ERCP

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Preface ERCP PAST, PRESENT AND FUTURE ERCP past

1 Since its initial description over 3–2 decades ago, ERCP has evolved from a diagnostic to a therapeutic procedure. Such an evolution, however, has required developments in technology to include marketing of a side-viewing duodenoscope with an elevator to facilitate cannulation, use of therapeutic instruments with larger accessory channels, and creation and marketing of a wide variety of endoscopic accessories. In addition to technology evolution, there have been evolutions in techniques and training to bring us to ERCP present. From the latter standpoint, ERCP is currently recognized as an advanced therapeutic procedure usually requiring an additional year of training beyond a standard 3-year gastroenterology training program.

ERCP present With the exception of performing concomitant sphincter of Oddi manometry (SOM), diagnostic ERCP has largely been supplanted by non-invasive imaging to include abdominal CT, MRI-MRCP and EUS. Therapeutic ERCP was initially described over 30 years ago when Classen and Kawai independently described endoscopic sphincterotomy in Germany and Japan, respectively. From a diagnostic standpoint, ERCP is still used to define the etiology of acute relapsing pancreatitis (divisum, anomalous PB union, annular pancreas, SOD . . .), to differentiate chronic pancreatitis from intraductal papillary mucus secreting neoplasm (IPMN), to define the presence or absence of common bile duct stones in jaundice, cholangitis, or acute pancreatitis and to distinguish benign from malignant biliary strictures. From the latter standpoint, however, ERCP remains an imperfect technology, and meta-analyses of series reviewing brush cytology or endoscopic biopsy to distinguish benign from malignant biliary stenoses suggest only a 30–50% positivity, even in the setting of malignancy. ERCP is also used diagnostically to define the etiology of smoldering pancreatitis to include diagnosis of ductal disruption and sphincter edema. Currently, ERCP has evolved into a primary therapeutic modality. For the past three decades, therapeutic maneuvers have been centered on, and facilitated by, endoscopic sphincterotomy. Despite changes in sphincterotome design (pull, push, needle-knife, long-nose, 20–30 mm wire, monofilament vs braided cutting wire, standard vs rapid-exchange system, single/double/triple lumen technology), technique of use (pure cut, blended current, pulsed current/Erbe generator) and length and direction of incision, enlarging the pancreaticobiliary orifice to facilitate access to strictures, stones, and ductal disruptions remains the most common therapy undertaken with ERCP. While balloon dilation of the biliary sphincter may theoretically offer comparable access to biliary sphincterotomy without the potential risk of bleeding and perforation complications, the rates of procedural pancreatitis, often severe, are prohibitive without the use of adjunctive measures such as pancreatic duct stent placement. As such, the use of balloon dilation of the papilla has been relegated to bit parts in our therapeutic armamentarium, most commonly in the setting of coagulopathy and Billroth-II anatomy. Changes that have occurred over the past decade in the endoscopic treatment of biliary stones have included improved mechanical lithotriptors and electrohydraulic and laser lithotripsy under direct cholangioscopic visualization. Changes in malignant stricture therapy include evolution from plastic prostheses to self-expandable metal stents (SEMS). For benign strictures, dilating balloons have become stronger and have been marketed with larger diameters. Treatment has evolved from placement of a single polyethylene prosthesis to 2, 3, 4, and even 5 stents in parallel. Studies are currently underway looking at the use of completely covered 8–10 mm SEMS in an attempt to treat a subgroup of these patients with a single endoscopic manipulation. The treatments of postoperative biliary leaks have become routine and endoscopic papillectomy has replaced surgical resection for most ampullary adenomas. On the pancreatic side, obstructing calculi have become a major indication for pancreatic endotherapy although approximately 50% of such patients require pretreatment with extracorporeal shock wave lithotripsy (ESWL) prior to removal. Obstructing strictures are also routinely being treated, although results remain more nebulous than those reported for benign biliary stenosis and there appears to be discordance between resolution of the stricture (20–30%) and symptomatic improvement (67–80%). Treatment of ductal disruption has now become standard therapy in high-volume ERCP centers. The latter include amenable pancreaticocutaneous fistulas (external fistula) and internal fistulas (pseudocyst, high amylase pleural effusion, pancreatic ascites, pancreaticoenteric or pancreaticobiliary fistula). Data are clear that fistulas are much more likely to close if a transpapillary stent bridges the area of duct disruption. In contrast, a glandular disconnection (disconnected gland syndrome) in which the major ix

PREFACE

component of ongoing glandular secretions is from the disconnected upstream duct is unlikely to close unless there is concomitant transgastric or transenteric drainage of an associated fluid collection.

ERCP future There are multiple possible scenarios for ERCP in the future. These include widespread application of techniques or technology that are currently used only in high volume centers. Examples include semi-routine use of cholangioscopy to rule out retained CBD stones or to better define the etiology of biliary strictures. The latter will likely require disposable cholangioscopes. On the other hand, widespread application of durable video cholangioscopes or pancreaticoscopes is potentially feasible. Other procedures that are utilized infrequently may become commonplace if technologic and reimbursement issues can be solved. These include endoscopic delivery of brachytherapy or photodynamic therapy (PDT) to patients with unresectable, hilar cholangiocarcinoma. They include a more widespread approach to the endotherapy of pancreatic necrosis, treating not only the ductal disruption that is invariable in severe necrosis but also its consequences, to include drainage of associated fluid collections and debridement of necrotic debris. It is possible that ERCP in the future will become aggressively more therapeutic. An example might be injection of a litholytic agent into the pancreatic duct in patients with chronic calcific pancreatitis. Prostaglandin inhibitors as well as long-acting neuromodulators may also be injected intraductally in painful chronic pancreatitis. Stent placement may evolve to solve the problems of occlusion by bacterial biofilm or mucosal hyperstasia with plastic and metal prostheses, respectively. It is possible that intraductal injection of chemotherapeutic or immunomodulating drugs may play a bit part or a major role in the future management of pancreaticobiliary malignancies. Certainly work will continue on ways to minimize procedurally-related pancreatitis, the major complication of ERCP. The latter will include modifications of technique, prophylactic PD stents and pre- or intra-procedure injection of drugs, intravenously or directly into the pancreatic duct. On the other hand, protenomics promises what conventional tumor markers (CA19-9, CEA, alterations in p53, K-Ras . . .) have not delivered: early diagnosis of PB malignancy or definition of an extremely high risk patient group who perhaps require more, as opposed to fewer, diagnostic procedures. The future of ERCP is like, “The check is in the mail.” It may or may not arrive. Even if it does, the check may be so delayed as to prove almost worthless. The evolution of ERCP, of course, will not occur in a vacuum and its future will be contingent upon parallel advancements in imaging and lab testing and breakthrough technology or techniques in other disciplines such as laparoscopic or transgastric surgery, more effective and less toxic chemoirradiation, or even alternative endoscopic therapies delivered by EUS. Nevertheless, we predict a bright decade for ERCP and suggest that even at its 50th anniversary, it will remain a vibrant technology and technique in the care of patients with PB disease. It is with this timeline and cumulative perspective that the editors have assembled this ERCP text. Many of the world’s experts have contributed chapters and video material in an attempt to make this book not only relevant, but comprehensive, for any endoscopist who utilizes ERCP in their practice. Omissions, if any, are ours. Technology changes rapidly and reusable cholangioscopes (e.g. Spy ScopeTM) will have been introduced by the time this text is published and it is likely that other technology may be rendered obsolete. Clinical trials may fuel or dampen our enthusiasm for one procedure or another. Despite this, the editors have done their best to produce a text that will put both evolving technology and current techniques into clinical perspective. After all, ERCP remains a clinical tool to facilitate patient care and improve clinical outcomes. It is our hope and intention that this book facilitates and improves that care. Todd H. Baron, MD Richard A. Kozarek, MD David L. Carr-Locke, MD

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List of Contributors Dr Douglas G. Adler Assistant Professor of Medicine, Director of Therapeutic Endoscopy Huntsman Cancer Center University of Utah School of Medicine Salt Lake City UT USA Dr Sushil K. Ahlawat Assistant Professor of Medicine Department of Medicine, Gastroenterology Division Georgetown University School of Medicine Georgetown University Hospital Washington DC USA Dr Jawad Ahmad Assistant Professor of Medicine and Co-Medical Director of Liver Transplantation University of Pittsburgh Pittsburgh PA USA Dr Firas H. Al-Kawas Professor of Medicine and Chief of Endoscopy Gastroenterology Division Georgetown University Hospital Washington DC USA Dr Raed M. Alsulaiman Assistant Professor of Medicine and Consultant Internist, Gastroenterologist King Faisal University King Fahd Hospital of The University Alkhobar Kingdom of Saudia Arabia Dr Tiing Leong Ang Consultant Gastroenterologist Department of Medicine Changi General Hospital Singapore Dr John Baillie Professor of Medicine Division of Gastroenterology Wake Forest University Health Sciences Winston-Salem NC USA Dr Alan Barkun Professor of Medicine and Chairholder the Douglas G. Kinnear Chair in Gastroenterology Director, Division of Gastroenterology McGill University and the McGill University Health Centre Montréal, Québec Canada

Dr Todd H. Baron Professor of Medicine Mayo Clinic College of Medicine Rochester MN USA Dr Suryaprakash Bhandari Associate Consultant Institute of Advanced Endoscopy Jaslok Hospital Mumbai India Dr Kenneth F. Binmoeller Director, Interventional Endoscopy Services California Pacific Medical Center San Francisco CA USA Dr William R. Brugge Associate Professor of Medicine, Harvard Medical School Director of Endoscopy, GI Unit Massachusetts General Hospital Boston MA USA Dr Jonathan M. Buscaglia Therapeutic Endoscopy Fellow Division of Gastroenterology and Hepatology The Johns Hopkins University School of Medicine Baltimore MD USA Dr David L. Carr-Locke Director The Endoscopy Institute Brigham & Women’s Hospital Boston MA USA Dr Annie On-On Chan Associate Professor of Medicine Department of Medicine University of Hong Kong Queen Mary Hospital Hong Kong Dr Suyi Chang Gastroenterologist Kaiser Permanente Walnut Creek CA USA Dr Ann M. Chen Clinical Instructor University of California, Irvine Comprehensive Digestive Disease Center Orange CA USA xi

LIST OF CONTRIBUTORS

Professor Guido Costamagna Professor of Surgery and Gastroenterology Digestive Endoscopy Unit Universita Cattolica “A Gemelli” Roma Italy Dr Giovanni D. De Palma Chief, Section of Diagnostic and Therapeutic Endoscopy Department of Surgery and Advanced Technologies University of Naples Federico II Naples Italy Dr Jacques Deviere Professor of Medicine Chairman, Department of Gastroenterology and Hepatopancreatology ULB—Hôpital Erasme Brussels Belgium Dr James J. Farrell Director of Pancreaticobiliary Endoscopy and Endoscopic Ultrasound Division of Digestive Disease UCLA School of Medicine Los Angeles CA USA

Dr Gregory G. Ginsberg Professor of Medicine Director of Endoscopic Services Gastroenterology Division Hospital of the University of Pennsylvania Philadelphia PA USA Dr Jaquelina M. Gobelet Fellow of The Latin American Advanced Gastrointestinal Endoscopy Training Center Santiago Chile Dr Khean-Lee Goh Professor of Medicine Head of Gastroenterology and Hepatology Chief of GI Endoscopy Faculty of Medicine University of Malaya Kuala Lumpur Malaysia

Dr Paul Fockens Professor of Gastrointestinal Endoscopy Director of Endoscopy Academic Medical Center University of Amsterdam Amsterdam Netherlands

Dr Nalini M Guda Clinical Assistant Professor of Medicine University of Wisconsin School of Medicine and Public Health Pancreatic Biliary Center St Luke’s Medical Center Milwaukee WI USA

Dr Victor L. Fox Director GI Procedure Unit and Endoscopy Program Children’s Hospital Boston Harvard Medical School Boston MA USA

Dr Robert H. Hawes Professor of Medicine Division of Gastroenterology/Hepatology Digestive Disease Center Medical University of South Carolina Charleston SC USA

Dr James T. Frakes Clinical Professor of Medicine University of Illinois College of Medicine at Rockford and Rockford Gastroenterology Associates Ltd Rockford IL USA

Dr Jürgen Hochberger Chefarzt Med Klink III—Gastroenterologie— Intervent. Endoskopie St Bernward Krankenhaus Hildesheim Germany

Dr Martin L. Freeman Professor of Medicine, University of Minnesota Director, Pancreaticobiliary Endoscopy Fellowship University of Minnesota and Hennepin County Medical Center Minneapolis MN USA

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Dr Joseph E. Geenen Clinical Professor of Medicine Medical College of Wisconsin Director, Pancreatic Biliary Center St Luke’s Medical Center Milwaukee WI USA

Dr Kunal Jajoo Advanced Endoscopy Fellow The Endoscopy Institute Brigham and Women’s Hospital Boston MA USA Dr Ann Marie Joyce Gastroenterologist Gastroenterology Department Lahey Clinic Burlington MA USA

LIST OF CONTRIBUTORS

Dr Anthony N. Kalloo Professor of Medicine Director, Division of Gastroenterology and Hepatology The Johns Hopkins University School of Medicine Baltimore MD USA Dr Peter B. Kelsey Assistant Professor of Medicine Harvard Medical School Gastrointestinal Unit Massachusetts General Hospital Boston MA USA Dr Michael B. Kimmey Professor of Medicine Division of Gastroenterology University of Washington Medical Center Seattle WA USA Dr Michael L. Kochman Professor of Medicine and Professor of Medicine in Surgery Gastroenterology Division Hospital of the University of Pennsylvania Philadelphia PA USA Dr Tadashi Kodama Chief of Gastroenterology Kyoto Shimogamo Hospital Kyoto Japan Dr Tatsuya Koshitani Chief of Endoscopy Unit Department of Gastroenterology Kyoto City Hospital Kyoto Japan Richard A. Kozarek Executive Director, Digestive Disease Institute Virginia Mason Medical Center Clinical Professor of Medicine University of Washington Seattle WA USA Dr Yuk Tong Lee Honorary Clinical Associate Professor The Chinese University of Hong Kong Prince of Wales Hospital Shatin, NT Hong Kong Dr Glen A. Lehman Indiana University Medical Center Indianapolis IN USA Dr Joseph W. Leung Mr & Mrs C.W. Law Professor of Medicine Division of Gastroenterology and Hepatology UC Davis Medical Center Sacramento CA USA

Dr Chi Leung Liu Honorary Professor of Surgery Department of Surgery University of Hong Kong Queen Mary Hospital Hong Kong Dr Simon K. Lo Director of Endoscopy, Cedars-Sinai Medical Center Clinical Professor of Medicine David Geffen School of Medicine at UCLA Division of Digestive Diseases Cedars-Sinai Medical Center Los Angeles CA USA Dr Jürgen Maiss Department of Medicine I University Erlangen-Nürnberg Erlangen Germany Dr Amit Maydeo Director, Institute of Advanced Endoscopy Chief, Department of Endoscopy and EUS Jaslok Hospital Mumbai India Dr Detlev Menke Leading Consultant Department of Medicine III St. Bernward Hospital Hildesheim Germany Dr Desiree E. Morgan Associate Professor, Diagnostic Radiology Department of Radiology University of Alabama at Birmingham Birmingham AB USA Dr Claudio Navarrete Director of Minimally Invasive Surgery Clinica Alemana-Universidad del Desarrollo Chair of The Latin American Advanced Gastrointestinal Endoscopy Training Center Santiago Chile Dr Horst Neuhaus Professor of Medicine Department of Gastroenterology Evangelisches Krankenhaus Düsseldorf Düsseldorf Germany Dr Wai Choung Ong Asian Institute of Gastrenterology Jubilee Hills Hyderabad India Dr Wai Choung Ong Asian Institute of Gastrenterology Jubilee Hills Hyderabad India xiii

LIST OF CONTRIBUTORS

Dr William M. Outlaw Fellow Division of Gastroenterology Wake Forest University Health Sciences Winston-Salem NC USA

Dr Chan-Sup Shim Professor of Medicine Digestive Disease Center Soon Chun Hyang University Seoul Korea

Dr Bret T. Petersen Professor of Medicine Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine Rochester MN USA

Dr Lalit Shimpi Professor of Medicine Department of Gastroenterology & GI Endoscopy Jehangir Hospital in association with Apollo Hospitals Pune India

Dr Jeffrey L. Ponsky Department of Surgery University Hospital of Cleveland Cleveland OH USA Dr G. Venkat Rao Asian Institute of Gastroenterology Jubilee Hills Hyderabad India Dr Nageshwar Reddy Asian Institute of Gastroenterology Jubilee Hills Hyderabad India Dr Banerjee Rupa Asian Institute of Gastroenterology Jubilee Hills Hyderabad India Dr Stefan Seewald Professor of Gastroenterology Department of Interdisciplinary Endoscopy University Medical Center Hamburg-Eppendorf Germany Dr Dong Wan Seo Associate Professor of Medicine and Director of Endoscopy Unit Division of Gastroenterology, Department of Internal Medicine Asan Medical Center, University of Ulsan College of Medicine Seoul South Korea

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Dr Hardeep M. Singh Fellow, Department of Gastroenterology Kaiser Permanente Los Angeles Medical Center Los Angeles CA USA Dr Adam Slivka Professor of Medicine University of Pittsburgh Pittsburgh PA USA Dr Nib Soehendra Professor of Surgery, Director, Department of Interdisciplinary Endoscopy University Medical Center Hamburg-Eppendorf Germany Dr Ellert J. van Soest Department of Gastroenterology and Hepatology University of Amsterdam Amsterdam The Netherlands Dr Geoffrey Spencer Instructor of Medicine Division of Gastroenterology Hospital of the University of Pennsylvania Philadelphia PA USA Dr Joseph Sung Professor of Medicine Director, Institute of Digestive Disease The Chinese University of Hong Kong Prince of Wales Hospital Shatin, NT Hong Kong

Dr Syed G.Shah Consultant Gastroenterologist Department of Gastroenterology Pinderfields General Hospital Wakefield UK

Dr Paul R. Tarnasky Clinical Associate Professor of Medicine University of Texas Southwestern Methodist Dallas Medical Center Dallas TX USA

Dr Stuart Sherman Professor of Medicine and Radiology Clinical Director of Gastroenterology and Hepatology Director of ERCP Indiana University Medical Center Indianapolis IN USA

Dr Yoshihide Tatsumi Chief, Department of Gastrointestinal Diseases Matsushita Health Care Center Moriguchi Osaka Japan

LIST OF CONTRIBUTORS

Dr Mark Topazian Associate Professor of Medicine Mayo College of Medicine Rochester MN USA Dr Eduardo Valdivieso Professor of Surgery Pontificia Universidad Javeriana, Colombia Fellow of The Latin American Advanced Gastrointestinal Endoscopy Training Center Santiago Chile

Dr Benjamin Chun-Yu Wong Professor of Medicine Department of Medicine University of Hong Kong Queen Mary Hospital Hong Kong Dr Gregory Zuccaro Jr Director, Center for Endoscopy and Diseases of the Pancreas and Bile Ducts Department of Gastroenterology and Hepatology Cleveland Clinic Cleveland OH USA

Dr James L Watkins Division of Gastroenterology and Hepatology Indiana University Medical Center Indianapolis IN USA

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Dedication To our families, friends and colleagues who tolerate us To our teachers and students who taught us everything we know To our patients who amaze us and To our contributors who helped us, We dedicate this to you.

Acknowledgements Virginia Mason Medical Center:

Mayo Clinic Brigham & Women’s Hospital:

Hannah Scott, Word-Processing Terrance King, AV Support Donna Smith, Practice Support Mindy K. Parker, Secretarial Support Sandra Healey, Secretarial Support

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SECTION 1

Chapter

1

GENERAL TOPICS

Medicolegal Issues James T. Frakes

INTRODUCTION TO MEDICOLEGAL ISSUES The medicolegal environment Medicine is an imprecise science, influenced by the vagaries and unpredictable nature of biologic systems and the art of interpersonal relationships. Human illnesses are, from the outset, adverse outcomes of life, and it is often difficult for physicians to correct or mitigate these illnesses. Furthermore, the techniques, tools, and technology available to aid in this task often have associated inadequacies or risks. Therefore, restoring biologic function to its former healthy state is oftentimes incomplete, sometimes unsuccessful, and occasionally complicated by iatrogenic injury. Negative or adverse outcomes may include cognitive or technical failures, ineffective therapies, complications of therapy, high costs and extended hospitalizations, and missed work and life activities. Any or all of these may lead to patient dissatisfaction and a desire to assign blame and seek compensation. It is in this environment of personal illness and fear, limited medical art and science, patient dissatisfaction, and legal avenues for redress that medicolegal issues arise. Especially in the United States, there has been a steady increase in both lawsuits filed for medical malpractice and the size of awards granted for damages.1 Physicians and insurance companies generally blame unrealistic patient expectations, avaricious trial lawyers and inappropriately high jury awards for the increased number of lawsuits, which in turn lead to high malpractice insurance rates, diminished access to certain types of medical care and the costly practice of defensive medicine. Alternatively, attorneys and some patients blame true medical negligence, high medical costs, inadequate policing of incompetent physicians, and poor financial management by insurance companies for the worsening medicolegal climate. It is therefore appropriate for physicians to study medicolegal issues, especially in their specialty areas of practice, to optimize patient outcomes, limit patient harm and dissatisfaction, and minimize the risk of malpractice litigation.

Medicolegal issues in gastroenterology and gastrointestinal endoscopy Gastroenterologists, like all physicians, have reason to be concerned about malpractice litigation. But, data specific to gastroenterology and endoscopy are scarce. Many commercial insurance carriers are unwilling to share data on claims and awards, regarding this as proprietary information and fearing possible adverse publicity or stimulation of even greater malpractice litigation activity. One association of insurers, the Physician Insurers Association of America (PIAA), pools information from approximately 30 physician-owned

or managed insurance companies in the United States and periodically publishes data. These data probably provide the best picture of medical malpractice claims currently available. It is interesting to note that despite the increasingly complex nature of gastroenterology and gastrointestinal endoscopy, gastroenterologists are sued less often than most other specialty groups, ranking 21st of 28 specialty groups in the number of claims reported in the PIAA data.2 Gastroenterologists accounted for about 2% of claims and 1.4% of PIAA indemnity payments. About one of five gastroenterology claims resulted in indemnity payment. The highest indemnity payment has been $2.9 million, almost triple the largest gastroenterology payment reported in 1999.3 According to PIAA data, despite the fact that most gastroenterologists spend most of their time performing procedures, the basis for claims in gastroenterology from 1985 to 2004 involved cognitive issues 60% of the time, including consultations, diagnostic interviews, evaluations, medication prescriptions, injections and vaccinations. Procedural misadventures accounted for about 40% of the claims during that time period, including procedures on the hollow gut or biliary tract, including endoscopic retrograde cholangiopancreatography (ERCP). The vast majority of these endoscopy cases involved perforation of the gut, while a much smaller percentage included pancreatitis, hemorrhage, dental injury or falling from the bed while sedated. Issues involving informed consent as a secondary allegation occurred about 17% of the time.

Medicolegal issues in ERCP Because ERCP is one of the most technically difficult procedures performed by gastrointestinal endoscopists and because complications, sometimes severe, are more common than with other endoscopic procedures, ERCP might be expected to account for a disproportionate number of claims against gastroenterologists. However, the relative risk of litigation arising from ERCP, despite the significantly higher rate of complications, appears to be less than twice that of significantly less complex procedures such as flexible sigmoidoscopy or gastroscopy.4 In one Canadian database, ERCPrelated events accounted for only about 6% of gastrointestinal-related legal actions from 1990 to 1997.5 One possible explanation for this seeming paradox is the more intensive informed consent processes for ERCP when compared with simpler endoscopic procedures. This hints at the importance of adequate informed consent as a risk management strategy. After a discussion of legal principles of importance in medical practice, specific risk management strategies for ERCP will be outlined below, including sound medical practice, avoidance of complications, and truly informed consent. 3

SECTION 1 GENERAL TOPICS

IMPORTANT LEGAL PRINCIPLES IN MEDICAL PRACTICE Elements of a malpractice case: the principles of tort law

The general concept

The most common form of a medical malpractice action falls under the principles of tort law, a “civil wrong” rather than a criminal action. Such civil wrongs are generally compensated by monetary redress. To succeed in a medical malpractice action, the plaintiff must prove four basic legal elements by a preponderance of evidence (the fact at issue is more probable than not) rather than proving beyond a reasonable doubt as in criminal actions.4,6,7 These four basic elements that must be proven are: 1. The physician owed a duty of care to the patient. 2. The physician breached that duty by violating the applicable standard of care. 3. The breach of duty caused an injury. 4. The patient’s injury is compensable (damages).

The standard of care is a legal concept describing the duty that physicians must fulfill in their care of patients.4,7,8 A failure to practice within the standard of care is a breach of that duty, one of the four central elements of a malpractice case. The standard of care is usually established through expert testimony, published data and accepted practice guidelines. Of these, the most important in court is expert testimony. Expert testimony seeks to establish a standard of care reflecting the practice that is customary among competent gastroenterologists in good professional standing who are practicing with reasonable diligence, and should reflect the current practice at the time of the injury. Simply stated, the standard of care is “good patient care.” It is not defined as optimal or best medical practice exhibited by only a few noted experts in the field but rather what would be expected from a reasonable peer under the same circumstances.

Duty

Majority and minority standards

The physician’s duty to the patient arises from the physician–patient relationship. If there is no physician–patient relationship there is no malpractice risk. The relationship is usually created through an office visit, hospital visit or performance of a procedure, but may be created without actual face-to-face meeting between the physician and patient. For example, an appointment for an office visit or endoscopic procedure or the prescribing of a colon cleansing agent prior to colonoscopy might create such a physician–patient relationship. Clearly defining a physician’s duty or role in the management of a patient, thereby limiting the scope of the duty, might help to reduce subsequent liability. Once established, the physician-patient relationship continues until officially and appropriately terminated by the patient or physician.

Because there are often many ways to manage a clinical problem, more than one standard of care may be applicable for evaluating or treating a condition. Practicing the “majority” standard, or most commonly taken approach by most peers, is usually the most defensible method of practice. A less common approach, the “minority” standard, may be acceptable, but should be explained in terms of why a strategy differing from the usual was employed. As stated in one recent publication, “physicians who practice in ignorance of the majority standard do so at their peril.”7

Breach of duty The duty of the physician once the physician–patient relationship has been established is to practice within a reasonable standard of care. Failure to meet the standard of care constitutes negligence and is the central issue in most medical malpractice litigation. While often difficult to define, a reasonable standard of care is usually established with the aid of expert witnesses acting as medicolegal consultants.

Causation To be successful in a medical malpractice suit, the plaintiff must prove that substandard care was the proximate (substantial rather than minor) cause of injury.

Injury Further, to succeed, the plaintiff patient must establish that some type of physical or psychological injury occurred. Having shown that a breach of duty caused an injury, one or more of three types of damages might be awarded in the form of monetary payments. These include general damages for pain and suffering; special damages for past, present and future medical expenses, loss of income, wages and profits; and punitive damages for gross negligence such as intentional harm, conscious indifference, or fraud. Punitive damages are generally not covered by malpractice insurance. 4

STANDARDS OF CARE

Guidelines Guidelines, or so-called practice parameters, developed by specialty societies, federal agencies, or panels of experts may be useful in establishing standards of care. These professional guidelines are often widely available and provide consensus statements codifying professional custom which may then form the actual basis for a legal standard of care. The validity of such guidelines stems from the sponsoring organization’s expertise and prestige, the nature and purpose of the guideline, conflicting views held by other authorities, and the direct applicability of the guideline to the case under consideration. While it might be tempting to assume that clinical guidelines would reduce malpractice risk by helping physicians understand a consensus of “good care,” in reality such guidelines are more likely to be used in malpractice litigation by the plaintiff as evidence that the physician failed to meet the standard of care.

Expert testimony The most common method of establishing a standard of care and subsequently a breach of duty is to rely on expert testimony from a medical witness. Such an expert witness should be appropriately licensed and board certified and should have been practicing in the medical specialty area in question for at least 3 of the previous 5 years.9,10 For such testimony the expert should receive reasonable compensation not based on a contingency fee. The opinion of the medical expert should be unbiased and non-emotive, and as such it should not matter whether the expert is retained by the plaintiff or the defendant. Expert testimony requires a review of the medical record and an opinion regarding the patient’s care. Such an opinion

Chapter 1 Medicolegal Issues

may be given in a variety of formats including affidavit, deposition or even testimony in court. The expert medical witness provides an important service to patients, physician colleagues, and the courts provided that such opinions are thoughtful, accurate and unbiased.

