 in prune-belly syndrome, 1771, 1780, 1783, 1783f-1785f, 1787f-1788f, 1789 presentations of, 1771 repair of complications of, 1778-1 780, 1779f-1780f endoscopic injection in, 1776, 1777f imbrication in, 1775-1776, 1776f indications for, 1772-1 773 lower, 1773, 1774f-1777f, 1775-1776 peristalsis and, 1778, 1779f robot-assisted, 54t, 55 upper, 1773, 1776, 1778, 1778f summary of, 1780 types of, 1771, 1772f ~ l u m e1, pages 1-1 140; Volume 2, pages 1141-21
Melanocytic nevi, congenital, 2063-2064,2065f Melanoma, malignant nevus degenerating to, 2063, 2064 of soft parts, 547 Melanotic neuroectodermal tumors in infancy, 671 Melanotic spots, in Peutzjeghers syndrome, 1417, 1418 Melorheostosis, 21 14 Melphalan, 423t Membranoproliferative glomerulonephritis, renal graft loss in, 711 Membranous croup, 831 MEN. See Multiple endocrine neoplasia entries. Menarche, early, obesity and, 1245 Meninges. See Dura mater; Leptomeninges. Meningioma, 679 pineal region, 678 Meningitis cerebrospinal fluid leak and with otorrhea, 816 with rhinorrhea, 820 nasal encephalocele associated with, 820 neurenteric cyst and, 966 otitis media progressing to, 816 sepsis secondary to, in neonate, 170, 171, 173 skull fracture associated with basilar, 366 temporal bone, 817 Meningocele, 1808, 1821, 1987 anterior thoracic, 966 Meniscus, tissue-engineered, 22 Menstrual disorders congenital anomalies with, 1568 liver dysfunction with, 1613 Meperidine, 241, 241t for burn patients, 394t patient-controlled analgesia and, 243, 243t Mercaptopurine, 423t for Crohn's disease, 1455 for ulcerative colitis, 1466 Mesalamine for Crohn's disease, 1455 for pouchitis, 1471 for ulcerative colitis, 1465, 1466 Mesenchymal hamartoma, 495, 496,497-498, 497f-498f malignant transformation of, 505 vs. nonparasitic cyst, 499 Mesenchymoma, pulmonary, 642 Mesenchymopathies, intestinal, 1547, 1548 Mesenteric adenitis, 1505 Mesenteric and omental cysts, 1399-1405 as lymphatic malformations, 1365-1366 chylous ascites associated with, 1410 classification of, 1399, 1404, 1404f clinical presentation of, 1400-1402, 1401f-1402f, 1401t, 1402t definition of, 1399 diagnosis of, 1402, 1403f differential diagnosis of, 1400, 1400t vs. cystic lymphangioma, 1399 vs. duplication cyst, 1400, 1402 epidemiology of, 1399, I399 t etiology of, 1399-1400 locations of, 1400, 1400t malrotation associated with, 13461347 outcomes with, 1404 pathologic features of, 1400, 1401t summary of, 14041405 treatment of, 1403-1404, 14041 Mesenteric artery, superior, trauma to, 378 Mesenteric ischemia burn-related, 384 short-bowel syndrome secondary to, 1369
INDEX Mesenteric vein, superior, thrombosis of, 2130 Mesenteric vein-to-left portal vein bypass (Rex shunt), 1662,1662f, 1663, 1665 Mesentery gastrointestinal stromal tumors in, 515 of small intestine, desmoid tumor of, 1422 postoperative defects in, 1363 Mesoblastic nephroma, congenital, 450 Mesocaval shunt, 1660, 1663 Mesocolic (paraduodenal) hernia, 1348-1349, 1349f, 1350, 1356, 1361, 1362f MESS (Mangled Extremity Severity Score), 345, 379, 379t, 2055, 2056t Metabolic acidosis. See also Acidosis. after urinary tract reconstruction, 1800-1801, 1836 congenital diaphragmatic hernia with, 939 in cardiac failure, extracorporeal life support and, 135 in fetus and neonate, 96, 96t in malignant hyperthermia, 231, 232, 232t in necrotizing enterocolitis, 1435, 1440 in neonatal sepsis, 170 in parenteral nutrition patients, 207, 208, 209 mafenide acetate as cause of, 389 Metabolic alkalosis. See also Alkalosis. gastrocystoplasty as cause of, 1836 hypertrophic pyloric stenosis with, 1217 in fetus and neonate, 96t in hyperaldosteronism, 636 parenteral nutrition and, 207 Metabolic rate. See Resting energy expenditure (REE). Metabolic syndrome, 1246 Metabolism. See also Energy metabolism; Nutritional requirements. in burn patient, 391-393, 392f-393f in neonate of energy, 9699,98f biliary atresia and, 212 postoperative, 105, 105f, 107, 108, 212 protein and, 104, 108 of nutrients, 100-104, 101t, 103f postoperative, 106, 107-108, 107f, 21 1 stress and, 104-108, 105f, 107f Metaiodobenzylguanidine (MIBG), 630, 632 Metalloproteinases, 418 angiogenesis and, 2095, 2104 Metanephrine, urinary, pheochromocytoma and, 631,635 Metaphyseal fractures, 342, 347 in child abuse, 403 Metaphysis, 337, 338f tumors in relation to, 652f, 654 Metastasis, molecular biology of, 418, 419 Metatarsus adductus, 2023-2024, 2023f Methadone, 241, 241t, 242 patient-controlled analgesia and, 243, 243t Methemoglobin, 122 nitric oxide and, 162 Methemoglobinemia, prilocaine-induced, 243,244 Methicillin-resistant Staphylococcus aureus colonic strictures and, 1495 in osteomyelitis, 2037, 2038 in septic arthritis, 2040 Methimazole, 853 Methohexital, dose versus age, 222f Methotrexate, 422, 423t for Crohn's disease, 1455-1456 Methylene blue in thoracoscopic lung biopsy, 441 oxygen saturation and, 122
Methylprednisolone. See also Corticosteroid therapy. for transplant rejection heart, 761 kidney, 708 liver, 739 lung, 771 in spinal cord injury, 370 Metoclopramide for gastroesophageal reflux, 1126 postoperative ileus and, 1361 Metronidazole, for Crohn's disease, 1456, 1458 Metronomic dosing, of cancer chemotherapy, 422 MFR (maintenance fluid requirement), 225 MHC (major histocompatibility complex), 161, 163, 165, 166, 167 MIBG (metaiodobenzylguanidine), 630, 632 Microarray analysis, 40, 419-420, 425, 437 Microchimerism. See Leukocyte chimerism. Microcolon in functional ileus, 1519 in jejunoileal atresia, 1272, 1293, 1293f, 1294 in meconium ileus, 1275f, 1291,1292, 1293f in meconium peritonitis, 1273f in megacystis-microcolon-intestinal hypoperistalsis syndrome, 1496, 1548-1549 Microelectromechanical devices, 57-58, 57f as vascular networks, for tissue engineering, 27, 27f Microgastria, congenital, 1237-1238 Micrognathia, in cerebrocostomandibular syndrome, 917 Microlithiasis, testicular tumor with, 622, 623 Micropumps, for drug delivery, 58 Microsatellite instability, in colorectal carcinoma, 521 Microsomia, craniofacial, 788-789, 789f-790f Microtubules, inhibitors of, 422, 424t Microwave energy, for tissue ablation, 41 Midaortic syndrome, 21 18, 21 19, 2120, 2121 Midazolam for burn patients, 394, 394t in trauma patient, for intubation, 267 preoperative, 224, 229 propofol with, 233 Mikulicz resection, 1297, 1297f, 1298, 1299, 1300 Milk. See also Breast-feeding. cow's allergy to, 1386 constipation and, 1592, 1594 Crohn's disease and, 1453 for burn patient, 393 iron deficiency and, 180 vitamin Kin, 186 human, 202 epidermal growth factor in, 1430 erythropoietin in, 1430 fat content of, 100, 102, 212 immunoglobulins in, 104, 168, 202 in short-bowel syndrome, 1372 necrotizing enterocolitis and, 104, 1430, 1432, 1433, 1434, 1444 PAF acetylhydrolase in, 1445 preoperative feeding of, 224, 224t protective factors in, 1444 proteins in, 104 vitamin K deficiency and, 186 Milk curd syndrome, 1365 Milk line, 885, 886, 2066 Millard rotation-advancement cleft lip repair, 806807, 807f-808f Milrinone, for heart failure, 150t, 151 Volume 1, pages 1-1140; Volume 2, pages 1141-21
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Milroy's familial lymphedema, 2141 Mineralocorticoid receptors, blockade of, for heart failure, 148 Mineralocorticoids. See also Aldosterone; Corticosteroid therapy. adrenal synthesis of, 628, 629 insufficiency of, 636-637 Minerals. See Trace elements. Minimal access surgery. See also Laparoscopy; Robotic surgery. computerized image guidance for, 42,43 for biopsy, 437, 439442, 441f instruments for, 48, 48f robotic systems and, 47, 48, 51, 52,52t, 55,57 Minimum alveolar concentration (MAC), 222f, 222t, 228 Minoxidil, for hypertension, 2120 Minute ventilation, 120, 127 mechanical ventilation and, 123, 124, 125, 128 Mirror hand, 2075 Mirror syndrome, sacrococcygeal teratoma and, 85, 559 Misoprostol, peptic ulcers and, 1230 Mitomycin C, 428 for caustic esophageal injury, 1083 for laryngeal webs, 988 Mitosis, cell cycle and, 413, 413f Mitotane, for adrenocortical tumors, 635-636 Mitotic karyorrhexis index (MKI), of neuroblastoma, 472, 472t, 473f Mitral valve endocarditis of, 21 15-21 16,2116f trauma to, 285, 286f Mitral valve prolapse, pectus excavatum with, 898,922 Mitrofanoff procedure, 1794, 1795, 1797-1798, 1797f-17985 1832-1833, 1833f imperforate anus and, 1822, 1824 robot-assisted, 53, 54t with gastrocystoplasty, 1827 with sigmoid cystoplasty, 1826 with Young-Dees-Leadbetter bladder neck reconstruction, 1829 Mivacurium, 23Ot Mixed germ cell tumor, 555 extragonadal, 567, 568-569 ovarian, 607, 613 Mixed gonadal dysgenesis, 1912f, 1915t, 1917 diagnosis of, 1918t, 1920 Mixed tumor. See Pleomorphic adenoma. Mixed venous oxygen saturation, 118t, 122-123 in extracorporeal life support, 138 in malignant hyperthermia, 231 mechanical ventilation and, 127, 128 Mobius' syndrome, 789,907,2071 Molecular diagnostic methods, 419420, 420t Molecular genetics, 11-15, 12f, 13t. See also Cancer, molecular biology of. Molecular imaging, 38-40 Molybdenum, 199 Monfort abdominoplasty, for prune-belly syndrome, 1782f-1783f Monoclonal antibodies for burns, in animal models, 384 for immunosuppression, with transplant heart, 761, 761f islet cell, 724, 726 liver, 738t, 739 lung, 770-771,771t pancreas, 720 renal, 707, 709 for systemic inflammatory response syndrome, 172
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INDEX
Monoclollal antibodies (Continued) in cancer treatment, 425,426, 427 OK432, for lymphangioma, 1404,2107,2139 to tumor necrosis factor, for Crohn's disease, 1456 Monocyte chemotactic protein 1 (MCP-1), 160,161, 165 Monocytes, 159, 160, 161, 164, 165, 166 in neonate, 167, 170 Mononucleosis, infectious, 822, 837, 848 Montgomery, areolar glands of, 888, 890 Montgomery's tubercles, 890 Monti-Yang ileal channel, 1798, 1798f Morgagni diaphragmatic hernia of, 937, 945-946 robot-assisted repair of, 53, 54t hydatid of, 1205, 1206 Morphine, 2 4 1 , 2 4 1 ~242 caudal, 248 epidural infusion of, 248, 248t, 249 for burn patients, 394t in neoriates, 106, 240 in patient-controlled analgesia, 243, 243t Morrison's pouch, ultrasonography of, in trauma patient, 296, 296f Motility, gastrointestinal. See Enteric nervous system; Esophageal dysmotility; Gastric emptying; Intestinal dysmotility; Intestinal pseudoobstruction. Mowat-Wilson syndrome, 1523 Moyamoya disease, 21 17 MRA. See Magnetic resonance angiography (MU). MRI. See Magnetic resonance imaging (MRI). MRU (magnetic resonance urography), 1730, 1731f MRV (magnetic resonance venography), 2126,2127,2128f Mucin(s) in cystic fibrosis, 12, 1529 in Hirschsprung's disease, 1528, 1529 Mucocele, oral, 826 Mucociliary transport system, 813, 818 Mucocutaneous lymph node syndrome, 848 Mucoepidermoid carcinoma pulmonary, 641,642f salivary gland, 827, 840 Mucormycosis, in bone marrow transplant patient, 781 Mucosal immunity, 164. See also Immunoglobulin A. Mullerian agenesis, 1912f Mullerian anomalies, anorectal malformations with, 1568 Mullerian inhibiting substance, 1912-1913, 1916 cryptorchidism and, 1197, 1198 granulosa-theca cell tumors and, 604 testicular descent and, 1193, 1194, 1194f Mullerian remnant prostatic utricle as, 1904 robot-assisted excision of, 54t, 55 Multicystic dysplastic kidney, 1705, 1706, 1710-1711, 171Of-1711f, 1725, 1727 with ureterocele, 1762 Multidetector computed tomography (MDCT), 35,35f Multidrug resistance (MDR)-associated protein gene, in neuroblastoma, 474,487 Multiorgan system failure activated macrophages in, 162 extracorporeal life support for, 141 trauma-related, 266
Multiple endocrine neoplasia type 1 (MEN 1) gastrin-secreting tumor in, 1231, 1685 insulin-secreting tumor in, 1683 parathyroid hyperplasia in, 858 Multiple endocrine neoplasia type 2 (MEN 2) chronic intestinal pseudoobstruction in, 1548 medullary thyroid carcinoma in, 855, 857 parathyroid hyperplasia in, 858 pheochromocytoma in, 632 RETgene mutations in, 1520f, 1521, 1523 Multiple subpial transection, 2007 Multivisceral graft, 745, 746f-747f, 747-748, 751f Multivitamins, parenteral, 206 Mumps orchitis, 1205-1206 Mupirocin (Bactroban), 389t Murmur, heart myocardial rupture and, 286 pectus excavatum with, 895 Muromonab. See OKT3 (muromonabCD3). Muscle (s) cell culture of, 22 congenital anomalies of, 2070-2071,2070f, 2072f disuse atrophy of, 231 malignant hyperthermia and, 231-232 Muscle flaps, 352 Muscle relaxants, 229-231, 230t adverse effects of, 230-232,23Ot, 232t for laryngospasm, anesthesia-related, 223 in trauma patient, for intubation, 267 monitoring of effects of, 235 Musculoaponeurotic fibromatosis, 542 Musculoskeletal trauma, 337-347. See also Fracture(s). evaluation of, 339,341-342, 341f high-priority child abuse as, 347,401t compartment syndrome as, 344-345, 349 femoral neck fracture as, 345,345f joint penetration as, 344 mangled extremities as, 345, 379, 379t open fractures as, 344 spine trauma as, 345-346, 346f immediate treatment of, 342 in children vs. adults, 337-339, 338f-341f myc gene (s) c-myc gene in B-cell lymphomas, 581 in germ cell tumors, 557 endodermal sinus, 596 N-myc gene in germ cell tumors, 557 in neuroblastoma, 472, 474, 474t, 475, 476t, 480, 481, 482, 483 bone marrow transplantation and, 484 prognosis and, 486,487 MYCNproto-oncogene, 417,419, 425,426 Mycobacterial infection atypical, 832 adenitis as, 845-846 pulmonary, 1003-1004 in HN-infected patient, 1009 Crohn's disease and, 1453 tuberculous. See Tuberculosis. Mycophenolate mofetil (CellCept) in transplantation heart, 760t, 761, 761f intestinal, 749 liver, 738t, 739 lung, 771, 771t pancreas, 721, 722, 722f renal, 708, 709 mechanism of action, 708, 738t side effects of, 708, 738t slume 1, pages 1-1 140; Volume 2, pages 1141-21
Mycoplasma pneumoniae, 1002-1003, 1013 Mycotic aneurysm, 21 15-21 16, 21 16f Myectomy anorectal, 1531, 1543-1544, 1544f-1545f internal sphincter for constipation, 1594 for intestinal neuronal dysplasia, 1563 small bowel, in Hirschsprung's disease, 1540, 1543f Myelinolysis, central pontine, 389 Myelodysplasia. See also Myelomeningocele. neuropathic bladder and, 1807-1810, 1809f-181Of, 1817, 1821-1822, 1821f-1822f occult, 1805, 1806f, 1822, 1993-1994, 2102 cutaneous lesions in, 1993 Myelomeningocele, 1987, 1987f, 1990-1992. See also Myelodysplasia; Neural tube defects; Spina bifida. cloaca1 exstrophy with, 1867 cryptorchidism associated with, 1195 fetal surgery for, 83t, 84-85, 1991-1992, 1992f, 2062 hydrocephalus associated with, 84, 1993 intrauterine repair of, in animal model, 55, 56t lumbosacral, vs. sacrococcygeal teratoma, 559 neurologic deterioration in, 1995 neuropathic bladder and, 1807f, 1808-1809, 181Of, 1821 nutritional support with, 214, 214t urinary diversion in, 1794 Myenteric plexus. See also Enteric nervous system. disorders of, 1547, 1548 Myocardial contusion, 285-286 Myocardial rupture, 286 Myocarditis, extracorporeal life support for, 141t Myofibromatosis, 542 Myofibrosarcoma, 544t Myoglobinemia, in malignant hyperthermia, 231 Myoglobinuria, electrical burns with, 396 Myopathies, visceral, 1547, 1547f, 1548-1549 Myringotomy, 815, 816 Myxoma, ovarian, 614
NADPH-diaphorase staining, Hirschsprung's disease and, 1527 Naloxone, 239, 240t Nanotechnology, 57, 58-59, 59f Nasal. See also Nose. Nasal airways, 828 Nasogastric feeding, 199, 203 Nasogastric tube. See aho Gastric tube. esophageal injury caused by, 1047-1048, 1049, 1049f in burn patient, 386 in esophageal stricture management, 1085, 1086, 1088 in trauma patient, 272 with skull injury, 363 with spinal injury, 369 with thoracic injury, 277 Nasojejunal feeding, 199, 1484 Nasopharyngeal angiofibroma, juvenile, 821 Nasopharyngoscope, fiber-optic, 972 Nasopharyngoscopy, in airway obstruction, 983 Nasopharynx, 822 benign masses of, 826 branchial anomaly associated with, 868 lymphoma of, 827