Vicarious liability While most medical malpractice actions are taken against an individual directly involved with an alleged wrongdoing, there is also a legal concept which allows liability to be extended beyond someone who directly caused an injury to persons on whose behalf that person may have acted. This may mean that physicians may be held liable not only for their own actions but also for the actions of others in some type of subordinate role. Such liability is referred as vicarious liability.11,12

Respondeat superior Respondeat superior is a legal principle that holds a master responsible for the wrongdoings of his servants. These “master–servant” definitions have evolved to include employer–employee relationships, corporate agent relationships, and teacher–student relationships.12–15 These relationships may apply to preceptors, proctors, administrators or employers. Such a concept allows blame to be shared among doctors, trainees, nurses, institutions, etc. and may provide additional financially responsible defendants, some with potentially greater resources than the original defendant, to share the liability for an injury.

Preceptor The concept of a preceptor as a teacher or instructor in the area of gastrointestinal endoscopy is central to the training of young physicians new to the specialty and to practicing physicians acquiring new skills. Such a preceptor endoscopist might be found vicariously liable for current or future acts of his trainee. More to the point of ERCP, a supervising endoscopist might be held liable for part of the damages arising from a trainee learning the procedure, an experienced colleague acquiring new skills, or either in future misadventures. The degree of liability attributable to each of the principals would depend on many factors, including knowledge on the part of the patient that the procedure would be performed by a trainee, the experience of the trainee and whether the trainee was performing the procedure within an appropriate standard of care such that the procedure was done for reasonable indications and with appropriate skill. With regard to future injuries after completion of training, liability would hinge on the appropriateness of training and the veracity of credentials.

Proctor A physician who observes and monitors another physician, particularly one seeking privileges, is known as a proctor. Proctors have no duty to the patient and therefore no liability since their role is simply to assess the capabilities of the physician being monitored. If the proctor becomes involved in the care of the patient, however, this could change. To avoid such entanglement, the proctor should not interfere with the proctored physician, should have a thorough understanding of proctoring and hospital endoscopy privileges, should not offer advice or interact with the patient, should only report to the hospital or regulatory committee, and in the event he/she witnesses substandard medical care which is harmful to the patient, should consider contacting an appropriate superior,

asking the proctored physician to discontinue the questionable actions, or, as a last resort, intervening with careful appropriate documentation.

Employer liability A physician may be held responsible for an adverse outcome attributable to substandard service by office staff such as violations in patient confidentiality, violations in sterile technique, or failure to provide appropriate training and supervision to ensure the proper functioning of office staff.

Administrator If a physician acts in an administrative capacity in an endoscopy unit or gastroenterology division, he/she has a duty to patients receiving care in that unit. Failure to develop policies and procedures that ensure a safe environment and comply with state and federal regulations may constitute vicarious liability. Such responsibilities may include the acquisition and maintenance of endoscopic equipment, privileging, infection control and workplace safety. Further, if the responsible director knew or should have known that an unskilled physician was practicing in the unit and did not take appropriate corrective actions, vicarious liability could exist.

Hospital liability Hospitals may be held responsible for the mistakes of a hospitalbased physician employed by that institution or for inadequate oversight provided by endoscopy unit or gastroenterology division directors. They may also incur vicarious liability for improperly privileging physicians who are inadequately trained to perform a certain service.13,15

Summary In summary, the gastroenterologist or gastrointestinal endoscopist may incur liability for mistakes of individuals whom they supervise even if they themselves were unaware of the improper actions and even after their immediate supervisory role had ended. All of the aforementioned roles of preceptor, proctor, employer and administrator should be approached with care and forethought. An understanding of potential vicarious liability may allow better risk management strategies to minimize exposure to liability.

INFORMED CONSENT Introduction Medical malpractice actions most commonly involve the “tort of negligence” wherein a physician is felt to have practiced below the standard of care (“breach of duty”). There is, however, a common and independent cause of malpractice action involving the failure to obtain informed consent.16–19 This is often a secondary allegation filed along with an allegation of practicing below the standard of care.

Theory of informed consent The ethical and legal requirement to obtain informed consent prior to a procedure comes from the concept of personal patient autonomy and is rooted in the theory of patient self-determination. Against such a backdrop, the courts have found that a person’s right to selfdetermination warrants that a physician obtain informed consent. The competent patient, after receiving appropriate disclosure of 5

SECTION 1 GENERAL TOPICS

material risks of the procedure in question, and understanding the risks, benefits and alternative approaches, then makes a voluntary and uncoerced informed decision of whether to proceed. Early on, the consent process operated under a provider-based standard (professional standard of disclosure) whereby the physician was expected to disclose information about the treatment that reasonable physicians believed relevant and that reasonable physicians generally disclosed to their patients in similar circumstances. More recently, however, courts have been moving toward a patient-based standard which mandates that a treating physician disclose as much information as a reasonable patient would wish to know. The essential elements of informed consent include: 1. The nature and character of the proposed procedure, preferably in non-technical terms. 2. The reason or indication for the procedure. 3. The likely benefits of the procedure. 4. The material risks and complications of the procedure, including their relative incidences and severities. 5. The alternatives to the procedure, including those which may be more or less hazardous than the one proposed, and the alternative of no treatment. The consent process should also include an assessment of the individual’s competence to understand the information presented and the opportunity for patients to ask questions. Obtaining informed consent is a process that includes more than placing a signature on a standardized consent form. It involves mutual communication and decision making and can advance the physician–patient relationship. It can also be a risk management tool, transferring responsibility for risk to the patient who has understood and accepted that even competently performed procedures can have adverse outcomes.

Material risks One essential element of disclosure is discussion of the risks and potential complications of the procedure. These risks should include procedure-specific material risks, those that a reasonable patient would want to know in order to make an appropriate decision. The four elements of risk that the physician needs to consider include: 1. The nature of the risk. 2. The magnitude of the risk. 3. The probability that the risk may occur. 4. The timing of the risk, whether contemporaneous with the procedure, post-procedure or delayed. Deciding what material should be disclosed is often not easy. One authoritative text on informed consent states: “The physician must walk a fine line between providing pertinent risk information and overwhelming the patient with frightening statistics. Providing too much extraneous information may be as likely to impair informed decision making as providing too little.”20

Controversial areas The trend toward a patient-oriented standard of disclosure has allowed for a broader interpretation of the “material risks.” What a “reasonable patient would wish to know” in making an appropriate decision might now argue for pertinent disclosure of the experience level and personal complication history of the specific physician, rather than national averages, as well as any pertinent economic interests of the physician. This question of the endoscopist’s personal experience might be especially applicable to complicated

6

endoscopic procedures such as ERCP. In a legal case involving difficult and risky brain surgery, a physician was found liable for not informing the patient regarding his lack of experience.18

Exceptions to informed consent There are several exceptions to the informed consent process. These include: 1. emergencies where the patient is incapacitated to a degree that consent cannot be obtained and delay would put the patient at risk; 2. waiver of the right of self-determination, where the patient assigns that right to the physician; 3. therapeutic privilege, where the physician believes that informed consent would be detrimental to the patient, usually in an emotional sense; 4. legal mandate, whereby the court orders the patient to undergo medical therapy without the patient’s consent; 5. incompetency, where the patient is unable to make a decision and that responsibility is given to the patient’s legal guardian.

Informed refusal This doctrine holds that a patient who refuses a procedure or treatment must do so in a well informed way and that it is the physician’s duty to ensure that such refusal is informed.

Legal consequences of failing to obtain informed consent Failure to obtain informed consent is most often a secondary allegation attached to a charge of practicing below the standard of care. However, it can be an independent cause of malpractice action alleging that even though the injury was not due to substandard care, the patient would have refused the treatment or procedure if material risks had been known. The plaintiff would have to show, however, that a reasonable person in the same position would not have undergone the procedure knowing that a small risk of injury existed. If there was absolutely no consent obtained for medical treatment, or if the treatment went well beyond the scope of consent, a charge of battery could be lodged. Although rare, a charge of battery is a criminal charge and is not covered by most malpractice insurance.

RISK MANAGEMENT STRATEGIES FOR ERCP Introduction Risk management is a process designed to identify reasons for poor patient outcomes and to suggest corrective actions to prevent both patient injury and malpractice risk. The formal process includes defining situations that place the patient and physician at risk, determining the likelihood and significance of these circumstances, applying risk management strategies to individual cases and developing preventive measures. The following risk management strategies are generalizable to all medical practice and all gastrointestinal endoscopic procedures, but have been adapted to apply specifically to ERCP. They include sound medical practice, including proper training; rigorous privileging; understanding and avoiding complications and lawsuits; and dealing with lawsuits once filed.

Chapter 1 Medicolegal Issues

Sound medical practice The best defense against adverse outcomes and malpractice suits is good medical practice. The first step in developing sound medical practice is attaining competence through proper training.

Competence Competence is defined as the “minimal level of skill, knowledge, and/or expertise derived through training and experience that is required to safely and proficiently perform a task or procedure.”21 Simply stated, this means having been trained adequately to develop endoscopic skills and acquire the knowledge required not only to recommend and perform endoscopic procedures, but to interpret and correctly manage the findings of these procedures. Thus competence assures a safe, accurate, technically safe procedure. Conversely, incompetently performed endoscopy, particularly ERCP, can result in patient injury, incorrect or missed diagnoses, and incomplete procedures, which in turn lead to missed or delayed diagnoses, additional procedures and other testing for the same condition. There are two components to ensuring competence: training and subsequent demonstration of competence.

Training The American Society for Gastrointestinal Endoscopy (ASGE) has promulgated guidelines to ensure adequate training in gastrointestinal endoscopy, patient monitoring and sedation and analgesia.22 Training in ERCP should take place within the context of a global clinical training program in the fields of adult or pediatric gastroenterology or general surgery. Training obtained outside of a formal training program must conform to the same guidelines as for formal fellowship or residency training, and short courses on endoscopy, or ERCP in particular, are not adequate to attain competence. Once training is complete, competence should be assessed and evaluated by the training program director who can provide documentation of the individual’s competence. Alternatively, direct observation by an impartial credentialed endoscopist might also suffice for an endoscopist who received training outside of a formal training program. Complex diagnostic and therapeutic procedures are employed less frequently than standard procedures and are more prone to have complications and adverse outcomes. These advanced endoscopic procedures, including ERCP, require greater skill and are concentrated in the hands of fewer individuals. The ASGE recommends that trainees wishing to acquire advanced endoscopic skills should have first completed a standard endoscopy training program during an approved GI fellowship (or equivalent training) and then receive further training in specific advanced procedures. Training in ERCP is covered elsewhere in this book (Chapter 7), and the information will not be recounted in detail here, but available data suggest that at least 180–200 ERCPs are required for the usual trainee to achieve competence.23,24 In addition, expert endoscopists are generally expected to perform at a 95–100% technical success level, and current research supports establishing a standard of 80–90% technical success before trainees are deemed competent in a specific skill.21 This type of training in ERCP is necessary to assure good patient outcomes and minimize complications and failed procedures which could subsequently result in malpractice litigation.

Continued competence Ensuring continued competence is an additional safeguard against adverse patient outcomes and malpractice litigation. Maintaining

clinical and endoscopic skills in ERCP requires an ongoing effort. This effort includes staying current with GI literature concerning ERCP, engaging in continuing medical education activities and achieving familiarity with new endoscopic technologies. In addition, the endoscopist performing ERCP must also maintain an adequate case volume to maintain expert procedural skills. In general, studies have shown a correlation between higher case volumes and greater technical success.24–26 Furthermore, higher ERCP volume has been associated with lower complication rates, especially with respect to severe complications. Also, there is probably an important effect of lifetime experience. Some experienced individuals may, based on that lifetime experience, be able to maintain high success rates and low complication rates despite performing only a modest volume of ERCPs.26

New technology ERCP has been a robust field for the development of new endoscopic techniques and procedures. New techniques require new skills both major and minor. A major skill is a new technique or procedure that involves a high level of complexity. Such techniques require formal training within a training program or through the guidance of a preceptor before competence can be assessed. Within the realm of ERCP, these major skills require interventions beyond standard biliary stone removal and simple stent placement. Minor skills include new non-experimental developments that are merely minor extensions of an accepted and widely available technique or procedure. These techniques for ERCP require limited education and practical exposure such as that which can be obtained from short courses, training videos, CD-ROMs, DVDs and interactive computer programs. A few caveats regarding malpractice exposure are needed with regard to new endoscopic technology. Endoscopists wishing to acquire new technologies should not overestimate the need for these nor overestimate their own skill level in seeking to acquire such techniques. Who is “experienced” enough to appropriately incorporate new or more advanced skills into one’s practice and how is the training acquired? No rigid standards apply, but my personal guideline for experience and skill would be three years of experience beyond training, 95% technical success in gaining access to the desired duct, and a low personal complication rate compared to national averages. Further, there should be a compelling clinical need in one’s practice and a persuasive lack of an alternative expert to refer to. Skills should be acquired in a formal training program or through a hands-on preceptorship with an experienced expert. It would not be wise to undertake a newly described but inadequately assessed technique or to engage in cases which are risky or difficult early in the endoscopist’s experience. Ignoring these caveats will expose patients to adverse outcomes and endoscopists to malpractice litigation. A further caveat relates to vicarious liability. The expert endoscopist should not train the unprepared novice endoscopist to take on complex difficult tasks before that trainee has the necessary training and experience to safely acquire these skills. Furthermore, training less-than-expert ERCP endoscopists for a technically difficult and seldom needed procedure exposes patients, endoscopists, and trainers to lawsuits, including lawsuits involving vicarious liability. These procedures should probably be conducted at advanced centers for complex or high risk cases, and ERCP, particularly with advanced techniques, should be concentrated among fewer

7

SECTION 1 GENERAL TOPICS

endoscopists who would thereby perform these procedures more frequently.

Ensuring competence through privileging Privileging is the process by which an institution authorizes an individual to perform a specific procedure.21 These privileges should be determined separately for each type of procedure, particularly for advanced procedures such as ERCP. The privileging process includes a review of credentials provided by the training program or trainer, and a review of the training experience and case load for each procedure for which privileges are requested. Finally, an actual observed level of competency should be assured through proctoring, particularly for advanced procedures. Additionally, institutions should have guidelines on recredentialing and reprivileging which ensure continued competence in all procedures, but particularly the more complex advanced procedures such as ERCP. Hospitals have a duty to exercise due care in granting privileges to physicians and they expose themselves to liability for granting specialized privileges to the poorly trained or inexperienced.12,13,15 This vicarious liability extends not only to the hospital, but also to individuals in administrative roles such as the director of the endoscopy unit.

Peer review Peer review is intended to identify problems related to adverse outcomes, prevent their recurrence and help in the reprivileging process. Ideally, this should be done in a non-threatening manner, but should be a formal process with a written record. Each physician should have a personal compilation of his/her own adverse events for comparison with peers.7,21,27 Patients have a right to know, in general terms, the physician’s outcome profile.

Interpersonal skills Another component of sound medical practice, in addition to cognitive and procedural competence and careful privileging, is the interpersonal skill of the practitioner. This must be developed during training and polished once in practice. Effective communication with the patient and family and with other physicians and healthcare providers is a critical element in good healthcare and risk management. Conversely, patient dissatisfaction with physician interpersonal and communication skills can be a major factor in the decision to file a lawsuit.28,29 Displaying a positive caring attitude and communicating honestly, beginning with the initial interview and extending to informed consent and beyond, are critical in forming a healthy physician–patient relationship. This good patient rapport decreases the likelihood of lawsuits. It also helps define the role of the physician, limiting the physician duty, and transferring some of the responsibility for an adverse event to the informed patient.

UNDERSTANDING WHY COMPLICATIONS AND LAWSUITS OCCUR ERCP has evolved from a diagnostic tool to a predominately therapeutic procedure for a variety of pancreaticobiliary problems. It is a complicated and sometimes dangerous procedure which can result in a wide range of short-term complications including pancreatitis, hemorrhage, perforation and infection. These complications and other adverse outcomes can lead to patient injury, dissatisfaction and lawsuits. 8

COMPLICATIONS OF ERCP Complications of ERCP and sphincterotomy have been covered in excellent detail by Freeman elsewhere in this book (Chapter 6). Discussions of risk management strategies, however, require reviewing some of the information presented elsewhere. The complications of ERCP and sphincterotomy can vary widely in different clinical circumstances. These complications appear to be related primarily to patient-related factors, including the indication for the procedure, and to the technical skill of the endoscopist.26 The risk factors for overall complications include suspected sphincter of Oddi dysfunction and technique-related factors such as difficult cannulation, the use of precut sphincterotomy in inexperienced hands, failure to achieve biliary drainage, and use of percutaneous transhepatic biliary access. All of these risk factors result in higher rates of complications for endoscopists who have low case volumes. Patient related risk factors for post-ERCP pancreatitis include younger age, female sex, suspected sphincter of Oddi dysfunction, prior post-ERCP pancreatitis, absence of jaundice and absence of chronic pancreatitis. Furthermore, many of the patient-related risk factors are cumulative. Technique-related risk factors include difficult cannulation, multiple contrast injections of the pancreatic duct, performance of pancreatic sphincterotomy, balloon dilation of the biliary sphincter and precut sphincterotomy in inexperienced hands. Risk factors for hemorrhage include coagulopathy, acute cholangitis, bleeding during the procedure, resumption of anticoagulation immediately after the procedure, and endoscopist inexperience. Although rare, perforation during ERCP is probably more common with Billroth II anatomy, with needle-knife access sphincterotomy, and in patients suspected of having sphincter of Oddi dysfunction. Furthermore, the sequelae of perforations are sometimes magnified by delays in recognition and management. Cholangitis complicating ERCP results mainly from failed or incomplete biliary drainage, or from failure to give preprocedure antibiotics in the patient with biliary obstruction.

Why are lawsuits filed? Data regarding lawsuits involving endoscopy are scarce and usually relate to the more common endoscopic procedures. Information on the total volume and causes of ERCP-related lawsuits is even more scarce. However, an analysis of a personal series of reviews of 59 cases of alleged ERCP malpractice is particularly instructive as to the reasons for ERCP lawsuits.30 Half of the cases involved pancreatitis; 16 sustained perforation after sphincterotomy (8 of which involved precutting), and 10 had severe biliary tract infection; 15 of the patients died. In this series, the most common allegation, in 32 cases, was that the procedure or associated therapeutic maneuver was not indicated. This was also a secondary allegation in another 16 patients. These allegations were based on inadequate or weak evidence for biliary or pancreatic pathology. The second commonest allegation, in 19 cases, was that procedures were performed negligently. This was a secondary allegation in 4 additional cases. Poor post-ERCP care was alleged in a total of 15 cases and inadequate informed consent was cited as a secondary allegation in 15. The author and accompanying editorials30–32 concluded that ERCP carries a risk of life-threatening complications, that it should be performed only for good indications and after non-invasive techniques have been exhausted, and only with truly informed consent. Also,

Chapter 1 Medicolegal Issues

precutting for marginal indications is particularly hazardous. Finally, it was stated that “Speculative ERCP, sphincterotomy, and precuts, are high risk for patients and for practitioners.”

STRATEGIES TO AVOID COMPLICATIONS AND LAWSUITS A risk-factor assessment may help the endoscopist decide whether or not to perform ERCP and, if ERCP is undertaken, aids in making decisions regarding the techniques to be utilized.

Indications Patients with marginal indications for ERCP are most likely to develop complications,26 or as stated by Peter Cotton in a 2001 editorial, “ERCP is most dangerous for people who need it least.”33 Based on his more recent analysis of lawsuit reviews,30 he would likely add “and they are most likely to sue.” As a risk management strategy, marginal cases should be avoided and alternative imaging techniques such as endoscopic ultrasonography (EUS), magnetic resonance cholangiopancreatography (MRCP), or intraoperative cholangiography should be utilized instead. Although “marginal cases” are admittedly difficult to define, some clinical settings that fit this description include patients with vague abdominal pain without objective evidence of biliary or pancreatic pathology, mildly abnormal serum liver chemistries without jaundice, precholecystectomy, or suspected sphincter of Oddi dysfunction.

Technique Useful technique-related risk management strategies exist in addition to patient- or indication-related risk factors for complications, particularly for post-ERCP pancreatitis. These include avoiding multiple injections of the pancreatic duct and avoiding either pancreatic sphincterotomy or precut sphincterotomy in inexperienced hands. Regarding post-sphincterotomy hemorrhage, attention to preexisting coagulopathy is important, as is delaying restarting anticoagulants for at least three days after sphincterotomy. Avoiding sudden precipitous “zipper cuts” is also important, as is injecting the edges of the sphincterotomy if any bleeding is detected or coagulopathy is present. With cholangitis, care should be taken not to inject an obstructed segment if the endoscopist is unprepared to establish drainage. Some feel that it is helpful to aspirate the obstructed or infected segment before injecting contrast. Careful stent selection to maximize successful drainage is also important, as are pre- and post-procedure antibiotics. The risk of perforation can be lowered by avoiding repeated “hook and pull” maneuvers with the duodenoscope, difficult anatomies (Billroth II or Roux-en-Y gastroenterostomies, minor papilla cannulations, short intramural segments), and riskier pathologies (sphincter of Oddi dysfunction, multiple large stones or snare removal of ampullary neoplasms). Of course, good technique is important for the sphincterotomy including appropriate length, good control and orienting the cut in the 11:00 to 1:00 o’clock position. One of the big problems with perforation is delayed diagnosis, so a high index of suspicion and early evaluation with CT scanning with oral contrast is important. Surgery should be considered for large leaks or fluid collections, in patients with severe pain, guarding or crepitus, with signs or symptoms of major sepsis, or in the clinical situation of deterioration or no improvement within the first 24 hours. Risk of cardiovascular complications is decreased by remembering that these are the

leading cause of death from ERCP.34 One should not be hesitant to use an anesthesiologist for assistance in appropriate clinical situations. As a further risk management strategy, if ERCP is performed in high-risk patients such as younger patients, women with normal bilirubin or possible sphincter of Oddi dysfunction, prolonged attempts at cannulation and other high-risk maneuvers should be avoided and the placement of a pancreatic stent should be considered in appropriately experienced hands.26 Pancreatic stents appear to be particularly helpful in preventing post-ERCP pancreatitis in patients with sphincter of Oddi dysfunction and in those who have undergone pancreatic sphincterotomy or precut access sphincterotomy. However, such stenting has not been proven to be safe or effective in less experienced hands. Furthermore, needle-knife access sphincterotomy is probably best avoided entirely by the less experienced. A final word on technique concerns contrast allergies. The appropriate risk management strategy is simply to have and adhere to a specific policy regarding contrast allergies. Short-cutting the policy regarding contrast allergies simply for patient convenience may well result in an adverse outcome and would be extremely hard to defend in court. Either not having a policy (ignorance of the problem or having not dealt with it) or ignoring a well-thought-out policy would be indefensible.

Informed consent As described earlier, obtaining informed consent is a process which extends beyond the actual signing of a signature on a standardized form. It includes assessing the competence of the individual, disclosure of appropriate information to allow an informed decision, and ensuring that the decision made by the patient is voluntary. It is a communication and decision-making process which can cement the physician–patient relationship and serve as a risk management tool. Within the realm of gastrointestinal endoscopy, this management of risk is especially important with ERCP. Transferring some responsibility for the appreciable risks to the patient, who has understood and accepted that even competently performed ERCP can result in severe adverse outcomes, is a significant risk management tool. The possibility of severe adverse outcomes with ERCP is so real that they cannot be glossed over or minimized if the patient is to be truly informed and the decision making is to be truly shared. Some even advocate disclosing personal experience level and outcomes in the consent process.27

Documentation Good documentation is an essential risk management tool and also a component of good medical care. The old adage “If it isn’t written down, it didn’t happen” is often true in litigation. If a discussion is well documented in the notes, a court will generally accept that something was discussed or did occur. Conversely, lack of documentation may persuade a court or jury that a conversation did not occur if the patient denies it. Written documentation has generally been viewed as adequate, although some have advocated videotaping the consent process as an extreme method of documenting exactly what occurred.7 Documentation of informed consent is extremely important with ERCP. A simple note affirming that discussions occurred regarding the nature of the procedure, alternatives, risks (enumerating the major risks), sedation, and an opportunity for questions goes far in assuring that the physician has fulfilled this part of the duty to the patient and that the patient has participated in the decision9

SECTION 1 GENERAL TOPICS

making process, thereby accepting some of the risk of the procedure.

Managing complications ERCP is difficult and complex. Complications will occur even with good patient selection and good technique. The risk is real and unavoidable. Complications happen with all endoscopies and it is important that they be handled well. The fact that a complication has occurred is not malpractice in and of itself. The failure to make a timely diagnosis of the complication could be, however. It is important that the endoscopist recognize the possibility of post-ERCP complications and be attentive to their signs and symptoms. Early diagnosis and treatment are often vitally important. As important as early diagnosis and treatment is communication with the patient and family. A full explanation of the situation and the plan of treatment is necessary. Empathy, compassion, and honesty are essential. But this does not require self-denigration or an unnecessary admission of wrongdoing. Complications are a known risk of ERCP and informed consent has allowed the patient to accept and share in that risk. During the treatment of complications, it is important to maintain contact with the patient and family so as not to engender feelings of abandonment and further to ensure that all necessary consultations are obtained expeditiously. Although often personally uncomfortable for the physician, such continued contact with the patient and family promotes good medical care, demonstrates compassion and helps manage legal risk. Finally, it is important to inform the insurance carrier following any major complication or significantly litigious situation.

LIMITING FINANCIAL AND PSYCHOLOGICAL COSTS OF LAWSUITS

A SUMMARY OF RECOMMENDATIONS

Insurance

Freeman’s analysis has suggested that avoidance of marginal indications for ERCP may be the single best way to avoid complications.26 Cotton’s article on ERCP-related lawsuits suggests that avoidance of marginal indications also may be the single best way to avoid medical litigation.30 These insights plus recent opinions on medicolegal issues31,32 suggest the following risk management strategies to avoid ERCP-related complications and lawsuits: 1. Practice within a reasonable standard of care and avoid risky cases. See Box 1.1. 2. Use good ERCP technique, avoiding advanced ERCP techniques if inexperienced and utilizing pancreatic duct stents for high risk patients if appropriately experienced. 3. Utilize informed consent as a communication and decisionmaking process to transfer some responsibility for risk to the patient, who has understood and accepted that even competently performed procedures can have adverse outcomes. 4. Employ good documentation of clinical events, decision making and informed consent. 5. Be vigilant to assure early recognition and management of complications, communicating honestly and with empathy and compassion with the patient and family, and maintaining contact with them throughout the post-complication period. Drs. Freeman and Cotton have persuasively demonstrated that to minimize the risk of ERCP-related complications and lawsuits one should avoid ERCP that is marginally indicated, too difficult for one’s experience level or if ERCP is performed infrequently. 10

BOX 1.1 RISKY CLINICAL SITUATIONS FOR ERCP-RELATED COMPLICATIONS AND LAWSUITS Marginal cases Vague abdominal pain without objective evidence of biliary or pancreatic pathology Mildly abnormal serum liver chemistries without jaundice in the pre-cholecystectomy patient Suspected sphincter of Oddi dysfunction Technically difficult cases Past history of difficult cannulation or post-ERCP pancreatitis Precut (access) sphincterotomy Minor papilla cannulation Percutaneous biliary access Billroth II or roux-en-y gastroenterostomy Obstruction at the biliary bifurcation Infrequent cases Sphincter of Oddi manometry Pancreatic therapeutics Large or intrahepatic stones Snare ampullectomy

Every physician should have adequate indemnity coverage for lawsuits that occur now or in the future. Keeping adequate malpractice insurance is important to ensure that injured patients have access to compensation if they are inappropriately injured and to safeguard the financial well-being of the individual physician and institution.

If a lawsuit is filed The possibility of being sued is unavoidable. Nothing, not even superb medical practices, will absolutely protect one from a lawsuit. The severity of adverse patient outcomes is a more important predictor of plaintiff success in winning a malpractice claim than whether the physician was indeed negligent.35 Sympathetic juries and judges often wish to reward an injured plaintiff irrespective of actual negligence. It is important that physicians, particularly those involved in high-risk procedures such as ERCP, accept realistic goals and realize that lawsuits may occur. It is also important to remember that medical litigation is a long and stressful process for physicians and their families. Psychologic support is important, but casual discussion of lawsuits is inadvisable since discussions with friends and colleagues can be elicited through subpoena. It is also heartening to note that physicians win the majority of malpractice suits. In Cotton’s recent analysis of 59 ERCP lawsuit cases, where the final outcome was available in 40, 16 were withdrawn, 14 were settled, and of the 10 going to trial, half were decided for the plaintiff and half for the defense.30 Obviously if a lawsuit is filed, the physician’s insurance carrier must be notified and it is the responsibility of the physician to aid the insurance company in the defense of the case.

Chapter 1 Medicolegal Issues

Physicians should become educated in the litigation process. Depositions generally benefit plaintiffs and are used as tools to gain information to help press cases against defendants. During deposition, physicians should be truthful but volunteer as little information as possible. Excessive elaboration can only harm the defendant. In deposition and at trial demeanor is important. Arrogance, anger, or dismissive behavior will only reflect poorly upon the physician and engender sympathy for the plaintiff. It is also important to be well prepared for any type of testimony. Malpractice attorneys are usually intelligent and well versed. Physicians should be similarly knowledgeable and well prepared and should be deliberate in their testimony, pausing before every answer to ensure a proper and accurate response.

standards of care and informed consent. The pancreaticobiliary endoscopist must realize that the deviations from a reasonable standard of care most likely to lead to ERCP related medical litigation include procedural indications, procedural technique, post-ERCP care and issues of informed consent. With this understanding, the endoscopist performing ERCP can formulate and adopt risk management strategies to improve patient safety, satisfaction and outcomes while minimizing the risk of litigation. These strategies include practicing within a reasonable standard of care, focusing attention on the informed consent process and documentation, and understanding specific patient-related and technique-related risk factors for complications and lawsuits (Box 1.1).

SUMMARY ERCP is a complex and difficult procedure with significant risks for adverse patient outcomes and for medical litigation. It is important for endoscopists performing ERCP to understand liability issues related to ERCP, including vicarious liability, and to understand the legal principles important in medical practice, including the elements of a malpractice case,

Acknowledgements The author is pleased to acknowledge Martin L. Greene, MD for help with access to data from the Physicians Insurers Association of America, Arnold M. Rosen, MD for constructive suggestions in editing the manuscript, and Brenda Paulson for preparation of the manuscript.

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Feld AD, Walta D. Malpractice, tort reform, and you: an introduction to risk management. Am J Gastroenterol 2004; 99(2):977–980. Physician Insurers Association of America: PIAA risk management review: Gastroenterology. Rockville, MD, Research Department, Physician Insurers Association of America, 2005. Physician Insurers Association of America: A risk management review of malpractice claims: gastroenterology summary report. Rockville, MD, Research Department, Physician Insurers Association of America, 2000. Gerstenberger PD. Malpractice in gastrointestinal endoscopy. Gastrointest Endosc Clin N Am 1995; 5(2):395–389. Springer J. ERCP: new standards, new challenges. Can J Gastroenterol 2002; 16(3):175–176. American Society for Gastrointestinal Endoscopy. Medical Malpractice. In: Petrini JL, Feld AD, Gerstenberger PD, et al. (eds.) Risk management for the GI endoscopist. Oak Brook, IL: American Society for Gastrointestinal Endoscopy; 2001:10–13. Norton I, Schroeder KW. Reporting, documentation, and risk management. In: Ginsberg GG, Kochman M, Norton I. Gostout CJ, eds. Clinical Gastrointestinal Endoscopy. London: Elsevier Science; 2005:107–112. American Society for Gastrointestinal Endoscopy. Standards of care. In: Petrini JL, Feld AD, Gerstenberger PD, et al. (eds.) Risk management for the GI endoscopist. Oak Brook, IL: American Society for Gastrointestinal Endoscopy; 2001:2–3. American College of Physicians. Guidelines for the physician expert witness. Ann Intern Med 1990; 113:789. Greene ML. Medical-legal consultation in gastroenterology. Gastrointest Endosc Clin N Am 1995; 5(2):403–419. Gerstenberger PD. Risk management for the endoscopy center. Gastrointest Endosc Clin N Am 2002; 12(2):367–384. American Society for Gastrointestinal Endoscopy. Vicarious liability. In: Petrini JL, Feld AD, Gerstenberger PD, et al. (eds.) Oak

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23. Jowell PS, Baille J, Branch S, et al. Qualitative assessment of procedural competence: a prospective study of training in endoscopic retrograde cholangiopancreatography. Ann Intern Med 1996; 125:983–989. 24. Freeman ML. Training and competence in gastrointestinal endoscopy. Reviews in Gastroenterological Disorders 2001; 1(2):73–85. 25. Petersen BT. ERCP outcomes: defining the operators, experience and environments. Gastrointest Endosc 2002; 55(7):953–958. 26. Freeman ML. Adverse outcomes of endoscopic retrograde cholangiopancreatography. Reviews in Gastroenterological Disorders 2002; 2(4):147–168. 27. Cotton PB. How many times have you done this procedure, doctor? Am J Gastroenterol 2002; 97(3):522–523. 28. Hickson GB, Federspiel CF, Pichert JW, et al. Patient complaints and malpractice risk. JAMA 2002; 287:2951–2957.

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29. Levinson W, Roter DL, Mullooly JP, et al. Physician-patient communication: the relationship with malpractice claims among primary care physicians and surgeons. JAMA 1997; 277:553–559. 30. Cotton PB. Analysis of 59 ERCP lawsuits; mainly about indications. Gastrointest Endosc 2006;63:378–382. 31. Peterini JL. Fools rush in . . . Gastrointestinal Endosc 2006;63: 383–384. 32. Frakes JT. The ERCP-related lawsuit: “Best avoid it!” Gastrointest Endosc 2006;63:385–388. 33. Cotton P. ERCP is most dangerous for people who need it least. Gastrointest Endosc 2001; 54:535–536. 34. Freeman ML. Sedation and monitoring for gastrointestinal endoscopy. In: Yamada T, ed. Textbook of Gastroenterology. Philadelphia, PA: Lippincott, Williams & Wilkins; 1999:2655–2667. 35. Brennan TA, Sox CM, Burstin HR. Relation between negligent adverse events and the outcomes of medical-malpractice litigation. N Engl J Med 1996; 335(26):1963–1967.

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GENERAL TOPICS

The ERCP Room Michael B. Kimmey

INTRODUCTION Physicians, staff and patients all appreciate the benefits of an ERCP procedure performed in a pleasant and efficient working environment. A well-planned procedure room can contribute to a successful and comfortable procedure for the patient and the medical staff. In this chapter, the components of the ideal ERCP room will be reviewed. Most ERCPs are performed in the hospital, usually in the outpatient department. This facilitates doing the procedure on hospitalized patients and allows ready access to inpatient hospital facilities for patients who need observation following the procedure. Although ERCPs can be performed in ambulatory surgery centers, current reimbursement policies in the United States do not include ERCP as an approved procedure for this setting. In addition, the higher capital costs for radiographic equipment and the ongoing costs of single-use ERCP accessories discourage the performance of ERCPs in this environment. The ERCP room can be a part of a gastrointestinal endoscopy unit where other endoscopic procedures are performed, or may be part of the hospital’s radiology department. The choice of location is often dependent on the number of ERCP cases done at the facility.1 The efficiencies of having the ERCP room in the endoscopy unit should not be overlooked. These include time savings for the physicians, nurses and technical personnel as well as reduction in time spent transporting patients and equipment. The financial benefit of these time savings is likely to justify the capital cost of the fluoroscopy equipment for endoscopy units doing over 300–400 procedures per year. In addition, fluoroscopy can be used for other endoscopic procedures such as dilation of complex strictures, placing esophageal and enteral stents, and facilitating overtube placement for enteroscopy.

DESCRIPTION OF THE ROOM The ERCP room should be large enough to accommodate all of the necessary equipment to do ERCP as well as a comfortable space for the patient, physician and two endoscopy assistants. When ERCP needs to be performed under deep sedation or general anesthesia due to patient intolerance of conscious sedation, there should also be sufficient space for anesthesia equipment and personnel. If fluoroscopy is performed using a C-arm, there needs to be sufficient room around the patient table to allow the image intensifier arm to move without being encumbered by other equipment in the room. All of these factors add up to a need for the ERCP room to be 50–100% larger than procedure rooms where routine endoscopy is performed. A room size of approximately 300 square feet has been recommended by some authorities.2,3

The ERCP room is best configured around the location of the fluoroscopy equipment and patient table. This is usually placed centrally in the room to allow access to both sides of the table and to allow adequate room for movement of the fluoroscopy unit’s C-arm. A more complete description of the options for fluoroscopy equipment, including the use of spatially fixed or mobile units can be found below. Figure 2.1 shows a generic diagram of a typical ERCP room layout and an actual ERCP room in use is shown in Figure 2.2. The patient table should be at least 30 inches wide to accommodate large patients and also allow safe patient repositioning during the procedure. It should also be sturdy enough to accommodate heavy patients, preferably to at least 400 pounds. There should be room under the head of the table for the assistant’s knees while sitting at the patient’s head and attending the patient’s airway. There should be adequate shielding below the table to reduce exposure of personnel to scattered radiation. Tables that are fixed to the fluoroscope should have a movable top for positioning the patient under the fluoroscope. Some physicians also prefer to have the table tilt to facilitate gravitational movement of contrast and air bubbles, although modern ERCP techniques and accessories have made this requirement less important than previously. Controls for table movement should be readily accessible to the endoscopist who should be able to move the table top while simultaneously holding the endoscope, if an assistant or x-ray technologist is not available. Appropriate placement of fluoroscopic and endoscopic monitors is very important. Monitors can be mounted on movable carts or booms that are fixed to the ceiling of the room. Poor monitor placement has been identified as a major contributor to endoscopist musculoskeletal injuries.4 Monitors should be set so that the endoscopist’s eye level is three-quarters toward the top of the monitor screen. Since not all endoscopists are the same height, provision for adjusting monitor position is necessary. Monitors should be placed on the opposite side of the patient, generally at a level above the head of the table directly in front of the endoscopist so that neck rotation and strain are avoided. Monitors should not restrict movement of the C-arm of the fluoroscopic unit and should not be obstructed by the airway nurse or anesthesiologist. Ideally, endoscopic and fluoroscopic image monitors should be mounted side by side. A second fluoroscopic monitor that displays the last captured radiographic image is optional. An additional monitor that can be used interchangeably for intraductal ultrasound, cholangioscopy and sphincter of Oddi manometry is also appropriate for units that perform these specialized procedures (Fig. 2.3). Older monitors built with cathode ray tube technology are being increasingly replaced with flat screen monitors as the quality of these smaller flat screen monitors is rapidly improving. Vital sign monitors are usually placed at a lower level for primary viewing by the seated endoscopy assistant or nurse, although most 13

SECTION 1 GENERAL TOPICS

A

Accessory cart

B

C

B Monitors A

Endoscope processor

Patient

C

D C-arm

D Sink

Fig. 2.3 This photograph shows A a ceiling-mounted boom holding monitors for fluoroscopy, B the endoscopic image, C accessories such as endoscopic ultrasound, and D patient vital signs.

Lead aprons

Storage cabinets

Fig. 2.1 A schematic diagram of a typical ERCP room is shown, indicating the positions of personnel including A the endoscopist, B airway nurse, C accessory assistant, and endoscopic trainee, D radiology technician.

Fig. 2.4 Endoscopic processors and the endoscope are shown on this boom.

D

B A

C

Fig. 2.2 An ERCP is being performed by A the endoscopist, assisted by B the airway nurse, C accessory assistant, and D GI trainee. 14

endoscopists also prefer to be able to observe vital signs intermittently when there are any concerns raised by the assistant. The endoscope processor, light source and electrosurgery generator are generally kept together on a cart or boom that is behind the endoscopist (Fig. 2.4). The top shelf of the cart is best left open to use as a working surface. The endoscope can either be laid on top of the cart when not in use, or hung on the side of the cart. A water pump for irrigation is another useful tool that can be kept on this cart or stand. There are a number of types of electrosurgery generators that can be used during ERCP. Monopolar current is commonly used for sphincterotomy; however, bipolar current should also be available for the control of bleeding. Generators that contain both monopolar

Chapter 2 The ERCP Room

Digital vs conventional imaging

and bipolar cautery are preferred to reduce the number of generators on the cart and conserve space. Recently, an electrosurgical generator that uses a microprocessor to automatically adjust current has become popular in ERCP rooms, and may reduce the frequency of “zipper” cuts and endoscopically visible but not necessarily clinically significant post-sphincterotomy bleeding.5

Most modern x-ray imaging units use digital techniques for image manipulation and capture, although older conventional radiographic units are still used by some hospitals. Digital imaging has several advantages over conventional analog imaging including better image quality, the capability of image manipulation after acquisition, and easier and less expensive image storage and transfer. In addition, radiation exposure is reduced because less radiation is needed to produce an image. Image quality in pancreatography has been shown to be better for digital over conventional imaging, especially for evaluating side branch abnormalities.7

RADIOLOGIC IMAGING EQUIPMENT Radiologic imaging will also be addressed in Chapter 3. ERCP involves the use of fluoroscopy to monitor contrast injections and to guide the use of accessory devices that are inside the pancreatic or biliary ducts. Image capture and storage capability is also necessary to document radiographic findings for patient care and follow-up. The key components of the radiographic equipment include the xray tube, image intensifier, monitor, table, and hardware for image capture and storage. These components will be described and their critical specifications discussed. A comparison of commercially available radiographic equipment can be found in Table 2.1.

Imaging components and specifications The tube that generates the x-rays is usually placed under the fixed table or at the bottom of the mobile C-arm. X-rays then go up through the patient and are either scattered or penetrate through to be captured by the image intensifier which is placed over the patient. The size of the image is determined by the diameter of the image intensifier. For ERCP, a 12 or 14 inch image intensifier is ideal so that the entire biliary tree or pancreatic duct can be visualized on one screen without patient or fluoroscope movement. The image intensifier is also the most important component for achieving optimal image resolution, an important feature for seeing small diameter guidewires.8 Staff exposure to radiation is mostly due to scatter of the x-ray beam as it passes through the patient.9–11 This exposure can be greatly reduced with adequate shielding around the image intensifier and also below the table top (Fig. 2.5). Thin lead shields can be custom fitted to most parts of the image intensifier and table to block the scattered radiation. Images can be captured on radiographic “spot films” or increasingly as digital images. The former requires manual placement of x-ray cassettes and subsequent film development or conversion to digital images. Newer units capture digital images directly, reducing the need for x-ray technologists and making the images available for viewing immediately.

Fixed versus portable equipment The first decision to be made about the radiographic equipment is whether the fluoroscope and image intensifier are fixed to the patient table or whether a portable or mobile radiographic unit is used in conjunction with a freely movable table or stretcher for the patient. The main advantage of a portable radiographic unit is that it is generally of lower cost than a fixed unit. This allows mobility to other parts of the GI suite and hospital so that the capital costs can be shared and its use maximized. Hence, it is an option to be considered for low volume ERCP units. In addition, patients can be moved in and out of the ERCP room on the same stretcher that they lie on during the procedure. The main disadvantage of a mobile radiographic unit is it requires a separate operator or technician to be present during the ERCP procedure. The portable unit or patient stretcher must be moved during a procedure, and imaging parameters changed using controls that are not easily accessible to the endoscopist. In addition, radiation exposure to staff and patients is substantially higher with the mobile units due to difficulties providing adequate shielding and generally higher power outputs.6 These portable units formerly had inferior image quality compared to fixed units, however equipment is currently available that provides image quality that is comparable to fixed units.

Controls Ideally, all controls for fluoroscopy and image capture should be within close reach of the endoscopist. This allows the endoscopist to perform all aspects of the ERCP procedure without assistance from a radiologist or technician. Newer equipment makes this quite

Manufacturer

Model

Minimum room size

Mobile (Y/N)

C-arm (Y/N)

Digital (Y/N)

PACSb Compatible (Y/N)

General Electric/OEC Omega Philips Philips Philips Siemens Siemens Siemens

9900 elite CS-50 Pulsera Easy Diagnost Eleva MultiDiagnost Eleva Iso-C Sireskop SD Artis MP

Variable 16′ × 20′ Variable 15′ × 21′ 19′ × 22′ 10′ × 10′ 16′ × 20′ 16′ × 20′

Y N Y N N Y N N

Y Y Y N Y Y N Y

Y Y Y Y Y Y Y Y

Y Y Y Y Y Y Y Y

Image intensifier diameter (inches)

Resolution

List pricea

12 14 12 15 15 12 16 16

1000 × 1000 1024 × 1024 1000 × 1000 1024 × 1024 1024 × 1024 1024 × 1024 1024 × 1024 1024 × 1024

$179 600 $650 000 $175 000 $511 600 $933 000 $150 000 $435 000 $735 000

Table 2.1 Comparison of radiographic equipment used for ERCP a

Manufacturer’s list price in October 2005; actual cost will vary with local purchasing contracts. Picture Archiving and Computerized Storage system.

b

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SECTION 1 GENERAL TOPICS

A

B

Fig. 2.5 Lead shields mounted on A the image intensifier and B patient table reduce radiation exposure to staff from scattered radiation.

feasible and many busy units no longer involve radiology personnel during the procedure. Older units and mobile units usually require the presence of a technologist to set up the examination, make changes to x-ray parameters during the procedure and in some cases move the mobile C-arm unit.

Image capture and storage Most current hospitals store radiographic images using a Picture Archiving and Computerized Storage (PACS) system. Images obtained during ERCP are ideally transferred to the PACS system for access by referring physicians, and in some settings, review and interpretation by a radiologist. Using the central hospital PACS system is preferred over local storage within the endoscopy unit for ease of access and to avoid the need for endoscopy unit quality controls for storage and retrieval of images. A local computer hard drive to store images temporarily and a writable CD drive can be useful for downloading images for educational conferences, however.

Radiographic hardware Fixed fluoroscopy units usually have housing units for the x-ray tube and associated hardware. These units can take up considerable space in the procedure room which needs to be included in planning room dimensions. In addition, a console for entering individual patient data and setting imaging parameters is usually placed outside the ERCP room or behind a leaded glass shield to reduce radiation exposure to technical personnel. If placed in a separate room, the presence of a window for the technologist or assistant to see into the room is desirable (Fig. 2.6).

Equipment and device storage Accessories are integral to the practice of ERCP. A range of accessories are needed for ERCP (Table 2.2; see also Chapter 4) and should be readily available during each procedure. There are a number of options for storage of these accessories. Mobile carts are available for this purpose or customized cabinets or shelves within the room can be used (Fig. 2.7). Accessories should be clearly labeled for quick access during a procedure. A regularly updated inventory 16

Fig. 2.6 A console for entering patient data is outside the ERCP room. The procedure can be viewed by technical personnel through a leaded glass window, thereby reducing their radiation exposure.

system is also essential to avoid the problem of not having a needed accessory for a specific procedure.Endoscopes are generally stored with the other endoscopes for the endoscopy unit, outside of the procedure room. The endoscopes should hang free and not be coiled within an instrument case. Air and suction valves should be removed from the endoscopes during storage. Lead aprons and thyroid collars should be stored near a door, either inside or outside of the room. This minimizes disruption of fluoroscopy when someone enters the room and needs to put on lead shielding.

MISCELLANEOUS ISSUES Each staff member involved with an ERCP procedure should have a radiation dosimeter. Provision should be made for storage of these dosimeters outside of the procedure room to avoid recording of scattered radiation that is not associated with the individual to whom the dosimeter is assigned. The dosimeter should be in a convenient location to serve as a reminder to staff to wear the dosimeter during each procedure.Drugs used during the procedure should be readily available. Sedative medications are usually checked out for each individual patient from a central medication storage area. Emergency drugs, such as atropine, naloxone, and flumazenil need to be readily available for each case and not be locked up in an area that delays access to them in an emergent situation.

Chapter 2 The ERCP Room

Essential accessories for all ERCP rooms

Additional accessories for specialty centers

Electrosurgery generator Ground pads Guidewires (0.018–0.035 inch) Cannulas Sphincterotomes Stents Plastic—range of diameters (3–10 French) and lengths (3–15 cm) Self-expanding metal Stone retrieval balloons (8.5–15 mm balloon diameters) Stone retrieval baskets Mechanical lithotriptor and catheters Dilating balloons—range of diameters (4–10 mm) and lengths (2–6 cm) Dilating catheters Brush cytology catheters Intraductal biopsy forceps Snares and foreign body forceps for stent retrieval Injection needles Multipolar electrocautery probes

Manometry catheters Intraductal ultrasound catheters Intraductal “baby” scopes Electrohydraulic or laser lithotriptor fibers Argon plasma coagulation probes

Table 2.2 Accessories for the ERCP room Fig. 2.7 A cart holding the accessories commonly used during ERCP should be stored nearby the procedure table.

REFERENCES 1. Lennard-Jones JE, Williams CB, Axon A, et al. The Working Party of the Clinical Services Committee of the British Society of Gastroenterology Provision of gastrointestinal endoscopy and related services for a district general hospital. Gut 1991; 32:95–105.

2. Sivak MV Jr, Manoy R, Rich ME. The endoscopy unit. Chapter in: Gastroenterologic Endoscopy, 2nd edn. Edited by MV Sivak; Philadlelphia: WB Saunders, 1999. 3. Gostout CJ, Ott BJ, Burton D, et al. Design of the endoscopy procedure room. Gastrointest Endosc Clin N Am; 1993:509–524. 17

SECTION 1 GENERAL TOPICS

4. O’Sullivan S, Bridge G, Ponich T. Musculoskeletal injuries among ERCP endoscopists in Canada. Can J Gastroenterol 2002; 16:369–374. 5. Perini RF, Sadurski R, Cotton, PB, et al. Post-sphincterotomy bleeding after the introduction of microprocessor-controlled electrosurgery: does the new technology make the difference? Gastrointest Endosc 2005; 61:53–57. 6. Johlin FC, Pelsang RE, Greenleaf M. Phantom study to determine radiation exposure to medical personnel involved in ERCP fluoroscopy and its reduction through equipment and behavior modifications. Am J Gastroenterol 2002; 97:893–897. 7. Uomo G, deRitis R, Rabitti PG, et al. Does endoscopic digital pancreatography constitute an advance in pancreatic imaging? Gastrointest Endosc 1998; 48:67–71.

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8. Bushong SC. Radiologic science for technologists: physics, biology, and protection. 8th edn. St Louis: Mosby, 2004. 9. Chen MYM, Van Swearingen FL, Mitchell R, et al. Radiation exposure during ERCP: effect of a protective shield. Gastrointest Endosc 1996; 43:1–5. 10. Campbell N, Sparrow K, Fortier M, et al. Practical radiation safety and protection for the endoscopist during ERCP. Gastrointest Endosc 2002; 55:552–557. 11. Buls N, Pages J, Mana F, et al. Patient and staff exposure during endoscopic retrograde cholangiopancreatography. Br J Radiol 2002; 75:435–443.

SECTION 1

Chapter

3

GENERAL TOPICS

Radiologic Issues in ERCP Desiree E. Morgan

The scope and practice of ERCP has changed dramatically over the past 10 years. With the advent of MRCP, in academic and in private settings alike, the proportion of therapeutic to diagnostic ERCP cases has greatly increased,1,2 This shift in practice patterns heightens the importance of communication between the endoscopist and radiologist in order to provide the patient with the best possible interpretation of images acquired during ERCP. It cannot be stressed enough that the interaction between physicians leads to the most accurate and consistent reporting,3 whether the patient is undergoing a diagnostic or a therapeutic ERCP examination. This chapter will focus primarily on techniques of image acquisition during ERCP, using examples of pathology (discussed in depth elsewhere in the book) to demonstrate imaging principles. Prior to the ERCP procedure, review of other imaging studies (CT, MRI, or ultrasound) is often helpful to plan and expedite the case. If therapeutic endoscopic interventions are intended, availability of the pancreatobiliary surgeon or vascular/interventional radiologist for treatment of potential complications or participation in combined procedures is desirable. The patient’s history of medical allergies, including contrast material, should be ascertained during the consent process. ERCPs may be performed in dedicated rooms with fixed fluoroscopy (conventional or digital system) units, or with C-arm fluoro units in endoscopy suites or outpatient centers. While the benefits of lower expense, convenience and versatility for C-arm units make them desirable to some users, the cost of dramatically increased xray dose to patients and ERCP personnel must be considered.4 Our ERCPs take place in dedicated digital fluoroscopy rooms within an endoscopy suite located in our hospital. The images acquired in the endoscopy fluoro rooms are transmitted to and archived within the Department of Radiology PACS (picture archiving and communication system), and the digital images are available throughout the hospital and clinics of our medical center once they are transmitted to the PACS. Fluoroscopy rooms designed for ERCP should be large enough to accommodate the video endoscope machinery, supply cart, patient monitoring devices, and the conventional or digital x-ray device. Digital systems allow “on the fly” change in magnification factors and rapid image acquisition generally ranging from two to seven films per second, features often helpful during ductal evaluation. Exchange of x-ray film cassettes in conventional fluoroscopy units adds time both for acquisition and development of images, and generally requires the assistance of a radiology technologist. Most fixed fluoroscopy units, whether digital or conventional, have the x-ray beam source in the table and an image intensifier in the tower. Consideration of the x-ray source is important when shielding the patient is necessary, such as during ERCP in pregnant patients. During most ERCPs, the patient is generally positioned in either a prone or left lateral decubitus (LLD) position. Changes in the patient position are key to visualization of both normal ducts and

duct pathology. In this chapter, the patient position will be described relative to the tabletop rather than the image intensifier. For example, left anterior oblique (LAO) refers to prone patient with left side angled down against the table top and right side angled up. Radiation dose is important to patients and ERCP personnel, and should be monitored with quality assurance testing of the equipment and monthly quantification of exposure measured by radiation badges worn by the endoscopist, his or her technical assistants, and the nurses involved in the procedure. The amount of exposure to personnel varies according to their position relative to the patient. In a controlled, phantom study of radiation doses to personnel during ERCP, Johlin et al.4 described that the largest doses are received by the person at the head of the table, generally the nurse who monitors the patient and administers drugs. The next highest dose is received by the endoscopist, who stands at the right hand corner of the fluoro table, and the lowest dose is received by the assistant who stands alongside the endoscopist at the level of the patient’s abdomen. The low dose received by the assistant at the patient’s abdomen is explained by the use of vertically oriented lead drapes that attach to the fluoro tower and diminish the amount of scatter radiation. Some fluoro units are equipped with right angled vertical lead drapes which can be maneuvered to shield both the head and side of the tower. Alternatively, some centers utilize a lead bead curtain at the head of the table to diminish dose to personnel in this position. Other means that should be employed to decrease dose to patients and personnel alike during ERCP include lowering the tower as close to the patient as possible during the procedure (anytime the fluoro is on as well as when making exposures), collimating the x-ray beam manually (using buttons generally located on the tower), and standing back from the table. The scatter radiation is inversely proportional to the distance squared from the x-ray beam, so even stepping back a small amount is helpful. Conversely, leaning over the head of the patient while fluoro is on greatly increases the dose to the nurse.4 Finally, measures to conserve exposure in the first place by using minimal fluoro time or pulsed fluoro will decrease the dose to all persons in the ERCP room. For pregnant patients, limiting fluoro time is critical. Also, to reduce dose to the fetus, shielding of the mother’s abdomen (from the direction of the x-ray source) with lead aprons is warranted. While the above discussion pertains to ERCPs performed with either fixed fluoroscopy or C-arm equipment, it should be stressed that the amount of scatter radiation produced by most C-arm units is of the order of 100-fold that of fixed equipment. This is due to lack of shielding at the x-ray source and lack of shielding of the x-ray beam that enters the patient, as well as issues of fixed distance from the x-ray source to the patient and “enhanced fluoro” features which double the energy of the x-ray beam for “higher resolution.” Readers are referred to several articles in the radiology literature5,6 and an excellent therapeutic ERCP specific article on this subject,7 19

SECTION 1 GENERAL TOPICS

and are strongly urged to pay particular attention to these issues when purchasing equipment for their endoscopy centers. During the ERCP procedure, the orientation of the fluoroscopic image on the image intensifier tower may be viewed in a number of ways. Some endoscopists prefer to view the fluoroscopic image just as it is obtained, that is, with the prone patient’s left side on the right side of the image intensifier screen and the cephalad portion projecting at the bottom of the screen (Fig. 3.1). The “head” of the ERCP table equals the “foot” of the x-ray fluoro table; in this scenario, what you see is what you get. Most prefer to flip the image so that the anatomy appears upright and in anatomic position on the image intensifier (Fig. 3.2). But when the fluoro tower is moved, one must remember this inverse relation to achieve the desired location of the x-ray beam in the patient’s body. The orientation of the image on the tower may easily be changed during the exam. Contrast preferences also vary among endoscopists. Some prefer to dilute contrast to half strength when looking for stones. Others use full strength contrast injected slowly while looking stringently for filling defects, or employ the technique of chasing the initial contrast injection with saline to achieve a lesser opacity through which stones may become more evident. Still others use full strength

contrast with the argument that the bile in a potentially obstructed or dilated system (Fig. 3.3) will dilute the contrast enough to preclude having to do so proactively. In addition, the use of fullstrength contrast allows earlier detection of pancreatic duct injection, minimizing the volume and potentially reducing the risk of pancreatitis. Also, with conventional radiographic film screen combinations, the exposure creates a “white duct on black background” image. With digital images, the “black on white” images that appear similar to the fluoroscopic image can be filmed or viewed as such, or converted to a standard “white on black” appearance on PACS or film, if preferred. In my opinion, retroperitoneal and free air (Fig. 3.4) are easier to detect with “white on black” images, as are small stones (Fig. 3.5), but to my knowledge, there has been no formal, controlled perception study to support this theory. The sequence of images obtained during ERCP should tell the story of the examination, whether diagnostic or therapeutic. Initially, a scout radiograph obtained with the patient prone reveals any residual contrast, calcifications, tubes, drains, or stents already in place, and any other material that may obscure the region of interest during contrast injection (Fig. 3.6). Most gallstones are nonradiopaque and will not be seen on the scout radiograph, however pancreatic stones frequently may (Fig. 3.7). Once contrast is administered, radiopaque stones in either ductal system may be obscured (see Fig. 3.7). The

Fig. 3.1 Direct projection of ERCP image on fluoroscopic tower. Early injection into the CBD in this patient with Mirizzi Syndrome and cholelithiasis demonstrates orientation without adjustment. The patient’s head is at the foot of the table, and he is prone, so that the right side projects to the left of the screen. Fig. 3.3 Spot radiograph demonstrating adequate visualization of multiple small faceted gallstones (arrows) in a dilated Type 1 choledochal cyst.