Nasotracheal intubation, 127, 129 in trauma patient, 267, 276 Natural killer (NK) cells, 162, 163, 165, 166, 168 NCAM (neural cell adhesion molecule), 1525-1526 Neck. See also Cervical entries; Head and neck masses. clinical evaluation of, 831-832 cysts and sinuses of, 826, 830, 861-872. See also Branchial anomalies; Cystic hygroma. dermoid, 865,870-871 embryogenesis of, 861-865,862f, 863t, 864f-865f enteric, 964 incidence of, 865 malignancy in, 861, 866,870 preauricular, 871 thymic, 865,872,961,962f thyroglossal duct, 826, 861, 865, 865f, 869-870,871f inflammatory and infectious masses of, 832-833 in branchial anomalies, 866, 867 retropharyngeal/parapharyngeal, 823,823f malignant neoplasms in, 833 stereotactic radiosurgery of, 46 thymic tissue in, ectopic, 961 trauma to, vocal cord immobility in, 988 vascular injuries in, 378 webs in, congenital, 2064 Necrosis. See Ischemic necrosis, gastrointestinal. Necrotizing enterocolitis, neonatal, 1427-1 445 breast milk and, 104, 1430, 1432, 1433, 1434,1444 classification of at laparotomy, 1440-1441 for staging, 1438, 1438t clinical features of, 1434-1435 complications of, 1442-1443 colonic stricture as, 1495, 1495f intraoperative liver hemorrhage as, 1440 short-bowel syndrome as, 1369, 1369f, 1441,1443 cytokines and growth factors in, 1430-1432, 1430t, 1433,1434 epidemic clusters of, 1436 formula feeding and, 202, 1428-1429, 1432, 1433, 1434,1435, 1439, 1444,1445 gastric perforation in, 1235, 1237 historical perspective on, 1427 hyperglycemia in, 102 imaging in, 1436-1438, 1436f incidence of, 1427 ketorolac contraindicated in, 239 laboratory findings in, 1435 management of, 1438-1442 ileostomy in, 1482, 1483f, 1484, 1486 microbiology of, 1435-1436 overview of, 1385 overwhelming sepsis in, 173 pathogenesis of, 1432-1434 pathology of, 1434, 1434f prevention of, 1443-1 445 protein turnover in, 108 rectal bleeding in, 1385, 1435 recurrent, 1443 risk factors for, 1427-1430 staging of, 1438, 1438t survival with, 1442, 1442t taurine supplementation in, 209 Necrotizing fasciitis in urethral injury, female, 331 umbilical, 1146
Necrotizing granuloma, PET-CT imaging of, 39f Needle biopsy, 437, 438-439, 439f, 439t. See also Core needle biopsy; Fineneedle aspiration biopsy. laparoscopically directed, 440 of lung abscess, 1016 Neoadjuvant chemotherapy, 421-422 Neomycin, for outpatient burns, 396 Neonatal isoimmune thrombocytopenia, 182 Neonate (s) acid-base balance in, 95,96, 96t anesthesia in hypothermia and, 99 physiology of, 221,222f, 222t, 228 cardiovascular management in of arrhythmias, 151, 152t, 153 of congenital heart disease, 153 of congestive heart failure, 148, 150t, 151, 153 cardiovascular physiology of, 146-147, 147f energy metabolism in, 9 6 9 9 , 98f postoperative, 105, 105f, 107, 108, 212 protein metabolism and, 104, 108 with biliary atresia, 212 extracorporeal life support in, 140-141, 140t, 142 fluid and electrolyte balance in, 91-96, 93f, 94t, 96t gestational age of, 89,90, 90f-9lf mortality and, 90, 92f necrotizing enterocolitis and, 1428 total body water and, 92 growth rate of, 194 infection in. See also Sepsis, in neonate. host defenses against, 166-168, 170 prevention of, 1444 mechanical ventilation in, high-frequency, 126,141 mortality of, 89, 90-91,91t, 92f nutrient metabolism in, 100-104, 101t, 103f surgery and, 106, 107-108, 107f, 21 1 nutrition for parenteral, 205f requirements, 195, 196, 197, 198 organ failure score for, 91, 92t pain in, 221,236 clonidine for, 248 hyperglycemia associated with, 102 opioids for, 240, 241, 242 epidural, 248, 249 half-life of, 221 operative stress and, 105, 106 polycythemia in, 2115 premature. See Premature infant. renal function in, 93-94, 96 size of, 89-90,9lf energy metabolism and, 98 nutrient metabolism and, 101, 102, 103 stress response in, 104108, 105f, 107f thermoregulation of, 99-100 trauma in rectal, 312 vaginal, 312 vitamin K deficiency in, 186 Neostigmine for Ogilvie's syndrome, 1496 with neuromuscular blockade, 231 Nephrectomy. See also Nephroureterectomy. fetal, pulmonary hypoplasia and, 117 for renal vein thrombosis, 2130 for renovascular hypertension, 2120, 2121 in end-stage renal disease, 1835 in kidney donor, 702 in kidney recipient, 700-701
Nephrectomy (Continued) of multicystic dysplastic kidney, 1711 robot-assisted, 54t, 55 Nephroblastoma. See Wilms' tumor. Nephroblastomatosis. See Nephrogenic rests (nephroblastomatosis) . Nephrogenic rests (nephroblastomatosis) , 446,447, 448,450-451,451f bilateral Wilms' tumor with, 457 in multicystic dysplastic kidney, 1711 Nephrolithiasis. See Urolithiasis. Nephroma congenital mesoblastic, 450 cystic, 1712-1713, 1712f Nephrostolithotomy, percutaneous, 1751-1753 Nephrostomy, percutaneous after pyeloplasty, 1737 for megaureter, 1773 for transplant complications, 707 for urolithiasis, 1751 with urethral valves, 1793 Nephrotic syndrome primary peritonitis in, 1475, 1476 transplantation in patient with, 700-701 Nephroureterectomy, partial, 1767, 1768 Nerve blocks, 243, 244247, 245f-247f digital, for fracture reduction, 352 Nerve graft(s), in upper extremity trauma, 35 1 Nerve stimulator, 235 Nerves, peripheral, trauma to, 377 in hand injury, 348-349,349f-350f, 351 Neuhauser's sign, of meconium ileus, 1274 Neural cell adhesion molecule (NCAM), 1525-1526 Neural crest cell development, 1523-1524, 1524f, 1525, 1560 Neural tube defects, 1987-1995. See also Myelomeningocele. associated anomalies with, 1992-1993 capillary malformation as, 2098 congenital diaphragmatic hernia as, 932 cryptorchidism as, 1195 classification of, 1987-1988 closed, 1805,1806f, 1822,1987,1993-1994 diagnosis of, 1991 embryological basis of, 1987, 1988-1990, 1988f-1989f epidemiology of, 1988, 1990 etiology of, 1990 folic acid and, 1808, 1988, 1990 outcome and prognosis of, 1995 pathology of, 1990-1991 treatment of, 1991-1992, 1992f Neuraxial block, 243, 244, 247-249, 2472 248t Neurenteric cyst, 963, 965-966, 1393, 1994 Neuroblast, 467, 472 Neuroblastoma, 467-488 anatomic sites of, 467-468,468f, 628 brain as, 671 mediastinurn as, 959 neck as, 833,848 urachal remnants as, 1149 angiogenesis in, 419 bilateral, 483 chemotherapy for, 483-484 targeted, 426 clinical presentation of, 468-469, 469f congenital, 467 cystic, 482-483, 482f diagnosis of, 470-471, 470f-471f antenatal, 467 vs. adrenal hemorrhage, 630
Volume 1, pages 1-1140; Volume 2, pages 1141-2146.
xliv
INDEX
Neuroblastoma (Continued) differential diagnosis of, 470, 544t epidemiology, 467 etiological factors in, 467 future directions for, 487-488 genetics and molecular biology of, 415, 417, 418, 419, 425,467,474475,474t immunotherapy for, 427,485 in infancy, 480-481, 480f of stage IV-S, 469, 471, 471t, 472, 474, 481-482, 481f, 482t vs. hemangioendothelioma, 496 mass screening for, 468 metastatic to bone, 664 multifocal, 483 nutrition and, 486487 operative management of, 475-480,477f-479f palliative radiotherapy in, 484485 parasympathetic, 470 pathology and histology of, 472-473, 472t, 4735 486 prognosis of, 467,485-487 radiation therapy for, 484-485 accelerated hyperfractionation in, 429 risk-based management of, 425, 437, 475, 476t spontaneous regression of, 467, 468, 482, 483,486,487 staging of, 471-472, 471t summary of, 487 Neuroblastoma in situ, adrenal, 467 Neurocristopathies, 1520, 1520t, 1521, 1522, 1523,1528 Neuroendocrine tumors. See Carcinoid tumors. Neuroenteric cyst. See Neurenteric cyst. Neurofibromatosis neck tumors in, 833 renal artery stenosis in, 21 18, 21 18f Neurofibromatosis type 1 (NF1) macrodactyly in, 2075 tumor susceptibilities in, 421 bone tumors, 654 glioma, 679 neuroblastoma, 467 nonrhabdomyosarcomatous sarcomas, 543,546 pheochromocytoma, 632 rhabdomyosarcoma, 524 suorasellar astrocvtoma as. 676 ~eurokbromatosis&e 2 (NFZ),meningioma in, 679 Neurofibrosarcoma, 543, 546547 Neurogenic bladder. See Neuropathic bladder. Neurogenic sarcoma, 5 4 6 5 4 7 Neurogenic shock, 368 Neurologic evaluation, in traumatic emergency, 272 Neuroma, facial nerve, 817 Neuromuscular blocking agents, 229-231, 230t adverse effects of, 230-232, 230t, 232t in trauma patient, for intubation, 267 monitoring of effects of, 235 Neuromuscular function, monitoring of, 235 Neuromuscular syndrome, intensive care, 231 Neuronal dysplasia. See Intestinal neuronal dysplasia. Neuron-specific enolase, in neuroblastoma, 470,487 Neuropathic bladder, 1807-1811, 1808f-1810f, 1820-1822, 1821f-1822f assessment of, 1805-1807, 1806f-1808f, 1821, 1821f, 1822 renal prognosis with, 1817
Neuropathy (ies) compression, amniotic bands and, 2075 peripheral demyelinating, 1523 visceral, 1547, 1548 Neurosarcoma, 54G547 Neurosurgery planning for, functional MRI in, 37 spatial tolerance in, 42 Neurotrophins in hypertrophic pyloric stenosis, 1216 in neuroblastoma, 426, 474, 486 Neurturin, 1521, 1522, 1523t, 1525 Neurulation, 1987, 1988-1990, 1988f-1989f Neutropenia chemotherapy-induced, 1005-1006 in bone marrow transplant patient, 780, 781 in necrotizing enterocolitis, 1435 Neutropenic enteropathy, after bone marrow transplantation, 780, 780f Neutrophils, 159-161, 160f, 164, 165, 166 abdominal packing and, 302 abnormal, delayed umbilical cord separation and, 1145 in burn patient, 384385 with inhalation injury, 395 in neonate, 167, 170 sepsis and, 171 in systemic inflammatory response syndrome, 168, 169f, 172 Nevus(i). See also Basal cell nevus syndrome; Blue rubber bleb nevus syndrome. Becker's, of breast, 886 congenital, 2063-2064, 2065f Nevus flammeus neonatorum, 2098 Nevus sebaceus of Jadassohn, 2064 NF. See Neurofibromatosis. NF-KB. See Nuclear factor-kappa B (NF-KB). Nicotine, for ulcerative colitis, 1466 Nipple adenoma of, 888,891 congenital anomalies of, 886, 887f, 2066 in Poland's syndrome, 907,908f development of, 885 discharge from, 888, 8885 890, 891 inverted, 886 Nipple valve, 1832, 1832f Nissen fundoplication, 1127, 1127f after esophageal repair for atresia, 1065, 1069 for congenital stenosis, 1072 complications of, 1133 laparoscopic, 1128-1 130, 1129f-1130f outcomes of, 1133 robot-assisted, 53, 54t Nitric oxide arginine and, 196, 1431 arterial injury and, 380 for heart transplant recipient, 760 for reperfusion injury, after lung transplantation, 773 from macrophages and monocytes, 161-162, 167 in gastrointestinal tract, 1430t, 1431-1432 aganglionosis and, 1525, 1527-1528, 1527f enteric nervous system and, 1527, 1527f in hepatopulmonary syndrome, 1656 in necrotizing enterocolitis, 1430t, 1431-1432, 1433 in neonatal sepsis, 171 in respiratory management neonatal, 127, 135, 141 of ARDS, 127 of congenital diaphragmatic hernia, 940 ~ l u m e1, pages 1-1 140; Volume 2, pages 1141-2146.
Nitric oxide (Continued) in systemic inflammatory response syndrome, 169, 169f, 171 reactions of, 161-162, 162t uterine contractions and, 86 Nitric oxide synthase aganglionosis and, 1528 esophageal achalasia and, 1112 hypertrophic pyloric stenosis and, 1216 in cystic fibrosis, 12 in gastrointestinal inflammation, 1431-1432, 1433 in hypertrophic pyloric stenosis, 14 interferon-y and, 166 isoforms of, 161, 1431 penile development and, 1878, 1878f systemic inflammatory response syndrome and, 169 Nitrofen model, 934, 945 Nitrogen mustard, 423t Nitrogen washout test, 118 Nitroglycerin, as tocolytic agent, 79 ~itroprusside,for makgnait hypertension, 2120 Nitrous oxide, 227, 227t, 228 Nizatidine, for peptic ulcer disease, 1230 NK (natural killer) cells, 162, 163, 165, 166, 168 nm23, in neuroblastoma, 474 Nocturnal enuresis, 18141815 Nodular hyperplasia, focal (FNH), 495, 498-499,499f Non-Hodgkin's lymphoma, 580-589. See aL~o Lymphoma. classification of, 580,581,582-583,582f-583f clinical presentation of, 583-585, 584f cervical lymphadenopathy in, 82G827, 833,848 complications of, 588 cytogenetics of, 581-582 diagnosis of, 585 epidemiology of, 580-581 histopathology of, 582-583, 582f-583f in breast, 892 in mediastinum, 581, 583, 584, 584f, 586-587,586f, 588,959,960t, 961 lymphocyte development and, 581,581f-582f molecular biology of, 581-582 oral, 826827 post-transplanr, 584585, 712, 739 prognostic factors in, 588-589 staging of, 585, 585t, 587, 588 summary of, 589 testicular involvement by, 625 treatment of, 585-588, 586f, 588t osteogenic sarcoma secondary to, 653 vs. seminoma, 556 vs. soft tissue sarcomas, 544t Non-ossifying fibroma, 652, 652f, 654 Nonpolyposis colorectal cancer, hereditary, 520 Nonshivering thermogenesis, in neonate, 99 Nonsteroidal anti-inflammatory drugs (NSAIDs), 238-239,238t. See also Aspirin. colonic stenosis caused by, 1495-1496 for first-degree burns, 385 for inflammatory pseudotumor gastrointestinal, 1365 pulmonary, 641 for osteoid osteoma, 654, 658 peptic ulcers caused by, 1226, 1228, 1229 postoperative ileus and, 1361 preemptive analgesia with, 237 Nonvalidated procedures, 259-260 Noonan's syndrome, 1112,2141
Norepinephrine (noradrenaline) adrenal imaging and, 630, 63'2 adrenal synthesis of, 628, 6'29 postoperative levels of, 107, 107f Norwood procedure, 1977, 1977f Nose, 817-82 1. Srr cclso Nasal entrir~. anatomy of, 817-818 airway and, 984 congenital ~nalforrnationsof, 819-820, 8 19f-820f embryology of, 818 examination of', 818 Sol-eign body in, 821 inflammatory conditions of, 818-819 acute pharyngitis with, 822 sleep apnea and, 825 trauma to, 820-821 tumors of, 1 NP-59 (iodomethyl-I-19-norcholesterol), 630, 635 NSAIDs. Srr Aspirin; Nonsteroidal antiinflammatory drugs (NSAIDs). Nucleal- factor-kappa B (NF-KB),106 apoptosis and, 414 in systemic inflammatory response syndrome, 169, 173 necrotizing enterocolitis and, 1432 Nuclear medicine. Srr Radionuclide studies. Numhy Stuff; 244, 244t Nuss procedure, for pectus excavatum, 921-929, %Sf-%Sf, 928t Nutcracker esophagus, 1110-1 111, 111If Nutritional requirements, 195-199, 195t, 196t, 197s. Srr ccko Caloric requirements; Metabolism. aftel- bal-iatric surgery, 1250, 1252 for iron, 180 Nutritional status, assessment of, 194-196 Nutritional support enteral. Srr Ente~.alnutrition. for biliary atl-esia, 212, 212t vitamin E in, 198 for burn patient, 393, 39% fix chylothorax, 290 for disabled children, 214, 214t for failure to thrive, 213-214 for obese patients, 213 for ostoinate, 1488 fo~.shot-t-bowelsyndrome. Srt Short-bowel syndrome. fix surgic;ll patients, 210-212 historical perspective on, 194 in Crohn's disease, 1456 in ulcerative colitis, 1466 parenteral. Srr Total parenteral nutrition (TPN). Nystagn~us,neuroblastoma with, 469, 486 Nystatin for burns, 389, 389t, 390 for heart transplant patient, 761 for lung transplant patient, 775
a
Obesity. Sw rcko Bariatric surgery in adolescents. algorithm for rrlanagement of, in adolescent, 1250, 1251f definition of; 1244, 1244f epidemiology of, 1242, 1244-1 245 hcalth consequences of, 1245-1246, 1245t in disabled child, 214 maternal, fetal developn~entand, 1252 overview of, 213 science of, 1243-1 244