A

Fig. 3.2 Vertically and horizontally flipped projection of ERCP image on fluoroscopic tower. Later injection into the CBD in the same patient (Fig. 3.1) with Mirizzi Syndrome and cholelithiasis demonstrates orientation with adjustment so that it is viewed in anatomic position with the patient’s head at the top and his left side on the left of the screen. Note stone (arrow) impacted in cystic duct approximately 1 cm above its insertion into the common hepatic duct. 20

B

Fig. 3.4 Subhepatic free intraperitoneal air (arrow) after biliary sphincterotomy comparing A “black on white” to B “white on black” image presentation. Note large amount of air in the extrahepatic duct after sphincterotomy.

Chapter 3 Radiologic Issues in ERCP

A

B

A

Fig. 3.5 Small distal common bile duct stone (arrow) in dilated system comparing A “black on white” to B “white on black” image presentation.

B

Fig. 3.6 Scout radiograph in a patient about to undergo ERCP. The radiopaque oral contrast from abdominal CT performed 12 hours earlier is located in the hepatic flexure of the colon, potentially interfering with visualization of the extrahepatic bile duct. Because this patient was being evaluated for suspected post traumatic (gun shot wound) bile leak from the intrahepatic ducts more superiorly, the exam was performed (see Fig. 3.20). diagnostic images should include early filling as well as full duct opacification and generally are acquired with a nine inch or six inch image intensifier field of view mode. These overview images of the bile and or pancreatic ducts should be supplemented with spot radiographs of abnormal or suspicious findings. The spot images may be obtained at different degrees of magnification (six or 4.5 inch mode) for emphasis. Delayed films often are critical for assessing biliary drainage (Fig. 3.8) or lack thereof, or for demonstrating small calculi. A final film obtained with a large image intensifier field of view (12 or 15 inch) is helpful to evaluate potential retroperitoneal (Fig. 3.9) or intraperitoneal air. For calculation of actual duct size with digital or standard radiographic images, knowledge of the scope caliber enables a simple proportion to be created to determine the exact magnification for each image (Fig. 3.10). In a hypothetical example, if an older 13.5 mm caliber therapeutic endoscope is used during an ERCP where there is biliary dilation above a strictured region, the exact degree of duct dilation may be calculated by measuring the dilated portion of the duct as well as the scope on the image. The following simple proportion is then set up: 17 (measured caliber of scope 25 (measured caliber of on film) = dilated duct) 13.5 mm (actual scope caliber) X mm

C

Fig. 3.7 Severe chronic pancreatitis. A Innumerable pancreatic calcifications are present on the ERCP scout radiograph. B Following injection of contrast into the main pancreatic duct, the radiopaque intraductal calcifications are obscured by contrast. Parenchymal calcifications should project apart from the opacified duct lumen; however in markedly dilated ductal systems the sheer caliber of the opacified duct may obscure even parenchymal calcification. C Corresponding abdominal CT image through the body of the pancreas shows parenchymal and ductal calcifications in this patient.

21

SECTION 1 GENERAL TOPICS

Fig. 3.8 ERCP drainage film. Spot radiograph after stent insertion above the level of obstruction by the impacted cystic duct stone in this patient with Mirizzi syndrome (same patient as Figs 3.1 and 3.2) reveals emptying of the right and extrahepatic bile ducts. If the patient is turned to a supine position and the head of the table tilted up, drainage of the left intrahepatic ducts may also be verified.

Fig. 3.10 Calculation of individualized magnification factor during ERCP. The caliber of the upstream CBD (arrow) may be set up in a proportion to the measured scope caliber (arrowhead) on the film to correct for magnification produced by short object-to-image distance of the x-ray beam.

The hypothetical duct measures 19.9 mm. If the scope was a newer 11.5 mm model, the caliber of the duct would be 16.9 mm. Solving for X alleviates the need to calculate pixel correction measurements (for digitally acquired spot images) or to estimate magnification on standard radiographic spot images. This is also important when calculating the length from the papilla to a stricture in order to select the appropriate length stent, although the use of a ruled catheter or wire withdrawal may be more accurate for selecting stents than use of x-ray film measurements8 (see Chapter 16 for further details). If a new or different size scope is utilized for a particular procedure, this information should be communicated to the radiologist to insure accuracy of measurements.

BILE DUCT OPACIFICATION

Fig. 3.9 Retroperitoneal air after sphincterotomy. Final film obtained after scope removal reveals air outlining the right upper renal pole (arrow) and right adrenal gland (arrowhead), indicating duodenal perforation. 22

The distal portion of the common bile duct is readily opacified by injection of the major papilla or ampulla of Vater. The normal caliber of the injected extrahepatic bile duct ranges from 3 mm up to 9 mm, with the larger normal caliber more typically seen in older individuals9–12 and in patients who have undergone cholecystectomy,12–16 although the wider caliber does not significantly increase in the postoperative period.9 This is opposed to the relatively smaller upper limits of normal for duct caliber as measured by cross sectional imaging such as ultrasound or CT, where there is not active injection occurring to distend the duct,13–16 yet the same trends in larger normal calibers in older and post-cholecystectomy patients are seen.12,15,16 Variability of insertion of the cystic duct leads to different degrees of obliquity required for adequate visualization. In the case of a long common channel between the CBD and cystic duct

Chapter 3 Radiologic Issues in ERCP

(Fig. 3.11), the best position to identify entrance of the cystic duct or to visualize potential cystic duct stones is typically left anterior oblique (Fig. 3.12). The best position to identify the confluence of right and left hepatic ducts, particularly important in the evaluation of hilar tumors (Fig. 3.13), is right anterior oblique. With the patient prone or in left lateral decubitus position, there is preferential opacification of the left intrahepatic ducts (Fig. 3.14A) due to gravity. Placing the patient

A B

C

in a right decubitus position or supine position helps to opacify the right-sided ducts. The posterior segmental branches may be best seen with the patient supine. In some patients, it is necessary to tilt the head of the table down to opacify the right intrahepatic ducts, and other endoscopic measures such as proximal CHD injection or balloon occlusion injected may help to opacify all of the IHD concurrently (Fig. 3.14B). If there is complete opacification of the intrahepatic duct system and the cystic duct and gallbladder do not fill despite changing the patient’s position, cystic duct obstruction should be suspected.17 Changing the patient’s position (Fig. 3.15) in attempts to visualize all intrahepatic ducts is especially critical in patients with strictures near the confluence, as is injecting near the stricture (Fig. 3.16). Inadequate filling may result in overestimation of strictures, and the “shouldered” feature of malignant strictures may not be ideally demonstrated without adequate duct filling (Fig. 3.17). Likewise the characteristics of benign strictures are better delineated with adequate duct filling (Fig. 3.18). Changing the patient’s position may also help to correctly identify the source of bile leak if aberrant or overlapping ductal structures are present (Fig. 3.19). As in the case of injecting near a stricture to better characterize its extent and character, injecting near the site of a bile leak

D

Fig. 3.11 Long common cystic duct/ common bile duct channel, ERCP/CT correlation. A ERCP spot radiograph revealing a large amount of amorphous stone debris in the long cystic duct and common duct which overly one another in a straight anterior to posterior (AP) direction. B–D Corresponding successively caudal axial CT images obtained after ERCP reveal the relationship of the cystic duct and common hepatic duct in this patient, with the wall between the lumens well depicted on B (arrow) and C by the presence of residual biliary contrast. The wall ends approximately 1 cm above the ampulla on D.

Fig. 3.13 Hilar stricture. The very tight stricture (arrow) of the right main bile duct is well seen in the right anterior oblique projection in this patient with a Klatskin tumor. The patient underwent right hepatectomy and L hepaticojejunostomy with biliary margin free of tumor.

A

Fig. 3.12 ERCP depiction of long common cystic duct/common hepatic duct channel with left anterior oblique projection. When the prone patient is angled with the left side down on the fluoro table, the wall between the cystic duct and common bile duct lumens is better seen. The distal, smooth common bile duct stricture is due to a nonhyperfunctioning neuroendocrine tumor of the pancreatic head in this patient.

B

Fig. 3.14 Preferential flow of contrast due to gravity. A Early filling of the common bile duct with the patient in prone position reveals stone (arrow) impacted at cystic duct remnant. B after stone retrieval, the entire intrahepatic duct system is opacified during injection using balloon occlusion technique. 23

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A

B

Fig. 3.15 Hilar strictures due to lymphoma. A The long, relatively smooth stricture (arrowheads) of the main left and right bile ducts in the hilum is well seen on the prone image. There is also dilation of the posterior segmental branch duct (arrow) which drains aberrantly into the left duct. B With the patient obliqued, the strictured region (white arrow) of the aberrant duct is now evident.

A

Fig. 3.18 Chronic pancreatitis stricture. Opacification of the bile and pancreatic ducts reveals a smooth conical stricture of the distal common bile duct and upstream dilation in a pattern typical of inflammatory stricture. There is dilation of the main and side branch pancreatic ducts, and a stricture is present in the mid body region of the main pancreatic duct in this patient with severe chronic pancreatitis.

B A

Fig. 3.16 Primary sclerosing cholangitis. A Injection of contrast in the mid common bile duct reveals partial visualization of the tight strictures of the right and left ducts in the porta, with some reflux of contrast into the cystic duct and gallbladder. B Injection within the right bile duct just above the confluence demonstrates improved visualization of the diffusely strictured ductal system in this patient with primary sclerosing cholangitis. The left ducts were not opacified further during ERCP, making it difficult to exclude cholangiocarcinoma.

A

Fig. 3.19 Post cholecystectomy bile leak. A Prone image during filling of the common and intrahepatic ducts reveals contrast within the drain in the right upper quadrant. Both the stapled end of the cystic duct and an aberrant right branch overlie the drain. No early film was obtained to determine the site of leak; however, with the patient obliqued slightly in B, contrast appeared to extravasate from the aberrant duct rather than the cystic duct stump. Note air bubbles in distal CBD after stent placement in B.

B

Fig. 3.17 Shouldered stricture. A Early injection of the distal common bile duct demonstrates narrowing in the superior pancreatic head. B With further filling the persistent shouldering (arrow) of the malignant stricture is better depicted. Note the layering of contrast in the underfilled duct above the stricture on A, underestimating the extent of upstream dilation, better seen on B. Gallstones are present within the gallbladder. 24

B

(Fig. 3.20) or obstructing stone (see Figure 3.2) is important to fully understand the pathology. In the case of the endoscope obscuring portions of the bile duct (generally this occurs in the suprapancreatic portion of the extrahepatic duct) (Fig. 3.21), attempts to change scope position to allow direct visualization of the duct may be necessary. For long bile duct strictures, obtaining orthogonal view spot images may help characterize the stricture and demonstrate extrinsic effect. The same is true for intrahepatic bile duct abnormalities produced by hepatic parenchymal disease such as polycystic liver disease (Fig. 3.22) or cirrhosis. Drainage films may be facilitated by tilting the head of the table up for several minutes prior to image exposure (see Fig. 3.8).

PANCREATIC DUCT OPACIFICATION The pancreas is oriented with the head and tail located relatively more posteriorly within the patient compared to the neck and body

Chapter 3 Radiologic Issues in ERCP

A

B C

D

E

Fig. 3.20 Post traumatic bile leak. A Initial ERCP injection into the bile duct shows extravasation from two right-sided intrahepatic ducts. B After stent placement the ducts have emptied, with residual intrahepatic extravasated contrast remaining near the drain. C Axial CT image reveals the disrupted hepatic parenchyma due to gun shot wound. D Two weeks later, repeat ERCP with injection into the extrahepatic CBD reveals no extravasation. E Injection directly into the affected right duct structures (arrow) further characterizes the ducts as sealed.

Fig. 3.21 Endoscope obscuring majority of the malignant stricture of the common bile duct in a patient with pancreatic adenocarcinoma involving the superior head region. Note adjacent stricture of the main pancreatic duct. See Fig. 3.31 for biopsy image of same patient. region. Thus, with injection at the level of the papilla, contrast must travel against gravity, or posteriorly in the patient, to reach the tail region when the patient is prone on the fluoroscopic table. Changing the patient to the supine position will often allow more prompt visualization of the duct in the pancreatic tail (Fig. 3.23). The main pancreatic duct is approximately 20 cm long and variable in caliber.17 In general, the caliber of the duct is greatest in the downstream or head region next to the papilla, tapering continually towards the upstream or tail region. Normal caliber of the injected pancreatic duct in general is 4 mm in the head, 3 mm in the body, and 2 mm in the tail,17,18 though larger diameters are considered normal in advanced age.19 If the patient has a pronounced anterior to posterior

Fig. 3.22 Deviation of intrahepatic bile ducts due to polycystic liver disease. Injection into the right biliary duct system demonstrates a long, smooth stricture of the extrahepatic and central right-sided ducts, with superior displacement and draped appearance of peripheral ducts in a patient with large intrahepatic parenchymal cysts.

curve of the pancreas within the abdomen (readily noted with CT or MR axial images), combined RAO and LAO images may best lay out the duct for complete visualization. Because the normal pancreatic duct drains rapidly, image acquisition during active contrast injection at a rate of two to three images per second may avoid repeated injections and allow complete visualization of all portions including pathologic regions of the duct. This may be critical in that repeated pancreatic injections have been shown to increase risk for post ERCP pancreatitis.20–22 In general, it is the focal change in caliber of either the bile or pancreatic duct that indicates pathology and warrants further image acquisition. If the catheter is placed farther into the duct up to the 25

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Fig. 3.23 Complete visualization of the main pancreatic duct. Injection into the distal main pancreatic duct reveals normal smooth transition from largest caliber in the head to smallest caliber in the tail.

A

B

Fig. 3.24 Chronic pancreatitis. A Early filling of the main pancreatic duct shows dilation in the tail region, upstream from a smooth stricture (arrow) in the proximal body region. B With further injection and repositioning of the scope, there is better demonstration of the stricture in the body (white arrow), as well as side branch dilation and a second focal inflammatory stricture of the main pancreatic duct in the neck region (black arrow).

A

B

Fig. 3.25 Acinarization during pancreatic duct injection. A Early filling of the main pancreatic duct reveals a loop variation in the head region and obscuration of the pancreatic duct by the scope. B With further injection under pressure there is acinarization of contrast and filling of the tight malignant stricture (arrowheads) in the pancreatic neck region, accompanied by upstream dilation in a patient with pancreatic adenocarcinoma.

location of a suspected stricture or filling defect, the interpreting physician can be relatively certain that the affected area is visualized adequately (Fig. 3.24). Although most often not intentionally produced, when acinarization occurs distal or downstream to a stricture (Fig. 3.25), one may be sure that the diminished caliber or obstruction of the duct is not due to technical factors. 26

It is also important to remember that when contrast passes through a strictured region to fill a more dilated proximal duct segment, there will be dilution of the contrast and sometimes layering (see Fig. 3.17) of the contrast,3 making estimation of the length of stricture or the degree of upstream dilation potentially inaccurate. In addition, extravasation from the duct upstream to the strictured region, as is often seen in patients with chronic pancreatitis who have a dominant stricture and chronic pseudocyst formation, may only be seen with deep cannulation and injection immediately adjacent to the affected portion of the main pancreatic duct. Likewise to show that a leak has sealed, injection of contrast near the site of prior extravasation (see Fig. 3.20) during follow-up studies is helpful to exclude technical factors such as underfilling of the affected duct that may produce false negative results. If extravasation occurs from either the pancreatic or bile duct, the size of the cavity (if contained rather than freely extravasated contrast is present) may be underestimated on ERCP due to the relative limited volume of contrast injected, and is better assessed with crosssectional imaging (Fig. 3.26). The evaluation of the filling defects within either duct may be difficult without good communication between the endoscopist and radiologist. Distinguishing between air bubbles that tend to be round or oval (Fig. 3.27) and small gallstones or pancreatic concretions that tend to be angular or faceted (see Fig. 3.3) but which may also be round, can generally be accomplished by changing patient position.23,24 With the head of the table tilted up, gallstones will proceed downward within the duct system, and air bubbles will rise upward (Fig. 3.28). Air bubbles are to be expected after sphincterotomy. Sometimes, such a large amount of air enters the duct that identification of stones is no longer possible (see Fig. 3.4). In the case of precut sphincterotomy to access the duct, there will be no initial injection to clearly document the presence of stones prior to the introduction of air into the duct system. Paying particular attention to the shape and movement of intraductal filling defects may help distinguish between the two, even in this circumstance. When filling defects are removed without documentation of their presence on the images, there is no way for an accurate interpretation to occur after the fact. Since the most common indication for endoscopic retrograde cholangiography remains “suspected biliary obstruction”17 and for endoscopic sphincterotomy continues to be “choledocholithiasis,” documentation of stones on images obtained prior to stone removal and/or communication of real-time endoscopic findings help to ensure consistent reporting. In addition, the performance of sphincterotomy must be communicated Since there is a slightly higher risk of perforation during ERCP when sphincterotomy is performed,25–27 the presence of retroperitoneal and free air should be sought more stringently in those patients. On the other hand, the radiologist cannot assume that a sphincterotomy has occurred because the instrument is documented on an image; the sphincterotome may simply be used to cannulate the major papilla in patients with a difficult entry angle.28 Similarly, pancreatic guidewire or stent placement may be performed solely to facilitate biliary cannulation29,30 and images documenting this event do not imply pancreatic disease. Communication of the endoscopist’s thoughts during a procedure is helpful to avoid errors related to misinterpretation of these phenomena and to provide the most accurate report. In the case of minor papilla injection or therapeutic maneuver (minor papillotomy and/or stent placement), the long scope position (Fig. 3.29) typically employed to access the more proximal papilla

Chapter 3 Radiologic Issues in ERCP

A

B

D

E

C

Fig. 3.26 Extravasation from pancreatic duct. A Early film obtained during ERP demonstrates smooth distal main pancreatic duct and sidebranches in the head region. B and C With deeper cannulation and further injection, extravasation into an amorphous cavity is present in the mid body region. D After pancreatic duct stent is placed and the patient is placed supine, the contrast spreads out further within the cavity. E Accompanying axial CT image demonstrates cystic collection in the mid body region in this patient with duct disruption due to evolving subacute pancreatitis.

A

Fig. 3.27 Gas bubbles in main pancreatic duct. With wire exchange and deep cannulation there is introduction of air and formation of smooth, round bubbles in the main pancreatic duct.

may be a hint to the interpreting radiologist that the duct of Santorini has been injected, even if the major papilla and typical features of pancreas divisum (Fig. 3.30) are not documented elsewhere in the procedure. But again, for the most effective reporting, this information should be rapidly communicated by the endoscopist. Some therapeutic maneuvers and their respective images speak for themselves such as biopsy (Fig. 3.31), stone extraction (Fig. 3.32) or stent placement (Fig. 3.33) so long as an image is obtained to document the event. However, in other circumstances such as in patients with sphincter of Oddi dyskinesia, both the bile and pancreatic ducts may be morphologically normal, and the diagnosis cannot be made on the basis of images alone. Communication of manometric measurements, if acquired, and clinical factors in these patients is critical to insure an accurate interpretation of the radiographs. In summary, the modern-day practice of ERCP involves a large percentage of therapeutic procedures and frequently does not permit

B

C

Fig. 3.28 Gallstones versus air bubbles. A Initial injection into a type 4 choledochal cyst demonstrates multiple filling defects (arrow) in the distal aspect of the dilated duct. B After sphincterotomy, several rounded filling defects suggestive of air bubbles are more clearly seen within the more superior aspect of the duct. C With the head of the table tilted up, there is downward migration of the stones/debris (arrow); the rounded air bubbles have risen and are no longer evident. 27

SECTION 1 GENERAL TOPICS

Fig. 3.29 Long scope position. Spot radiograph obtained during injection of the minor papilla demonstrates long scope position often, but not always, utilized to cannulate the minor papilla in patients with pancreas divisum. Note changes of mild chronic pancreatitis.

the radiologist to be in the endofluoroscopy suite concurrently with the endoscopist; therefore communication is critical to the rendering of adequate radiologic reporting and concurrence with endoscopic findings. Some centers are equipped with inter-departmental intercoms and videomonitors to allow real-time discussion between the endoscopist and radiologist while they are physically located in different rooms. In the case of more remote (both spatial and temporal) endoscopy/radiology cooperation, voice recognition dictation systems that allow immediate reporting, digital medical record archiving, and hospital system-wide accessibility to documents enable rapid reporting of ERCP but cannot replace real-time communication. If real-time exchange is not feasible, then careful documentation of normal or abnormal structures and image documentation of endotherapeutic maneuvers during ERCP are of paramount importance!

Fig. 3.30 Pancreas divisum. Injection of the major papilla in short scope position reveals concurrent visualization of bile duct and typical arborizing ventral pancreatic ducts in a patient with pancreas divisum.

Fig. 3.31 Endoscopic biopsy. Spot radiograph reveals open forceps deployed to region of malignant biliary stricture for tissue sampling of suspected tumor.

A

B

C

Fig. 3.32 Stone extraction. A Spot image reveals mild common duct dilation with rounded 7 mm stone and balloon inflated above the stone prior to sweeping the duct. B After unsuccessful balloon sweeping, a wire basket was placed around the stone and in C retrieved successfully. 28

Chapter 3 Radiologic Issues in ERCP

A

B

C

Fig. 3.33 Restenting through tumor overgrowth. A Injection into the lumen of the distal common bile duct in a pancreatic carcinoma patient who underwent wire mesh stent placement three months earlier for palliative biliary drainage reveals near occlusion of the lumen due to tumor ingrowth. B After deep wire cannulation and injection of dilated upstream bile ducts, C, a longer stent was successfully placed through the occluded stent, re-establishing biliary drainage.

REFERENCES 1. Cotton PB. Evaluating ERCP is important but difficult. Gut 2002; 51:287–289. 2. NIH state-of-the-science statement on endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and therapy. NIH Consensus Sci Statements. 2002; 19(1):1–26. 3. Technical Considerations in Imaging. In: Taylor AJ, Bohorfoush AG III (eds) Interpretation of ERCP with Associated Digital Imaging Correlation. Philadelphia, Lippincott-Raven, 1977: pp 1–24. 4. Johnlin FC, Pelsang RE, Greenleaf MG. Phantom study to determine radiation exposure to medical personnel involved in ERCP fluoroscopy and its reduction through equipment and behavior modifications. Am J Gastroenterol 2002; 97:893–897. 5. Cousin AJ, Lawdahl RB, Chakraborty DP, et al. The case for radioprotective eyewear/facewear: practical implications and suggestions. Invest Radiol 1987; 22:747–750. 6. Boone JM, Levin DC. Radiation exposure to angiographers under different fluoroscopic imaging conditions. Radiology 1991; 180:861–861. 7. Heyd RL, Kopecky KK, Sherman S, et al. Radiation exposure to patients and personnel during interventional ERCP at a teaching institution. Gastrointest Endosc 1996; 44:287–292. 8. Seibert DG. Biliary stricture measurement and stent selection. Am J Gastroenterol. 1997; 92:1510–1514. 9. Mageed AW, Ross B, Johnson AG. The preoperatively normal bile duct does not dilate after cholecystectomy: results of a five year study. Gut 1999; 45:741–743. 10. Mahour G, Wakim K, Ferris D. The common bile duct in man: its diameter and circumference. Ann Surg 1967; 165:415–419. 11. Edholm P, Jonsson G. Bile duct stones related to age and duct width. Acta Churg Scand 1962; 124:75–79. 12. Kaim A, Steinke K, Frank M, et al. Diameter of the common bile duct in the elderly patient: measurement by ultrasound. Eur Radiol. 1998; 8:1413–1415. 13. Morgan B, Rathod A, Crozier A, et al. Biliary distensibility during per-operative cholangiography as compared with preoperative ultrasound: a four year follow up study. Clinical Radiology 1996; 51:338–340.

14. Sauerbrei EE, Cooperberg PL, Gordon P, et al. The discrepancy between radiographic and sonographic bile-duct measurements. Radiology 1980; 137:751–755. 15. Bowie JD. What is the upper limit of normal for the common bile duct on ultrasound: how much do you want it to be? Am J Gastroenterol. 2000; 95(4):897–900. 16. Daradeh S, Tarawneh E, Al-Hadidy A. Factors affecting common bile duct diameter. Hepatogastroenterology 2005; 52:1659–1661. 17. Schoeman MN, Huibregtse K, Reeders JWAJ. Endoscopic Cholangiography and Pancreatography (ERCP), In: Van Leeuwen DJ, Reeders JWAJ, Ariyana J (eds), Imaging in Hepatobiliary and Pancreatic Disease: A Practical Clinical Approach. London, W. B. Saunders, 2000: pp 309–332. 18. Ohnuma N, Takashi H, Tanabe M, et al. The role of ERCP in biliary atresia. Gastrointest Endosc 1997; 45:365–370. 19. Hastier P, Buckley MJ, Dumas R, et al. A study of the effect of age on pancreatic duct morphology. Gastrointest Endosc. 1998; 48:53–57. 20. Cheng CL, Sherman S, Watkins JL, et al. Risk factors for post-ERCP pancreatitis: a prospective multicenter study. Am J Gastroenterol. 2006; 101:139–147. 21. Testoni PA. Why the incidence of post-ERCP pancreatitis varies considerably? Factors affecting the diagnosis and the incidence of their complication. J Pancreas 2002; 3:195–201. 22. Freeman ML. Post-ERCP pancreatitis: patient and technique related risk factors. J Pancreas 2002; 3:169–176. 23. Thompson WM, Halvorsen RA, Foster WL, et al. Optimal cholangiographic technique for detecting bile duct stones. AJR 1986; 146:537. 24. Train JS, Novick A, Dan SJ, et al. Radiolucency in the common bile duct simulating a gallstone. AJR 1987; 148:136. 25. Siegel J, Ben-Zvi J, Pullano W, Cooperman A. Effectiveness of endoscopic drainage for pancreas divisum: endoscopic and surgical results in 31 patients. Endoscopy 1990; 22:129–133. 29

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26. Suissa A, Yassin K, Lavy A, et al. Outcome and early complications of ERCP: a prospective single center study. Hepatogastroenterology 2005; 62:352–355. 27. Masci E, Toto G, Mariani A, et al. Complications of diagnostic and therapeutic ERCP: a prospective multicenter study. Am J Gastroenterol 2001; 96:417–423. 28. Gulliver D, Cotton P, Baillie J. Anatomic variants and artifacts in ERCP interpretation. AJR 1991; 156:975–980.

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29. Maeda S, Hayashi H, Hosokawa O, et al. Prospective randomized pilot trial of selective biliary cannulation using pancreatic guidewire placement. Endoscopy 2003; 35:721–724. 30. Goldberg E, Titus M, Haluszka O et al. Pancreatic-duct stent placement facilitates difficult common bile duct cannulation. Gastrointest Endosc 2005; 62:592–596.

SECTION 1

Chapter

4

GENERAL TOPICS

Endoscopes, Guidewires and Accessories Sushil K. Ahlawat and Firas H. Al-Kawas

INTRODUCTION ERCP (endoscopic retrograde cholangiopancreatography) has become the preferred technique for the management of patients with a variety of benign and malignant pancreaticobiliary disorders. Success and safety of the procedure depends to a large extent on the indication of the procedure, skills of the examiner and an organized and functional ERCP unit. In addition to a dedicated ERCP room and a fluoroscopy unit, essential equipment for ERCP includes a duodenoscope and a variety of ancillary devices or accessories. A growing range of ERCP accessories have been developed to support the increasing demands and complexity of therapeutic ERCP. This chapter describes current and emerging accessories that are currently available to use during diagnostic and therapeutic ERCP.

ment channel, accessory elevator, and a working length of 120 cm. These features provide an adequate angle of approach and allow intubation of difficult bowel loops and performance of complex therapeutic maneuvers. Initial experience with this oblique-viewing therapeutic endoscope allowed duct access and therapy in two patients with surgically altered anatomy.1 In both patients, prior multiple attempts at ERCP with standard duodenoscope and colonoscope had failed.

ACCESSORIES

ENDOSCOPES

Accessories are devices or pharmacologic agents that help the endoscopist accomplish his diagnostic or therapeutic intent. Cannulation of the desired duct is a prerequisite to successful diagnostic and therapeutic ERCP. A variety of devices are currently available to gain duct access. In particular, the use of sphincterotomes/guidewires and precut sphincterotomes has increased our ability to achieve biliary cannulation.

Duodenoscopes

Cannulas

Side viewing video endoscopes are equipped with an elevator and are used routinely for diagnostic and therapeutic ERCP procedures. The elevator facilitates cannulation and placement of some accessories (Fig. 4.1), while large diameter working channel of therapeutic duodenoscopes (4.2 and 4.8 mm) allow the use of large accessories. Many current ERCP endoscopes combine a large, “therapeutic” channel with a standard size insertion tube. Smaller, 7.4 mm pediatric duodenoscopes with a 2.2 mm channel are available for examination in neonates. Unfortunately, the small channel limits the use of the endoscope to mostly diagnostic purposes since the use of smaller accessories restricts the therapeutic potential of this endoscope. In general, the standard adult duodenoscope can be used in most children above the age of two. A jumbo-size duodenoscope (5.5 mm channel) was previously available as a “mother/baby” scope system. However, this system was difficult to manipulate and is now rarely used.

Standard ERCP cannulas are 5 Fr (French) to 7 Fr catheters, with a straight, tapered or a rounded tip that can accept up to a 0.035-inch guidewire (Fig. 4.2A). Use of a triple-lumen device or the attachment of a side-arm adaptor will allow contrast injection without removing the guidewire. The use of tapered (4.5 Fr-4 Fr-3.5 Fr) or ultra-tapered (5 Fr-4 Fr-3 Fr) tip catheters may allow better duct access in some patients. However, some tapered tip cannulas will only accommodate a smaller-caliber guidewire (= 0.025-inch). No published studies have directly compared cannulation success rates between standard and tapered catheters. Tapered tip catheters may be associated with a higher risk of submucosal injection. Standard cannulas with or without guidewires are limited in their ability to vary the angle of approach to the papilla. The Swing-tip catheter (Olympus America Inc., Lehigh Valley, PA) (Fig. 4.2B) overcomes the limitations of conventional catheters and offers the endoscopist the ability to bend the cannula tip in either direction, thereby facilitating biliary cannulation2,3 or selective entry into the right or left hepatic ducts. The Cremer needle tip catheter (Cook Endoscopy, Winston-Salem, NC) is 1.8 mm in diameter and has a metal needle tip design that facilitates minor papilla cannulation (Figs 4.3a and 4.3b). The standard pancreaticobiliary manometry catheter is a water-perfused 5 Fr catheter with a tip diameter of 3.5 Fr and is used during sphincter of Oddi motility studies (Fig. 4.4A). A variety of catheter types can also be used. Some manometry catheters have a longer “nose” to help maintain catheter position. The standard catheter has three side ports spaced 2 mm apart for simultaneous pressure measurement. The Lehman (Cook Endoscopy) catheter sacrifices

Forward-viewing endoscopes Upper endoscopes, colonoscopes, and enteroscopes are occasionally used in patients with altered anatomy such as previous choledochoduodenostomy, Billroth II gastrectomy, or in patients with hepaticojejunostomy. Since conventional forward viewing endoscopes do not have an elevator, they are limited with respect to control of accessories during cannulation or therapy. In addition, visualization of the ampulla may be limited. A prototype oblique-viewing endoscope is currently available (Pentax Medical Montvale, NJ) with a viewing angle of 45° and a field of view of 130°, a 3.8-mm-diameter instru-

31

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eter became available. Early data suggest that this catheter is associated with a lower risk of post procedure pancreatitis.5

Sphincterotomes

Fig. 4.1 4.2 mm channel duodenoscope (courtesy of Pentax Medical, Montvale, NJ).

A

B

Fig. 4.2 A ERCP cannulas (courtesy of Cook Endoscopy, Winston-Salem, NC). B Swing-tip ERCP cannula (courtesy of Olympus America Inc., Lehigh Valley, PA).

B A

32

Pull type (Erlangen) sphincterotomes were originally designed for the performance of sphincterotomy. They consist of a Teflon catheter containing a continuous wire loop with 2–3 cm of exposed wire exiting at a variable distance from the tip (Fig. 4.5A). In precut sphincterotomes, the cutting wire extends to the tip (Fig. 4.5A). The other end of the wire is insulated and connected to an electrosurgical unit. Over the last decade or so, endoscopists have recognized the need to angle the catheter upward to selectively enter the bile duct.6 Subsequently, prospective randomized trials comparing standard catheters with sphincterotomes have shown a cannulation rate of 84–97% with sphincterotomes compared with 62–67% with standard catheter.7,8 Therefore, in many institutions, sphincterotomes have become the primary cannulation device in ERCP. Currently, sphincterotomes are available with single, double and triple lumens. Double lumen sphincterotomes allow for the introduction of a wire to facilitate cannulation or to accomplish a therapeutic task. Contrast can be injected after removing the wire or by adding a side arm. Triple lumen sphincterotomes allow injection of contrast without removing the wire. Unfortunately, because of the small size of the injection lumen, contrast flow is slow and difficult for the assistant because of the force required during infusion. The use of a small syringe facilitates injection. A sphincterotome is available that incorporates a combination of cutting and balloon stone extraction (Boston Scientific, Natick, MA); however, adding the lumen increases the catheter diameter and tip size which may make cannulation more difficult. When sphincterotomy is performed, a variety of generator currents can be used: cutting, auto-cut, coagulation or blended. Limited data suggest that the use of a pure cutting current is associated with a lower risk of pancreatitis after sphincterotomy9 while the use of an “auto-cut” is associated with a lower risk of bleeding during sphincterotomy. This autocut feature has essentially eliminated the Zipper cut phenomenon after sphincterotomy. When performing pancreatic sphincterotomy, pure “cutting” current is often used to reduce the risk of pancreatic duct injury and subsequent stricture formation. Rotatable sphincterotomes have recently been introduced to offer the endoscopist the ability to change the orientation of the sphincterotomes. Preliminary data suggest that this may be useful in improving cannulation, especially in patients with unusually oriented or distorted papillae,10 or in patients with Billroth II anatomy. Rotatable sphincterotomes may also help orient the cutting wire during sphincterotomy. However, no published data is available to support this theory.

Fig. 4.3 A Cremer cannula (courtesy of Cook Endoscopy, Winston-Salem, NC). B Endoscopic view showing Cremer cannula and minor papilla.

Access sphincterotomes

one port for aspiration of water out of the pancreatic duct during infusion to prevent overfilling of the pancreatic duct and thereby reduce the risk of post procedure pancreatitis.4 Standard water perfused motility recording systems are used for sphincter of Oddi manometry (Figs 4.4B and 4.4C). Recently a micro transducer cath-

Precut or “access” sphincterotomy refers to a variety of endoscopic techniques used to gain access to the bile or pancreatic duct after conventional methods of cannulation have failed (see Chapter 9). Needle-knife and precut sphincterotomes are the two most commonly used devices to gain access into the bile duct. The needleknife was first described by Kees Huibregtse in 1981 and is essentially a bare wire that protrudes 4–5 mm from the end of a Teflon catheter (Fig. 4.5B). Several papers have discussed the use of this device.

Chapter 4 Endoscopes, Guidewires and Accessories

A

B

Duodenal baseline

C

Fig. 4.4 A Endoscopic view showing motility catheter. B Manometry tracing (normal sphincter of Oddi pressure). C Sphincter of Oddi motility recording system.

A

B introduced.12 It has the advantage of having separate lumens for contrast and guidewire. Biliary sphincterotomy can be immediately completed by using the same instrument and is facilitated by having a preloaded slippery wire. Data comparing different precut techniques are limited.13

Guidewires Fig. 4.5 A Standard and precut sphincterotome (courtesy of Cook Endoscopy, Winston-Salem, NC). B Needle-knife sphincterotome (courtesy of Cook Endoscopy, Winston-Salem, NC).

Newer versions include additional lumen for wire (double lumen) and both wire and contrast (triple lumen) introduction. The precut sphincterotome was first reported by Nib Soehendra and the Hamburg group in 1996 (Fig. 4.5A). This sphincterotome allows “papillary roof incision.”11 A double lumen version has been recently

Guidewires are the cornerstone of diagnostic and therapeutic ERCP. During ERCP, guidewires are used for achieving and maintaining access and placing and exchanging devices. Examples include difficult cannulation, sphincterotomy, navigating strictures, stricture dilation, tissue sampling, stent placement, mini-scope placement, and manometery. Ideal guidewire characteristics for gaining access to lumen differ from those for advancement of accessories. Guidewires with slippery and flexible leading tips are generally used to gain access through tight biliary strictures. On the other hand, stiff and taut guidewires are best used for advancement of devices such as biliary 33

SECTION 1 GENERAL TOPICS

stents or dilators. Stiff and taut wires also minimize lateral deviation and facilitate forward axial transmission of forces. Friction can aid in maintaining wire tensions but it hinders both wire and device movement. A variety of guidewires are currently available (Table 4.1) and these vary in materials, length, diameter, and design to optimize performance.14 In general, three guidewire designs are available for ERCP applications: (1) Monofilament wires are designed for rigidity and are made of stainless steel. (2) Coiled wires are stiff and flexible and have an inner monofilament core and outer spiral coil made of stainless steel. Inner core and outer spiral coil provide stiffness and flexibility respectively. Most coiled wires are Teflon painted in order to minimize resistance and are optimal for traversing tortuous biliary strictures because of their improved trackability resulting from combination of stiffness and flexibility. (3) Coated or sheathed wires have a monofilament core made of stainless steel or nitinol and an outer sheath made of Teflon, polyurethane, or another lubricious polymer. The outer sheath material can be designed to improve radiopacity, slipperiness, and electrical insulation properties. Coated wire tip flexibility depends on the taper of the inner core. Many wires have platinum tipped core to improve fluoroscopic visualization. The configuration of the guidewire can be straight or angled (J-shaped) (Fig. 4.6A). Some wires have graduated or continuous markings for visual endoscopic measurement or movement detection. Most wires are only minimally steerable in the radial direction.

Guidewires are advanced under fluoroscopic monitoring through ERCP catheter or sphincterotome that imparts stiffness and direction. Guidewire passage is easier after flushing water through dry or contrast-filled devices because of minimal friction. Moistening of exposed portions of hydrophilic wires prevents drying and sticking. Maintenance of wire position is critical for safe and effective use of over the wire accessories such as dilators and stents. The risk of

B

A

Fig. 4.6 A Straight and angled tip guidewires (courtesy of Boston Scientific, Natick, MA). B Endoscopic view showing the markings on the guidewires.

Wire type/name (manufacturer)

Diameter (inch)

Length (cm)

Core material

Sheath material

Tip material

MONOFILAMENT Axcess 21 (CE) Cope (CE)

0.021 0.018

480 480

Nitinol SS

None None

Platinum Platinum

COILED Standard Wires (CE)

0.018, 0.025, 0.035, 0.038

400–480

SS

Stainless coil, Teflon painted

Stainless tapered core + coil

COATED Tracer (CE) Protector Plus (CE) Roadrunner (CE) Zebra (BS) Jagwirea (BS) Hydra (BS) Glidewire (BS)

0.035 0.035 0.018 0.025, 0.035, 0.038 0.035, 0.025 0.035 0.018, 0.025, 0.035

260–480 480 480 260, 450 450 260, 450 450, 260

Nitinol Nitinol Nitinol Nitinol Nitinol Nitinol Nitinol

Platinum, hydrophilic Platinum Platinum Platinum, endoglide Platinum, hydrophilic Tungsten, hydrophilic Platinum

Geenen Endotorque (CE) Pathfinder (BS) LinearGuideV (O) X wirea (CM)

0.035 0.018 0.035 0.035, 0.025

450 450 270, 450 260, 450

SS Nitinol Nitinol Nitinol

Teflon Teflon Teflon Teflon Teflon Endoglide coating Polyurethane hydrophilic coat on entire length Teflon Endoglide Polytetrafluoroethylene Hydrophilic

Table 4.1 Currently available Guidewires for ERCP applications (adapted with permission from reference no. 14)

a Available in a stiff version. SS = Stainless Steel. CE = Cook Endoscopy, Winston-Salem, NC. BS = Boston Scientific, Natick, MA. CM = ConMed, Utica, NY. O = Olympus America Inc., Lehigh Valley, PA.

34

Platinum Platinum, hydrophilic Hydrophilic Nitinol

Chapter 4 Endoscopes, Guidewires and Accessories

wire displacement can be minimized by using guidewires that have graduated or continuous markings or movement detection printed distance markers and movement guides (Fig. 4.6b). In addition, fixation of the proximal end (outside of the patient) on an immobile accessory device can also lower the risk of wire dislodgement. Currently available guidewire types include conventional, hydrophilic, and “hybrid,” ranging from 0.018 to 0.035 inch in diameter and 260 to 480 cm in length.15 These are summarized in Table 4.1. Wire lengths above 400 cm are used for exchange of devices. Only coated wires should be used during electro-cautery applications. Data is limited regarding the relative efficacy of specific wires for ERCP applications. Clinical experience suggests that coated and hydrophilic wires improve the ultimate success of those ERCP procedures requiring access through difficult papillae or strictures. Completely hydrophilic wires are subject to inadvertent displacement from ducts or strictures and can make the catheter exchange difficult. However, newer combination wires such as Jagwire, Hydra jagwire (Boston Scientific, Natick, MA), FX, X (ConMed, Utica, NY), and Metro (Cook Endoscopy, Winston-Salem, NC) may provide the best combination of a slippery tip with a stiffer shaft (Fig. 4.6a) Limited data suggest that biliary cannulation using a guidewire through a sphincterotome lowers the risk of post-ERCP pancreatitis, presumably because of less pancreatic injection.16 Teflon coated wires are least expensive. Hybrid wires are more user friendly but more expensive. A useful and detailed review of guidewires can be found in a recent Americal Society for Gastrointestinal Endoscopy (ASGE) technology assessment report.14

Wire safety Perforation and failed device placement are the two main wirerelated risks in the pancreas or biliary tree during ERCP. Applying excessive force below a stricture or at an acute angle can result in wire-related perforation. Loss of wire tension or access from a stricture while using rigid devices such as biliary dilators can also result in perforation. Wire-guided sphincterotomy can transmit significant electric current from the cutting wire through standard Teflonpainted guidewires into the bile duct. Intact, coated wires are effectively insulated against transmission of short circuits or induced

currents. All damaged wires are potential sources of dangerous currents.

Exchange assistance devices Multiple devices are frequently required for a successful therapeutic ERCP. Frequently, an exchange or series of exchanges over a previously placed guidewire is required to introduce subsequent device(s). Several exchange assistance devices have been developed by different manufacturers to facilitate exchange of over-the-wire accessories in order to reduce reliance on an expert assistant and to allow the use of a short (260 cm) wire. These devices may reduce fluoroscopy time and increase efficiency.17 Potential problems with exchange assistance devices include a restriction in the choice of accessories, difficulty in re-using the same accessory during the procedure, and cost.

Rapid Exchange Biliary System The Rapid Exchange (RX) Biliary System (Boston Scientific, Natick, MA) is based on a monorail design that provides the endoscopist with control over the guidewire and subsequent exchanges. The system is composed of three integral units: a guidewire locking device (Fig. 4.7A), a specially designed RX catheter, and a 260-cm guidewire. A locking device secures the position of the guidewire during exchange of over-the-wire accessories, advancement of accessories, and manipulation. The locking device can accommodate multiple guidewires that can be secured at any time and thus allow for multiple therapeutic interventions. Cannulation devices (i.e. cannula, sphincterotome) have a proximal open-channel (beginning at 5 to 30 cm from the tip) that allows the guidewire to exit at this point rather than at the hub of the endoscope. Once cannulation is achieved, the wire is separated from the catheter (Fig. 4.7B) and is secured in the guidewire locking device at the suction cap. A variety of RX accessories are available to use with this system. Potential benefits of RX Biliary System include shorter total procedural and post cannulation times and a reduction of fluoroscopy exposure.18 However, the cost may be higher than the standard equipment and the endoscopist may be limited to using RX accessories. Cost-benefit studies using the RX Biliary System are not available.

Fig. 4.7 Rapid exchange system. A Locking device. B Guidewire stripping from the catheter. (A and B Courtesy of Boston Scientific, Natick, MA).

A

B

35

SECTION 1 GENERAL TOPICS

B

A

Fig. 4.8 Fusion system A Fusion catheter. B Biopsy valve with locking mechanism. (A and B Courtesy of Cook Endoscopy, WinstonSalem, NC).

Fusion system This system is made by Cook Endoscopy (Winston-Salem, NC). It consists of either a double lumen catheter or a triple lumen sphincterotome. The design of this system facilitates the exchange of accessories without removing the guidewire or exchanging the initially placed catheter/sphincterotome over the full length of the guidewire. The main difference between this new system and the conventional design is that a side hole is placed at 6 cm from the tip of the catheter (or any accessories from this line of products except the stent introducer system in which the side hole is placed at 2.5 cm) (Fig. 4.8A). The total length of the guidewire is 185 cm and the length of most accessories is 220 cm. To provide proper control of these much shorter accessories and guidewire, the system utilizes a special disposable biopsy valve with a locking mechanism to anchor the guidewire while performing exchanges (Fig. 4.8B). A major advantage of the Fusion system is in the ability to place multiple stents without removing the guidewire. With this system, the guidewire is left within the bile duct across the stricture or papilla, and this facilitates deployment of subsequent stents without concerns about losing access across the stricture. In situations where intervention requires the use of standard length or conventional accessories, a standard length guidewire can be inserted through the end of the catheter or sphincterotome after removing the inner nylon stylet, and exchange can be performed in the usual manner. Controlled data regarding the efficiency with Fusion system is not available.

V-system The Olympus V-system (Olympus America Inc., Lehigh Valley, PA) integrates Olympus endoscopes and endotherapy devices. This design offers the option of guidewire manipulation by the physician or by the assistant and may allow easier exchange of catheters using a short guidewire. The V-endoscope has an increased elevator angle and V-groove that allows the endoscopist to “lock” the wire when the elevator is closed. This endoscope design may also enhance selective biliary cannulation capability. The V-system features a C-Hook, Vmarkings, and V-sheath for device control in addition to the Vgroove on the elevator of the duodenoscope (Fig. 4.9A). The C-Hook attaches the device to the endoscope just below the biopsy port (Fig. 4.9B) and allows a choice of control of the device 36

A

B

Fig. 4.9 V-system A V-scope tip. B Hook. (A and B Courtesy of Olympus America Inc., Lehigh Valley, PA).

by the physician or the assistant. V-markings are present on the proximal portion of all V-system devices. When the V-marking on the accessory device reaches the biopsy port of the endoscope, the tip of the catheter has reached the endoscope elevator V-groove indicating that raising the elevator at that point would lock the guidewire in the V-groove. The V-sheath design allows the guidewire sheath and the injection/handle sheath to be separated offering the choice of control by the endoscopist or the assistant. The V-scope and V-system accessories can also be used with long 0.035″ and smaller guidewires and with ERCP accessories from other device manufacturers. Initial evaluation using this system (V-scope) has shown improved reliability of guidewire fixation;19 however, limited data exist on efficiency of catheter/guidewire exchanges.20

Drainage devices Drainage devices include stents and nasobiliary drains. Stents are used for a variety of purposes and are available in various materials and configurations. Nasobiliary and nasopancreatic drains are infrequently used in the US.

Plastic stents Plastic stents are made of polyethylene or Teflon and are available in varying size, shapes and length for biliary and pancreatic pathologies. A pusher tube is used to place plastic stents over a guidewire with or without a guiding catheter. Delivery systems are available for plastic stents that combine the pushing and guiding catheters. The standard stent delivery system for 10 Fr comprise a 0.035 inch guidewire (480 cm) and a 6 Fr radio-opaque Teflon (260 cm in length)

Chapter 4 Endoscopes, Guidewires and Accessories

guiding catheter with a tapered tip to facilitate cannulation and a pusher tube. Some guiding catheters have two metal rings (placed 7 cm apart) at the distal end that helps in identification and measurement of the stricture length. The pusher tube is made of Teflon (8, 10, and 11.5 Fr) and used for positioning the stent during deployment. Most plastic stents are made of radiopaque polyethylene and are available in sizes varying from 3 to 11.5 Fr. They also vary in length and configuration. There is no inner catheter for the 3–7 Fr stent delivery systems. Straight “Amsterdam” type stents are predominantly used for biliary drainage (Fig. 4.10a). Based on Poiseuille’s law there is a clear relationship between stent diameter and duration of stent patency (Fig. 4.11).21 A straight configuration also appears to improve stent patency. Attempts to improve stent patency by eliminating side holes, changing stent material or coating the inner surface with a hydrophilic substance have generally not been successful.22,23 Double pigtail configurations (Fig. 4.10A) help anchor

A B

the stent to prevent upward or downward migration. These stents are frequently used to maintain drainage in patients with difficult bile duct stones and in some patients with hilar strictures. Single pigtail stents (Fig. 4.10B) are frequently used in the pancreatic duct to prevent inward migration. Limited data suggest that smaller stents (i.e. 3 and 4 Fr) will lead to less damage when used in a normal pancreatic duct and that elimination of side holes and flaps may prolong patency and promote spontaneous migration of pancreatic stents.24 New pancreatic stents have become available recently that are constructed to have running channels and no side holes (GI Supply, Camp Hill, PA). Limited data are available in reference to their superiority over currently used stents.25 Stents are usually removed using snares, baskets and foreign body forceps. Large bore (10 Fr) stents can be removed through the channel of a therapeutic endoscope with the aid of a snare. Smaller stents, i.e. 3 Fr and 5 Fr pancreatic stents can also be removed via the working channel of the endpscope using a foreign body forceps (e.g. rat tooth forceps). The Soehendra stent retriever (Cook Endoscopy, Winston-Salem, NC) consists of a screw-tipped wire-guided device that allows stent removal while maintaining guidewire position. It is also available with an extended tip design to facilitate cannulation. In patients with difficult strictures, maintaining wire access can also be accomplished by using a wire and a snare.26

Self-expandable metal stents

Fig. 4.10 A Straight and double pigtail stents (courtesy of Olympus America Inc., Lehigh Valley, PA). B Single pigtail stent (courtesy of Cook Endoscopy, Winston-Salem, NC).

Patency rate of prostheses

Prostheses diameter*

12F

10F

Multiple 7F

Self-expandable metal stents (SEMS) were introduced to prolong stent patency over plastic stents. SEMS expand to 8–10 mm in diameter and do not occlude from bacterial biofilm. In the US, commonly available SEMS have an open mesh design and include the Wallstent (Boston Scientific, Natick, MA), the Spiral Z-Stent and Zilver stent (Cook Endoscopy, Winston-Salem, NC), and Flexxus (ConMed, Utica, NY) (Table 4.2, Figs 4.12A and 4.12B). SEMS are made of stainless steel or nitinol, a nickel–titanium alloy that provides a high degree of flexibility and is kink resistant. However nitinol is less radiopaque than stainless steel and additional radiopaque (gold or platinum) markers are added to the stents to improve radiopacity in order to facilitate proper positioning during deployment. Covered SEMS are also available. One example is the Wallstent (Boston Scientific, Natick, MA) which has a polymer (Permalune) coating on the inside of the stent except for the proximal and distal 1 cm. This membrane is designed to prevent tumor in growth and prolong stent patency.27 The delivery system for preloaded self-expanding metal stents (SEMS) varies in design (Table 4.2). The wire mesh metal stents are collapsed and constrained on a 6/6.5 Fr introducer catheter by an

7F

1

2

3 4 Patency rate (months)

5

6

7

* 3 French = 1mm

Fig. 4.11 Bar graph showing relationship between stent diameter and the duration of functional patency (adapted from reference #21 with permission © 2004 American Society for Gastrointestinal Endoscopy).

Material Length (cm) Diameter (mm) Stent foreshortening Introducer Diameter (Fr)

Wallstent a (BS)

Luminexx a (CM)

Zilver a (CE)

Elgiloy 4/6/8/10 8/10 Y 7.5/8

Nitinol 4/6/8/10 8/10 N 6/7.5

Nitinol 4/6/8 6, 8, 10 N 7

Table 4.2 Self-expandable biliary metal stents

a According to the manufacturer Magnetic Resonance Imaging compatible. CE = Cook Endoscopy, Winston-Salem, NC. BS = Boston Scientific, Natick, MA. CM = ConMed, Utica, NY.

37

SECTION 1 GENERAL TOPICS

A

A

B

B

Fig. 4.14 A Fluoroscopy image of dilator balloon. B Soehendra dilator (courtesy of Cook Endoscopy, Winston-Salem, NC). Fig. 4.12 Self-expandable metal stent. A Endoscopic view of the stent. B Fluoroscopy image of the stent. B A

A B

Fig. 4.13 A Cytobrush (courtesy of Cook Endoscopy, WinstonSalem, NC). B Fluoroscopy image showing biliary biopsy forceps (arrow).

8/8.5 Fr overlying plastic sheath. Smaller 7/7.5 Fr introducer systems are also available. The entire system is advanced over the guidewire through the endoscope channel and passed under fluoroscopic guidance across the stricture using radiopaque markers. The Wallstent delivery system allows recapture and repositioning of the stent before reaching the 80% marker. Major limitations of currently available SEMS are cost and the difficulty in removing uncovered stents after placement.

Nasobiliary and pancreatic drainage catheters Nasobiliary drainage catheters are used for temporary drainage of the biliary tree and are available as 250 cm long 5 Fr to 7 Fr diameter catheters with 5 or 9 sideports that facilitate drainage flow. Multiple tip configurations are available. Nasopancreatic drainage catheters are 5 Fr in diameter and may be used to drain the main pancreatic duct after sphincterotomy or to irrigate and drain pancreatic pseudocysts. Biliary and pancreatic indwelling drainage catheters are placed over the wire using a 0.035 inch guidewire. A nasal transfer tube is needed for rerouting the tube from the mouth to the nose. A connecting tube is needed for irrigation and drainage.

Tissue sampling devices Brush cytology devices are available as single or multiple lumen systems. Using the single-lumen cytology system, cell loss is inevitable because the brush is pulled back through the whole length of the catheter. It is useful to aspirate bile from the catheter to collect any dislodged cells within the catheter to improve the diagnostic yield. Double-lumen cytology brush systems are preferable (Fig. 4.13a) and allow the guidewire and brush to pass through two 38

Fig. 4.15 A Stent retriever (courtesy of Cook Endoscopy, WinstonSalem, NC). B Endoscopic view showing stent retrieval (arrow).

separate lumens so that access is not lost. In addition, this design minimizes cell loss by eliminating the need to pull back the brush through the entire length of the catheter. Biliary biopsy forceps (Olympus America Inc., Lehigh Valley, PA and ConMed, Utica, NY) are useful for selectively obtaining biopsy specimens from the bile duct under fluoroscopy (Fig. 4.13b).28

Stricture dilation devices In general, pancreaticobiliary dilation can be accomplished using balloons (Fig. 4.14A) or bougies (Fig. 4.14B). Balloon dilators are made of non-compliant polyethylene and are available in different sizes and lengths: 4, 6, 8, or 10 mm in diameter and 2–4 cm long. Balloons are passed over a guidewire through the accessory channel of the endoscope. A radiopaque band proximal to the taper indicates the point of maximal dilation. Soehendra dilators (Cook Endoscopy, Winston-Salem, NC) are standard-shaped bougies that are available in 6–11.5 Fr diameters. These are passed over a guidewire, the 10 Fr and 11.5 Fr size dilator require the use of a large accessory channel. Threaded-Tip “Soehendra” Stent Retrievers have also been used to dilate very tight pancreaticobiliary strictures that otherwise allow only passage of a guidewire. The wire-guided screw-tipped device is used to negotiate high-grade strictures (Figs 4.15A and 4.15B). A modified device is now commercially available as a dilator (Cook Endoscopy, Winston-Salem, NC).