Obturator nerve, fascia iliaca block and, 246 0ctl.eotide for chylothorax, 1026-1027 for diarrhea, in short-bowel syndrome, 1373 for intestinal pseudo-obstruction, 1366 for pancreatic pseudocyst, 1678 for persistent hyperinsuline~nic hypoglycemia in infancy, 1681 for postoperative ileus, 1361 for variceal herr~orrhage,1658 esophageal, 1387 after portoenterostomy, 1612 P Dysphagia. Odynophagia. S ~nL\o evaluation of, 1125b OEIS (on~phalocele-exstrophy-imperforate anus-spinal defects) complex, 1160, 1161, 186'2 Ogilvie's syndron~e,1496 0 1 (oxygenation index), in congenital diaphragmatic hernia, 938, 942-943 OK43'2, for lymphangioma, 1404, 2107, 2139 OKT3 (muromonab-CD3), 707 in heart transplantation, 761, 761f in islet cell transplantation, 726 in liver transplantation, 7381, 739 in lung transplantation, 770, 771t in renal transplantation, 709 Oligodendroglioma, 671 Oligogenic disorders, 12, 12f, 13 Oligohydramnios multicystic dysplastic kidney with, 1710 polycystic kidney disease with, 1709 renal agenesis with, 1706 treatment of, 83 Ollier's disease, 651 ovarian tumors in, 593, 606 Omental cyst. See Mesenteric and omental cysts. Omentum, gastrointestinal stromal tumors in, 515 Omeprazole for gastroesophageal reflux, 1126 for peptic ulcer disease, 1229 Omphalitis, 1146 bacterial hepatitis associated with, 1644 Omphalocele, 1157-1158, 1157f, 1158t. See nl.~oUmbilical hernia. associated conditions with, 1160-1 161, 1162, 1162t cloaca1 exstrophy as, 1862, 1865 cryptorchidism as, 1195 ectopia cordis as, 913, 914, 1160 intestinal atresia as, 1270, 1277 intestinal rnalrotation as, 1346 clinical features of, 1161-1 162 complications of, 1166, 1167 embryogenesis of, 1159-1 160 giant, 1164 incidence of, 1162 obstetric delivery with, 1161 outcome of, 1166, 1167 prenatal diagnosis of, 1161 small, 1145, 1149, 1151 bladder exstrophy with, 1153 treatment of, 1163-1165 umbilicoplasty after repair of, 1153 vs. umbilical cord hernia, 1160 Omphaloileal fistula, 1304, 1307f, 1310-131 1, 1311f Omphalomesenteric duct. SerVitelline (omphalomesenteric) duct. Oncogenes, 413f, 414, 415t, 417,425-426. See also myc gene; KAS proto-oncogene; RET proto-oncogene; Trk entries. gene therapy and, 18 targeted therapy and, 425 Volume 1, pages 1-1 140; Volume 2, pages 1141-21
Ondine's cursr. Srr (:entral hypovel~tilatioi~ syntlromc (Ondine's curse). Onion skiiu~ing,radiographic, 654 Onlay island flap hvpospadias I-epair; 1884-1885, 1886s-1887f Oophorectoiny, rol,ot-assisted, 53, 54t Ophthalmologic evaluation in basilar skull fr;~cturc,J66 in child abuse, 363 Opioid reccptoi antagonisi, 239, 240t Opioids, 236, 239-242, 240t, 241 t, 24% Analgesic 1,addci-; I I I ~2:46, , 237f coi~tir~uous i i ~ f ~ ~of, s i242 o~~ ei~tloger~oirs, in rlcon;ctcs, 105 epiduial infusior~of, 248-249, 248t for burn patielits. 394, JY4t foi- diart-hea, 1373, 1466 in neonates. 240, 24 1 , 242 half-lif of', 22 l operative stress aitd, 105, 106 in patier~t-c-or~trollrti analgesia, 242-243, 24% for burn paiients, 394 rnitia~olar~~ with, 224 preemptive analgesia with, 2:37 propofbl with, 233 regional anesthesia and, 244, 248-2411 side effects of; 239, 241 inanagcment of, 239, 2401 on gastrointrsdt~almotility, 1360-1361 Opitl-(; syncirotne, 995 Opaite for- donor sites, 391 for second-degree burns, 390 Opso~nyocloi~~~s, neui-ohlastoma with, 469, 486 Opsoni~ation,159, 160, ItiOt; Itis, 164, 165 in neonate, 167, 168 Optic chiasin, astrocytoma of; 676677, 6766 679 Optic nerve compression of, tumor-related, 672 trauma to as birth injury, 405 basilar skull fracture with, 366 Oral cavity anatomy of, 821 benign lesions ot; 826, 831 caustic injury to, 1084, 1088 disorders of, %?5-82ti, 8251-826f herpetic git~givostoinatitisof, 822 malignant lesions ot; 826827 Oral contraceptives esophageal atresia and, 1051 fibrocystic breasts and, 891 gastroschisis and, 1160 hepatocellular adenoma and, 495 ovarian cancer and, 593, 594 Orbit cellulitis of; 818-819 rhabdoinyosarcon~aof, 531-532 Orchidectomy for testicular tumors alpha fetoprotein and, 6'22 technique of, U25 with teratoma, 567, 6'23 with yolk sac tumor, 623 of ischemic gonad, after torsion, 1207 Orchidopexy, 1200, 120lf-I202f, 1203 complications of, 1203-1 204, l204t for intermittent testicular pain, 1207 ilioinguinal-iliohypogastric block for, 245-246, 245f in prune-belly syndrome, 1781, 1785, 1786 laparoscopic, 1203 in prune-belly syndrome, 1785 testicular cancer and, 622, 1205
Orchitis, 1205-1206, 1205f, 12061 Organ failure score, for neonates, 9 1, Y2t Organ preservation, 694-695 Organ procurement, 693-694, 694f P Organ transplantation. S ~ Transplantation. Oropharynx anatomy of, 821, 822 caustic injury to, 1084, 1088 erythema of, in Kawasaki disease, 848 infections of, 822 malignant lesions of, 826427 Ortolani maneuver, 2019, 2021 Osler-Weber-Rendu disease. See Telangiectasia, hereditary hemorrhagic. Osmotherapy, for brain injury, 273, 363, 364 Ossicles, 813, 814 injury to by cholesteatoma, 816 in otitis media, 815 in temporal bone fracture, 817 reconstruction of, 815, 816 Ossification centers, 337, 338f, 341 Osteoarthritis, after cartilage repair, 22 Osteoblastoma, 652f Osteochondrodystrophy, Jeune's syndrome as, 915-917, 917f Osteochondroma diaphyseal aclasis secondary to, 651 location of, in relation to physis, 652f, 654 malignant degeneration of, 651 multiple, 651 resection of, 659 Osteogenic sarcoma (osteosarcoma), 652-653,652f-653f age of diagnosis, 650t, 664 chemotherapy for, 656-657 fine-needle aspiration biopsy of, 438 in breast, primary, 892 metastases from, 666-667 pulmonary, 645-646,645t, 666 radiation therapy for, 657 radiography of, 654 resectiorl of, 658, 661 reconstructior~following, 663f-665f secondary, in sarcoma survivors, 550 serum alkaline phosphatase and, 654 Osteoid osteoma, 652f, 654 treatment of, 658 Osteornalacia in parenteral nutrition patients, 209 in ulcerative colitis, 1465 Osteomas, in Gardner's syndrome, 1422 Osteomyelitis actinomycotic, 2044 acute hematogenous, 2033-2039, 2034f-2037f, 2038t chronic, 2039 chronic recurrent multifocal, 2041-2042 coccidioidomycotic, 2044, 2045f foot puncture with, 2042, 2043f sacroiliac, 2041 sternal, 1028 subacute, 2041 vertebral, 2042 Osteopetlia, in parenteral nutrition patients, 209 Osteoporosis, in ulcerative colitis, 1465, 1466 Osteosarcoma. SPYOsteogenic sarcoma (osteosarcoma). 0stling9sfolds, 17'23, 1724f, 1737 Ostomy. SPYEnterostoma(s). Otitis media acute suppurative, 815 cornplicatiorls of, 815-816, 816f chronic, 816 with effusion, 815
Otomandibular dysostosis, 788 Otorrhea cholesteatoma causing, 816 first branchial anomaly with, 861 of cerebrospinal fluid, trauma-related, 817 Ovarian cysts, 597, 597t after ileoanal pouch procedure, 1470 clinical presentation of, 594 diagnosis of, 595t,596597,596f-597f laparoscopy of, 599f syndromes associated with, 593 treatment of, 600-601, 600f, 602 Ovarian tumors, 593-615 Burkitt's lymphoma as, 584 classification of, 597, 598t, 602 clinical presentation of, 594 diagnosis of, 594-597,594t, 595t, 596f-597f epidemiology of, 593-594 epithelial-stromal, 593, 598t, 602-604, 603f genetics of, 593-594,595-596 germ cell, 554, 556, 557, 558, 566, 567, 568, 607-613,608f, 610f-612f chemotherapy for, 613-614 classification of, 598t, 607 diagnosis of, 594-596, 594t, 5951, 597f incidence of, 602,607 mixed, 607,613 robotic surgery for, 53 staging of, 598, 599, 613 surgical guidelines for, 613 in Peutz-Jeghers syndrome, 593, 606, 1418 incidence of, 593, 602 initial resection of, 597, 599 laparoscopy of, 599-600,599f, 601,602,613 non-neoplastic, 597, 597t. See nlso Ovarian cysts. clinical presentation of, 594 treatment of, 600-602,600f secondary (metastatic), 615, 615t sex cord-stromal, 593, 594, 595t, 598t, 604607,605f staging of, 597-599, 598t, 599t, 613 summary of, 615 unclassified benign, 614 malignant, 614-615 Ovary(ies) age-related changes in, 596 embryology of, 1912, 1912f inguinal hernia with incarceration of, 1184, 1186 radiation injury to, 579 splenic tissue fused to, 1189 Overactive bladder svndrome. 1813-1814 Overfeeding, parenteral, complications from, 210 Overweight, 1244-1245, 1244f. See also Obesity. Ovotestis, 1189 Oxalosis, renal graft loss in, 71 1 Oxandrolone, for burn patient, 392, 393 Oxidative phosphorylation, 97, 99-100 nitric oxide and, 161 Oxybutynin after hypospadias repair, 1893 for increased intravesical pressure, 1817-1818 for overactive bladder syndrome, 1814 Oxycodone, 240-241, 2401 Oxygen fractional inspired (Fio,) in emergency management, 269 mixed venous oxygen saturation and, 122,128 ventilator setting for, 127, 128 supplemental for burn patient, 385
Volume 1, pages 1-1140; Volume 2, pages 1141-214
Oxygen (Continued) for inhalation injury, 395 for trauma patient, 269 with thoracic in,jury, 277 Oxygen consumption, metabolic rate and, 195 P Reactive oxygen Oxygen free radicals. S ~ olso intermediates (ROIs). in ischemia-reperfusion injury, 386 mechanical ventilation and, 128 r~ecrotizingenterocolitis and, 14'29, 1433 parenteral nutrition and, 108, 21 1 Oxygen index (01), 135 Oxygen partial pressure (Po,) congenital diaphragmatic hernia and, 938, 939,942-943,945 extracorporeal life support and, 135 in trauma patient, 269 with brain injury, 273 measurement of, 123 intraoperative, 235 transcutaneous, 122 mechanical ventilation and, 127, 128 Oxygen saturation, 118t in congenital diaphragmatic hernia, 939,943 mixed venous, 118t, 122-123 in extracorporeal life support, 138 mechanical ventilation and, 127, 128 monitoring of, 121-123, 234, 235 in thoracic trauma, 277 Oxygen toxicity, 123, 127, 128 Oxygenation index (01), in congenital diaphragmatic hernia, 938, 942-943 Oxyhemoglobin dissociation curve, 121, 121f pulse oximetry and, 122
p53gene and p53 protein, 413,418,419, 421 brain tumors and, 679 Wilms' tumor and, 459 Pacemaker, cardiac, implanted, in neonate, 151 Paclitaxel, 424t Paco,. See Carbon dioxide, arterial. PAF. See Platelet-activating factor (PAF). Paget-von Schroetter syndrome, 2131 Pain. See nlso Abdominal pain. assessment of, 237 bone tumors with, 654, 658 hypersensitization to, 23WL37 in compartment syndrome, 344 in neonate, 221, 236 hypergiycemia associated with, 102 in spinal injury, 368, 369 perception of, in children, 236 undertreatment of, 236, 242 untreated, 236237 Pain management, 236243 Analgesic Ladder for, 236, 237f appropriate use of, 236, 249 for burns, 394, 394t in acute injury, 274 in neonate, 221, 236 opioids for, 105, 106, 221, 240, 241, 242, 248,249 nonopioid analgesics for, 236, 237-239, 237f. 238t nonpharmacologic techniques for, 236 opioid analgesics for. See Opioids. oierview of236 patient-controlled, 242-243, 2431 for burn patients, 394 244, 249 preemptive, 23-37, regional anesthesia for, 24.%244, 247, 248-249 withholding of, for diagnosis, 236
INDEX Palate. See also Cleft anomalies. anatomy of, 821 benign lesions of, 826 primary vs. secondary, 803 rhabdomyosarcoma of, 826 Palatine tonsils. See Tonsils. Palliative radiation therapy, 430 Pallister-Hall syndrome, 995 Palmaris longus tendon, congenital absence of, 2063 Pancreas anatomy of, surgical, 1672 congenital anomalies of, 1671-1672, 1671t. Ste also Annular pancreas; Pancreas divisum. pancreatitis and, 1673, 1674-1675 cystic neoplasms in, 1684 cysts associated with, 1677-1678 duplications as, 1391, 1392f, 1394, 1678 mesenteric, 1402, 1404 ectopic tissue of at umbilicus, 1149 in Meckel's diverticulum, 1304 embryology of, 1671-1672 hyperinsnlinism and, 102, 1679-1683, 1679t, 1681f, 1682t, 1683f islet cell transplantation and, 717, 723-727, 724f-725f neoplasms of, 1683-1686 pseudocysts of, 307-308, 309, 309f-310f, 309t, 310, 1678-1679, 1679f transplantation of; 717-723, 719f-722f history of, 685, 686t, 693, 717-718, 717f immunosuppression for, 720-721, 722-723 indications for, 720 intestinal transplant with, 745, 748 trauma to, 295, 299, 303, 307-310, 307f-310f, 308t, 30%. Set also Pseudocyst. pancreatitis caused by, 1673, 1674 with renal injury, 322 Pancreas divisum, 1672, 1673, 1674-1675, 16761677, 1676f Pancreatectomy for chronic pancreatitis, 1676 for pancreatic pseudocyst, 1678 for persistent hyperinsulinemic hypoglycemia in infancy, 1681, 1682t, 1683, 1683f Pancreatic enzyme replacement, complications of, 1498 Pancreatic insufficiency in cystic fibrosis, 1011 in Shwachman-Diamond syndrome, 1673 Pancreaticobiliary malunion, 167'2, 1673, 1674, 1675, 1677 Pancreaticoduodenectomy (Whipple procedure) for chronic pancreatitis, with islet autotransplantation, 724 for duodenal duplication, 1394 for duodenal trauma, 304,307 for pancreatic carcinoma, 1686 for pancrratic pseudocyst, 1678 Pancreaticojejunostorny, 1675f, 16761677 Pancreatitis acute, 1672-1674, 1673t pseudocyst in, 1678 choledochal cyst and, 1624, 1625, 1631, 1672-1673, 1677, 1677f choledochocele with, 1629 choledocholithiasis with, 1672, 1674, 1675 cholclithiasis with, 1637, 1642, 1672, 1673 chronic, 167'2, 1674-1677, 1675f-1677f, 1675t islet autotransplantation for, 72.3-724, 724f duplication as cause of, 1391, 1394, 1678 overview of, 167'2
Pancreatoblastoma, 1685, 1686 Pancreatogastrostomy, 1676 Pancuronium, 230t Panda eyes, neuroblastoma with, 469, 469f Pao2. See Oxygen partial pressure (Pog). Papillary cystadenoma lymphomatosum, 839 Papillary-cystic endothelial tumor of pancreas, 1684 Papilloma choroid plexus, 671, 678-679 laryngeal, 831,989,989f web secondary to treatment of, 988,989, 990 mammary, intraductal, 888 squamous laryngeal, 831 oral, 831 pharyngeal, 826 Papillomatosis juvenile, of breast, 891 recurrent respiratory, 831, 831f, 989-990, 989f Paracentesis, 1408, 1409, 1410 in necrotizing enterocolitis, 1439 in primary peritonitis, 1476 Paraduodenal (mesocolic) hernia, 1348-1349, 1349f, 1350, 1356, 1361, 1362f Paraganglioma, extra-adrenal, 515-516 with pulmonary hamartoma, 641 Paralysis. See also Paraplegia. in spinal cord injury, 368 muscle relaxants as cause of, 231 Paranasal sinuses. See Sinuses, paranasal. Paraplegia. See also Paralysis. neurenteric cyst and, 966 postoperative, after aortic repair, 290, 291 traumatic, ureteral injury associated with, 326 tumor-related, with neuroblastoma, 469, 477-478 Parasitic infections appendicitis in, 1502 ascariasis as, 1365 in Meckel's diverticulum, 1311 pulmonary, 1005, 1005f Paraspinal tumors, rhabdomyosarcoma as, 534 Parastomal hernia, 1363, 1489 Parathyroid glands adenoma of, 858, 858f embryology of, 850,863,864,864f-865f hypercalcemia and, 857, 857t, 858 injury to, in thyroidectomy, 856 physiology of, 857 Parathyroidectomy, 858 Paraumbilical block, 245, 245f Parenteral nutrition. SeeTotal parenteral nutrition (TPN). Parents, ethical issues and, 258 Parkes Weber syndrome, 2096, 2098, 2101, 2112,2128,2129 Parkland formula, 386, 388t Parotid gland(s). See also Salivary glands. anatomy of, 835 facial nerve and, 835, 836, 837, 867-868, 868f hypoplasia of, 789 surgery of, 840, 841f, 842 for branchial anomaly, 867-868, 868f Parovarian cysts, 601, 602 Parvovirus B19 infection, 1693 Passerini genitovaginoplasty, 1945 Patch abdominoplasty, 303, 303f Patella, congenital dislocation of, 2026 Patient-controlled analgesia, 242-243, 24% for burn patients, 394 Pavlik harness, 2021, 2021f
Volu m e 1, pages 1-1140; Volume 2, pages 1141-21
xlvii
Pc:~,.See Carbon dioxide. PCR (polymerase chain reaction), of tumors, 419, 420t, 425,437 PDGF. See Platelet-derived growth factor (PDGF). Peak inspiratory pressure (PIP), 124, 127, 128 P E W - 1 (platelet-endothelial cell adhesion molecule 1 ), 159-160, 173 Pectoral muscles, anomalies of. Set Poland's syndrome. Pectus carinatum, 904-907, 905f-906f pulmonary function and, 896 Pectus excavatum, 894-904 cardiovascular function in, 895, 897-898 cause of, 894, 894t clinical presentation of, 894-895, 895f conservative treatment of, 921-922,922f epidemiology of, 894 minimally invasive surgery for, 921-929, 922f-929f, 928t complications of, 928-929, 928t pulmonary function and, 897, 922,929 mitral valve prolapse in, 898, S'L'L open surgical repair of, 898-899, 900f-903f complications of, 899, 901, 904, 904f prune-belly syndrome with, 1786 pulmonary function in, 895, 89G897, 922,929 spontaneous resolution of; 894 Pediatric anesthesiologists, 221, 2'22-223 Pediatric surgery. See also Surgery. history of, 3-10, 3f-5f, 8b, 9f-10f PEEP. See Positive end-expiratory pressure (PEEP). PEG (percutaneous endoscopic gastrostomy), 199, 1131 PELD score, 1658, 1664, 1664f Pelvic inflammatory disease, with perihepatitis, 1645 Pelvic kidney, 1715,1717f-1718f Pelvic osteotomy, for hip dysplasia, 2023, 2023f Pelvis fracture of, urinary tract injuries with, 318, 327, 328, 328f, 329, 330-331 reconstruction of, after tumor resection, 662f, 665-666 tumors of, rhabdomyosarcoma as, 535 Penicillamine, macromastia caused by, 887 Penile block, 246247, 242; 1893 Penis. See alro Prepuce. anomalies of. See also Epispadias; Hypospadias. agenesis as, 261, 1907 bladder exstrophy with, 1845, 1845f-1846f repair of, 1851-1852, 1851f-1852f, 1853-1857, 1854f-1857f, 1858 cloaca1 exstrophy with, 1862, 1867 duplication as, 1904, 1907, 1907f torsion as, 1907 hematoma of, 331 secondary to nerve block, 246, 247 injury to, 331, 404 lymphedema of, 2144 meatal stenosis of, 19061907 normal anatomy of, 1877-1 878, 1877f-1878f Penn pouch, 1826 Penoscrotal transposition, 1907-1908 Pentalogy of Cantrell, 912, 945, 1157, 1158t, 1160, 116'2 treatment of, 1165 Pentamidine, aerosolized, 771, 1008 Pentoxifylline endotoxic shock and, 173 neonatal sepsis and, 171