Stone extraction accessories Accessories useful for stone extraction include double-lumen balloon catheters, wire baskets and mechanical lithotriptors. The stone

Chapter 4 Endoscopes, Guidewires and Accessories

extraction balloon (Fig. 4.16A) consists of a 5–6.8 Fr double-lumen catheter with a balloon at the tip (8–18 mm size). Multi-size stone extraction balloons are currently available (8.5, 12, and 15). Prior to insertion into the endoscope it is useful to ensure that the balloon inflates correctly. The balloon catheter can be inserted over a guidewire or directly into the desired duct without guidewire. Stones can also be removed using a wire basket (Fig. 4.16B). The basket is shaped such that the wires open like a trap to engage the stones. Basket function varies depending on the number of wires. Newer design baskets can be advanced over a preplaced wire allowing the basket to reach difficult areas (Trapezoid Basket, Boston Scientific, Natick, MA and Flower basket, Olympus America Inc., Lehigh Valley, PA). The Trapezoid basket has a handle that is designed to provide the endoscopist with the ability to perform mechanical lithotripsy. Unfortunately, the small basket size limits its efficacy in capturing and crushing large (>1.5 cm) stones.

Mechanical lithotriptors Lithotripsy wire baskets facilitate removal of large (>1.5 cm) common duct stones by crushing the stones before extraction. The original

B

A

Soehendra lithotriptor (Cook Endoscopy, Winston Salem, NC) requires cutting the handle of the basket and removing the endoscope prior to stone fragmentation. This device consists of a 14 Fr metal sheath and a self-locking crank handle (Fig. 4.17A). The lithotriptor can be used with most standard stone extraction baskets. Another mechanical lithotriptor is a pre-assembled through-thescope lithotripsy basket which can be inserted through a therapeutic duodenoscope (Fig. 4.17B and 4.17C) (BML lithotripsy baskets by Olympus Medical Inc., Lehigh Valley, PA). This device is available in disposable and reusable versions. A single-piece disposable mechanical lithotriptor with the basket, metal sheath and crank handle is also available (Monolith, Boston Scientific, Natick, MA). In one report, the disposal lithotripter was easy to use and its performance was comparable to a standard reusable lithotriptor.29

Cholangioscopes Duodenoscope-assisted cholangiopancreatoscopy (Figs 4.18A and 4.18B) allows for the direct visualization of the biliary and pancreatic ducts. In the past, a dedicated mother–daughter system was required. Currently, a variety of electronic and fiberoptic miniscopes are available that can be passed through a 4.2 mm channel therapeutic duodenoscope for direct visualization of the biliary and pancreatic duct.30–31 These instruments are now available in 8 Fr and 9 Fr sizes.32 They have a small working channel (1.2 mm) that allows passage of small diameter forceps and fibers for tissue acquisition and for the application of laser and electrohydraulic lithotripsy. Limitations include the fragility of these devices, the small working channel and the need for two endoscopists (one for each endoscope). Recently, a “homemade” support system was reported, allowing one endoscopist to use the system.33 These devices are discussed in more detail in Chapters 20 and 21.

Ultrasound probes

Fig. 4.16 A Endoscopic view of stone extractor balloon. B Stone extractor basket (courtesy of Olympus America Inc., Lehigh Valley, PA).

Increased availability of high frequency ultrasound probes have made it possible for experts to use these devices for evaluating biliary strictures. Endoscopic ultrasound probes are introduced free hand or over the wire (Fig. 4.19) through the working channel of the duodenoscope allowing for “real time” evaluation of biliary strictures and surrounding vascular structures. Limited data suggest that these

C

A B

Fig. 4.17 A Soehendra mechanical lithotriptor Handle (courtesy of Cook Endoscopy, Winston-Salem, NC). B Through the scope mechanical lithotriptor (courtesy of Olympus America Inc., Lehigh Valley, PA). C Fluoroscopy image of mechanical lithotriptor. 39

SECTION 1 GENERAL TOPICS

B

A

Fig. 4.20 Endoscopic view showing identification of pancreatic duct orifice using methylene blue spray (arrow). Fig. 4.18 A Cholangioscope (courtesy of Pentax Medical, Montvale, NJ). B Fluoroscopy image of cholangioscope. “reverse” sphincterotomes are available for use in patients with Billroth II type anatomy. In most patients, however, sphincterotomy can be performed using standard accessories such as needle-knife. The endoscopist should make sure that appropriate accessories are available before initiating ERCP.

Single vs reusable accessories

Fig. 4.19 Intraductal ultrasound probe (courtesy of Olympus America Inc., Lehigh Valley, PA).

probes can enhance our ability to distinguish between benign and malignant biliary strictures.34 Patient selection, operator experience and cost continue to be limiting factors before wider use of this technology is advocated.35

OTHER “ACCESSORIES” Pharmacologic and chemical agents are not considered accessories in the classic definition. However, secretin injection, with or without the use of methylene blue has been reported to facilitate cannulation of the pancreatic duct, especially in patients with pancreas divisum (Fig. 4.20).36,37 These agents are also helpful in identifying the pancreatic duct opening after biliary sphincterotomy or endoscopic ampullectomy. Glucagon and hyoscyamine often are used to relax motility and have been found to be of similar efficacy but were never compared with placebo in a randomized controlled trial.38

Accessories for use in patients with altered anatomy Standard accessories are designed for use with a duodenoscope and are usually 200 to 260 cm in length. However, in patients with surgically altered anatomy such as Roux-en-Y gastroenteric anastomosis, the standard ERCP scope may not be able to reach the ampulla, and the use of a longer scope such as pediatric colonoscope or enteroscope may be needed. Some accessories such as balloons, sphincterotomes and push catheters are available in longer versions for this purpose (Cook Endoscopy, Winston-Salem, NC). In addition, 40

The choice between single use, disposable and reusable accessories for ERCP depends on various medical and economic factors.39 Additionally, there are liability issues that may result from reusing single use devices. Several studies have evaluated reuse of ERCP accessories. Lee et al. found that a reusable sphincterotome could be safely and efficiently used.40 A disposable sphincterotome was costeffective after 2.2 uses and a reusable sphincterotome after 7.9 uses. A recent study also found reusable sphincterotomes and stone extraction baskets to be safe and cost-effective when compared with single-use devices.41 According to a recent ASGE guideline on disposable endoscopic accessories, the selection of reusable or disposable devices must be based upon local purchase costs, reprocessing costs and abilities, storage and disposable facilities, and personal preferences.39

Storage of accessories A special room with a fluoroscopy unit offers the advantage of a better floor plan, organization and ready access to stored accessories that are required for the procedure (see Chapter 2). The room is organized to facilitate the use of needed equipment such as endoscope/processor, monitors, and the fluoroscopy unit. The fluoroscopy and endoscopy monitors should be placed side by side at the endoscopist eye level to avoid the need for repeated turning, which can displace scope position and additionally puts body strain on the endoscopist. The dedicated ERCP room should be large enough to house and store accessories in cabinets that are properly labeled and easily accessible to the assistant at the time of procedure. Easily retrievable accessories at the time of procedure will increase procedure efficiency by reducing time lost in looking for accessories when needed.

RADIATION EXPOSURE ERCP relies on the use of fluoroscopy but the risks associated with radiation exposure to patients and to personnel during the procedure are not well documented (see Chapter 3). A recent prospective study suggested that personnel as well as patients may be exposed to radiation doses that equate to an estimated additional lifetime fatal cancer

Chapter 4 Endoscopes, Guidewires and Accessories

risk of 1 in 3500–7000.42 Radiation exposure to the personnel is proportionally related to the distance and duration of fluoroscopy. Higher voltage and lower current for fluoroscopy is used to minimize radiation exposure to the personnel. Various other strategies that are used to minimize radiation exposure include protective lead shielding, the use of digital imaging, and an “under-couch” X ray emitter tube. Doubling the distance from the source reduces the radiation dose received by a factor of 4. Therefore, the operator should be vigilant in avoiding prolonged use of fluoroscopy and should stand as far back as possible from the patient during exposure. Exposure to patients particularly those at high risk such as young patients and pregnant women (discussed further in Chapter 23) can be minimized by shielding the pelvic area with a lead-lined apron. In addition, obtaining “hard copy” fluoroscopic images in lieu of spot radiographs can further reduce exposure.43 Ongoing quality assurance programs should be instituted with hospital radiation safety officers.

Stability

Incremental innovation • Simpler • Cheaper

Rapid adoption

Learning curve: safety and efficacy issues Time

CONCLUSIONS

Fig. 4.21 Graph illustrating the natural history of an endoscopic device (adapted from reference # 44 with permission © 2004 American Gastroenterological Association).

The natural history of an endoscopic device involves an initial learning curve followed by rapid adoption and then a relatively slow phase of stability followed by an incremental innovation (Fig. 4.21).44 ERCP accessories have also followed this natural history. Major advances have been made over the last decade. In general, many new accessories are in fact evolutions of old ones as a result of innovations by endoscopists in collaboration with product engineers and specialists. In addition, several products developed for other intra-luminal interventions such as vascular, cardiac and urologic diseases have similar applications in ERCP. Guidewires and expandable metal stents are examples. Therefore, many “new” accessories are in fact

new applications or modifications of available products. This means that many products are approved using 510K pre-market notification to the Food and Drug Administration. Therefore, many products may not have rigorous pre-marketing evaluation and their use may be based on word of mouth, personal experience or at best, case series. Major limitations continue to be cost compared to reimbursement and the lack of cost-effectiveness and pre-marketing studies.45,46

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Law N and Freeman ML. ERCP by using a prototype obliqueviewing endoscope in patients with surgically altered anatomy. Gastrointest Endosc 2004; 59:724–728. Igarashi Y, Tada T, Shimura J, et al. A new cannula with a flexible tip (swing tip) may improve the success rate of endoscopic retrograde cholangiopancreatography. Endoscopy 2002; 34:628–631. Laasch HU, Tringali A, Wilbraham L, et al. Comparison of standard and steerable catheter for bile duct cannulation in ERCP. Endoscopy 2003; 35:669–674. Sherman S, Troiano FP, Hawes RH, Lehman GA. Sphincter of Oddi manometery: decreased risk of clinical pancreatitis with the use of modified aspirating catheter. Gastrointest Endosc 1990; 36:462–466. Wehrmann T, Stergiou N, Schmitt T, et al. Reduced risk for pancreatitis after endoscopic micro transducer manometery of the sphincter of Oddi: A randomized comparison with the perfusion manometery technique. Endoscopy 2003; 35: 472–477. Rossos PG, Kortan P, Haber G. Selective common bile duct cannulation can be simplified by the use of a standard papillotome. Gastrointest Endosc 1993; 39:67–69. Schwacha H, Allgaier HP, Deibert P, et al. A sphincterotomebased technique for selective transpapillary common bile duct cannulation. Gastrointest Endosc 2000; 52: pp 387–391. Cortas GA, Mehta SN, Abraham NS, et al. Selective cannulation of the common bile duct: a prospective randomized trial comparing

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14.

15. 16. 17.

standard catheters with sphincterotomes. Gastrointest Endosc 1999; 50:775–779. Elta GH, Barnett JL, Wille RT, et al. Pure cut electrocautery current for sphincterotomy causes less post-procedure pancreatitis than blended current.Gastrointest Endosc. 1998 Feb; 47(2):149–153. Shah RJ, Antillon MR, Springer EW, et al. A new rotatable papillotome (RP) in complex therapeutic ERCP: indications for use and results. [abstract] Gastrointest Endosc (2003) 57: AB206. Binmoeller KF, Seifert H, Gerke H, et al. Papillary roof incision using the Erlangen-type pre-cut papillotome to achieve selective bile duct cannulation. Gastrointest Endosc (1996) 44:689–695. Uchida N, Tsutsui K, Kamata H, et al. Precutting using a noseless papillotome with independent lumens for contrast material and guidewire. J Gastroenterol Hepatol 2005; 20:947–950. Al-Kawas FH. Biliary access during endoscopic retrograde cholangiopancreatography: How to precut and a word of caution! J Gastroenterol Hepatol 2005; 20:805–806. American Society of Gastrointestinal Endoscopy (ASGE). Guidewires in gastrointestinal endoscopy. Gastrointest Endosc 1998; 47:579–583. Jacob L, Geenen JE. ERCP guide wires. Gastrointest Endosc 1996; 43:57–60. Lella F, Bagnolo F, Colombo E, et al. A simple way of avoiding post-ERCP pancreatitis. Gastrointest Endosc 2004; 59:830–834. Farrell RJ, Howell DA, Pleskow DA. New technology for endoscopic retrograde cholangiopancreatography: improving 41

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18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30. 31. 32.

42

safety, success, and efficiency. Gastrointest Endoscopy Clin N Am 2003; 13:539–559. Aliperti G, Branch S, Geisman R, et al. Comparison of new rapid exchange technique with standard device during ERCP. A multicenter trial. Digestive Disease Week, May 16–19, Orlando, FL. Beilstein MC, Ahmad NA, Kochman ML, et al. Initial evaluation of a duodenoscope modified to allow guidewire fixation during ERCP. Gastrointest Endosc 2004; 60:284–287. Joyce AM, Ahmad NA, Kochman ML, et al. Multicenter comparative trial of the V-System for therapeutic ERCP. Gastrointest Endosc 2005; 61:AB208. Siegel JH, Pullano W, Kodsi B, et al. Optimal palliation of malignant bile duct obstruction: Experience with endoscopic 12 French prostheses. Endoscopy 1988; 20:137–141. Catalano M, Geenen J, Lehman G, et al. Tannenbaum: Teflon stents versus traditional polyethelene stents for treatment of malignant biliary stricture. Gastointest Endosc 2002; 55: 354–358. Costamagna G, Mutignani M, Rotondano G, et al. Hydrophilic hydromer-coated polyurethane stents versus uncoated stents in malignant biliary obstruction: a randomized trial. Gastrointest Endosc. 2000; 51(1):8–11. Rashdan A, Fogel EL, McHenry L Jr, et al. Improved stent characteristics for prophylaxis of post-ERCP pancreatitis. Clin Gastroenterol Hepatol. 2004; 2(4):322–329. Raju GS, Gomez G, Xiao SY, et al. Determinants of pancreatic injury induced by short-term indwelling stents and modulation of the same by a novel stent design. Gastrointestinal Endoscopy 2004; 59(5):106. Tarnasky PR, Morris J, Hawes RH, et al. Snare beside-a-wire biliary stent exchange: a method that maintains access across biliary strictures. Gastrointest Endosc 1996; 44:185–187. Isayama H, Komatsu Y, Tsujino T, et al. A prospective randomized study of “covered” versus “uncovered” diamond stents for the management of distal malignant biliary obstruction. Gut. 2004; 53(5):729–734. Tamada K, Higashizawa T, Tomiyama T, et al. Ropeway-type bile duct biopsy forceps with a slit for a guidewire. Gastrointest Endosc 2001; 53:89–92. Sorbi D, Van Os EC, Aberger FJ, et al. Clinical application of a new disposable lithotripter: a prospective multicenter study. Gastrointest Endosc 1999; 49:210–213. Shim CS, Neuhaus H, Tamada K. Direct cholangioscopy. Endoscopy 2003; 35:752–758. Kodama T, Tatsumi Y, Kozarek RA, et al. Direct pancreatoscopy. Endoscopy 2002; 34:653–660. Kodama T, Tatsumi Y, Sato H, et al. Initial experience with a new peroral electronic pancreatoscope with an accessory channel. Gastrointest Endosc. 2004; 59:895–900.

33. Farrell JJ, Bounds BC, Al-Shalabi S, et al. Single-operator duodenoscope-assisted cholangioscopy is an effective alternative in the management of choledocholithiasis not removed by conventional methods, including mechanical lithotripsy. Endoscopy. 2005; 37(6):542–547. 34. Levey MJ, Vasquez-Sequerios E, Wiersema MJ. Evaluation of pancreatobiliary ductal system by intraductal US. Gastrointest Endosc 2002; 55:397–408. 35. Jha R, Al-Kawas FH. Nothing quite new is perfect. How good is IDUS in patients with isolated biliary strictures? Am J Gastroenterol 2004; 99:1690–1691. 36. Devereaux BM, Fein S, Purich E et al. A new synthetic porcine secretin for facilitation of cannulation of the dorsal pancreatic duct at ERCP in patients with pancreas divisum: a multicenter, randomized, double-blind comparative study. Gastrointest Endosc 2003; 57:643–647. 37. Park SH, de Bellis M, McHenry L et al. Use of methylene blue to identify the minor papilla or its orifice in patients with pancreas divisum. Gastrointest Endosc 2003; 57:358–363. 38. Lahoti S, Catalano MF, Geenen JE, et al. A prospective, doubleblind trial of L-hyoscyamine versus glucagon for the inhibition of small intestinal motility during ERCP. Gastrointest Endosc 1997; 46:139–142. 39. ASGE Technology Status Evaluation Report: disposable endoscopic accessories. Gastrointest Endosc 2005; 62: 477–479. 40. Lee RM, Vida F, Koarek RA, et al. In vitro and in vivo evaluation of a reusable double-channel sphincterotome. Gastrointest Endosc 1999; 49:477–482. 41. Prat F, Spieler JF, Paci S, et al. Reliability, cost-effectiveness, and safety of reuse of ancillary devices for ERCP. Gastrointest Endosc 2004; 60:246–252. 42. Naidu LS, Singhal S, Preece DE, et al. Radiation exposure to personnel performing endoscopic retrograde cholangiopancreatography. Postgrad Med J 2005; 81: 660–662. 43. Axelrad AM, Fleischer DE, Strack LL, et al. Performance of ERCP for symptomatic choledocholithiasis during pregnancy: techniques to increase safety and improve patient management. Am J Gastroenterol 1994; 89(1): 109–112. 44. Pasricha PJ. The future of therapeutic endoscopy. Clin Gastroenterol Hepatol. 2004; 2(4):286–289. 45. Narain MA, Cockel R. How should endoscopic accessories be selected: trial and error? Gut 2000; 46:305–306. 46. Ganz RA. The development and implementation of new endoscopic technology: what are the challenges? Gastrointest Endosc 2004; 60:592–598.

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Sedation and Analgesia for ERCP Gregory Zuccaro Jr

INTRODUCTION From the technical perspective, endoscopic retrograde cholangiopancreatography (ERCP) is unlike routine upper endoscopy and colonoscopy. The instrument itself is side viewing rather than forward viewing. The procedure goal is not to simply reach the cecum or duodenum, but rather to cannulate small openings with even smaller devices. The time to completion is often significantly longer. We now require trainees to spend extra time acquiring these advanced skills before we consider them competent to perform this demanding procedure. However, in most units, sedation and analgesia is provided in a fashion similar to routine procedures. This chapter will address issues of sedation and analgesia for ERCP, with emphasis on those aspects that might distinguish it from routine endoscopy. An increasing number of endoscopists have chosen to have another provider (i.e. a nurse anesthetist or anesthesiologist) provide sedation for their patients, including ERCP. In some units, deep sedation (defined below) is administered, and in others general anesthesia is routine. The comments in this chapter are directed toward those units and endoscopists that provide sedation and analgesia themselves.

PHYSIOLOGY OF SEDATION AND ANALGESIA FOR ERCP As endoscopists we describe the sedation and analgesia we provide as “conscious sedation.” Not only is that term oxymoronic, but it further incorrectly implies that all sedation and analgesia for endoscopy is the same. To explore this fully, it is essential to review the American Society of Anesthesiologists’ statement on the Continuum of Sedation.1 In this statement, four discrete levels of sedation are described (Table 5.1). For most routine endoscopy, it is assumed that what we incorrectly and imprecisely refer to as conscious sedation actually corresponds to the ASA’s category of moderate sedation. However, note the differences between moderate sedation, and the next category, referred to as deep sedation. In moderate sedation, the patient is able to make a “purposeful” response to verbal or verbal plus gentle tactile stimulation; for example, the patient might be sleeping, but arouses with calling of his/her name or gentle tap on the shoulder, and can give a “thumbs up” or other positive response when asked. Due to the length and difficulty of some ERCP procedures, the level of sedation is often further along the continuum. In the definition for deep sedation, repeated or even painful stimulation may be necessary to obtain a response. Many endoscopists will admit that for at least part of the time, their ERCP patients’ responsiveness better

fits the deep rather than moderate category. We have found that, during serial assessments of level of sedation during ERCP, 85% of patients are deeply sedated for a portion of the procedure.2 Obviously, responsiveness alone during an ERCP procedure is not of high importance, in that the patient’s cooperation or movement is not necessary to complete the procedure. Rather, it is the cardiopulmonary correlates of this level of responsiveness that are essential to consider. It must be recognized that sedation is a continuum, and that it is impossible for the endoscopist to target a specific level of sedation with accuracy. More frequently, patients undergoing sedation for gastrointestinal endoscopy may go from minimal to moderate to deep sedation during the same procedure. A tenet of the ASA guidelines is that skills must be present to rescue patients from a level of sedation deeper than the intended target; i.e. if moderate sedation is the goal, skills must be present to effectively manage any situation that might arise in deep sedation, thereby bringing the patient back to a state of moderate sedation. Similarly, if the goal is provision of deep sedation, skills must be present to effectively manage any situation that might arise in general anesthesia.

SAFETY OF SEDATION AND ANALGESIA Before we discuss the specific actions appropriate for deep sedation during ERCP, we should consider what is known about the safety of our sedation practice. It may be argued that the safety of existing endoscopic practice is not entirely known. Our colleagues in anesthesiology have devoted considerable time defining the safety of general anesthesia, and it is helpful to consider their literature as a prelude to analyzing ours. Death does occur as a result of anesthesia. Prior to the 1980s, there were approximately 2 deaths per 10 000 anesthesias administered. The Institute of Medicine has asserted that this rate has fallen to approximately 1 death per 200 000 to 300 000 anesthesias administered.3 This dramatic change is attributed to improved monitoring, development and implementation of practice guidelines, and other systematic approaches to reducing errors.4–7 To corroborate this, Legasse reviewed mortality rates from anesthesia published by 21 different investigators, and further examined anesthesia experience in a suburban vs urban hospital system between 1992 and 1994. Preventable deaths persist despite an ongoing quality improvement process. Peer review determined that human error contributed to 2.6% of deaths in the suburban system, and 4.7% of deaths in the urban hospital system.8 Not all deaths related were to error; among other factors patients’ preoperative ASA physical status (Box 5.1) correlated with anesthesia mortality.9 A few conclusions may be drawn from reviewing the anesthesia literature: • Morbidity and mortality rates, and factors that contribute to them, can be identified in the literature. 43

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Minimal sedation (anxiolysis)

Moderate sedation/analgesia (“conscious sedation”)

Responsiveness

Normal response to verbal stimulation

Purposeful response to verbal or tactile stimulation

Airway

Unaffected

No intervention required

Spontaneous Ventilation Cardiovascular Function

Unaffected Unaffected

Adequate Usually maintained

Deep sedation/analgesia

General anesthesia

Purposeful response following repeated or painful stimulation Intervention may be required May be inadequate Usually maintained

Unarousable even with painful stimulus Intervention often required Frequently inadequate May be impaired

Table 5.1 ASA levels of sedation (reproduced with permission from the American Society of Anesthesiologists)

Conventional sedation

BOX 5.1 ASA PHYSICAL CLASSIFICATION SYSTEM

10

Silvis Quine11 Arrowsmith12 Sieg13

(reproduced with permission from the American Society of Anesthesiologists)

Death

NR 0.07% 0.5% 0.008%

0.001% 0.03% 0.03% 0%

0.3% 0.2% 0.3% 0.38%

0 0 0 0

Propofol Walker37 Rex38 Huss39 Clark40

Class 1: Patient has no organic, physiologic, biochemical or psychiatric disturbance. The pathologic process for which operation is to be performed is localized and does not entail systemic disturbance. Class 2: Mild to moderate systemic disturbance caused either by the condition to be treated surgically or by other pathophysiologic processes.

Adverse effects

Table 5.2 Large case series reflecting mortality and severe cardiopulmonary adverse eventsa related to sedation and analgesia for endoscopy a

including aspiration, laryngospasm, respiratory arrest.

Class 3: Severe, systemic disturbance or disease from whatever cause, even though it may not be possible to define the degree of disability with finality. Class 4: Severe systemic disorders that are already life threatening, not always correctable by operation. Class 5: The moribund patient who has little chance of survival but is submitted to operation in desperation.

• As expected, sicker patients are at increased risk of adverse outcomes from anesthesia. • Morbidity and mortality rates can be improved with better monitoring, training, and implementation of practice guidelines and systems to reduce error. • Despite all efforts to improve anesthesia’s safety record, human error continues to cause death. How do endoscopists fare with respect to sedation and analgesia? Considering the millions of endoscopic procedures performed every year, safety data for sedation and analgesia are relatively scant (Table 5.2). Most clinical series and controlled trials focus on objective endpoints such as oxygen desaturation, use of reversal agents, or subjective endpoints like patient satisfaction. Many of these studies are not large enough to allow relevant observations on morbidity and mortality. In the 1974 ASGE endoscopy survey, three deaths were attributed to sedation (0.001%).10 In the early 1990s Quine surveyed 36 hospitals where upper GI endoscopic procedures were performed and reported death likely attributable to sedation in 0.03%, and 44

cardiopulmonary arrest in 0.07%. Midazolam and diazepam were equally likely to have been the benzodiazepine utilized. There was a strong correlation between higher doses of benzodiazepines and lack of patient monitoring with adverse outcomes.11 Arrowsmith analyzed data from over 21 000 procedures, and determined a death rate of 0.03% related to sedation and analgesia and 0.5% due to cardiorespiratory arrest.12 Complications were similar with midazolam and diazepam. In distinction, Sieg et al. found no deaths and 16 significant cardiopulmonary adverse events related to sedation (0.008%) among 190 000 EGD and colonoscopy procedures performed in several facilities.13

PRACTICE GUIDELINES FOR SEDATION AND ANALGESIA BY NON-ANESTHESIOLOGISTS The American Society of Anesthesiologists have developed practice guidelines for the provision of sedation and analgesia by nonanesthesiologists, which may apply to all settings outside the operating room, including the emergency department, pulmonary and cardiology suites, and the gastroenterology lab.14 These guidelines were developed by a rigorous analytic process, in an attempt to create evidence-based guidelines. A series of statements regarding all aspects of care for sedated patients was generated, focusing on a clinical intervention and the desired outcome (example: availability of an individual solely dedicated to patient monitoring and safety improves clinical efficacy and/or reduces adverse outcomes). Then, the available evidence from the literature for each statement was

Chapter 5 Sedation and Analgesia for ERCP

judged as supportive (sufficient information from adequately designed studies to describe a statistically significant relationship between an intervention and a clinical outcome), suggestive (evidence from case reports and descriptive studies provides a directional assessment of the relationship between an intervention and clinical outcome, but the type of information does not permit a statistical assessment of significance), equivocal (while studies exist, no clear direction can be determined for clinical outcomes related to an intervention), inconclusive (while studies exist they are not useful to judge a relationship between an intervention and a clinical outcome), insufficient (too few studies to assess a relationship) and silent (no studies were identified). In addition to an assessment of the literature, a group of consultants from all specialties administering sedation was assembled, and their opinion sought on the validity of each of the statements, rated on a scale of 1 (strongly disagree) to 5 (strongly agree). Summarized below is a portion of the literature assessment, consultant opinion, and recommendations for moderate and deep sedation for each aspect of patient care discussed in the ASA guidelines, followed by selected comments, focusing specifically on those aspects most relevant to ERCP:

airway which respond to mechanical and chemical stimuli by affecting tone of the upper airway muscles; this mechanism may help to prevent aspiration. The second influence on upper airway muscles is related to the level of wakefulness of the patient (e.g. snoring reflects an increased airway resistance). Agents used in moderate or deep sedation affect the upper airway muscles more than the diaphragm and produce more depressant effects on airway function than on diaphragmatic function.21–23 Topical anesthetics may contribute to airway obstruction by removing airway mediated reflex brainstem stimulation.24 Given the potential for ventilatory problems surrounding the upper airway, the ASA as well as individual practitioners have focused considerable attention on recognition of patients who are at greater risk of airway failure before any sedative or analgesic agent is administered.14 This evaluation is intended to identify patients in whom positive pressure ventilation, with or without tracheal intubation, may be difficult or impossible. The patient history should identify prior problems with anesthesia or sedation, including difficult airway. Patients with sleep apnea or habitual stridorous snoring are also at high risk for airway problems related to sedation. Other risk factors include advanced rheumatologic or osteoarthritic cervical spine disease, and chromosomal abnormalities such as trisomy 21. Head and neck findings potentially associated with difficulty in positive pressure ventilation include a short neck with limited neck extension, decreased hyoid-mental distance (55 years and a history of snoring.25 The presence of any of these findings on history or physical examination does not necessarily imply that only an anesthesiologist may safely provide sedation or analgesia for endoscopy; rather, they are signals that the use and amount of sedation, type of procedure contemplated, or other factors might be modified to minimize risk to the patient. In extreme examples, or when there is significant doubt regarding safety, involvement of an anesthesiologist is reasonable.