Pcpiic ulcer disease, 1225-1 232 after massive entereciomy, 1372 bleeding in, 1386 classification of; 1225, 1225t clinical presentation of. 1228-1 229, 1228t diagnosis of, 1229 epidemiology, 1225-1226 etiologies of; 1225, 1225t historical iirlderstanding of, 1225 in ectopic gastric nlucosa, 1307, 1386, 1389, 1391, 1395, 1678 in Zol1inge1--Ellisonsyndrome, 1231, 1685 neonatal, bleeding or perforated, 1230 pathophysiol~~gy cot', 1226-1228, 12271 pel-fo~ationin, 12'29, 1230, 1231, 1236 stress ulcers in, 1225t, 1226, 1227-1228, 1229, 1231-1232 treatment of, 1229-1232, 1230t Percutaneous endoscopic gastrostomy (PEG), 199, 1131 Perfl11orocarboi1s as plasma substitutes, 188 for liquid ventilation, 126127, 945, 945f Pericardial cyst, !)(is. 1393 Pericardial effusion, 278, 287f, 291. Src also (2ardiac Gttnponade. chylous, 1027 lymphoblastic lymphoma with, 587 thoracoscopic treatment of; 977, 978 Pel-icardialtamponadc. Sw (krdiac tamponade. Pericardial window, subxiphoid, 291 Pericardioce~~tesis, of acuic iamponade, 277, 278, 286 chylous, 1027 Pericardiu~n,565 teratoma ot; 565, 962 trauma to, '278, 285, 28W287, 291 FAST sonography in, 296, 296f Perihcpatitis, 1645 Peritleal fistula. 1569. 15(i9f-l57"f, 1571, 1573 Perinephiic abscess, :Y24 Perintwm bul-11sto, 403 extra openings on, d11p1ic;ttionswith, 1396, 1397 rl~;tbdomyosarco~~a of, 535 trautna to, 312, 318, 929. 331 in clrild abuse, 404 Pel-iosieal chondi-oma, 659 Pcriosteum, 537 fracture healing and, 338 fi-acttu-cI-cduction and, 337, S39f; 342, 344 in mangled extremity, 34.5 radiogl-aphic signs ;und, 654 Peripheral demyelinating neuropathy, 1523 Peripher-a1 ncl-ve slleath tumor, malignant, 543, 544t, 546-547 tumor, 515 vs. gastrointestinal st~-omal Peristalsis esophageal. Srr Esophag~is,motility of: intestinal. Sro liitestinal tlysmotility. ureteral in prune-belly syndro~nr,1783-1784 1778, 1779f with meg;t~u-cte~; Peritoneal bands, congenital, 1498 Peritoural cavity. Srr ( r h o Asciies. diagnostic lapal-oscopy of, 439-440 Peritoneal.dialysis, 701, 702, 710 aftel- hrart ti-anspl;tntation, 762 gastroesoph;\geal reflux caused by, 1123 inguinal hernia and, 1187 peritonitis associated with, 1476-1477, 14771 Pcritone;tl drainage, for intestinal pel-fol-at ion, in neonate, 1237, 1440
Peritoneal lavage, diagnostic, 297 in necrotizing enterocolitis, 1439 Peritoneovenous shunt, 1409, 1411, 2140 Peritonitis amebic abscess with, 1646 appendicitis with, 1503 biliary, 1615 meconium, 1291, 1296, 1298 jejunoileal atresia with, 1271, 1273f, 1274, 1282, 1283 necrotizing enterocolitis with, 1435, 1436, 1437, 1440 primary, 1475-1477, 1475t, 1477t strangulated inguinal hernia with, 1174, 1182, 1183 v o l \ ~ ~ l with, u s 1347, 1356 Permissive hypercapnia, 128 PET. Srr Positron emission tomography (PET). Peut~~Jeghers syndrome, 1417-1418, 1418f carcinoma in, 519, 1418 intussusception in, 1321f ovarian tumors in, 593, 606, 1418 Peyer's patches, intussusception and, 1319, 1335, 1386 Pfannenstiel approach, to incarcerated inguinal hernia, 1184 Pfeiffer's syndrome, 798 P-glycoprotein in germ cell tumors, 596 in neuroblastoma, 474 pH, 95, 96, 120, 121. See a130 Acid-base balance; Acidosis. congenital diaphragmatic hernia and, 938, 940 esophageal monitoring of, 1039, 1069 in gastrocsophageal reflux, 1124, 1125b in ~notilitydisorders, 1109, 1110, I1 1If, 1113 mechanical ventilation and, 127, 128 PHACE syndrome, 2102 Phagocytosis. Sre r ~ D oMacrophages; Neutrophils. bacterial evasion of, 159 by macrophagcs, 161 by ncutrophils, 160, 160f; 168 helper T cells and, 163 in neonates, 167, 168 opsonization and, 159, 160, 160f, 163, 164, 165 in neonate, 168 Phagolysosomes, 158, 160-1 61, 160f, 162, 168 Phantorn phenomenon, 2058-2059 Pharyngeal space infection, thrombophlebitis secondary io, 2132' Pharyngeal tonsil. Sre Adenoid (pharyngeal tonsil). Pharyngitis, 822-823, 823f, 844. Srr nlro Sore throat. jugular thrombophlebitis and, 2132 torticollis secondary to, 877 Pharynx anatomy of, 822 benign masses of, 826 caustic injury to, 1084, 1088 cyst of, brarlchial cleft, 866 ernbryoloLqof; 863, 864f-865f malignant lesions of, 8 2 6 8 2 7 obstruction at level of, 828 sleep-disordered breathing and, 823-825, 824f Phenobarbital, for seizures, in head trauma paticnt, 273 Phenoxvbenzarnine, for malignant hype1 tension, 2120 'olume 1, pages 1-1140; Volume 2, pages 1141-2146
Phenytoin during pregnancy cleft anomalies associated with, 805 neuroblastoma associated with, 467 for seizures, trauma-related, 273, 366 Pheochromocytoma, 6'28, 630-633, 63lf, 631 t, 633f ectopic ACTH secretion and, 635 imaging of, 630 laparoscopic adrenalectomy and, 638 RETproto-oncogene in, 632, 1521 Phimosis, 1905 in chronic graft-versus-hosi disease, 782 Phlebitis, 2131, 2132 Phlebography. SPPVenography (phlebography). Phlebolith, in venous malformation, 2099, 2103 Phlegmasia, 21 31 Phlegmon. Srr (:ellulitis. Phocomelia, 2051f, 2073 Phosphodiesterase inhibitors, for systemic inflammatory response syndrome, 173 Phosphorus in failure to thrive, 214 in parenteral nutrition, 206, 2061, 207, 208-209 Photodynamic therapy, 41 PHOX2B (paired like homeobox 2B), 1521, 1523, 1523t Phrenic nerve, injury to diaphragmatic eventration caused by, 935,946 during birth, 405 in lung transplantation, 772 Phyllodes turnor, of breast, 890, 892 Physiologic dead space, 120 Physis ablation of, contralateral to tumor resection, 663 amputation and, 2050 anatomy of; 337, 338f fracture of, 937-338, 339, 339f imaging of, 3411; 342 rnanagrrnent of, 342, 343t; 344 premature closur-e caused by, 345 osteomyelitis and, 2033, 2039 premature closure of fracture-related, 345 radiation therapy causing, 657 tumors in relation to, 651, 652f, 654 management issues with, 660, 66Of, 665 Pierre Robin sequence, 803, 806, 812, 825 esophageal dysn~otilityassociated with, 11 12 Pigmented villonodular synovitis, MRI of',654 Pili, 158 Pineal gland, tumors in region of, 678 diagnosis of; 673 germ cell, 557, 678 choriocarcinoina as, 568 gerrninoma as, 567 teratoma as, 563 yolk sac tumor as, 567 resection of, 673-674 Pineoblastoma, 678 Pineocytoma, 678 Pinna. Srt. Auricle (pinna). PIP (peak inspiratory pressure), 124, 127, 128 Piriform sinus, 861, 863, 868-869, 869f PIRO system, 171-172 Pituitary adenoma, (:ushing's synclro~neand, 633,634, 635 Pituitary tumors, ilipple discl~argecaused by, 888
Placenta choriocarcinorna of, 609 chorionic gonadotropin produced by, 556 fetal circulation and, 148 i~nmunoglobulinC; transport across, 164, 167-1 68 therapeutics delivered via, 81, 821 transfusion to neonate fi-om, 92 Placental alkaline phosphatase (PLAP), germ cell t~imorsand, 556, 565, 568 pineal, 673, 678 Placentomegaly, sacr-ococcygeal teratoma and, 559, 560 Plagiocephaly, tol-ticollis as cause of, 878, 878s Plain radiography. Sr? Radiography. Plasma. Srr Fresh frozen plasma. Plas~nacell granuloma. Srr Inflammatory pseudot~unor. Plastna substitutes, 187, 188 Plasinacytoid lymphoma, 583 Plasrnaphercsis, tbr recurrent focal segmental glomerular sclerosis, 71 1 Plasmit~ogenactivator. Sup Tissue plasminogen activator (tPA). Platelet colunt, 183, 184t Platelet-activating factor (PAF), 160, 165, 166 in systemic inllarnrnatoty response syndrome, 168, 170-171, 173 necroiizing enterocolitis and, 1432, 1433, 1444, 1445 Platelet-derived growth factor (PDGF), 414, 425,426 ii-om ne~u-oblastorna,475 in cystic lung masses, 957 Platelet-endothelial cell adhesion rnolecule 1 (PECAM-I), 159-160, 173 Platelets. Srr nlro Thrombocytopenia. disorders of function of, 183, 190 ketorolac causing, 239 inflammation and, 166 transf~~sion of, 183, 189-190 dill-ii~g exiracor-pol-eal life support, 138, 139, 1 40 during surge~-y, 226-227 for dissen~inatedintravascular coagulation, 186 in trauma patient, 273 Pleo~norphicadcnoma, salivary gland, 826, 8311, 839f Plethysmograph): total-body, 118 P l c ~ ~ rdbbride~ncnt, al for ernpyema, 977, 978, 980 Ple111-aleffhsion. Srr also E~npyema; Hemothorax. chest tube insertion Sol; 1023, 1023t cliylotis, 1024, 1025, 1026, 10'27, 2141 decortication Sol; 1018 Iymphangiectasia with, 2140 pulmonary contusions with, 282 Pleural space. Srr alto Pncumothorax. thoracoscopy o f ; 440, 441 Pletirodesis fix pleural eff~ision 1027 chylo~~s, ~y 2140 in p t ~ l ~ n o n alynlphangiectasia, for pnrutnothorax, 980 spontaneous, 1021 l'le111-operitonealshunt, fat- chylothorax, 1027 Plexus block, 243, 244, 245-246, 245f I'loidy, of cancer cells, 415, 438 PLUG therapy. Srr TI-achealocclusion. PNETs. SPPPrimitive neul-oectodermal tumors ( PNETs).
Pneumatocele, 1014-1015, 1016f empyema with, 1018 post-traumatic, 282 Pneumatosis intestinalis, in necroti~ing enterocolitis, 1433, 1434, 1434f, 14361437, 1436f, 1438, 1439 Pneumococcal (Streptococru.~ pneumonzue) infection as meningitis, after basilar skull fracture, 366 as peritonitis, 1476, 1477 as pneumonia, 1001 postsplenectotny, 1697, 1698 Pnrumocyslis cnrinii pneumonia corticosteroid therapy and, 994, 1007 extracorporeal life support for, 141t in cancer patient, 1007-1008, 1007f in HIV-infected patient, 1008, 1010 in transplant patient heart, 761 liver, 740t lung, 771 Pneumocytes, 115, 116, 116f; 117, 933 oxygen toxicity to, 128 Pneurnography, impedance, 122 Pneumomediastinum esophageal perforation with, 1047, 1048, 1048f-1049f in barotrauma, 128 in birth injur): 405 Pneurnonectomy for bronchiectasis, 1014 lung transplant subsequent to, 769 Pneumonia. See also Lung(s), infections of. after inhalation injury, 395 aspiration. Sre also Aspiratiorl, pulmonary. abscess in, 1015-1016, 1017f recurrent, 1011, 1015 vs. pulmonary contclsion, 281 atypical, 1002-1003 bronchiolitis obliterans organi~ing (BOOP), 781 chronic or recurrent, 1011-1012, 1012f aspiration as cause of, 1011, 1015 classificatiorl of; 1011 community-acquired bacterial, 1001-1004, 100'Lf complications of, 1014-1020, 1015f-10176 1019f-1020s cytomegalovirus, in bone marrow transplant patient, 1007 extracorporeal life support for, 140t, 141, 141t in cystic fibrosis, 1300 in HIV-infected children, 1008 mimicking appendicitis, 1503, 1504 nosocomial, in ventilated patient, 128 Pne?tmoc:ystzs. See Pnrumoc~sliscarznii pneumonia. recurrent, gastroesophageal reflux as cause of, 1125b tuberculous, 1003 Pneurnonitis interstitial chronic, in cytomegalovirus infection, 1009-1 0 10 lymphocytic (LIP), 1008, 1009f tracheoesophageal fistula causing, 10.57, 1058, 1066 Pneunioperitoneum diagnostic, inguinal hernia and, 1181 during reduction of intussusception, 1330, 1334 in necrotizing enterocolitis, 1436, 1437, 1439 in newborn with colon perforation, 1494 with gastric perforation, 1236, 1236f
Pneumothorax causes of barotraurna as, 128 birth injuty as, 405 esophageal rupture or perforation as, 1047, 1048, 1049 intermittent mandatory ventilation as, 124 ruptured pneurnatocele as, 1014-1015 thoracoscopic biopsy as, 442 trauma as, 269, 276, 277, 278, 279-281, 280f-281t 282 epidemiology of, 275, 275t, 276 chest tube insertion for in neonate, 1021-1023, 1022f in older child, 1023, 1023t in sponlancous pneun~otlrorax,1021 in trauma patient, 280, 280f-281f, 281, 282 during extracorporeal life support, 140 high-frequency \'entilation for, 126 spontaneous, 10'20-1 021 tension, 280-281, 28 1 f , 283 esophageal ruptur-e with, 1047 spon tancous, 1020, 1021 thoracoscopic treatment of',977, 980 Po,. SPPOxygen pal-tial pressure (Po,). Poland's syndrome, 907-912, 2071, 207% arnastia in, 886, 907, 908f, 912, 2071 pectus carinatum in, 904, 910,912, 2072s ulnar deft-cts in, 2073 Polyalveo1a1-lobe, 958 Polyalveolosis, 958 Polycystic kidney disease autosomal dominant, 170(i-1707, 1707s autosomal rcccssive, 1707, 1707f-1708f, 1709 hepatic cysts in, 499 hepatic fibrosis in, I657 nephrcctomy in, 701 Polycystic ovary syndl-ome, vs. ~nrlliiplc fi)llicular cysts, 601 Polycythemia neonatal, 21 15 placental transfnsion causing, 92 Polydactyly, 2075 Polydimethylsiloxane, for vesicourcte~-al I-eflux, 1748 Polyembryotna, 555, 568 ovarian, 609 Polyethylene glycol 3350, 1550, 15501' Polygenic disorde~.~, 12, 12f, 13- 14 Polyhydramnios cystic lung mass and, 955, 956 diaphragmatic hernia and, 936, 937 duodenal atrcsia with, 1262 esophageal atresia and, 1056 jejimoileal atresia with, 1271, 1271t mcconium ileus with, 1291 microgastria with, 1237 pyloric atresia and, 1232 teratolna and cervicotacial, 564 mediastinal, 565 sacrococcygeal, 559, 560 Polymastia, 2066 Polymcrase chain reaction (I'(:R), of tumors, 41% 420t, 425, 437 Polymyositis-dernlato~nyositis, esophageal dysmotility in, 11 11 Polymyxin B, for outpatient burns, 396 Polyp(s) gallbladder, 1636-1637 gastrointestinal, 1414-1422 Srr nbso Fa~nilial adenomatous polyposis. bleeding with, 1387, 1414, 1415, 1416
Volume 1, pages 1-1 140; Volume 2, pages 1141-2146.
Polyp(s) (Continued) ileoanal pouch for, 1421, 1469,1470,1472 in Peutzjeghers syndrome, 519, 1321f, 1417-1418, 1418f intussusception with, 1319, 1320, 1320f, 1321f, 1335, 1364 juvenile, 519, 1364, 1387, 1414-1417, 1415f, 1417f lymphoid, 1418-1419, 1419f obstruction with, 1364 rectal, 1416, 1596 nasal and sinus, 818 sleep apnea and, 825 vs. encephalocele, 820 vs. glioma, 820 nasopharyngeal, 826 umbilical, 1147f, 1307f, 1310 ureteral, 1724 Polyposis syndromes, 421, 519. See also Familial adenomatous polyposis. Polysorbate 80, for meconium ileus, 1295, 1296 Polysplenia syndrome, 1604, 1606, 1693 congenital short pancreas in, 1672 Polysporin, for burns, 389t, 390, 396 Polytetrafluoroethylene. SeeTeflon injection. Polythelia, 2066 Pontine glioma, 673, 675f, 676 Popliteal artery, injury to, 378, 379 Popliteal vein, aneurysm of, 2129 Portacaval shunt, 1660, 1661 for portal vein aneurysm, 2126 Portal hypertension, 1651-1665. See czlso Varices. after liver transplantation, 1653, 1654, 1654f after portoenterostomy, 1612-1 613 causes of, 1652-1 654, 1652t, 1653f-1654f, l653t clinical presentation of, 1654-1656, 1655f collateral circulation in, 1652 definition of, 1652 diagnosis of, 16561657 embryological basis of, 1651-1652 hemorrhoids in, 1598-1599 historical perspective on, 1651 in congenital obstruction of inferior vena cava, 2124 in cystic fibrosis, 766, 1659, 1660f in polycystic kidney disease, 1709 liver transplant for patient with, 732, 733, 1658 portal vein aneurysm with, 2126 summary of, 1665 treatment of', 1657-1663, 1660f-1662f complications of, 1663 options for, 1663-1665, l664f Portal vein aneurysm of, 21 26 cavernous transformation of, 1653, l653f, 1657 congenital absence of, 2125, 2126 congenital anomalies of, 2124-2126 gas in, in necroti~ingenterocolitis, 1436, 1436f, 1437, 1438, 1439 inflammation of. See Pylephlebitis. preduodenal, 1261, 1262, 1266,2126 biliary atresia with, 1606 thrombosis of, 1653, 1655, 1657, 1659,2131 Rex shunt for, 166'2, 166'2f, 1663, 1665 secondary to aneurysm, 2126 splenorenal shunt for, 1661 Portoenterostomy, 1603, 1607-1609, 1609f complications of, 1611-1613 laparoscopic, 1608 liver transplantation and, 732, 1613 outcomes of, 1610-1611 robotic, porcine, 55, 56t
Portosystemic shunt(s), 1653, 1654, 1655 complications of, 1663 congenital, 2125, 2126 decision making for, 1663-1665, 1664f emergency, 1663 for portal vein aneurysm, 2126 hepatopulmonary syndrome and, 1656 surgical methods of, 1660-1662, 1661f transjugular intrahepatic (TIPS), 1387, 1409, 1654, 1657, 1659, 1660f Port-wine stain. See Capillary malformation (port-wine stain). Positive end-expiratory pressure (PEEP), 123, 124, 125, 127-128 in extracorporeal support patient, 138 thoracic duct flow and, 1026 Positron emission tomography (PET), 37-38, 39f, 40 in epilepsy, 2004 in PET/CT scanning, 38, 39f of bone tumors, 655 of pheochromocytoma, 630 of sarcomas, 547 Postconcussion syndromes, 367 Posterior fat pad sign, 341, 341f Posterior urethral valves. Sre Urethral valves, posterior. Post-thrombotic syndrome, 2133, 2133t after caval thrombosis, 2130 Post-transplant lymphoproliferative disorder (PTLD), 584-585, 712,739, 750-751, 762, 774 Post-traumatic intestinal stricture, 1365 Potassium. ,'Tee also Hyperkalemia; Hypokalemia. in failure to thrive, 214 in fluid therapy, 225 in parenteral nutrition, 2061, 207 in short-bowel syndrome, 213 serum, in neonate, 94-95 Potter facies, 1706, 1709, 1710 Potter's syndrome, 1411 Pott's puffy tumor, 2010, 2010f Pouch continent urinary, 1799, 1799f ileoanal. See Ileoanal pouch procedure. in familial adenomatous polyposis, 1421-1422 Pouch of Douglas, ultrasonography of, in trauma patient, 296, 296f Pouches, branchial, 861,862f, 863t. See also Branchial anomalies. Pouchitis of ileoanal pouch, 1470, 1471 in familial adenomatous polyposis patient, 1421-1422 of Kock pouch, 1467 Povidone-iodine for burns, 3891 on dressings, for infected wounds, 352 Prader-Willi syndrome, nutrition in, 214t Prealbumin binding protein, nutritional status and, 195 Preauricular cyst, 871 Prednisone. See also Corticosteroid therapy. in transplantation, 686, 687-688, 687f,-693f, 708 heart, 760, 761f lung, 770, 771, 775 Preemptive analgesia, 236-237, 244, 249 Pregnancy, after portoenterostomy, 1613 Prekallikrein, 185-186 Preload, 146-147, 147f, 148 Premature infant. See also Low-birth-weight infant. acid-base balance in, 96 Aume 1, pages 1-1 140; Volume 2, pages 1141-2146
Prcmature infant (Continurd) apnea in, postoperative, 223 bowel perforation in, spontaneous, 1237 cryptorchidism in, 1197 definition of, 89 energy metabolism in, 97-98 enterocolitis in. See Necrotizing enterocolitis, neonatal. extracorporeal life support in, 135, 139 fluid therapy for, 225 gastric acid in, 1226, 1428, 1433 gastrointestinal tract of, 1428, 1432-1433 growth rate of, 90, 91f, 97, 194 Hirschsprung's disease in, 1532 hyaline membrane disease in, highfrequency ventilation for, 126 infection in, host defenses for, 167-168, 170 inguinal hernia in, 1173, 1176, 1185, 1186, 1187 insulin response in, postoperative, 107 isoflurane anesthesia in, 228 lactase deficiency in, 197 mortality of, 89,90-91,91 t, 92f nutrient metabolism in, 100-101, 102, 103, 104 nutrition for enteral, 199, 200t, 20'2 parenteral, 203, 204, 206-207, 208, 209 protein requirement, 196 taurine supplementation, 204 vitamin E, 198 pain management in, 236 subgroups of, 89 total body water in, 92 Prenatal counseling, 77 in hydronephrosis, 17'25-17'26 Prenatal diagnosis. See ulso Fetal interventions; Magnetic resonance imaging (MRI), fetal. genetics in, 14-15, 78 management of defects found in, 33, 77, 78t,81-82, 82t of abdominal aortic aneurysm, 21 11 of abdominal wall defects, I161 of adrenal hemorrhage, 637 of anorectal malformations, 1572 of ascites, 1408, 1411 of bladder exstrophy, 18461847 of bladder outlet obstruction, 1811 of cervicofacial teratoma, 563, 563f of choledochal cyst, 1623-1624, l623f of congenital adrenal hyperplasia, 1921 of congenital diaphragmatic hernia, 936, 936f, 937,938-939 of congenital limb deficiency, 2050 of conjoined twins, 2080, 2081f of cystic lung lesions, 955-956, 956f, 957, 958,958f of duplications, alimentary tract, 1391, 1394, 1395 of ectopia cordis, 91 3, 1161 of esophageal atresia, 1056 of facial deformities, 805-806 of hydrocolpos, 1941 of hydronephrosis, 1723, 1725-17'26, 17251, 1726f with megaureter, 1772 with posterior urethral valves, 1819, 1899 with ureteral duplication, 1763 of imperforate hymen, 1941 of lymphangioma, 2157 of lymphatic malformations, 2099 of megaureter, 1772 of omental cyst, 1402, 1402f of ovarian lesions, 596, 596f; 600 of posterior urethral valves, 1819, 1899
Prenatal diagnosis (Continued) of sacrococcygeal teratoma, 559-560, 560, 560f of small bowel obstn~ction,1262, 1262f. 1271 in ~ n e c o n i u ~ileus, n 1291 of third branchial cleft anomaly, 868 of ureteropelvic junction obstruction, 1723, 1725 ultrasound imaging in, 32-33, 77, 78 Prenatal interventions. See Fetal interventions. Preoperative planning, virtual reality in, 67-68,68f Prepuce bacterial colonization of, 1742 embryology of, 1872, 1873f Pressure sensors, rnicroelectromechanical, 58 Pressur-e support ventilation (PSV), 123, 124-125 weaning from, 128 Pressure-cycled ventilators, 119f, 124, 127, 128 Preterm delivery, defects managed by, 77, 78t, 81 Preterm infant(s). See Premature infant. PRETEXT staging system, for liver tumors, 505-506, 506s Priapism in spinal cord injury, 368 post-traumatic, 331 Prilocaine, 243, 24% 244, 244t Primary survey, 267-272,268f, 270f-271f, 277 burns and, 385 n~usc~tloskeletai injuries and, 339 Primitive neuroectodermal tumors (PNETs) central, 671, 671t, 674-675, 675f, 678 peripheral as Ewing's family tumors, 653 diagnostic features of, 542, 544t Pringle maneuver, 507,511 Probiotic bacteria, for prevention of necrotizing enterocolitis, 1444-1445 of pouchitis, 1471 Procainatnide, for supraventricular tachycardia, 151, 152t, 153 Processus vaginalis, 1173-1 174, 1173f, 1193 Proctocolecto~ny for Crohn's disease, 1457, 1459 for ulcerative colitis, 1466, 1467 Proctocolitis, eosinophilic, 1599 Programmed cell death. See Apoptosis. Prokinetic agents, 1126 Prolactinoma, 888 Properdin pathway, 164f, 165 Propofol, 221, 222f, 233 Proportional assist ventilation, 123, 125 Propranolol for burn patient, 39'2-393, 393f for hypertension, 21 20 for hyperthyroid symptoms, 853 for supraventricular tachycardia, in neonate, 151, 152t, 153 Prostacyclin for puln~onaryvascular disease, 766 for vasospasm, 2121 Prostaglandin(s) angiogenesis and, 2104 peptic ulcers and, 1228,1230 synthesis of, 197, 197s Prostaglandin E, in acute respiratory distress syndrome, 127 Prostaglandin El for reperfiision injury, after lung transplantation, 773 for vasospasm, 2121 to maintain patent ductus, 756 synthesis of, 197, 197f to nlaintain patent ductus, 153
Prostaglandin E, macrophage function and, 166 synthesis of, 197, 197s Prostaglandin E3, synthesis of, 197, 197f Prostate, tumors of, rhabdomyosarcoma as, 532-533 Prostatic utricle, 1904 Prosthesis, extensible, 663-664, 663s Protein malabsorption of, 213 metabolism of in burn patient, 392-393, 393f in neonate, 100, 104 postoperative, 108 nutritional requirement for, 195, 1951, 196, 196t Protein C, 184t, 186, 187,2130,2131 in systemic inflammatory response syndrome, 172-173 recombinant, for septic complications, 173, 2133 Protein kinase C, in neutrophils, 160 Protein S, 184t, 186, 187, 2130, 2131 Protein-calorie malnutrition, in burn patients, 393 Protein-losing enteropathy in diffuse juvenile polyposis, 1416 lymphatic malformation with, 2099, 2140 Proteomics, 419, 425 Proteus syndrome, 2101-2102 Prothrombin, 185, 186187 Prothrombin time (PT), 183, 184t, 185, 186 Proton beam radiation therapy, 430 fbr neur.obIastoma, 484485 Proton pump inhibitors for gastroesophageal reflux, 1122, 1123, 1125b. 1126 for peptic ulcer disease, 1229, 1230, 1230t, 1386 in short-bowel syndrome, 1372, 1373 in Zollinger-Ellison syndrome, 1231 prophylactic, stress ulcers and, 1231 Proto-oncogenes. See Oncogenes. Proximal femoral focal deficiency, 2050-2051, 2052f-2053f Prune-belly syndrome, 1780-1789 abdominal wall in, 1158,1781, 1781f-1783f, 1786 associated anomalies with, 1786 megalourethra as, 1905 urethral atresia as, 190'2 bladder in, 1783, 1783f-1784f, 1784 cryptorchidism in, 1195, 1781, 1785, 1786 kidneys in, 1781, 1783, 1783f, 1786, 1789 management of, 1786, 1787f-1788f, 1789 abdominal wall, 1781, 1782s-1783f, 1786 megaureter in, 1771, 1780, 1783, 1783f-1785f, 1787s-1788f, 1789 overview of, 1780-1781 umbilicus in, 1153, 1784 urethra in, 1784, 1785f urinary ascites in, 1411 Pseudoaneurysm carotid, after craniopharyngioma surgery, 677 iatrogenic, 2115 catheter-related, 380 traumatic, 21 14-21 15 intracranial, 366 renal, 319, 324 splenic, 299, 299f Pseudocyst pancreatic, 307-308,309,309f-310f, 309t, 310, 1678-1679,1679f splenic, 299, 299f-300f, 1693 ~ l u m e1, pages 1-1 140; Volume 2, pages 1141-21
Pseudoephedrine, maternal use of, intestinal atresia and, 1269 Pseudoexstrophy, 1846 Pseudohermaphroditism female, 1913, 1914t diagnosis of, 1918-1919, l918t, 191% medical management of, 1920-1921 surgical reconstruction in, 1921-1926, 1922s-1928f male, 1913, 1914t, 1916-1917 diagnosis of, 1918t, 1919-1920, 19191 medical management of, 1920-1921, 1921 surgical reconstruction in, 1026-1931, 192961932' preparation Sol; 1921-1922, 1Y22f Pseudomembranous colitis, in Hirschsprung's disease, 1529 Ps'srudomonasinfection in cystic fibrosis, 1010-1011 of wound, dressing for, 352 Pseudo-obstruction. See Intestinal pseudo-obstruction. Pseudosubluxation, of cervical spine, 346, 369 Pseudotumor, inflammatory hepatic, 499 pulmonary, 640-641 Psoas abscess, 2040 Psoas hitch. 327 PSV (pressure support ventilation), 123, 124-125 weaning from, 128 PT (prothrombin time), 183, 184t, 185, 186 Pterygia, 2064 PTLD (post-transplant lymphoproliferative disorder), 584585, 712, 739, 750-751, 762, 774 Puberty delayed in Crohn's disease, 1454 in ulcerative colitis, 1464, 1465 obesity and, 1245, 1251 precocious adrenocortical tumors with, 635 hypothyroidism with, 601 ovarian lesions with, 594, 600, 601, 609 pineal region tumors with, 678 premature thelarche in, 885 suprasellar astrocytoma with, 676 teratoma with, 563, 565 testicular tumors with, 622, 624 pseudoprecocious, ovarian lesions with, 594, 600, 604, 605f, 607 Pubic diastasis, 1842, 1843, 1843f-1844f, 1846 repair of, 1850-1851, 1850f in cloaca1 exstrophy, 1868 urethral duplication with, 1904 Pull-through, endorectal for Hirschsprung's disease, 1534, 1535s-1537f, 1536 redo of, 1543f, 1544, 1545f for intestinal neuronal dysplasia, 1563 for vascular malformation, 1598 Pulmonary. Y . ep ( ~ k Lung(s); u Respiratory ent~es. Pulmonary agenesis, unilateral, 1055 Pulmonary artery(ies). See also Great vessels, anomalies of. congenital diaphragmatic hernia and, 935,936 development of, 117 fetal circulation and, 148 sling of, 1978-1980, 1978t, 1982-1983, 1983f, 1984 airway obstruction by, 997, 998 tissue-engineered reconstruction of, 24, 24f
lii
I~nt;.s
Pulmonary artery cathetel-, 125, 235 Puhnonary at-tery occlusion press~u-e,123 Pn1mon;try aspii.ation. Svr Aspiration, p11lmona1-y. P~~linon;t~-y aircsia, lung transplant for, 767 Pulmonary blasto~na,(541-642, 6436 643t, 957 Puln~ona~-y blood flow, 118t 1'11l111onarychondl-onla, 5 15-5 16 Pulmon;~~-y circ~~lation, 120 neonatal establish~ncntof, 148 Pctlrnon;~~-y compliance, 119-120, 1l9f in congenital diaphragmatic hernia, 938, 944, 945 mechanic;11 ventilation ;md, 119, 119f; 124, 125, 127, 128 Pul~nona~-y contusion, 269, 272, 278, 281-282. 282f epidr~niolokyof, 275, 2751, 276 Pu11non;it.ye d e ~ n a dnring extracorporeal life support, 138 in inh;tl;iiion injt~r):395 in tramna patient, 271-272 Pulmon;~ryc~nbolism,213'2-2133 in ventil;lted p ~ t i t n t 129 , Pulmonary fibrosis gastroesophageal I-etluxand, 1l25b lung transplant for, 767-768, 769 Pi~lmonaryfnnction tests, 118 in congenii;tl diaphragmatic hernia, X38, 944 Pulmonary gas exchange, 120-1 21, 121f Pi11mona1-yhypertension congenital diaphragmatic hernia and, 123, 93.5, 936,939,940, 941, 943,944 heart Failure with, in neonate, 151 heart transplantation and, 756, 757, 760 Imlg transplantaiior~for, 766-767 persistent, of newborn extracorporeal life support for, 140, 140t pharmacologic treat~nentof, 940 portal hypertension with, 1656 PI-imax-y for, 766-767 lung tra~~splantation nitric oxide for, 127 ventilator settings in, 127 and, 123 radial artery catheterizatio~~ upper airway obstr~~rtion with, 983 laryngomal;~ciaand, 986 veno-occlitsive disease with, 781 Pulmonary hypoplasia. Srr rclso Diaphragmatic hernia. animal models of', 117, 934, 935, 935f, 939,945 ectopia cordis wiih, 914 extracorporeal life support and, 135, 139, 140, 142 fetal intervention for, 82t, 83-84, 939 lyinphatic effusion as cause of, 1026 posterior urethral valves with, 1811 prune-belly syndrome with, 1781, 1786 renal agenesis with, 1706 Pulmonary lymphangiectasia, 2140 Prllmonary physiology, 117-121, 118f-119f, 1181, 12lf Pu11nonai.yslings, 1978-1980, 1978t, 1982-1983, 19836 1984 airway obstrr~ctionby, 997, 998 Pulmonary toilet, tlxcheotomy for, 984 P~~lmonary valve, stenosis of, 86 in tetralo&gyof Fallot, 1971 in U'illian~ssvndro~ne,21 17 tl-anspositior, of great arteries wiih, 1975
Pulse oximetry, 121-122 during anesthesia, 234 during epidural infusion, 249 during opioid infirsion, 242, 243 of b11m patient, 385 of traurna patient, 267 Pulsus paradoxus, 286 Pumps, n~icroelectromcchanical,58 Purpi~ra Henoch-Schiinlein in, 1320, 13'27-1328 intnss~~sception renal grafi loss in, 71 1 siibrnucosal hemorrhage in, 1364 idiopathic (immune) th~-o~nbocytopenic, 182-183 accessory spleens and, 1692 splenectomy in, 183, 1693, 1696, 1698 Purpura fulminans, 186, 187, 2058 Push-back palatal procedure, 809, 809f Putty sign, of meconi11m ileus, 1291 Pyelogenic cyst, 1713 Pyclography. Ser alto Urography. antegrade, of megarrreter, 1772 intravenous (IVP) of trauma, 319, 523, 326 of ureteral duplication, 1761, 1762f retrograde of trauma, 320, 326 of ureteropelvic junction obstruction, 1730-1731, 1731f, 1735, 1736 Pyelolithotomy, robot-assisted, 541, 55 Pyelonephritis abscess secondary to, 1745 after pyeloplasty, 1737 clinical presentation of, 1741 imaging of, 1743, 1744, 1745 Pyeloplasty, 1734-1 737, 1734f-1736f complications of, 1737 in duplex system, 1767 laparoscopic, 1736-1 737 outcome of, 1737 reflux resolved by, 1730 retrograde pyelography for, 1730-1731, 1731f, 1735, 1736 robot-assisted, 54t, 55, 1736, 1737 Pyelostomy, cutaneous, 1793 with posterior urethral valves, 1819 Pyeloureterostomy, in duplex system, 1767 Pylephlebitis, after appendectomy, 1509, 1643 Pyloric atresia, 1232-1233, 1232f-1233f, 12321 Pyloric duplication, 1234 Pyloric stenosis, hypertrophic, 1215-1222 clinical features of, 1216 diagnosis of, 1217-1218, 1217f differential diagnosis of, 12161217 duplication in, 1234, 1394 epidemiology of, 1215 etiology of, 14, 1215-1216 hemorrhagic emesis in, 1386 pathology of, 1215, 1215f peptic ulcers secondary to, 1230 treatment of, 1218-1221, 1219f-1220f, 1221t, 1222t complications of, 1221, 1222, 1222t outcome of, 1222 umbilical incision in, 1153 Pyloroduodenal duplication cyst, 1232 Pyloromyotomy, for hypertrophic pyloric stenosis, 1153, 1218-1222, 1 2 1 9 s1220f, 1221t, 1222t Pyloroplasty for peptic ulcer disease, 1230 for pyloric atresia, 1233 for stress ulcers, 1231 gastric emptying and, 1130, 1133
Volume 1, pages 1-1140; Volume 2, pages 1141-2146.