Patient evaluation Statement:

Pre procedure patient evaluation improves clinical efficacy and/or reduces adverse outcomes. Literature: Insufficient Consultants: Strongly agree Summary of recommendations: Elements of the pre-sedation history should be established prior to the procedure, including abnormalities of any major organ system, previous experiences with sedation/anesthesia/surgery, current medications, history of allergic reactions, fasting interval prior to the procedure or test, and history of tobacco, alcohol, or substance abuse. Elements of the physical exam include vital signs, auscultation of heart and lungs, evaluation of the airway, head and neck. Laboratory testing should be guided by the patient’s underlying conditions, the procedure to be performed, and the likelihood that results of any test might influence the management of sedation. Comments: The airway consists of those structures through which air passes during ventilation, from the nose to the alveoli. A detailed discussion of the anatomy, physiology and response to sedation of the entire airway is beyond the scope of this review. There are, however, salient facts with which individuals administering sedation and analgesia must be familiar. Adverse outcomes in patients receiving sedation and analgesia are frequently due to airway difficulties.15–17 In particular, the upper airway is the “weak link” where airway obstruction is most likely to occur. With sedation, obstruction of the airway may occur due to the tongue falling posteriorly, causing obstruction at the level of the oropharynx.18,19 Analysis of sedated patients identified decreased diameter of the pharynx at the level of the soft palate and epiglottis as a potential cause of airway obstruction.20 Airway patency is controlled by a complex neuromuscular system. There are two main influences on the control of upper airway muscles. The first involves receptors throughout the upper and lower

Pre procedure preparation Statement:

Pre procedure patient preparation (e.g. counseling, fasting) improves clinical efficacy and/or reduces adverse outcomes. Literature: Insufficient Consultants: Agree for moderate sedation, strongly agree for deep sedation 45

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Summary of recommendations: Informed consent should be obtained in all cases. Patients should fast for the appropriate time preprocedure so as to ensure complete gastric emptying. Patients receiving sedation should be aware of the proscription against driving while the effects of sedation persist. Post-procedure instructions should be discussed prior to sedation and written instructions provided.

Nevertheless, this is a cumbersome technique not typically utilized in gastrointestinal endoscopy. Capnography is based on the principle that carbon dioxide absorbs light in the infrared region of the electromagnetic spectrum. Quantification of the absorption leads to the generation of a curve, which represents a real-time display of the patient’s respiratory activity (Fig. 5.1A–5.1C). Capnography has been utilized to allow the safe titration of propofol by a qualified gastroenterologist during ERCP and EUS.27 Bispectral index (BIS) monitoring represents a complex mathematical evaluation of electroencephalographic parameters of frontal cortex activity, corresponding to varying levels of sedation. The BIS scale varies from 0 to 100 (0, no cortical activity or coma; 40–60, unconscious; 70–90, varying levels of conscious sedation, 100, fully awake). Theoretically this index should reflect the same level of sedation regardless of the medications used, except for ketamine. In a preliminary observational study, involving 50 patients undergoing ERCP, colonoscopy, and upper endoscopy, BIS levels were found to correlate with a commonly used score for the degree of sedation.28 A BIS range of 75–85 demonstrated a probability of >96% that the patient would exhibit an acceptable sedation score. However, there was increasing variability of the BIS score with deeper levels of sedation. Additionally, there was no correlation between the BIS score and standard physiologic parameters such as pulse oximetry, blood pressure or heart rate. The BIS algorithm employed for this study was validated only for deeper levels of sedation, and therefore, may not be a sensitive indicator of moderate levels of sedation and analgesia that are utilized during endoscopy. Although only pulse oximetry is currently routinely utilized, these other advanced monitoring techniques merit further study, particularly given the increased frequency of undertaking deep sedation for endoscopic procedures.

Monitoring Statement:

Patient monitoring (i.e. level of consciousness, respiratory function, hemodynamics) at regular intervals improves clinical efficacy and/or reduces adverse outcomes. Literature: Insufficient Consultants: Strongly agree Summary of recommendations: Monitoring of patient response to verbal commands (for moderate sedation) or for stronger stimuli (for deep sedation) should be routine. All patients should be monitored by pulse oximetry. Ventilatory function should be monitored by observation and/or auscultation. Blood pressure and pulse should be monitored at 5-minute intervals during the procedure. EKG monitoring should be performed in all patients undergoing deep sedation. Comments: Just as has occurred in the field of anesthesiology, automated advance monitoring techniques have been increasingly utilized in gastrointestinal endoscopy. Pulse oximetry has become a de facto standard of care during sedation and analgesia for endoscopy, owing to the evidence that clinical observation alone is inaccurate in the detection of hypoxemia and that supplemental oxygen can minimize the degree of desaturation and hopefully its deleterious effects. To date, neither pulse oximetry nor supplemental oxygen administration has yet been shown to decrease the severity or incidence of cardiopulmonary complications. It is important to point out that pulse oximetry does not measure alveolar hypoventilation, which is measured by hypercapnea or a rise in arterial carbon dioxide pressure. Furthermore, it must be remembered that a pulse oximeter is not an apnea monitor; the early stages of significant hypoventilation may be concurrent with a normal pulse oximetry, particularly if the patient is receiving supplemental oxygen. Although oxygen administration may prevent hypoxemia and its deleterious effects, it will not detect the development of hypercapnea. Deleterious consequences of alveolar hypoventilation include myocardial depression, acidosis, intracranial hypertension, narcosis, and arterial hypertension or hypotension. Transcutaneous CO2 monitoring (PtcCO2) is a non-invasive method for measuring arterial CO2. An electrode is placed on the skin, which is heated to “arterialize” the microcirculation. CO2 then diffuses through the skin and into an electrolyte solution between the skin/electrode interface, which produces carbonic acid. A pH reading is then rendered and the CO2 value is obtained via the Henderson-Hasselbach equation. Nelson et al. utilized this technique in 395 patients undergoing ERCP and concluded that it did prevent severe CO2 retention better than standard monitoring.26 46

Availability of an individual responsible for patient monitoring Statement:

Availability of an individual who is dedicated solely to patient monitoring and safety improves clinical efficacy and/or reduces adverse outcomes. Literature: Silent Consultants: Agree for moderate sedation, strongly agree for deep sedation Summary of recommendations: An individual (not the endoscopist) should be present to monitor the sedated patient. During deep sedation, this person should have no other responsibilities. For moderate sedation, this individual may perform minor, interruptible tasks provided that adequate mechanical and personal monitoring is maintained. Comments: Fundamental to this discussion is the choice each unit makes as to the level of sedation they provide. If a unit contends that they provide moderate sedation, then their patients should meet those criteria, particularly with respect to level of responsiveness. If a unit

Chapter 5 Sedation and Analgesia for ERCP

A mmHg

60 30 0

CO2

B mmHg

60 30 0 CO2

C

V mmHg

60 30 0

CO2

SPO2

Fig. 5.1 A Capnography tracing reflecting normal respiration. B Capnography tracing showing an interruption in regular respiration, followed by resumption of normal breathing. C Simultaneous EKG, capnography and pulse oximetry tracings.

acknowledges deep sedation, then the appropriate level of monitoring must take place, both personal and automated.

Anesthetic induction agents used for sedation and analgesia (e.g. propofol) Statement:

Intravenous sedation/analgesic medications specifically designed to be used for general anesthesia (e.g. propofol) improve clinical efficacy and/or reduce adverse outcomes. Literature: Suggestive for moderate sedation, insufficient for deep sedation Consultants: Equivocal Summary of recommendations: Patients receiving propofol should be monitored as for deep sedation, even if moderate seda-

tion is the target level. Practitioners should be qualified to rescue patients from any level of sedation, including general anesthesia. Comments: Propofol is a highly lipophilic compound formulated in a glycerol, egg phosphatide and soybean emulsion. It is a substituted phenolic compound not related structurally to barbiturates, narcotics, or benzodiazepines. Due to its lipophilic nature, immediately upon administration it distributes first to peripheral tissues and the central nervous system. It is metabolized in the liver, and a conjugated metabolite is excreted in the urine. It is rapidly cleared from the blood, both due to its distribution to the central nervous system and peripheral tissues, and due to effective hepatic metabolism. The presence of liver disease or renal disease does not 47

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appear to significantly alter the effective dosing of this agent.29,30 Propofol possesses sedative and amnesic, but very limited analgesic properties. It may be utilized for moderate and deep sedation for minor procedures such as endoscopy, deep sedation in intensive care settings, and for induction and maintenance of general anesthesia. Similar to benzodiazepines, the sedative effects of propofol are mediated primarily through gamma-aminobutyric acid (GABA) receptors in the brain. The binding of GABA to its receptors, located in the cerebrum and cerebral cortex, leads to decreased ability of neurons to generate an action potential. Propofol binds to receptors which increase GABA affinity for its receptor, thereby producing decreased cognition, sensory, memory and motor function.31 Propofol does not work on the exact same GABA receptors as the benzodiazepines, and therefore pharmacologic antagonists for benzodiazepines do not reverse the effects of propofol.32 Sedation and amnesia are dose-dependent; however, propofol produces less amnesia than midazolam at equivalent sedative doses.33,34 There may be considerable adverse hemodynamic effects from propofol, particularly at doses required for deep sedation or general anesthesia. Cerebral blood flow may decrease by 50%, and systemic blood pressure by a third. Cardiac output may fall without a compensatory rise in pulse rate.35 These effects may be accentuated with concomitant use of a parenteral narcotic. Effects on blood pressure and ventilatory effort are accentuated in the elderly. It has been suggested that maintaining a constant blood level by continuous infusion of propofol will result in less hemodynamic compromise compared to periodic bolus infusion with resultant peak levels.36 There are in fact multiple clinical series and randomized controlled trials that support the use of propofol by gastroenterologist-nursing teams. An attribute of a large case series is that some comment can be made regarding safety and efficacy, and while smaller in patient number, controlled trials offer a comparison between two or more sedation and analgesia regimens. In the majority of these case series and controlled trials, propofol was administered in the periodic bolus technique. The largest case series where propofol was administered by an endoscopist-nurse team was published by Walker et al.37 Deep sedation was achieved in the majority of the 9152 cases. Due in large part to the rigorous training the care givers received, propofol sedation was quite safe, with no reported deaths, and only seven

instances of respiratory compromise which responded to temporary support with bag and mask ventilation. Rex, et al., reported a similar series of 2000 patients receiving propofol sedation with periodic bolus by an endoscopist-nursing team.38 Again, propofol delivery was quite safe in the hands of this highly trained and focused team, with no deaths and only four patients required temporary bag and mask ventilatory support. Heuss, et al., provided propofol for 2574 patients undergoing a variety of endoscopic procedures and found a similar safety profile.39 Clarke et al. also report a similar safety profile in over 28 000 patients.40 In these, the largest case series of endoscopist-nurse administered propofol, most patients requiring ventilatory support were undergoing upper endoscopy. Rex has speculated that increased bolus dosing to facilitate esophageal intubation contributes to the increased likelihood of transient ventilatory insufficiency.41 Several prospective, randomized controlled trials have compared endoscopist-nurse administered propofol with conventional parenteral sedation with narcotic and benzodiazepine combinations.42–45 In our experience with gastroenterologist-nurse administered propofol for ERCP and EUS, we found that while patient satisfaction was similar, recovery time was significantly shortened with propofol compared to conventional sedation, and patients had a higher recovery of baseline activity level and dietary intake 24 hours after the procedure.42 While the study was powered only to detect a difference in recovery times, physiologic monitoring parameters showed a trend of actually being better in the propofol group as compared to the conventional sedation group. That said, it is clear from our experience that propofol sedation requires a highly motivated and trained team of gastroenterologists and nurses. Moreover, in most units, if propofol is given as a sole sedation agent, it is more likely to be administered by an anesthesiologist or similarly skilled individual.

SUMMARY Our data indicate that a significant number of patients undergoing ERCP will at some point of the procedure be deeply sedated. Both personal and automated monitoring of these patients should be appropriate for this level of sedation. The ability to rescue a patient from any level of sedation should be available, if necessary, as spelled out by the ASA guideline.

REFERENCES 1.

American Society of Anesthesiologists Website; www.asahq. org.2004. 2. Patel S, Vargo JJ, Khandwala F, et al. Deep sedation occurs frequently during elective endoscopy with Meperidine and Midazolam: Am J Gastroenterol 2005; 100(12):2689–2695. 48

3. Committee on Quality of Health Care in America IOM: To Err is Human: Building a Safer Health System. Edited by Kohn L, Corrigan J, Donaldson M. Washington, National Academy Press, 1999; 241. 4. Sentinel events: approaches to error reduction and prevention. J Comm J Qual Improv 1998; 24(4):175–186.

Chapter 5 Sedation and Analgesia for ERCP

5. Gaba DM. Anesthesiology as a model for safety in health care. BJM 2000; 320:785–788. 6. Stoelting R. APSF response to IOM medical error report. Anesthesia Patient Safety Foundation Newsletter 2000; 15(1):1. 7. Cooper JB, Gaba DM, Liang B, et al. The National Patient Safety Foundation agenda for research and development in patient safety. Med Gen Med 2000; E38. 8. Lagasse R, Anesthesia safety; model or myth? Anesthesiology 2002; 09:1609–1617. 9. American Society of Anesthesiologists Website; www.asahq.org 2004. 10. Silvis SE, Nebel O, Rogers G, et al. Endoscopic complications: Results of the 1974 American Society for Gastrointestinal Endoscopy survey. JAMA 1976; 235:928–930. 11. Quine MA, Bell GD, McCloy RF, et al. Prospective audit of upper gastrointestinal endoscopy in two regions of England: safety, staffing, and sedation methods. Gut 1995; 36:462–467. 12. Arrowsmith JB, Gerstman BB, Fleischer DE, et al. Results from the American Society for Gastrointestinal Endoscopy/U.S. Food and Drug Administration collaborative study on complication rates and drug use during gastrointestinal endoscopy. Gastrointestinal Endoscopy 1991; 37:421–427. 13. Sieg A, Hachmoeller-Eisenbach U, Eisenbach T. Prospective evaluation of complications in outpatient GI endoscopy: a survey among German gastroenterologists. Gastrointestinal Endoscopy 2001; 53:620–627. 14. Gross JB, Bailey PL, Caplan RA, et al. Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology 2002; 96:1004–1017. 15. Keenan RL, Boyan CP. Cardiac arrest due to anesthesia, JAMA 1985; 252(16):2373. 16. Caplan RA, Posner KL, Ward RJ, et al. Adverse respiratory events in anesthesia: a closed claims analysis, Anesthesiology 1990; 72:828. 17. Cheney FW, Posner KL, Caplan RA. Adverse respiratory events infrequently leading to malpractice suits: a closed claims analysis, Anesthesiology 1991; 75:932. 18. Morikawa S, Safar P, DeCarlo J. Influence of the head-jaw position upon upper airway patency, Anesthesiology 1961; 22:265. 19. Safar P, Escarraga LA, Chang F. Upper airway obstuction in the unconscious patient, J Appl Physiol 1959; 14:760. 20. Shorten GD, Opie NJ, Graziotti P, et al. Assessment of upper airway anatomy in awake, sedated and anaesthetised patients using magnetic resonance imaging, Anaesth Intensive Care 1994; 22:165. 21. Hwang J-C, St. John WM, Bartlett D Jr. Respiratory-related hypoglossal nerve activity: influence of anesthetics, J Appl Physiol 1983; 55:785. 22. Nishino T et al. Comparison of changes in the hypoglossal and the phrenic nerve activity in response to increasing depth of anesthesia in cats. Anesthesiology 1984; 60:19. 23. Hillman DR, Platt PR, Eastwood PR. The upper airway during anesthesia. BR J Anaesth 2003; 91(1):31–39. 24. Deegan PC, Mulloy E, McNicholas WT. Topical oropharyngeal anesthesia in patients with obstructive sleep apnea. Am J Respir Crit Care med 1995; 151(4):1108–1112. 25. Langeron O, Masso E, Huraux C, et al. Prediction of difficult mask ventilation. Anesthesiology,2000 May; 92(5):1217–1218. 26. Nelson DB, Freeman ML, Silvis SE, Cass OW, Yashke PN, et al. A randomized, controlled trial of transcutaneous carbon dioxide monitoring during ERCP. Gastrointest Endosc 2000; 51:288–295. 27. Vargo JJ, Zuccaro G, Dumot JA, et al. Gastroenterologistadministered propofol for therapeutic upper endoscopy with

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graphic assessment of respiratory activity: a case series. Gastrointest Endosc 2000; 52:250–255. Bower AL, Ripepi A, Dilger J, Boparai N, Brody FJ, Ponsky JL. Bispectral index monitoring of sedation during endoscopy. Gastrointest Endosc 2000; 52:192–196. Servin F, Desmonts JM, Haberer JP, et al. Pharmacokinetics and protein binding of propofol in patients with cirrhosis. Anesthesiology 1988; 69(6):887–891. Ickx B, Cockshott ID, Barvais L, et al. Propofol infusion for induction and maintenance of anaesthesia in patients with endstage renal disease. Br J Anaesth 1998; 81(6):854–860. Trapani G, Altomare C, Sanna E, et al. Propofol in anesthesia. Mechanism of action, structure-activity relationships, and drug delivery. Curr Med Chem 2000; 7:249–271. Hales TG, Lambert JJ. The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurons. Br J Pharmacol 1991; 104:619–628. Peduto VA, Concas A, Santoro G, et al. Biochemical and electrophysiologic evidence that propofol enhances GABAergic transmission in the rat brain. Anesthesiology 1991; 75:1000–1009. Whitehead C, Sanders LD, Oldroyd G, et al. The subjective effects of low dose propofol; a double blind study to evaluate dimensions of sedation and consciousness with low-dose propofol. Anaesthes 1994; 490–496. Smith I, Monk TG, White PF, et al. Propofol infusion during regional anesthesia: sedative, amnestic, and anxiolytic properties. Anesth Analg 1994; 79:313–319. Karski JM, Tearsdale SJ, Boylan J, et al. Propofol for continuous intravenous sedation after aortocoronary bypass graft surgery. Dose finding study [abstract]. Can J Anaesth 1994; 41(pt 2):A17. Walker JA, McIntyre RD, Scleinitz PF, et al. Nurse-administered propofol sedation without anesthesia specialists in 9152 endoscopic cases in an ambulatory surgery center. Am J Gastroenterol 2003; 98:1744–1750. Rex DK, Sipe BW, Kinser KM, et al. Safety of propofol administered by registered nurses with gastroenterologist supervision in 2000 endoscopic cases. Am J Gastroenterol 2002; 97:1159–1163. Heuss LT, Schieper P, Drewe J, et al. Risk stratification and safe administration of propofol by registered nurses supervised by the gastroenterologist: a prospective observational study of more than 2000 cases. Gastrointest Endosc 2003; 57:664–671. Clarke AC, Chiragakis L, Hillman LC, et al. Sedation for endoscopy: the safe use of propofol by general practitioner sedationists. Med J Aust 2002; 176:158–161. Rex DK, Overley CA, Walker J. Registered nurse-administered propofol sedation for upper endoscopy and colonoscopy: why? when? how? Reviews in Gastroenterological Disorders 2003; 3:70–80. Vargo JJ, Zuccaro G, Dumot J, et al. Gastroenterologistadministered propofol versus meperidine and midazolam for ERCP and EUS: a randomized controlled trial with cost effectiveness analysis. Gastroenterology 2002; 123:8–16. Sipe BW, Rex DK, Latinovich D, et al. Propofol versus midazolam/ meperidine for outpatient colonoscopy: administration by nurses supervised by endoscopists. Gastrointest Endosc 2002; 55:815–825. Wehrmann T, Grotkamp J, Stergiou N, et al. Electroencephalogram monitoring facilitates sedation with propofol for routine ERCP: a randomized, controlled trial. Gastrointest Endosc 2002; 56:817–824. Ulmer BJ, Hansen JJ, Overly CA, et al. Propofol versus midazolam/ fentanyl for outpatient colonoscopy: administration by nurses supervised by endoscopists. Clin Gastroenterol Hepatol 2003; 1:425–423.

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SECTION 1

Chapter

6

GENERAL TOPICS

Complications of ERCP: Prediction, Prevention and Management Martin L. Freeman

INTRODUCTION ERCP has evolved from a diagnostic modality to a primarily therapeutic procedure for pancreatic as well as biliary disorders. ERCP alone or with associated biliary and pancreatic instrumentation and therapy can cause a variety of short-term complications including pancreatitis, hemorrhage, perforation, cardiopulmonary events, and others (Box 6.1). These complications can range from minor—with one or two additional hospital days followed by full recovery, to severe and devastating with permanent disability or death. Complications may cause the endoscopist significant anxiety and exposure to medical malpractice claims. Major advances in complications of ERCP have occurred in several areas: standardized consensus-based definitions of complications;1 large scale multicenter multivariate analyses that have allowed clearer identification of patient and technique-related risk factors for complications;2–7 and introduction of new devices and techniques to minimize risks of ERCP.

DEFINITIONS OF COMPLICATIONS, ADVERSE EVENTS, UNPLANNED EVENTS AND OTHER NEGATIVE OUTCOMES In 1991, standardized consensus definitions for complications of sphincterotomy were introduced1 (Table 6.1). Severity is graded primarily on number of hospital days and type of intervention required to treat the complication. This classification allows uniform assessment of outcomes of ERCP and sphincterotomy in various settings. Beyond immediate complications, there is an increasing awareness of the entire spectrum of negative (as well as positive) outcomes including technical failures, ineffectiveness of the procedure in resolving the presenting complaint, long-term sequelae, costs, extended hospitalization, and patient (dis)satisfaction. Accordingly, the terminology has evolved from “complications” to “adverse events” to “unplanned events.” Adverse events must be viewed in context of the entire clinical outcome: a successful procedure with a minor or even a moderate complication may sometimes be a preferable outcome to a failed procedure attempt without any obvious complication: failure at ERCP usually leads to a repeated ERCP, or to an alternative percutaneous or surgical procedure which may result in significant additional morbidity, hospitalization and cost.

ANALYSES OF COMPLICATION RATES Reported complication rates vary widely, even between prospective studies. In two large prospective studies, pancreatitis rates ranged

between 0.74% for diagnostic and 1.4% for therapeutic ERCP respectively in one study5 compared with 5.1% (about 7 times higher) for diagnostic ERCP and 6.9% (5 times higher) for therapeutic ERCP in another prospective study.3 Reasons for such variation include: (1) definitions used; (2) thoroughness of detection; (3) patient-related factors; (4) procedural variables, such as use of pancreatic stents, or extent of therapy. For all these reasons, it should not be assumed that a lower complication rate at one center necessarily reflects better quality of practice. Most recent studies have utilized multivariate analysis as a tool to identify and quantify the effect of multiple potentially confounding risk factors, but these are not infallible as many potentially key risk factors were not examined in most studies, and some are overfitted (too many predictor variables for too few outcomes). Only a limited number of studies have included more than 1000 patients. Tables 6.2, 6.3 and 6.4 show a summary of risk factors for complications of ERCP and sphincterotomy based on published multivariate analyses.

OVERALL COMPLICATIONS OF ERCP AND SPHINCTEROTOMY Most prospective series report an overall short-term complication rate for ERCP and/or sphincterotomy of about 5 to 10%.2–7 There is a particularly high rate of complications for sphincter of Oddi dysfunction (up to 20% or more, primarily pancreatitis, with up to 4% severe complications), and a very low complication rate for routine bile duct stone extraction, especially in tandem with laparoscopic cholecystectomy (under 5% in most).2 Sphincterotomy bleeding occurs primarily in patients with bile duct stones, and cholangitis mostly in patients with malignant biliary obstruction. Summaries of multivariate analyses of risk factors for overall complications of ERCP and sphincterotomy are shown in Table 6.2. Although relevant studies are heterogeneous and sometimes omit potentially key risk factors, several patterns emerge (Table 6.2): (1) Indication of suspected sphincter of Oddi dysfunction was a significant risk factor whenever examined. (2) technical factors, likely linked to the skill or experience of the endoscopist, were found to be significant risk factors for overall complications. These technical factors include difficult cannulation, use of precut or “access” papillotomy to gain bile duct entry, failure to achieve biliary drainage, and use of simultaneous or subsequent percutaneous biliary drainage for otherwise failed endoscopic cannulation. In turn, the ERCP case volume of the endoscopists or medical centers, when examined, has always been a significant factor in complications by both univariate or multivariate analysis.2–7 (3) Death from ERCP is rare (less than 0.5%), but most often related to cardiopulmonary complications, 51

SECTION 1 GENERAL TOPICS

highlighting the need for the endoscopist to pay attention to issues of safety during sedation and monitoring. Notably, risk factors found not to be significant are the following: (1) older age or increased number of coexisting medical conditions—on the contrary, younger age generally increases the risk

both by univariate and multivariate analysis; (2) smaller bile duct diameter, in contrast to previous observations; and (3) anatomic obstacles such as periampullary diverticulum or Billroth II gastrectomy, although they do increase technical difficulty for the endoscopist.2–7

PANCREATITIS BOX 6.1 COMPLICATIONS OF ERCP

Pancreatitis is the most common complication of ERCP, with reported rates varying from 1% to 40%, with a rate of about 5% being most typical. In the consensus classification, pancreatitis is defined as clinical syndrome consistent with pancreatitis (i.e. new or worsened abdominal pain) with an amylase at least three times normal at more than 24 hours after the procedure, and requiring more than one night of hospitalization1 (Table 6.1). Some events are difficult to classify in the consensus definitions, such as patients with postprocedural abdominal pain and elevation of amylase to just under three times normal, or those with dramatic amylase elevations but minimal symptoms that are not clearly suggestive of clinical pancreatitis. There are many potential mechanisms of injury to the pancreas during ERCP and endoscopic sphincterotomy: mechanical, chemical, hydrostatic, enzymatic, microbiologic, and thermal. Although the relative contribution of these mechanisms to postERCP is not known, recent multivariate analyses have helped to identify the clinical patient and procedure-related factors that are independently associated with pancreatitis.

• Pancreatitis • Hemorrhage • Perforation • Cholangitis • Cholecystitis • Stent-related • Cardiopulmonary • Miscellaneous

Pancreatitis

Bleeding

Perforation

Infection (cholangitis)

Mild

Moderate

Severe

Clinical pancreatitis, amylase at least three times normal at more that 24 h after the procedure, requiring admission or prolongation of planned admission to 2–3 days Clinical (i.e. not just endoscopic) evidence of bleeding, hemoglobin drop 38°C for 24–48 hr

Pancreatitis requiring hospitalization of 4–10 days

Hospitalization for more than 10 days, pseudocyst, or intervention (percutaneous drainage or surgery)

Transfusion (4 units or less), no angiographic intervention or surgery Any definite perforation treated medically 4–10 days

Transfusion 5 units or more, or intervention (angiographic or surgical) Medical treatment for more than 10 days, or intervention (percutaneous or surgical) Septic shock or surgery

Febrile or septic illness requiring more than 3 days of hospital treatment or percutaneous intervention

Table 6.1 Consensus definitions for the major complications of ERCP Any intensive care unit admission after a procedure grades the complication as severe. Other rarer complications can be graded by length of needed hospitalization.