Pyocolpos, 1568 Pyodern~agangrenosu~n,in ulcerative colitis, 1464, 1464f Pyogenic granuloma, vs. hen~angioma,2097 Pyogenic liver abscess, 1643-1644 Pyopneurnothorax, ruptured pneumatocele as cause of, 1014-1015 Pyramid hypospatiias repair, 1882, 1883f Pyriform aperiiive stenosis, 819 Pyruvate kinase deficiency, 182
Qiuadriceps ~n~lscle, biopsy of; fascia iliaca block for, 246 Quinsy, 823
R115777, 425-426 ~ r ~ a469, 46% Raccoon eyes, n e ~ ~ r o b l a s t owith, Radial artely caiheteri~ationof, 123, 235 ligation of, in traurna patient, 351 Radial deficiencies, 2073 Radial head, fiacture of, as birth inji~ry,404 Radial nerve, test of', 349, 350f Radial nerve palsy, in birth injury, 404 Radiation sensitizers, 428 Radiation therapy, 44, 427-431. Srr ( L k O \pec.ifir cancer: adverse effects of, 430-431, 43 1t cerebral, 46, 675, 676-677 hypomastia as, 886 in Hodgkin's disease therapy, 579, 891-892 fractionated, 44, 46-47, 429 image-guided, 429-430 intraoperative, 430 for bone tumors, 657, 657f, 659 rnalignancics secondary to breast, 891-892 cerebral, 675 colorectal carcinoma as, 520, 520f malignant fibrous histiocytoma as, 543 osteogenic sarcoma as, 653, 657 thyroid, 855 radioiodine, for thyroid carcinoma, 856, 857 stem cell transplantation following, 431, 779 Radiobiology, 43-44 Radiofrcquency ablation, 41 of bone tumors, 658 of fetal tumors or anomalous twins, 78 of liver tumors, 51 1, 733 metastatic, desmoplastic, 547 of lower esophageal sphincter, 1126, 1133 Radiography chest. Sru Chest radiography. in abdominal trauma, 295 in head trauma, 363 in musculoskeletal trauma, 341, 341f, 342 to hand, 349, 351, 352 to joint, 344 to spine, 346, 346f, 368, 369 of bone tumors, 649, 654 Radioimmunoguided sul-gery, 47 Radionuclide studies. Svr c ~ k oPositron emission tomography (PET); Single-photon emission computed tomography (SPECT). gallium 67 scan, in non-Hodgkin's lymphoma, 585 hepatobiliary, 1606, 161 1
INI)EX Radionuclide studies ((,'o?~lin~trd) of bile leak, 1410, 1615 of c1iolcdoch;tl cyst, 1625 Icttkocyte scan in appendicitis, 1504 iir 1nusc11loskclct;\1 infection, 2035 lymphatic. Srr I.yt~lpl~angiography, ~ldionnclide. molccrilar, 38, 40 of adrrual glaitds. (230, 635 of hone. Src, Bone scair. of esoph;~gus iir caustic inju~): 1084 in ~notilitydisordel-s, 1109, 1112, 1113 with g;~sti-ocsol)I~ageal reflux, I124 of g;~lll~l;lddc~; 1637 of' gastric ~l~ucosa. hcterotopic, 1308, 1308f, I :38(;, 1:wi in entci-ic duplicatio~~, 1392, 1395 of p a ~ ~ t h y r o gl;urds, id 858 782 of splenic platelet scq~~estration, of thoracic duct fistula, 1027 of thyroid. Src.Tliyl-oid scan. of' urin;~ry$1-act afirr infection. 1744t, 1745 after trauma, 325 in ureteropcIvic,juirctiou obstl-uction, 17'28-1 750, 1729i11730f; 1767 with 111e9;111retet;1771-1772 with ~nulticystickitl~re):1710-171 1 with u1-cte~11 nnoinalics, I7(iI, 1763, 17(i4-17(i5, 1765f; 1766, 1767 Radiosul-gel-):stercotactic, 43, 44-47, 45f-46f exttxci-anial, 43, 46, 47 in children, 4G47 staged, 45 Radiothciapy. Sw Radiatioir therapy. Ranitidine for gasirocsophageal reflux, 1126 for- peptic t~lccrdisease, 1230 RANTES (I-cgulatedon activation, normal T exp1.esst.d anti secreted), 165 Rantila, 826, 826I; 8.18, 838f Kapamycirr. Sw Sirolimus (raparnycin). R4S proto-oncogeile, 41 7, 421, 425-426 glionlas and, 679 rhabdon1yosa1-comaand, 525 R;lstclli procedure, 1975, 1977f Raynar~d'ssyntiroine, 2121 RB. Srr Rt~tiiioblastonla. RR(:s. Srr Erythrocytcs (RB(:s). RDA (reco~r~rnended dietary allowance), for e n r r p , 195, I96 Reactive oxygen i~rtertnediates(ROIs). Set also Oxygen f r r ~ radicals. in nlacroplrages, 161-162 in neonatal ~nonocytcs,167 in ncutl-opliils, l(i0-161 in nitric oxide I-eactions, 161-162, 162t in systenlic i11flammatoryresponse syitdromc, 168, 169f, 173 n?croti/ing enterocolitis and, 1432 I-cprrf11sioi1ii!j~u-yand, 158 Rectal atrcsia and stetiosis, 1578 Rectal biopsy in gr-aft-versus-hostdisease, 780 in Hirschspn~rrg'sdisease, 1517-1519, 1517f-15181' after pull-through, 1542, 1543f fiill-thickness, 1517, 1518-1519, 1532-1533, 1533f suggested by constipation, 1593 in intestinal ner~rotlaldvsplasia, 1561-1562, 15 6 2 5156%'
Rcctal bleeding, 1385, 1386-1387 11emo1-rhoidswith, 1598 in necrotizing cntcrocolitis, 1435 int~~ssusccption with, 1324, 1325 polyps with, 1414, 1415, 1416 juvenile, 1364 lymphoid, 1419 tumors with, 515, 520 varices with, 1655 Rectal examination in appendicitis, 1503 in chronic co~istipation,1593 in Hirschsprung's discasc, 1515 Rectal mucosectorny. 1467, 1461) for vetlous malformation, 2107 Rectal prolapse, 1595-1 596, 15951' bladder exstrophy with, 1596. 1845 in cystic fibrosis, 1299, 1595-1596 of it~tussusccption,1324 polyps with, 1596 juvenile, 1416 postoperative, with anorectal ~nalformations,1586, 1596 solitary rectal ulcer with, 1599 Rcctoanal dyssynergy, 1594 Rectourethral fistula, 1566, 1569, 1570f anorectoplasiy for, 1574-1577, 1575f-1576f postoperative care with, 1584 Rectovestibula~-fistula, 1566, 157I, 1571f-1572f anorectoplasty f'or, 1578 s~ ~?~trir.\. Kcctum. .SPP( ~ 1 Anorectal anal junction with, 1590, 1590f, 1591 defecation and, 1591 duplications of', 1392f, 1395-1 397, 1396f-1397f embryology of, 15661567 malformations of, sacrucoccygeal teratorna with, 557, 559, 560 normal motility reflex of, 1527 polyps of'. .SPPPolyp(s), gastrointestinal. sexual abuse and, 1599 trauma to, 312, 404 pelvic fracture with, 318 ~ Colorectal carcinoma. tumors of. S Palso carcinoid, 518 stromal, 515 ulcer of, solitary 1599 vascular malformations in, 1598 Rectum-bladder neck fistula, 1570f anorectoplasty fol-, 1577, 1577f-157% Rectus block, 245, 245f Recurrent respiratory papillomatosis, 831, 831f, 989-990,989f Red blood cells. SecErythrocytes (RBCs). 5cc-Reductase deficiency, 1915t, 1917, 1920, 1921 KEE. .SPPResti~igenergy expenditure (REE). Reed-Sternberg cells, 575, 576, 576t 577 Refeeding syndrome, 208 Reflex apnea, 997-998 Reflex sympathetic dystrophy, 2121 Reflux esophageal. Srr Gastroesophageal reflux. intrarenal, 1817 ureteral. Seevesicoureteral reflux. Regional anesthesia, 243-249, 245f-247f intravenous, 244 Reifenstein's syndrome, 1894, 1914t Reinke crystals, 607, (i24 Renal. Set a1.w Kidney (s) . Renal abscess, 1745 Renal agenesis, 1705-1706 Gartner's duct cyst with, 1950 Renal aplasia, 1705, 1711
Volume 1, pages 1-1140; Volume 2, pages 1141-2146
liii
Rcnal ;rrtci.y aneurysm of t>1.;1ncIrvcssc~l,21 20 c o ~ ~ g c n i t ;21 ~ l11 . ~I-;UIIII;I to, 31 7, 322, 329-324, 3251' :~i-tc~.iog~.;~i>Iry in, 319 qrading of', :Y2O, :121 t Rcnal artery stc,nosis, 2 1 17-2 1 20, 21 181-21 191: .%Pnl,o Rc.~~ov;isc~~l;rr Irylxrtcnsion. Rrnal blood Ilow, in frtus, 0:1 Rtwal cc.11 c;~rcino~ila I>I-castanomalies with, 20(i(i in 1101-scshockitinc): 1718 Renal dysgcncsis. 1705-1 706 Rcn;\l dvspl;rsi;t, 1705, I 706. SOPcrl\o M~~liicystic tiyspl;~stickidne). fetal 11rct11r;tI O ~ S ~ I . I tioil I( ; I I I ~ Wt, , 83, 1817 (;artnc~-'sduct cyst witlr, 11KO in duplex systcnls. 17fi0. 17(iOf, 1 i(i2 in p~rnc-hcllysvndromc, 1781, 1783, 1783f. 17x6, 1789 ~x>stcrioi. 111.et1iral \,alvcs with, I81 7, 1000. 1901 Rcnal Failure. Sr(, rrl\o 1)ialysis. i.cnal. acquired rc>nalcystic- disc;rsc in, 17 13 esophageal dysnlotility in, 11 12 hypu-pal-atl~yroidistn ill, 858 in hlu-n 1);iticnt. 384, 389 in polycystic kidncy discasc, 1707 Rcnal fi~nction bul-ns and, 3x4 in fetus, 93 in neonate, 93-94, 9(i scintigraphic s t ~ ~ d iorf s, 1728-1 730. I729f-1 7301 UI-etcralohstrnction and. 1732 Renal Ilypodyspl;tsia, 170fi Renal hypoplasia, 1705, 1706 renal ar-tcry stcirosis with, 21 18 Renal insufficiency dul-ing extracorporeal life suppoi-t, 138, 140 in utcro, pulinonai.y hyl~oplasia caused by, 142 Renal scarring as indication for s~u-gel-y, 1747 with megaureter, 1772 irrcidence of, 1741, 174:3 scintigraphy of', 1745 ureteral anonlalies ;md, 1762, 1766 Rcnal scintigraphy, .S(v Kadionuclidc studies, of UI-inarytract. Renal transplailtation, 699-713 hladdcl- augmentation prioi- to, 1835 complicatioi~sof, 71 1-71 3 early, 707 data registries for, 699 delayed graft function in, 710 dialysis access and, 700, 701-702 donol- for, 702-70:3, 7021 early dysfunction in, 70fi-707 historical perspective oil, 685, 686-688, 686t, 687E 692, (i93 immunosuppression for, 707-709, 71 I, 712-713 nephrectomy in relation to, 700-701 noncompliance of patient in, 71 1 organ preservation fi~r,693-605, (i04f outcomes of', 709-713, 709f pancreas transplant with, 7 18, 719, 7lYf, 7'20, 7'21-723, 721f-722f postoperative care with, 706 recipieut diagnoses in, 699-700, 699t for, 700-701, 7OOt r e c i p i e ~ evaluation ~t recurrent primary disease arld, 71 1
I~V
INDEX
Renal transplantation ((~ontinurrl) rejection in acute, 71 0-71 1 chronic, 71 1 graft f'ailr~recaused by, 710 treatment of, 708-709 sul-gel-yfor ad~nissionfo~;703 anesthesia for, 703-704 fluid man;~gementin, 704, 705 monitoring in, 704 in, 704-706 operative techniq~~es timing of, 701, 710 tissue typing fiw; 695-696 urologic isst~esin, 700, 701, 705-706, 1834-1835 Renal vein congenital anomalies ot; 2124 throtnbosis of, 1753-1 754, 1754t, 2130 after transplant, 707 trauma to, 322, 323-324, 325f, 326 Rendu-Oslcr-Weher discase. Srr Telangiecta!iia, hereditary hetnorrhagic. Reuin, 629, 636 Rcnography, diuretic, 1729, 1729f, 1733, 1737 Renovascular hypertension, 21 17-2121, 2118f-2119f, 211th congenital aneul-ysnl with, 21 11 post-traumatic, 324 Wilms' t ~ ~ m with, o r 448 Reno\~ascularinj11i.y 322, 323-324, 325f Repel-fusion it!jur): 157-158 after lung transplantation, 773 expel-imental thel-apies for, 173 in burned tissues, 386 necrotizing enterocolitis and, 1434 Reporter transgene technology, 38-40 Research. Srr Technological innovation. Residual volume, 118, 118f Respiration ahhrc-tiations and symbols for, 118, 1181 form~tlasfix, 118, 118t monitoring of; 121-123 physiology of, 117-121, 118f-ll9f, 118t, 121f Respiratory acidosis. Srr alto Acidosis. in fetus and neonate, 96, 96t lipogenesis and, 107 in malignant hyperthermia, 231 parentera1 nutrition and, 207 weaning f~.omventilator and, 128 Respiratol-yalkalosis, in fetus and neonate, 9(it Respiratol-yburst, 160, 165 Respiratory distress. Srr rrl\o Airway obstruction; Apnea. cl~oanalatresia with, 819 chylothorax with, 1026, 1027 congenital diaphl-agmatic hernia with, 936937.939 congenital lobar emphysema with, 959 congenital neck anomalies and, 861, 868, 870, 872 lymphatigioma as, 2138 cystic tnediasiinal lesions with, 959 enteric cyst with, 1393 esophageal rupture with, 1047 gastric perforation with, 1296 pulmonary lymphangiectasia with, 2140 Respiratory distress syndrome esophageal atresia with, 1061 extl-acorporeal life support for, 140, 140t
Respiratory disturbance index, 824 Respiratory failure. See also Acute respiratory distress syndrome (ARDS). after inguinal hernia repair, 1186 anesthesia-related, 223 definition of, 127 in congenital diaphragmatic hernia, 942-943 in congenital thoracic syndromes, 915-917, 918 in spinal cord injury, 370 in systemic inflammatory response syndrome, 168, 170 in traumatic asphyxia, 291 rnanagement of extracorporeal life support for, 134135, 139, 140-141, 140t, 142 mechanical ventilation for, 123, 127-129 pharmacologic agents in, 127 trauma-related, 269 Respiratory papillomatosis, recurrent, 831, 831f, 989-990,989f Respiratory quotient, 1181, 121 in neonate, 97 parenteral overfeeding and, 210 Respiratory rate measurement of, 122 ventilator setting foi; 127, 128 Respiratory syncytial virus (RSV) infection, 1004-1005, 1004f cystic fibrosis and, 1011 epidemiology of; 1001 extracorporeal life support for, 141 in bone marrow transplant patient, 1007 Resting energy expenditure (REE), 195-196 in cerehral pals): 214 in neonate, 97, 98-99, 98f post ope^-ative, 105, 108 with biliary atresia, 212 Resuscitation of newborn, overzealous, gastric perforation and, 1235, 1236 of' tractma patient. .YCF Et~iergency rnanagement. Res~~scitation phase, 267, 27'2-273, 277 RETproto-oncogene, 13, 131 Hirschsprung's disease and, 13, 131, 1520-1522, 1520f-1522f, 1523, 15231, 1524, 1525 pheochromocytoma and, 632, 1521 thyroid carcinoma and, 4'21, 855, 857, 1521 Retinal detachment, in protein C deficiency, 187 Retinal hemorrhage, in child abuse, 361, 401, 402 Retinoblastoma, familial, 421 osteogenic sarcoma associated with, 653 Retinohlastoma (RR) protein, 413 Retinoblastoma (KB)tumor suppressor gene, 418, 421 molecular imaging study of, 39 osteogenic sarcoma associated with, 653 13-czs-Retinoicacid (isotretinoin) during pregnancy, 805 for laryngeal papilloma, 990 for neuroblastoma, 483-484, 485, 486 Retinoids, for neuroblastoma, 483-484, 485, 486 Retinol binding protein, nutritional status and, 195 Retinopathy in premature infants, vitamin E and, 198 renovascular hypertension with, 21 18, 2120 Retroareolar cyst, 890-891
Volume 1, pages 1-1140; Volume 2, pages 1141-2146
Retrograde pyelograplly of trauma, 320, 326 of ureteropelvic ,jnnction obstruction, 1730-1731, 17Jlf, 1735, 1736 Retrograde urethl-ograplry, of trauma, 320, 320, 330, 1902 Retroperitoneal cyst, 1399, 1400, 1404, 1404s Retroperitoneal liernatoma, 322, 323 Retroperitoneal lymph node dissection, with testicular tumors, 623-624, 625-626, V25f-626f Retroperitoneal tumors desmoid, in Gardner's syndrorne, 1422 fetus in fetu as, 558, 558f rhahdomyosarcoma as, 535 rectal cancer aficr radiation for, 520, 520f tcratoma as, 557, 558, 558f; 566 yolk sac tumor as, 567 Retropharyngcal abscess, 823, 823f mediastinitis secondary to, 1027 torticollis secondary to, 877 Reversed vein graft fol- iatrogenic injury, catheter-relatrd, 380 for lower extremity trantna, 379 for- upper extremity trauma, 351 Rex shunt, 16V2, 16fi2f, 1663, I(iti5 Reye's syndrome, 238 Rhabdoid tumor of kidney, 450, 45lf, 460 of liver, 505 Rhabdoid/atypical teratoiti tumor; of central nervous system, (571, 678, 679 Rhabdomyotna, intracardiac, ventric~ilar tachycardia and, 153 Rliabdo~nyosarco~i~a, 524-537 clinical presentation of, 526 clinical trials fot; 524, 531 diagnosis of; 527, 527t biopsy for, 527, 529 differential diagnosis of, 543, 544t epidemiology of, 524525,542 genetics and molecular biology o f ; 524-525 histology of, 524, 525-526, 526t historical perspective on, 524 management of by site, 531-536 chemotherapy in, 530-531 complications of, 536 for metastatic disease, 530, 531, 536537 radiotherapy in, 531 surgery in, 528-530 metastatic, 526 management of, 530, 531, 536-537, 549 to lung, 526, 536, 645 outcomes with, 537 sites of, 524, 526 bladder, 532, 533, 3949 breast, 892 extremities, 535-536, 549 head and neck, 826, 833 liver, 505 lung, 535,536,642, 643t, 644f, 957 management and, 531-536 ovary, 6 14 pancreas, 1683 retroperitoneurn, 535 rectal cancer after radiation for, 520, 520f risk groups and, 528t, 531 salivary gland, 840, 840f staging and, 527t temporal bone, 817 urachal remnants, 1149 vagina, 534, 1902, 1949 staging and clinical grouping of; 527-528, 5 2 3 , 528t
Rhinorrhea, 820, 821 Rhinosinusitis, 818 heterozygous cystic fibrosis mutations with, 12 Rib(s). Srr also Chest wall, congenital deformities of. aplasia of, in Poland's syndrome, 907-908, 907t, 90%-9llf, 910-912 defects of, in diffuse skeletal disorders, 915, 917-918,917f-918f fracture of computed tomography of, 278 epidemiology of, 275, 275t, 276 in child abuse, 278, 279, 403, 404 lung trauma caused by, 282 pulmonary contusion with, 269 treatment of, 279 Rickets, in parenteral nutrition patients, 209 Rieger's syndrome, 1149 Right ventricular hypertrophy, in tetralogy of Fallot, 1971-1973 Right-sided heart failure, in pulmonary vascular disease, 766 Ring block, 247 Rings, vascular, 1978-1984, 1978t, 1979f-1983f robot-assisted division of, 541, 55 Rituximab (anti-CD20 monoclonal antibody) for B-cell lymphornas, 588 for post-transplant lymphoproliferative disease, 585, 751, 774 RNA microarrays, 419-420 Robinow's syndrome, 1149 Robodoc, 49, 491 Robotic surgery, 47-57 advantages of, 47-48, 48f, 51-52,52t, 57 applications of clinical, 47-48, 53, 54t, 55 experimental, 55, 56t to neck lesions, 867 in cholecystectomy, 53, 541, 1639, 1640, 1640f in pyeloplasty, 54t, 55, 1736, 1737 in splenectomy, 53, 541, 1696 conclusions on, 55, 57 development of, 48-49 limitations of, 52-53, 57 systems for, 49-51, 49t, 50f-51f, 52t thoracoscopy in, 977 Rocuronium, 230t ROIs. Set Reactive oxygen intermediates (ROIs) . Ropivacaine, 243, 243t epidural infusion of, 248t Rotationplasty, 660, 661f, 66'2, 2051 Roux-en-Y cystojejunostomy, for pancreatic pseudocyst, 1678 Roux-en-Y esophagojejunostomy, after failed fimdoplications, 1133 Roux-en-Y gastric bypass, 260, 1242-1243, 1248, 1248t, 1249f, 1250, 1252 Roux-en-Y,jejunostorny feeding, 1480t, 1481f, 1484 with choledochal cyst excision, 16'26-1631, 1627f-l628f, 1677 Rovsing's sign, 1503 RSV. Srr Respiratory syncytial virus (RSV) infection. RT-PCR (reverse transcriptase-polymerase chain reaction), 419, 420t, 425, 437 Rule of twos, for Meckel's diverticulum, 1304 Rule of nines, For burn surface, 386, 387f Rule of tens, for cleft lip repair, 806 Runnels, 904
Saccular cyst, laryngeal, 830 Sacral agenesis, 2029 neuropathic bladder in, 1810, 1822 Sacral ratio, 1567, 1567f, 1573 Sacrococcygeal teratoma, 557, 557f-561f, 558-563 prenatal treatment of, 82t, 85, 559 Sacrococcygeal yolk sac tumor, 559, 561,562, 567,608 Sacroiliac osteomyelitis, 2041 Sacrum congenital defects of, 1567, 1567f, 1569. See also Currarino's triad. presacral teratoma with, 560, 560f, 561 enteric duplications associated with, 1396 rectal suspension to, for prolapse, 1596 Saethre-Chotzen syndrome, 798 Saliva epidermal growth factor in, 1430 gastroesophageal reflux and, 1121-1 122 Salivary glands, 835-842 anatomy and physiology of, 835 calculi in, 836, 836f, 837 cystic disease of, 837-838 ranula as, 826, 826f, 838, 838f diagnostic evaluation of, 835-837, 836f embryology of, 835 inflammatory disease of, 837, 838f, 842 minor, 835 benign lesions of, 826, 837, 838, 839 biopsy of, in Sjogren's syndrome, 837 malignant lesions of, 840 neoplasms of, 827,838-840,839f-840f, 842 pathology of, 835 surgical considerations for, 840-842, 841f Salpingitis, acute, with perihepatitis, 1645 Salpingo-oophorectomy, robot-assisted, 54t Salter-Harris classification, 338, 339f, 343f, 344,349 child abuse and, 403 Santulli enterostomy, 1297F, 1298 Saphenous vein autogenous graft of, for renal artery stenosis, 2121 cutdown of, in trauma patient, 269-270,271f duplication of, varicosity and, 2130 Sarcoma(s) bone, 652-653. See also speciJic sarcomas. breast, 892 fine-needle aspiration biopsy of, 438, 542,548 hepatic, 505, 5051 ovarian granulocytic, 615 primary, 614615 soft tissue. See Rhabdomyosarcoma; Soft tissue sarcoma. Sarcoma botryoides, 1949 Sarfeh shunt, 1661 SBP (spontaneous bacterial peritonitis), 1475-1477, 1475t, 1477t Scalp, congenital aplasia of, 2063 Scardino-Prince vertical flap, 1735, 1735f Scarring. See Renal scarring. Schatzki ring, in eosinophilic esophagitis, 1112 Schiller-Duval bodies, 567, 609, 623 Schwann cells, in neuroblastoma, 472, 473 Schwannoma malignant, 546-547 vs. gastrointestinal stromal tumor, 515 Sciatic vein, persistent, 2128, 2129 SCID. See Severe combined immune deficiency (SCID).
Scintigraphy. See Radionuclide studies. SCMORA (spinal cord injury without radiographic abnormality), 346, 368-369 Sclerosing stromal tumors, ovarian, 593, 606 Sclerotherapy of capillary malformation, 2129 of complex malformation, in Parkes-Weber syndrome, 2129 of esophageal varices, 1043, 1045, 1612, 1613, 1659 of lymphangioma, 2107 mediastinal, 966 of mesenteric or omental cyst, 1404 of varicocele, 1209 of venous malformation, 2107 Scoiiosis compensatory, with torticollis, 878, 880 congenital, 2026-2027, 2026f, 2028 diaphragmatic hernia with, 944 osteoid osteoma with, 654 pectus carinatunl with, 904 pectus excavatum with, 894, 896 thoracoscopic diskectomy for, 977 Score for Neonatal Acute Physiology (SNAP), 90,9l Scorpion stings, 353 Scrotum. See e~hoHydrocele; Testis(es); Varicocele. acute, 1205-1207, 1205f, 1206t anomalies of, 1907-1908 sex assignment surgery and, 1930-1931, 1932f chyle fistula to, 2140 fat necrosis in, 1206, 1206t idiopathic edema of, 1206, 12061 lymphedema of, 21 44 trauma to, 331, 404 tumors of, rhabdomyosarcoma as, 526,533 Seat-belt injuries to abdomen, 311, 311f intestinal stricture secondal-y to, 1365 to breast, 891 to kidney, 317 to spine, 346, 346f, 368 Seat-belt sign, 31 1, 31 If, 346 cervicothoracic, 378 Sebaceous cysts, in Gardner's syndrome, 1422 Sebaceous nevus, 2064 Second messengers, 413, 413f Secondary injury, to central nervous system, 273,355-356,367 Secondary survey, 267 in thoracic trauma, 277 musculoskeletal injuries found in, 339, 341 Sedation for burn patient, 394, 394t of trauma patient for intubation, 267 with brain injury, 363, 364 preoperative, 221, 224 Seizures. See aho Epilepsy surgery. brain tumor with, 671, 672, 677, 677f in Addison's disease, 637 in Sturge-Weber syndrome, 2098 postoperative, with heart transplant, 762 post-traumatic, 273, 356, 366-367 assessment with, 363 early, 366367 in child abuse, 361 with cerebral contusions, 358 Selectins, 159, 160, 161, 167 in inhalation injury, 39.5 in systemic inflammatory response syndrome, 168, 169f, 173
Volume 1, pages 1-1140; Volume 2, pages 1141-2146.
Ivi
INDEX
Seleilium, l98t, 199, 206 Self-assembly, of narlomaterials, 57, 59 Seminoma, 554, 567, 622. Srr rclso Germinoma. gonadoblastoma degenerating to, 624 Sensors, microelectromechanical, 57-58, 57f Sentinel lymph node mapping, with soft tissue sarcomas, 549, 549f as rhabdomyosarcoma, 530, .536, 549 Seprafilm. Srr Hyaluronic acid membrane. Sepsis. Srr abo SIRS (systemic inflammatory response syndrome). arterial thrombosis in, 21 15 bal-riers against, 157f blood replacement in, 226 cytoki~iesin, 165, 166, 169 definition of, 156, 168 diagnosis of; 170, 171-17" epiderniology of, 156 extracorporeal life support for, 140t, 141t in burn patients, 389, 393, 394 in cystic fibrosis patient, 1300 in intestinal transplant patient, 749, 750 in neonate, 166-167, 170-171, 173 catheter-related, 204, 209-210 wiih ~ ~ e c r o t i ~enterocolitis, ing 173, 1435, 1436, 1438 in parenteral nutrition patient, 208, 209-2 10, 744 in surgical patient, nutrition and, 211-212 pathophysiology of, 169-170 posisplenectomy, 1698, 1699 in Hodgkin's disease, 579-580 trauma-related, 266 abdominal packing and, :102 in urethral irijury, female, 331 treatment of, 172-1 73 recombinant protein (; in, 2133 Sepsis-Related Organ Failure Assessment (SOFA), 9 1 Septic arthritis, 2033, 2034f, 2039-2041, 20401, 2041t Septic shock corticosieroids in, 173 extracorporeal life support for, 141 lipid A in, 159, 172 monoclonal antibody therapy for, 172 purpura fulminans secondary to, 2058 Serial transverse enteroplasty (STEP), 744, 1379, 1379f Serotonin. Ser 5-Hydroxytryptamine. Sertoli cells, in cryptorchidism, 1197, 1198 Sertoli-Leydig cell tumor ovarian, 593, 594, 5951, 606 testicular, 622, 623t, 624 in Peutz-Jeghers syndrome, 1418 Severe combined immune deficiency (SCID) for stem cell trarlsplantaiio~~ extracorporcal life support following, 779 prenaial, 86 X-linked (XSCID), gene therapy for, 1.5, 18 Sevoflurane, 2221, 2271, 228, 229 Sex assignment. Srr cclso Iniersex abnormalities. bladder exstrophy and, 1845, 1847 cloacal exstrophy and, 1864, 1867 ethics of, 261-262 hypospadias and, 1870 in col!joiued twin, 2087 in male psrudoher~naphroditism,1919, 1920 in pe~lileageneais, 261, 1907 with a r ~ i ~ u l tubules, ar Sex cord tu~nol-s oval-ian, 593, 606 -s, 594, 595t, Sex cord-stromal t u ~ n o ~ ovariat~, 51)8t, (i04-607, 60%'
Sexual abuse. See also Child abuse. anorectal pathology secondary to, 1599 gonococcal arthritis secondary to, 2040 injuries caused by, 312 primary peritonitis secondary to, 1475 Sexual differentiation, 1911-1913, l912f Shah-Waardenhurg syndrome, 1522, 1523 Shaken baby syndrome, 401, 402f Shenton's line, 2020, 2020f Shivering, meperidine for, 241 Shock abdominal trauma with as birth injury, 405 renal injury in, 319 vascular injury in, 378 burn-induced, 389 hypovolemic, 180 neurogenic, 368 septic. See Septic shock. Short-bowel syndrome, 1369-1380 after resection for Crohn's disease, 1458-1 459 for intestinal atresia, 1283-1284 for malrotation, 1356 for meconiurn ileus, 1298-1299 for necroiizing enterocolitis, 1369, 1369f, 1441, 1443 bacterial overgrowth in, 1373-1374 causes of, 743, 743t, 1369, 1369f clinical course in, 137'2 in aganglionosis, 1369, 1369f, 1540 intestinal adaptation in, 743-744, 745, 1369-1370, 1372, 1373, 1374 nutritional deficiencies in, 1371-1372 nutritional support for, 198, 199, 137'2-1374 enteral, 203, 212-213, 137'2-1373, 1374 lengthening procedure and, 1378 parei~teral(TPN), 206, 212-213, 743, 743f, 1372-1373, 1374, 1375 complicationsof, 209, 744, 745, 1373, 1374 dependence on, 1370-1372, 1371f, 1374 ileocecal valve and, 1375 lengthening procedure and, 1378 with jejunoileal atresia, 1282, 1283 prevention of, 1374 prognostic factors in, 1370-1372, 1371f treatment of algorithm for, 1379f conclusions on, 1379 intestinal transplant for, 1283, 1373, 1378, 1379 pharmacologic, 1373, 1374 surgical (Bianchi procedure, STEP, tapering enteroplasty), 1374-1379, 1375f-1379f tissue-engineered, 24-26, 1379 Shoulder birth injuries of, 404-405 reconstructiorl of, after tumor resection, 653f, 663f, 665 Shriners-Galveston formula, 386, 388t Shunt Blalock-Taussig,modified, 1972, 1977 for hydrocephalus, 1998-2002 brain tumor and, 674, 676 in aqueductal stenosis, 82t, 85 inguinal hernia and, 1185, 1187 spontaneous bacterial peritonitis with, 1477 vocal cord imrnohility and, 988 left-to-right, anesthetic induction with, 228 mesenieric vein-to-left portal vein, 1662, 1662f, 1663 peritoneovenous, 1409, 1411, 2140 pleuroperitoneal, for chylothorax, 1027 portosystemic. See Portosystcmic shunt(s). right-to-left, 120, 121, 935
Volume 1, pages 1-1140; Volume 2, pages 1141-2146
Shunt (Continued) anesthetic induction with, 227-228 arterial sampling and, 235 in congenital diaphragmatic hernia, 939 thoracoamniotic for cystic adenornatoid malformation, 83 for hydrops, 956,965 with enteric duplication, 1391 vesicoamniotic, 82t, 83 with posterior urethral valves, 1899 Shunt fraction, 118t Shwachman-Diamond syndrome, 1673 SIADH (syndrome of inappropriate ADH secretion), 94, 941 Sialadenitis, 837 Sialography, 836, 836f; 838f Sickle cell disease, 181-182 acute chest syndrome in, 1011, 1012f, 1636 after splenectomy, 1697 cholelithiasis in, 1635-1636, 1637, 1642, 1673 extracorporeal life support for, 142 malaria resistance in, 166 osteornyelitis associated with, 2042 splenectomy in, 1693, 1697, 1698-1699 thrombosis and embolism in, 2 1 15 SIDS (sudden infant death syndrome) sleeping position and, 794, 1I25 thyroglossal duct cysi and, 870 Sigmoid cystoplasty, 1797, 1X2Ci-1827 Sigmoidostomy, 1483, 1483f; 1485 Signal transduction, 41 3-414, 41 3f maligllailt transformatioil and, 414, 415, 417 Sildenafil, for esophageal motility disorders, 1111 Silicone inlplants, breast-feeding and, 1111 Silk string sign, of inguinal hernia, 1 174 Silo, Silastic in abdominal traiirna patieni, 301-30'2, 303f in gastroschisis reduction, 1164f, 1166 in omphalocele reduction, 1163-1 164 Silver nitrate in burn care, 383, 389, 389t, 390 in stoma care, 1488 Silver sulfadia~ine(Silvadene), 383, 389, :189t, 390, 396 Simulation, surgical, 59-70 commercial systems for training, 68-70, 69f for preoperative planning, 67-68, 68f principles of, 59-62 virtual realiiy fol; 62-69, 64f-661, 70 Simulect. See Basiliximab (Simtilect). Single-photon emission cornpuied tomography (SPECT) , 40 in epilepsy, 2004 Sintered biomaterials, 59 Sinus. See e1.w Neck, cysts allti sinuses of. dermal, 1994 umbilical, 1146, 1147, 1147f; 1304, 1307f urachal, 1148, 1148f Sinuses, paranasal, 8 18, 82 1 Sinusitis, 818-819 acute phary~lgitiswiih, 822 illtracranial abscess seconda~yto, 2009, 2010 nasotracheal intubation causing, 129 Sirolimus (rapamyciil) as anticai~ceragerli, 425 in transplantation heart, 76lf intestinal, 749 islet cell, 724 liver, 738t, 739 lung, 771, 7711 pancreas, 72 1, 722, 7221 renal, 708, 709 mechanism of action, 708, 7381 side effects of, 7:18t, 739
SIRS (systemic inflammatory response syndrome), 156157. See also Sepsis. diagnosis of, 168, 171-1 72 in neonate, 170 pathogenesis of, 168-171, 169s physiologic and metabolic consequences of, 169-1 70 I-iskfactors in, 168 trauma-related, 266 treatment of; 172-173 Situs inversus. Srr Heterotaxia. Sjiigren's syndrome, diagnosis of, 837 Skin anatomy of, 384 congenital anomalies of, 2063-2064, 2065s classificatior~of, 2061, 2062-2063 enlbryology of, 2061-206'2 of, 384, 2061 fi~nciior~s inteiitional injury to, 383, 383f, 401t, 403, 403f ulcerative colitis and, 1464, 1464f Skin cancer. Ser r~lsoMelanonla, malignant. after renal tl-a~lsplantation,712-713 basal cell carcinoma, 2064 gynecomasiia and, 2069, 2070 Skin expanders. Srr Tissne expansion. Skin flaps, 352 Skin grafts, :152 aftel- bone tumor resection, 662 for burtls, :NO-391, 391f; 392, 394 Skull c..I 1,al~;ll ,. .' defect of, congenital, 2063 osteomas of, in Gardner's syndrome, 1422 Skull fracture basilal; 366 with, 357, 358, 358s-359f, 363 brain i~?jui-y co~rlplic;~tions in, 366 in child abnse, 401, 402 in crnsh injury, 361, %If', 366 sul-gery tix, 364 co~ltplicationsot; 3ti6 growing, :Mi trmpor;~lbone. 816817, 817s Sleep-disol-derectbreathing, 823-825, 824f obesity a d , 1246, 12% Slide t~~acheoplasty, 997, Y97f, 998 Smati inter;lcting pwtcin-1 (SIPl), 1521, 1523, 15231 Small, 11oncleavrd cell (undifferentiated) lymphomas, 581, 58 If-582f, 582-583 clinic;~lpl-csentaiio~~ of, 583-584, 584f tt-eatiuent of; 585-586, 587-588, 588t S~nallcell c;it-ci~~oma, of ovary, 603 S111allcell ohtt.ogcnic sat-coma, 652 Sm;ill intcsti~lc.S(,r c~L\o1)uodcnal rntrir.\; Ileal n1/1,ir3:I~~tcstinal watrir.~; Jejut~-wztrks. a d c ~ ~ o c a r c i ~ ~of; o iill l ~duplication, :~ 1395 burn-rt2l;tted damage to, 384, 393 of; 1:300, 1391, 1391f-1392f, duplic;~tio~ls 139% ,394-1:3!)5, 1395s Fiil-schsprung's disease in, 1.531, 1539-1510, 1.59'261543f length of, in i~liant,1370 l y ~ ~ ~ p h a ~ ~ g i cof, c ~2' i140, s i i ~2 14 1 lymphatic obstrttctioi1 in, "40 111ese11te1.y of; drsmoid tunlor of, 1422 polyps in ;ltlcllolu:llolls, 51'1, 1420 in Peut/rjcgt~csssyndronle, 1417-1418 ti.;rllm;l to, 310, :31 1, Sl I t tumors of c;~rcinoid,5 18 stso111,1l,515, 516 S ~ n i ~IeSt l l colon s y n d r o ~ ~1496, ~ e , 1497f, 1498 vs. ~ncconiuinilcus, 1294, 12!)5f with Hirschsprung's disease, 1519
Small round blue cell tumors. See ulso Ewing's sarcoma; Leukemia; Neuroblastoma; Non-Hodgkin's lymphoma; Primitive neuroectodermal tumors (PNETs); Rhabdomyosarcoma; Small cell osteogenic sarcoma. fine-needle aspiration biopsy of, 438 Smith-Lemli-Opitz syndrome, 1528 Smoke. See Inhalation injury. Smoking maternal abdominal wall defects and, 1160 cleft anomalies and, 805 ulcerative colitis and, 1466 Smooth muscle tumors. See alto Leiomyoma; Leiomyosarcoma. gastric, with pulmonary hamartoma, 641 vs. gastrointestinal stromal tumors, 515 Snakebites, 352-353 SNAP (Score for Neonatal Acute Physiology), 90, 91 Snodgrass tubularized incised plate urethroplasty, 1880, 1883, 1884s-1885s Soap-bubble sign of colonic atresia, 1275 of mecorlium ileus, 1274, 1292, 1292s-1293s Soave procedure, 1532f, 1534, 1540, 1545 SOCS (suppressors of cytokine signaling), 166 Sodium. See also Hypernatremia; Hyponatremia. in fluid therapy, 225, 226 in parenteral nutrition, 206-207, 206t in short-bowel syndrome, 213 serum, in neonate, 94, 941 Sodium bicarbonate, for acidosis, 96 Sodium cronloglycate, for enterocolitis, in Hirschsprung's disease, 1530 Sodium ferric gluconate, 207 Sodium hypochlorite. See Dakin solution. SOFA (Sepsis-Related Organ Failure Assessment), 91 Soft tissue(s) benign tumors of, 541, 541t, 542 diagnosis of, 542-543 congenital anomalies of. See also Breast(s); Hand (s). classificatiorl of, 2061, 2062-2063 embryologic basis of, 2061-2062 of muscles, tendons, and co~~nective tissue, 2070-2071, 2070f, 2072f infections of, in bone Inarrow trarlsplarlt patients, 781 traunla to, 348, 350-351, 352 as birth injury, 404 Soft tissue sarcoma, 541-550, 541t. See nlso .specz$(. &arcomas. diagnosis of, 542-543 differential diagnosis of, 543, 544t incidence of, 541-542 rlonrhabdo~nyosarcomatous,543, 544t, 545-547 biopsy for surgical planning with, 548 extremity, 548-550, 54%-550f grading of, 542, 542t lymph node involvement in, 548-549 new itrlagi~lgmodalities for, 547 trunk, 550 pulmonary metastases from, 645 relatively benign, 541, 542, 543 rhabdomyosarcomatous. See Rhabdomyosarcoma. Soiling, fecal, 1549, 1549t, 1592, 1593, 1594, 1595. See also Incontine~icc. Vohune 1, pages 1-1 140; Volume 2, pages 1141-21
Somatostatin for chylothorax, 10261027 for esophageal varices, 1387 for pancreatic injury, 309 in short-bowel syndrome, 1370, 1373 receptors for, of neuroblastic tumors, 469, 486 Somatostatin analogues. See Ocireotide. Somites, 2062 Sore throat. See ulso Pharyngitis. in upper airway obstruction, 827 infectious, 822 pharyngeal cyst with, 866 piriform sinus with, 868 SOX10 transcription factor, 1521, 1522-1523, 1522f, 1523t, 1525 Soy formulas, 200t, 202 Soy intolerance, 1386 Spasmodic croup, 830 Specimen handling, 437-438 SPECT (single-photon emission computed tomography), 40 in epilepsy, 2004 Spermatic cord, hydrocele of, 1189 Spherocytosis, hereditary, 178, 182 accessory spleen and, 1692 cholelithiasis in, 1636, 1637-1638, 1642, 1673 splenectomy in, 1637-1638, 164'2, 1693, 1696, 1697, 1698 Sphincteroplasty, for chronic pancreatitis, 1676, 1677 Sphincterotomy, anal, 1597 Spider bites, 353 Spina bifida, 1987, 1990, 2062. Sre also Myelomeningocele. latex sensitization in, 29'2 urinary catheterization in, epididymoorchitis associated with, 1206 Spinal block, 247 Spinal cord. Srr alro Central nervous system; Myelodysplasia. arteriovenous malformation in, 21 11 cervicomedullary astrocytoma and, 676 compression of; mediastinal mass with, 959 ependymoma of, 675 malformations of lipomatous, 1993-1994 occult, 1993-1994,2 102 sacrococcygeal teratoma with, 557, 559 split, 1994, 2027 tethered anorectal malformations with, 1567, 1569, 1573 bladder dynamics and, 1809, 1822 constipation with, 1594 occult, 1805, 1806f; 1810, 18'22, 1993-1994, 2102 with cloaca1 exstrophy, 1867 Spinal cord irljtrry, 355-356, 367-370. See also Paraplegia. in child abnse, 403 transport in, 346, :146f, 356357 without radiographic abnormality, 346, 868-369 Spinal dysraphisrn. Ser Myelodysplasia; Neural tube defects; Spina bifida. Spine. Ser nlso (:el-vical spine; Lumbar spine; Thoracic spine. anatomical features of,,juvenile, 368, 369 anomalies of, 20262029, 2026f-2029t Srr ril,so Hemivertehra(e). anorect;tl ~ilalti)rin;~tions with, 1567, 1569, 1573 constipation with, 1594 sacl-ococcygraltci-atornawith, 557, 559, 561 epidural abaccs in, 201 3
lviii
INDEX
Spine (Continued) liponla in, 1594, 1806f, 1809f, 1810, 1822, 1993-1994,2027,2102 metastases to, from brain tumor, 673, 675 neurenteric cyst in, 965-966, 1994 osteomyelitis of, 2042 rhabdoid/atypical teratoid tumor in, 678 trauma to, 345-346,346f, 367-368,369,370 in child abuse, 403 MRI in, 342 surgical therapy for, 370 thoracic, 278, 346 Spinning top deformity, in dysfunctional elimination syndrome, 1813, 1814f Spiral flap, 1735, 1735f Spirometry, 118 Spironolactone for adrenocortical hyperplasia, 636 for ascites, 1409 for heart failure, in neonate, 148, 1501 Spleen. See rrl.\o Hypersplenism. abscess of, 1694 fungal, 1694 in leukemia patient, 1644 accessory, 1692, 1696, 1699 anatonlic abnormalities of, 1692-1693, 1692f in polysplenia syndrome, 1604, 1606, 1693 with short pancreas, 1672 splenogonadal fi~sionas, 1189, 1693 anatomy of, 1691 cysts of, 1692-1693, 1697, 1698 embryology of, 1691 functions of, 1691-1692 pseudocyst of, 299, 299f-SOOf, 1693 trauma to imaging of, 295, 296, 296f in birth injury, 405 laparoscopic repair of, 297, 1696, 1697 nonoperative treatment of, 295,297-299, 297t, 298t, 300, 1691 complications of, 299, 299f-300f operative intervention for, 298-299, 300 wandering, 1692, 1692f, 1696, 1698 Splenecto~ny after bone marrow transplantation, 782 complications of, 1697 infection as, 159, 1691, 1692 sepsis as, 1698, 1699 in Hodgkin's disease, 579-580 in hernolytic anemias, 181, 182, 1693 hereditary spherocytosis, 1637-1638, 1642, 1693, 1696, 1697, 1698 partial, 1697-1698, 1698f sickle cell, 1637, 1641, 1642-1643 in Hodgkin's disease, 577-578, 579-580, 1697 in idiopathic thrombocytopenic purpura, 183, 1693, 1696, 1698 in portal hypertension, 1661-1662, 1663 indications for, 1693-1694 outcomes of, 1698-1699 overview of, 1691 partial, 1697-1698, 1698f for cyst excision, 1692-1693 technique of, 16941698, 1694f-1695f, 1698f conversion to open, 1696, 1698 open, 1694, 1697 robot-assisted, 53, 54t, 1696 Splenic artery, aneurysm of, cotlgenital, 21 11 Splenogonadal fi~sion,1189, 1693 Splenornegaly, portal hypertension with, 1655, 1655f, 1656 Splenore~lalshunt, 1660, 1661, 166lf, 1663, 1664, 1664f, 1665 in polycystic kidney disease, 1709
Splinting for burns, 396 of fracture, 342 of hand, 352 Split notochord theory, 1390 Split-thickness skin grafts, 352 Spondylothoracic dysplasia, 917, 918f Squamous cell carcinoma laryngeal, 989 salivary gland, 827 Squamous papilloma laryngeal, 831,989-990,989f oral, 831 pharyngeal, 826 Stamm gastrostomy, 1131, 1131f Stapedius muscle, 813 Staphylococcus aureus antibiotic-resistant in acute lymphadenitis, 845 in enterocolitis, 1495 in mastitis, 887 in osteomyelitis, 2037, 2038 in septic arthritis, 2040 hepatic abscess caused by, 1644 mycotic aneurysm caused by, 2115 pneumonia caused by, 1002 pneumatocele secondary to, 1014 ~ta~hylococcus epidermidis, in neonatal sepsis, 170,172 Steatohepatitis, obesity-related, 1246 Steatosis, parenteral nutrition and, 208, 209, 210 Steeple sign, of subglottic edema, 828, 830 Stellate cells, 1652-1653 Stellate ganglion, neuroblastoma involving, 468,479 Stem cell factor from neuroblastoma, 475 gastrointestinal stromal tumors and, 516 gonadal embryology and, 554 Stem cell transplantation, 431-432. See also Bone marrow transplantation. in utero, 83t, 86 Stem cells in fetal therapy, 82, 831, 86, 87 for Hirschsprung's disease, 1526 in islet cell therapy, 727 in tissue engineering, 28 neonatal neutrophil pool and, 167 Stents airway after lung transplant, 772 for tracheomalacia, 1070 biliary, 303, 304f drug-eluting, 59 endovascular for central venous obstruction, 2124 for iliac vein compression, 2127 for renal artery stenosis, 2120 for renal artery trauma, 324 for subclavian-axillaryvein thrombosis, 2131 esophageal, for caustic injury, 1085, 1088 pancreatic duct, 308, 309f ureteral. See Ureteral stent. urethral, after hypospadias repair, 1893 STEP (serial transverse enteroplasty), 744, 1379, 1379f Stereotactic radiosurgery, 43, 44-47, 4 5 s46f extracranial, 43, 46, 47 for pineal tumors, 673 in children, 46-47 Sternal turnover, for pectus excavatum, 899 Sternomastoid tumor, 875-876,878-880, 879f Sternotomy, median, mediastinal infection secondary to, 1028
Volume 1, pages 1-1140; Volume 2, pages 1141-2146
Sternum congenital defects of. See also Chest wall, congenital deformities of. cleft defect as, 914-915, 914t, 915f-916f ectopia cordis as, 912-914, 913f-914f fracture of, 279 osteomyelitis of, 1028 Steroid cell tumor, 606-607 Steroid hormones, biosynthesis of, 1916f, 1916t Steroid therapy. See Corticosteroid therapy. Stertor, 828 ST1571 (Gleevec), 425 Stoma. See Enterostoma(s);Gastrostomy; Urinary diversion(s). Stomach. See also Gastric entrie.7; Pyloric entries. congenitally small, 1237-1238 herniated, through diaphragm, 284-285 perforation of, spontaneous, in newborn, 125551236, 1236f polyps in, 1417, 1420, 1421 tissue-engineered, 25, 25f, 26 transplantation of, in multivisceral graft, 745,748 trauma to, 310 laparoscopic repair of, 297 tumors of adenocarcinoma, 517-518 carcinoid, 518 peptic ulcer disease and, 1231-1232 smooth muscle, with pulmonary hamartoma, 641 stromal, 515-516 teratoma as, 566 volvulus of, 1234-1235, 1234t, 1235f Stomatitis aphthous, in ulcerative colitis, 1465 herpetic, 822 Stool, 203, 213 Streak gonads, 1917, 1=O gonadoblastoma in, 613, 19'20 Streptococcus group A R-hemolytic, 822, perianal dermatitis with, 159'2 peritonitis caused by, 1477 group B, neonatal sepsis caused by, 170, 171, 172 Streptococcus pneumoniae. See Pneumococcal (Streptococrus pneumoniae) infection. Streptokinase. See a l ~ Thrombolytic o (fibrinolytic) therapy. for empyema, 1018 for renal vein thrombosis, 1754 Streptolysin, 159 Stress gastritis, in neonate, 1385 Stress response in burn patient, 384 in trauma patient, 274 to surgery, in neonate, 104-108, 105f, 107f Stress ulcers, 12'25t, 1226, 1227-1228, 1229, 1231-1232 Strictureplasty, for Crohn's disease, 1457, 1457f, 1459 Stridor, 828, 829, 830, 831 definition of, 971 laryngonlalacia with, 986 laryngoscopic evaluation of, 971 location of lesion and, 828, 983 second branchial cleft anonlaly with, 866 tracheomalacia with, 996 Strip craniectomy, 795-796 Stroke, arterial ischemic, 21 17
INI)EX Stroke vol~un~e. 14G147 Stro~nalI ~ ~ t r o m606 a, Stuart Hamilton cq~ration,123 Stump overgrowth, 20.50, 2058 Sturge-Webel-syndl-ome,2098 S ~ t b a c ~thyroiditis, ~te 852 S~tbarachnoidhemorrhage as birth initu.): 405 traumatic, 358, 360f, 361, 362 Subclavian artery ii!j~ity to, 279 stenosis of, 21 17, 21 19f S~tbclavianvein, titrombosis of, 2131-2132 Subd~u-alcmpyema, 2009, 2010, 201 lf, 2012 Subdul-al liematoma, 359, 364, 364f ): as birth i n j r ~ ~405 in shaken baby syndrome, 401 St~bglottichem;~ngio~tia, 828, 830, 830f, 904-995, 994f, 21 03 Subglottic space, 984 S~tbglotticsteitosis, 829, 829f, 830, 990-994, 99Of-993f, 991t, 992t posterior cricoid split and rib graft for, 989 secoiid;~~-y to s~ipraglottoplasty,987 tracheototny tot; 984, 991 with laryngeal web, 988 Subinandibular gland. SPPnl,\o Salivary glands. brattchial anomaly associated with, 868 surgei-yof', 841-842 Subperiostcal abscess, 2034f iniracl-anial, 201 0, 201 Of Succitiylcholinc, 230, 23Ot, 231 fol- intubation, in trauma patient, 267 for laryngospasm, anesthesia-related, 223 Sucralfate for gasti-oesophageal reflux, 1126 for peptic nlccr disease, 1230 Slidden incant death syndrome (SSDS) sleepiiig position and, 794, 1125 thyroglossal duct cyst and, 870 Sufentanil, as anesthesia, during extrarorporeal life support, 139 Sugiltra operation, 1663 Suicidc gene therapy, for liepatocellular carcinoma, 510 Sulfaniylon. SPPMafenide acetate (Sulfamylon). Sulfasala~ine for (:I-ohn's disease, 1455, 1456 for ulcerative colitis, 1465 Sr~lindac,gasti-ointestinal polyps and, 1422 S~t~ibui-n, 385 Suitburst appearance, I-adiographic, 654 Superior vena cava. Srrl'ena cava. S~tperiorvena cava syndrome grant~lomatousmediastinitis with, 1028 mediastinal ttunol- with in Hodgkin's disease, 576 in non-Hodgkin's lymphoma, 584 tel-atonia as, 565 Superior vesical fistula, 1842, 1843f, 1846 Supernumerary arteries, of lung, 117 Superoxide, 160, 162, 16'Lt, 167 ~-rccrotizingeiiterocolitis and, 14% reperf~rsioninjury and, 158 Superoxide dismutase, 160 Supraglottitis, 830 S~~praglottoplasty, 98G987, 987f Stiprapobic cystostomy with delayed ~irethroplasty,330 Supraventriculai-tachycardia, in neonate, 148, 151, 152t, 153 Surface area. SPPTotal body surface area (TBSA), of burn. Surface rendering, 63, 64f
Surfactant, pulmonary compositional changes in, 116 high-frequency ventilation and, 125 in acute respiratol-y distress syndrome, 127 in congenital diaphragmatic hernia, 940 lung transplant for abnormalities in, 768 type IS pneumocytes and, 116, 116f, 117,933 Surfactant protein B deficiency 768 Surgery pediatric, history of, 3-10, 3f-5f., Ub, 9f-10f stress response to, 104108, 105f, 107f, 210-211 Surgical assist devices, 49, 49t Sutures, for soft tissue injury 352 Swallowing. SPPalso Dysphagia. acid clearance by, I122 endoscopic evaluation of, 1124 Swan-Ganz catheter. S ~Pulmonary P artery cathete~: Sweat chloride test, 1292, 1293 Swensoii procedure, 1532, 153'Lf, 1538, 1540, 1541f complications of, 1546 redo of, 1545f Swimming pool peritonitis, 1475 Synchl-onized intermittent mandatory ventilation, 124 Syncytiotrophoblasts, 556, 568, 594, 595, 609 Syndactyly, 2073, 2074, 2074f in Poland's syndrome, 907, 2071, 2074 Syndrome of inappropriate ADH secretion (SIADH), 94, 94t Synovial fluid, 2040, 2040t Syno~ialsarcoma, 543, 544t, 545-546 Synovitis pigmented villonodular, MRI of, 654 toxic, 2039, 2040t Syringocele, Cowper's, 1903 Syringomyelia, 1992f Systemic inflammatory response syndrome. SPPSIRS (systemic inflammatory response syndrome).
T lymphocytes, 161, 163, 165, 166. SPPalso Lymphocytes. autoreactive, in islet cell transplantation, 726 burns and, 385 development of, 581, 582f imtnunotherapy and, for neuroblastoma, 485 in Hirschsprung's disease, 1528-1529 in neonate, 167, 170 in systemic inflammatory response syndrome, I69 in ulcerative colitis, 1463, 1466 Wiskott-Aldrich syndrome and, 182 T, toxicosis, 853 TAC (tetracaine, adrenaline, cocaine), 244, 244t Tachyarrhythmias, in neonates, 148, 151, 152t, 153 Tachycardia, as shock indicator, 319 Tacrolimus in transplantation, 693, 693f heart, 760, 761s intestinal, 742-743, 749 islet cell, 724 liver, 689, 689f, 737, 738t, 739 lung, 770, 771, 771t, 775 pancreatic, 721, 722, 722f renal, 707-708 mechanism of action, 707-708, 738t side effects of, 708, 737, 738t, 739 ~ l u m e1, pages 1-1 140; Volume 2, pages 1141-21
lix
Takayasu's arteritis, 21 17, 21 20 Talipes equinovarrls, 20242025, 2024f Tapering entcroplasty, 13713-1377, 1377f TAR (thrombocytopenia-absent radius) syndrome, 1936, 2073 Target sign, of int~rssusception.1YL6, 1326f Taurine, 196, 202, 204, 209 Taurolidine, for systemic inflammatory response syndrome, 173 Taxanes, 424t TBSA (total body surface area), of bum, 383, 384,386, 387, 3871, 388f outcornes and, 383, 397 therapies and, 389, 390, 391, 393, 394, 395 TBW (total body water), in fetus and neonate, 91, 92, 98 Technetium 991n. SPPRatiion~rclidestudies. Technological innovation, 31-32, 32t ethics of, 258-260 surgical fellowship in, 70 Tectal glioma, 676 Teeth, abnormal, in Gardner's syrtdrorne, 1422 Teflon injection, for vesicor~rctcralreflux, 1747, 1766, 1767 with megaureter, 1776, 1780 Tegadernt, for superficial scrond-degree hurns, 390 Telangiectasia, hereditary hcrnorrhagic, 2096, 2101 hepatic lesions in, 497 Telangiectatic osteogcnic sax-coma,652 Teleoperator robots, 49-53, 491, 50f-51f, 52t applications of; 53, 54t, 55, 56t conclusions on, 55, 57 Tclomerase, 414 in ncul-obl;~stoina,474, 483 Telomerasr inhibitors, 426 Telomeres, 4 14 Te~nozoloniidc,423t Temperature rnonito~.ing,234 Temporal bonc branchial anomaly with involveinetit of; 868 fracture of', 816-817, 817s tumors with involvement of', 817 Temporomandibularjoitit,disk o f , tissueengineered, 22 Tendon (s) congenital anomalies involving, 2070-2071, 2070f; 2072f flexion deformities as, 2074-2075 trauma to, 351 in hand, 350, 350f-351f Teniposide, 4241 Tension pneulnotliorax, 280-281, 2Xlf, 283 spontaneous, 1020, 1021 Tensor tympani muscle, 813 Teratoma, 554, 555, 557-567. .SPPa150 Fetus in fetu. anomalies coexisting with, 557, 559, 564, 566 cardiac, 557, 558, 565-566 cervicofacial, 557, 563-,565, 563f-564f cytogenetics of, 557 embryogenesis of', 2080 gastric, 566 grading of, 558 hepatic, 496, 499, 505, 557 histology and pathology of, 557-558, 558f in mixed germ cell tumors, 568 iiitracranial, 557, 558, 563 mediastinal, 557,565,959,961,961f; 962-963 nasopharyngeal, 826 neuroblastoma foci in, 468 ovarian, 557, 558, 566, 593, 594t, 607, 609-612, 610f-61% computed tomography of, 557f
.Ic~-;itoni;t . ((.~IJI/I~II/P//) n~o~~odcl-mnl. ti1 2 ~xognosisot; 558 ~.rtrol)c~.itontal, 557, 558. 5.5Xt; 5(i(i s;tc~-ococcygciil,557, 557f-5(i1 t; 558-,353 tI.c';11I11('I11 of. 821. 85 1~l~cll;lt;l1 sites 01, 5.57, 5571 557, 567, (i'22, 623, (i2:lt, (i'241 tcsticr~l;i~; ~tgi11;11, 5(i(i 583 Tc~.nli~l;~l d c o ~ y ~ ~ i ~ c l e 11 o ;~nsfk~.;isc, ti~lc Trrn1in;ttion of' 1)rcgllanc.v..Sr,r, nlso Frti~\, sclccti\c I-cductionof. d c f c t s n~;~r~;iged I)!; 77, 78t. 81 gci~ctic; ~ s s c s s ~ ~ 01'1issl1c i'~~t ii.o~n.1.5 wit11 ;~l)donlin;~l \\.;illdcfbcts, I l(i1 \\.it11 l)owi~s y ~ ~ d ~ o i12(iO ~ic. Tcssicl- cl;issific;~iio~~, 788. 78Xf. 80:l. 8051 Tcstici~l;~~. ft.~ni~li/;~tio~t, 19141, 191(i-l!417 Tcstict11;11tuinol-s, 622-(i"(i, (i2:lt. (i24f-(i2(5t: of. Sr~r,///soS ~ I - o t u ~tunio~.s n, 1)iologic ~ n ; i ~ . kof; c ~ 556. s (?22-(i'2:4 I)iol)s\ of. 442, (22. (723 ca1cific;itions in, (222, t?L:l crvpto~'cl~itiisni : ~ n d(922, , 1198. 1205 gc~.~ninoni;r ;is, 567 cytogwictics ot. 557 g y ~ i c c o ~ i ~ ;;111d, ~ s t i ;2O(i!)-2070 ~ S ~ I ~ ( ~ I ~ O I14 I I I8 (~, in I'c~i~t~~]c~glnc~~s orchidopcxy ;anti, (i22. 120.5 scininorn;i ;IS. ,554. ,565. (i22 tc~.:ito~i~:t ;is, 557, 567, (i'22, (723. (Y2:lt. (84f vs. splc~iogo~~;~d;il fi15io11.I 1 89 yolk s;ic tuinor as, 567, (i22. (i23,(i23t. V24f Tcstis(cs). SPP/rL\o Sc~.otii~ii. id^-cn;il tissuc ;~tt;ic-lictito, 1 1 8e~'ica~-dial Tllol-acosto~nytr~ljc..Srv (:hest tulle. Tl~ol-acotoniy chylotl~ol-axscc011t1;iryto, 1026 in 11-aiun;~ xit tic lit enic~-gc~icy for ;tir c~nljol~ts, 282 illdieations ti)r; 277, 277t fol- ;~i~.w;i\ i11j111.y 283 f o ~;to1 . tic i n j u ~y, "10 Sol-llcll1otllol~;lx,281 gut, 285 fol- hc~.l~i;itrd Sol-pencil-;iling i~!jury,291 f o ~pcricarcli;~l . t;in~po~~;~ 286, ( I c 291 , illcision in, 279 Thl-cc-di~nrn~io~ial i111;1ges co~nputcdtomogl-;~pl~ic, :34, :35-36, :$(if for prcopc~.;iti~(~ ~ I ~ I I I I ~ (i7-(i8, I I ~ , (i8f in ilnagca-gt~idcdI-adiatio~~ tllt.i.;~py,420 in ~.ol)otics ~ ~ r g e ~50, . y 51, , 521, 53, 57 (il , 68-70 in training sin~~~l;rtions, i l l virtt~al~.c,;ility, (92, (i:$-(i5, 641, (i(i fix rxcopc~-;iti\~ pl;lnnii~g,67-68, (i8f of conjoined t~vins.2083, 20831. 2085, 2089 ultl.;~sor~nd, 33, :I:H in 1bt;tl intcrvcntio~~, 77 T l ~ r o ~ n h itinnr, n 1841 Tl~r-ornbocytopc~~ia, 182-18:3. Sr~r,nlso Knsabac11-Mel-$-it1 syndt.on~e. aficl- pol-toc~itc~.ostot~~y, l 612 benign liver tilmol-s with, IO5, 406, 497 witli niassivc t t ' i ~ ~ ~ s f i t s279 io~~, dilutio~~al, witli, 780 di~odcnalIjiopsy ill l);rtic~~t in hone nial-r-o\\,i ~ - a n s l ~ l ~xitic~lt, ; i ~ ~ t 782 1435, 1439, in necroti~ingc~~terocolitis, 1440 ill neonatal sepsis, 171 neo~latalisoi~nmiinc,182 platelet tra~isfi~sio~l fiw; 1!)0 ThroniI)ocytopcni;~-ahsm~.;~cli~ts (TAK) syndrorrrc, I!4:l(i. 2073 Tlnrombocyto~~c~~ic purpr~ra,idiop;itIlic (in~trlunc),182-183 accessory sljlccns ;it~d,I (592 s p l c ~ ~ c c t oin, ~ ~ 183, i y I (iW, I ($