Definitea

Maybeb

Noc

Suspected sphincter of Oddi dysfunction Cirrhosis Difficult cannulation Precut sphincterotomy Percutaneous biliary access Lower ERCP case volume

Young age Pancreatic contrast injection Failed biliary drainage Trainee involvement

Comorbid illness burden Small CBD diameter Female sex Billroth II Periampullary diverticulum

Table 6.2 Risk factors for overall complications of ERCP in multivariate analyses a

significant by multivariate analysis in most studies. significant by univariate analysis only in most studies. c not significant by multivariate analysis in any study. b

52

Chapter 6 Complications of ERCP: Prediction, Prevention and Management

Definitea

Maybeb

Noc

Suspected sphincter of Oddi dysfunction Young age Normal bilirubin History of post-ERCP pancreatitis Difficult or failed cannulation Pancreatic duct injection Pancreatic sphincterotomy (especially minor papilla) Balloon dilation of intact biliary sphincter Precut sphincterotomy

Female sex Acinarization Absence of CBD stone Lower ERCP case volume Trainee involvement

Small CBD diameter Sphincter of Oddi manometry Biliary sphincterotomy

Table 6.3 Risk factors for post-ERCP pancreatitis in multivariate analyses a

significant by multivariate analysis in most studies. significant by univariate analysis only in most studies. c not significant by multivariate analysis in any study. b

Definitea

Maybeb

Noc

Coagulopathy Anticoagulation 40 mm of Hg) on manometry are thought to be due to sphincter of Oddi stenosis and sphincterotomy in these situations has been shown to result in relief of symptoms.1,2 Sphincter of Oddi Manometry (SOM), though invasive, is considered the gold standard for measurement of biliary motility.3 Though there is some concern whether a few minutes of pressure observations would reflect the pressure dynamics over 24 hours, currently this is the accepted method of measurement. There are other non-invasive means of detecting the sphincter of Oddi dysfunction: Morphine-Prostigmin Provocative Test (Nardi Test), Ultrasonographic Assessment of Extrahepatic Bile Duct and Main Pancreatic Duct Diameter After Secretory Stimulation and Quantitative Hepatobiliary Scintigraphy. There are also limited data regarding the use of secretin stimulated MRCP and EUS in the evaluation of SO dysfunction. In a pilot study of 18 patients with idiopathic acute recurrent pancreatitis there appeared to be a high concordance

rate between ERCP and secretin MRCP in diagnosis of SO dysfunction.4 In a similar study secretin was injected and pancreatic duct diameter was subsequently measured by ultrasound in patients with idiopathic acute recurrent pancreatitis. Those with dilated duct diameter beyond 20 minutes were suspected to have sphincter of oddi dysfunction. All patients underwent SO manometry in 3–7 days. Using SO manometry as the gold standard the sensitivity and specificity of secretin stimulated ultrasound in diagnosis of SO dysfunction was 88% and 82%.5 These techniques have not been evaluated in larger series of patients and in those without pancreatitis. At the current time none of the non-invasive methods have superior operating characteristics compared to the conventional SOM (Table 10.1).6

TECHNIQUE Patient preparation As with all endoscopic procedures patients should be fasting for at least 6 hours. Drugs that either stimulate or relax the sphincter of Oddi should be avoided at least 12 hours prior to the scheduled manometry. Drugs that are thought to stimulate the sphincter include narcotic analgesics and other cholinergic agents. Drugs that relax the sphincter include nitrates, glucagon, calcium channel blockers and other anti-cholinergic agents. Midazolam in doses >2 mg has been shown to reduce the basal sphincter pressure.7 Benzodiazepines and Meperidine (Demerol) when given at a dose of 40 mm of Hg >350 mm of Hg >8/min >50% total

Table 10.2 Abnormalities in SO Manometry Interpretation of the Manometry recordings: Before interpretation of readings is done, care should be taken to establish a basic duodenal pressure recording. Typically this is the average of the three recordings when the triple lumen catheter is placed freely in the duodenum through the duodenoscope prior to cannulation. The elevator should be in the down position and the catheter should not touch any duodenal wall to avoid any errors. (Table 10.2) We currently use a triple lumen Arndorfer pneumohydraulic capillary perfusion system (Arndorfer Medical Specialties, Greendale, Wisconsin, USA) (Fig. 10.9). The Arndorfer catheter is perfused at 0.25 ml/minute with distilled water. Efficacy of perfusion with physiological solutions has not been established. The perfusion catheter has three side holes and pressure should be recorded at all the three side holes.13 Sacrificing one of the ports to provide for aspiration has been shown to reduce the incidence of pancreatitis when performing manometry of the pancreatic duct but not the bile duct.14,15 Aspiration cannot be done with wire-guided mano. Perfusion at a lower rate could accurately measure the basal sphincter but the accuracy of phasic waves is unreliable. Once pressure measurements have been made, one has to decide whether to do a sphincterotomy. Techniques of sphincterotomy are 94

described elsewhere in this book (see Chapters 12 and 14). For sphincterotomy one must have deep cannulation of the desired duct. Sphincterotomy is performed by a traction sphincterotome over a guidewire. The cutting wire should track up to the middle of the papilla and in biliary sphincterotomy should be oriented between the 10 o’clock and 12 o’clock position. Automated electrical generators delivering pulse current reduce excessive rapid cutting “zipper effect.” There is debate over the superiority of the type of current in prevention of bleeding and post-ERCP pancreatitis. In a meta-analysis it was shown that pure cut current was associated with a slightly increased risk of immediate post-sphincterotomy bleeding; however, there were no significant differences in the rates of delayed bleeding or pancreatitis.16 We recommend using pure cutting current for pancreatic sphincterotomy and blended current for biliary sphincterotomy using standard electrical generators. Irrespective of whether the pressure is elevated or not or whether biliary and/or pancreatic sphincterotomy is performed, it is a standard practice now to place a stent in the pancreatic duct to reduce the risk of post-ERCP pancreatitis post-manometry (Fig. 10.10). This has been documented well in various studies.17,18 It is not clear at this time whether a small caliber 3 Fr stent is better than a larger bore stent. Preliminary data indicate that a modified 5 Fr straight stent with the inner flange removed is associated with lower rates of pancreatitis compared to the 3 Fr pigtail stents.19 Insertion of 3 Fr pigtail stents is a little more difficult and one can use only a wire of 0.018 inch diameter. Catheters with microtransducers at the tips of the catheters are available and these can record real-time data when cannulation is achieved. Since there is no perfusion involved with these systems they may reduce the risk of post-ERCP pancreatitis. These catheters

Chapter 10 Sphincter of Oddi Manometry

ware to available esophageal manometry equipment. We currently use PolygramNet (Medtronic, Minneapolis, MN) to record and assess sphincter pressures. A manometry catheter with one port sacrificed to aid suction of the perfused saline is also available (Lehman SO Manometry catheter, Cook Endoscopy, Winston-Salem, NC). The catheter is 5 Fr in diameter and has a 5 mm or 1.5 cm tip. Both catheters are relatively easy to use for cannulation. While an Arndorfer catheter is an over-the-wire catheter, one could use the Lehman catheter without the wire or alternatively, it could be introduced over the wire. We use the Arndorfer infusion pump (Arndorfer Medical Specialties, Greendale, Wisconsin, USA).

COMPLICATIONS Fig. 10.10 Radiograph of the 3 Fr pancreatic stent to prevent postERCP pancreatitis.

Fig. 10.11 sleeve.

Picture of the new manometry catheter with Dent

are stiffer than the regular manometry catheters and are difficult to cannulate. Its usage is not widespread and data are limited.20 Sleeve catheters were recently developed. They have the advantage of perfusion of 0.04 ml/min and the fluid is collected back in the sleeve. The sleeve also helps stabilize the catheter in the sphincter zone without touching the side walls of the duct and providing erroneous values. This is not yet commercially available and clinical studies are in progress evaluating the efficacy of these catheters21 (Fig. 10.11).

Indications for sphincter of Oddi manometry • Pain if suspected to be pancreatobiliary in nature with or without liver function abnormality (Geenen—Hogan classification) • Idiopathic recurrent pancreatitis

EQUIPMENT The following is the standard equipment which is required for manometry. 1. Standard diagnostic or therapeutic duodenoscope 2. Hydraulic capillary Infusion system 3. Manometry catheter 4. Recording system: Dynagraph/computerized/solid state system

Catheters We prefer the Arndorfer catheter since it is a validated manometry catheter (Arndorfer Medical Specialties, Greendale, Wisconsin, USA). The pressure recordings can be done with addition of soft-

As with any ERCP, pancreatitis remains the foremost complication of pancreaticobiliary manometry (see also Chapter 6). It is the patient characteristics that predispose these individuals to increased frequency of post-ERCP pancreatitis. Manometry by itself does not pose any greater risk.22 Techniques that possibly reduce the risk of pancreatitis include initial injection of contrast into the pancreatic duct so that when the wire is introduced into the main duct repeated manipulations into side branches and duct disruption is avoided. One needs to perform a quick station pull through. There is concern of over-perfusing with saline for manometry and hence an aspiration catheter is thought to be beneficial for pancreatic manometry because of the ability to continuously aspirate saline.14 If wire-guided manometry is done first in the pancreatic duct, it is probably beneficial to leave the wire in the pancreatic duct and cannulate the bile duct alongside of the wire, to do biliary manometry. This will make sphincterotomy/stent placement in the pancreatic duct easier after biliary manometry. The wire might facilitate drainage of the pancreatic duct as well by keeping the PD opening patent. Care should be taken with pancreatic duct sphincterotomy. Unlike biliary sphincterotomy the length of sphincterotomy is relatively small, approximating to 5–6 mm. It is now recommended to place a small caliber pancreatic stent in most if not all patients with suspected sphincter of Oddi dysfunction who undergo pancreatic instrumentation of any kind, including those with normal pancreatic manometry.18,23 Three, 4, or 5 French stents have been used for this purpose. If a 3 Fr pigtail stent is placed one has to use 0.018 “wire in the pancreatic duct. Larger diameter wires will not allow for deployment of 3 Fr stents. Currently the pigtail end of the catheter is not marked. We recommend using a permanent marker to make a circumferential mark at the pigtail end of the stent so that when the stent is out of the scope one will know the end of the length of the stent to be placed in the pancreatic duct rather than deploying the entire stent in the pancreatic duct. Once the marking is visible, the stent is pushed out into the duodenum by lowering the elevator and moving the up/down wheel to the down position. Once the entire stent is out of the elevator of the scope, the inner wire is pulled out while keeping the pusher catheter in place. Care should be taken not to raise the elevator during this operation (tapered tip ERCP catheter) as there is a risk of pushing the pigtail portion of the stent into the pancreatic duct. If one is not comfortable and familiar with 3 Fr pigtail stents we recommend using a straight stent with inner flange removed so that the stent would migrate distally into the duodenum spontaneously similar to the unflanged 3 Fr stent. Bleeding both immediate and delayed is another major complication of sphincterotomy and is addressed in the chapter of sphincter95

SECTION 2 TECHNIQUES

otomy. If bleeding is seen, one could inject dilute epinephrine or sometimes even contrast material. A submucosal injection is required for tamponade effect. This could be done with the cannulating catheter itself and an injection with an injection needle catheter might not be necessary. In difficult situations hemoclips have been used. Bleeding is usually seen towards the apex of the sphincterotomy. In rare instances of continued major bleeding, octreotide infusion to reduce the splanchnic circulation might be beneficial. The risk of bleeding is especially high if one extends an existing sphincterotomy or in the presence of a periampullary diverticulum, and caution should be exercised. Papillary stenosis following sphincterotomy is a delayed complication more commonly seen with pancreatic sphincterotomy.

Post-sphincter of Oddi manometry patients should be monitored in the recovery area for at least 4–6 hours. In case of any complaints of significant pain or nausea, one should check serum amylase and lipase to help rule out procedural pancreatitis. Four-hour serum amylase and lipase levels have been shown to be predictive of postERCP pancreatitis.24 Patients could have pain only without pancreatitis after SO manometry and it might be reasonable to watch them overnight or to provide adequate analgesia.25 In case of suspected pancreatitis, we recommend adequate hydration and we routinely administer 1–2 liters of intravenous fluids over 6–8 hours. Analgesia is important. Patient-controlled analgesia might be beneficial. For detailed description of post-ERCP complications and management of the same, please refer to Chapter 5.

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Geenen JE, Hogan WJ, Dodds WJ, et al. The efficacy of endoscopic sphincterotomy after cholecystectomy in patients with sphincterof-Oddi dysfunction. N Engl J Med 1989; 320(2):82–87. Toouli J, Roberts-Thomson IC, Kellow J, et al. Manometry based randomised trial of endoscopic sphincterotomy for sphincter of Oddi dysfunction. Gut 2000; 46(1):98–102. Lans JL, Parikh NP, Geenen JE. Application of sphincter of Oddi manometry in routine clinical investigations. Endoscopy 1991; 23(3):139–143. Mariani A, Curioni S, Zanello A, et al. Secretin MRCP and endoscopic pancreatic manometry in the evaluation of sphincter of Oddi function: a comparative pilot study in patients with idiopathic recurrent pancreatitis. Gastrointest Endosc 2003; 58(6):847–852. Di F, V, Brunori MP, Rigo L, et al. Comparison of ultrasoundsecretin test and sphincter of Oddi manometry in patients with recurrent acute pancreatitis. Dig Dis Sci 1999; 44(2):336–340. Sherman S, Lehman GA. Sphincter of Oddi dysfunction: diagnosis and treatment. JOP 2001; 2(6):382–400. Fazel A, Burton FR. The effect of midazolam on the normal sphincter of Oddi: a controlled study. Endoscopy 2002; 34(1):78–81. Sherman S, Gottlieb K, Uzer MF, et al. Effects of meperidine on the pancreatic and biliary sphincter. Gastrointest Endosc 1996; 44(3):239–242. Goff JS. Effect of propofol on human sphincter of Oddi. Dig Dis Sci 1995; 40(11):2364–2367. Sherman S, Hawes RH, Madura JA, et al. Comparison of intraoperative and endoscopic manometry of the sphincter of Oddi. Surg Gynecol Obstet 1992; 175(5):410–418. Blaut U, Sherman S, Fogel E, et al. Influence of cholangiography on biliary sphincter of Oddi manometric parameters. Gastrointest Endosc 2000; 52(5):624–629. Raddawi HM, Geenen JE, Hogan WJ, et al. Pressure measurements from biliary and pancreatic segments of sphincter of Oddi. Comparison between patients with functional abdominal pain, biliary, or pancreatic disease. Dig Dis Sci 1991; 36(1):71–74. Toouli J, Roberts-Thomson IC, Dent J, et al. Manometric disorders in patients with suspected sphincter of Oddi dysfunction. Gastroenterology 1985; 88(5 Pt 1):1243–1250.

14. Sherman S, Troiano FP, Hawes RH, et al. Sphincter of Oddi manometry: decreased risk of clinical pancreatitis with use of a modified aspirating catheter. Gastrointest Endosc 1990; 36(5):462–466. 15. Sherman S, Hawes RH, Troiano FP, et al. Pancreatitis following bile duct sphincter of Oddi manometry: utility of the aspirating catheter. Gastrointest Endosc 1992; 38(3):347–350. 16. Guda N, Partington S, Freeman M. Does the type of current (pure vs blended) matter for post ERCP complications: a meta analysis. Gastrointest.Endosc. 61(5). 2005. Ref Type: Abstract. 17. Fazel A, Quadri A, Catalano MF, et al. Does a pancreatic duct stent prevent post-ERCP pancreatitis? A prospective randomized study. Gastrointest Endosc 2003; 57(3):291–294. 18. Freeman ML, Guda NM. Prevention of post-ERCP pancreatitis: a comprehensive review. Gastrointest Endosc 2004; 59(7): 845–864. 19. Thomas M, Catalano MF, Geenen JE. A prospective comparative stent study for prophylaxis of post ERCP pancreatitis: comparison of 5 Fr straight stent vs 3 FR pigtail stent. Gastrointest.Endosc 61(5), 196. 4–1-2005. Ref Type: Abstract. 20. Wehrmann T, Stergiou N, Schmitt T, et al. Reduced risk for pancreatitis after endoscopic microtransducer manometry of the sphincter of Oddi: a randomized comparison with the perfusion manometry technique. Endoscopy 2003; 35(6):472–477. 21. Craig AG, Omari T, Lingenfelser T, et al. Development of a sleeve sensor for measurement of sphincter of Oddi motility. Endoscopy 2001; 33(8):651–657. 22. Singh P, Gurudu SR, Davidoff S, et al. Sphincter of Oddi manometry does not predispose to post-ERCP acute pancreatitis. Gastrointest Endosc 2004; 59(4):499–505. 23. Tarnasky P, Cunningham J, Cotton P et al. Pancreatic sphincter hypertension increases the risk of post-ERCP pancreatitis. Endoscopy 1997; 29(4):252–257. 24. Testoni PA, Bagnolo F, Caporuscio S, et al. Serum amylase measured four hours after endoscopic sphincterotomy is a reliable predictor of postprocedure pancreatitis. Am J Gastroenterol 1999; 94(5):1235–1241. 25. Wong GS, Teoh N, Dowsett JD, et al. Complications of sphincter of Oddi manometry: biliary-like pain versus acute pancreatitis. Scand J Gastroenterol 2005; 40(2):147–153.

SECTION 2

Chapter

11

TECHNIQUES

Balloon Dilation of the Papilla Chan-Sup Shim

INTRODUCTION

TECHNIQUE

Endoscopic biliary sphincterotomy (EST) has become a cornerstone of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) of the biliary tree. The most common indication for EST is to enlarge the access of the bile duct for stone extraction. The possible adverse consequences of EST include bacterial colonization and chronic inflammation of the biliary tree, the clinical relevance of which is poorly understood.1 While increased incidence of primary choledocholithiasis is an acceptable and relatively harmless longterm result of EST, some experts express concern about the risk of biliary malignancy. Longitudinal studies of patients who have had biliodigestive anastomoses and surgical sphincteroplasty suggest an incidence of late bile duct cancer between 5.6 and 7.4%.2,3 Endoscopic papillary balloon dilation (EPBD) is an alternative to EST for removing bile duct stones.4–7 In an effort to avoid permanent destruction of the biliary sphincter, EPBD seemed to be an attractive alternative to early investigators, such as Staritz and Meyer zum Buschenfelde, who first reported it in 1983.8 In this procedure, a balloon is inflated to enlarge the opening of the bile duct at the level of the biliary sphincter. The main theoretical advantage of this technique is that it does not involve cutting the biliary sphincter. Therefore, acute complications such as bleeding and perforation should be less likely, and the function of the biliary sphincter is also preserved.5 The enthusiasm for the potential advantages of EPBD over EST for the avoidance of short-term complications of bleeding and perforation, while preserving the biliary sphincter and possibly reducing the long-term sequelae of EST was soon dampened by reports of serious post-procedure pancreatitis.9 Therefore, EPBD was nearly abandoned as a treatment for bile duct stones, but its use was revived with the development of laparoscopic cholecystectomy. With several groups reporting favorable results using EPBD for stone extraction, conservation of the biliary sphincter regained popularity in the 1990s. In 1995, Mac Mathuna et al. reported good results with EPBD for treating bile duct stones in 100 consecutively treated patients.4,5 The results of subsequent randomized, controlled trials comparing EST to EPBD are conflicting. Some authors have reported an increased incidence of post-procedure pancreatitis, while others have not, and an argument has been presented against EPBD and its failure to provide adequate access for extracting difficult (large or multiple) bile duct stones.6,7,10 The final success rates for EST and EPBD are comparable; the reported success rates of stone removal are 81–99% for EPBD 4,6,7,10 and 85–98% for EST.6,7 Randomized trials comparing EPBD with EST suggest that EPBD is at least as effective as EST in patients with small to moderate-sized bile duct stones.5,6,10–18

During the informed consent process, the risks and benefits of EPBD compared to EST should be discussed with patients and consent obtained if EPBD is being considered. Preprocedural antibiotics are administered as appropriate. The procedure is performed using a standard duodenoscope. During the procedure, identification of candidates for whom the EPBD is indicated can be simplified by comparing the bile duct stone size to the diameter of the duodenoscope on the same radiographic image; patients with stones that have a diameter equal to or less than that of the duodenoscope are considered eligible. After diagnostic ERCP and selective bile duct cannulation a standard 0.025 or 0.035 inch guidewire is inserted into the bile duct. After removing the cannula, an 8-mm balloon-tipped catheter (Fig. 11.1) (Hurricane RX dilation balloon or Wire-guided CRETM balloon; Boston Scientific, Natick, MA, USA; balloon length 3 cm, maximum inflated outer diameter 8 mm) is passed over the guidewire, positioned across the papilla, and inflated with diluted contrast medium at a pressure of 8 atm (Fig. 11.2). The balloon is expanded slowly with a mixture of contrast medium and saline (50/50) paying close attention to the waist of the balloon. When the waist disappears, the inflation is stopped. Care must be taken to avoid rapid application of excessive pressure (Fig. 11.2). The dilation is maintained for 15–30 seconds. When the bile duct is less than 8 mm in diameter a 6-mm × 2-cm balloon can be used. Other dilator balloons can also be used (e.g. Hurricane Rx dilation balloon; Boston Scientific, Natick, MA, USA, PET balloon; ConMed Endoscopic Technologies, Billerica, MA, USA, Quantum balloon; Cook Endoscopy Winston-Salem, NC, USA). The smaller balloons pass readily through a diagnostic duodenoscope, such as an Olympus JF-240, whereas the 24 Fr balloon requires a biopsy channel of at least 3.2 mm. After papillary dilation, the stones are removed using Dormia baskets and/or retrieval balloon catheters (Fig. 11.2). Mechanical lithotripsy (BML-3Q-1, -4Q-1; Olympus Medical System Corporation, Tokyo, Japan) can be used to fragment stones if they are over 10 mm in diameter as determined from the cholangiogram. If the stones are too large to engage within a mechanical lithotripsy basket, an electrohydraulic lithotripter can be in the next session used to crush the stones after introducing a baby cholangioscope (CHFBP30; Olympus Medical Systems, Tokyo, Japan) through the dilated papilla. The initial ERCP session is performed within 60 min, and if complete clearance of the stones fails, a biliary stent or nasobiliary catheter can be inserted to prevent stone impaction. Data from outside the US suggest that pancreatic duct stent placement is not required after EPBD is performed. The optimal size of the balloon in EPBD has not yet been established. Most studies have reported results with 8-mm diameter 97

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A

B

Fig. 11.1 Dilating kit consisting of 8-, 10-, 12-, 15-, 18-, and 20-mm balloons, syringe/gauge assembly and inflation handle. dilation balloons, although some studies have used balloons up to 15 mm in diameter.8 Theoretically, the larger the balloon, the easier it is to extract large stones, although more complications after dilation may be likely, and pancreatitis or damage to the sphincter may be expected. However, there is insufficient information to support these concerns. In contrast, Staritz et al. reported no complications, even after using 15-mm balloons.8 Other points of EPBD to be clarified are the optimal pressure for dilation, the optimal duration of dilation, and the optimal number of dilations. Other operators have reported the use of different protocols, such as a maximal pressure of less than 1.5 atmospheres,5 a duration of 45–60 seconds after the disappearance of the balloon waist,7 or repeated dilation protocols.4 It is still unknown which protocol is best for the complete removal of stones and the preservation of sphincter function. To answer these questions, more studies that focus on the various EPBD techniques are needed.

D

C

INDICATIONS FOR AND LIMITATIONS OF ENDOSCOPIC BALLOON DILATION In the recent meta-analysis by Baron et al., the incidence of bleeding was significantly less after EPBD compared to EST.16 Clinically significant post-EST bleeding occurs in 2–5% of EST patients.17,18 In addition, patients with coagulopathy and those requiring anticoagulation within 3 days of the procedure are at increased risk for bleeding.17 Thus, transient discontinuation of anticoagulation, correction of coagulopathy with fresh frozen plasma, or platelet transfusion are frequently used to avoid bleeding after EST, though these measures might be inadequate to prevent it. EPBD provides a useful alternative to EST in such cases. No articles have described bleeding after EPBD.4,6,7,10 In light of this, EPBD should be considered a viable alternative to EST in patients with an underlying coagulopathy or the need for anticoagulation following EST, as such patients have a higher incidence of post-EST bleeding.17 EPBD may significantly reduce the risk of bleeding compared to EST in patients with advanced cirrhosis and coagulopathy. In these patients, EPBD is recommended over EST for treating choledocholithiasis.19 Another population in which EPBD may be an attractive option is those patients who refuse blood transfusion for religious reasons, and patients with difficult anatomy that prevents safe orientation of the papillotome for EST (e.g. prior Billroth II gastrectomy, Fig. 11.3; or intradiverticular location of the papilla, Fig. 11.4).14 Bergman et al. reported a randomized trial of EPBD and EST for removing bile duct stones in patients with a prior Billroth II gastrectomy.14 Compared to patients with a normal anatomy, patients with prior Billroth II gastrectomy had a significantly increased risk of 98

E

Fig. 11.2 Endoscopic balloon dilation in a patient with multiple small CBD stones. A The endoscopic cholangiogram demonstrated multiple stones in the common bile duct. After diagnostic ERCP, a 0.035-inch guidewire was passed through the ERCP catheter into the common bile duct, and the catheter was removed. B–D A balloon-tipped catheter is inserted into the common bile duct over the guidewire. The balloon is inflated once it is located across the papilla. The biliary sphincter can be seen as a “waist” in the balloon. C The biliary sphincter is considered adequately dilated if the waist has disappeared completely. E After removing the balloon and guidewire, stones are extracted using a Dormia basket.

Chapter 11 Balloon Dilation of the Papilla

A

B

C

D

E

F

G

H

I

J

K

L

Fig. 11.3 Serial endoscopic images A–H and retrograde cholangiograms I–L show endoscopic papillary balloon dilation of the biliary sphincter in a patient with two bile duct stones and prior Billroth II gastrectomy. A Endoscopy shows an image of the papilla, upside-down. B Two filling defects are seen on the cholangiogram. C–F The balloon is advanced over a guidewire and is inflated with diluted contrast. G Transient oozing of blood is observed at the papilla after deflating the balloon, but it does not develop into serious hemorrhage. H–L A stone is removed with a basket catheter.

bleeding after EST. Early complications occurred in 19% of the patients who underwent EPBD as compared to 39% of the patients who underwent EST. Endoscopic stone removal in patients with a prior Billroth II gastrectomy and Billroth II anastomosis poses one of the great challenges to the biliary endoscopist. Several methods

and instruments have been developed to enable EST in Billroth II patients.10 Currently, the most widely accepted technique consists of a needle-knife sphincterotomy over a previously inserted endoprosthesis.20 Compared to standard EST in the normal anatomic situation, all of these techniques are more demanding and probably 99

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A

B

C

D

E

F

Fig. 11.4 Endoscopic images of EPBD in a patient with a CBD stone and a papilla with an intradiverticular location. A The major papilla is located in the diverticulum. B Small EST is performed. C,D After cannulation of a guidewire, the balloon catheter is inflated over the guidewire up to 15 mm. E,F After removing the balloon, the stone is evacuated with a basket catheter through the widely opened papilla.

associated with a smaller sphincterotomy incision, less successful stone removal, and a higher rate of acute complications.14 When EST is used for such patients, careful consideration must be given to the direction and length of the incision, and a high level of skill is required to avoid severe complications. With EPBD, however, once a catheter is inserted into the common bile duct, the balloon catheter is simply inserted and the balloon is inflated. Therefore, patients with Billroth II anatomy apppear to be especially suited for stone removal using EPBD.

LIMITATIONS OF EPBD The success of stone removal and procedure time varies between EPBD and EST. Vlavianos et al. performed a univariate logistic regression analysis assessing the success of bile duct stone removal after EPBD. The following parameters were analyzed: sex, age, randomization, presentation with jaundice, acute cholangitis or acute pancreatitis, diameter of the common bile duct (CBD) on the initial cholangiogram, number of stones, and size of the largest stone. Of these, age, diameter of the CBD, and size and number of stones were significantly associated with success (Table 11.1). Multivariate logistic regression analysis showed that only the size of the largest stone was an independent predictor of success for duct clearance. On average, these patients had a 12-mm diameter CBD and up to two 10-mm stones. These were taken as cut-off points in the statistical analysis.11 Larger stones are more difficult to remove using EPBD because the biliary opening is enlarged to a greater degree with EST. In fact, in many patients in the studies examined in the analysis by Baron et al. comparing EPBD to EST, patients were excluded based on 100

Variable a

Odds ratio

95% CI

Likelihood ratio c2

P Value

0.98

0.95–1.00

3.88

0.049

CBD diameter (mm) 2

2.08 1

0.90–4.80

7.5

0.024

Size of stone (mm) 5 mm in the body (Table 14.3). Type 1 pancreatic SOD has all three components. Type 2 SOD has pancreatic-type pain, plus (b) or (c). Type 3 SOD has just pancreatic-

type pain. In terms of biliary-type SOD, the criteria are very similar but involve the use of serum liver function tests and delayed drainage of contrast from the biliary tree during ERCP (Table 14.4). Isolated pancreatic-type SOD may be seen in 15–20% of all patients with acute recurrent pancreatitis of unknown etiology.19 It has been estimated to occur in 25% of all patients undergoing manometry for suspected SOD. The overall clinical response rate of endoscopic sphincterotomy for SOD (biliary and pancreatic) ranges between 55 and 95%. Patients with Type 1 pancreatic SOD are most likely to benefit from a pancreatic sphincterotomy. Several studies have shown that these patients may experience a significant reduc137

SECTION 2 TECHNIQUES

Fig. 14.6 Biliary sphincter of Oddi manometry. (Reproduced by permission of Gastroenterology and Hepatology, Johns Hopkins Hospital.) (a) pancreatic-type pain (b) amylase/lipase >1.5–2.0 X’s normal (c) pancreatic duct diameter >6 mm in the head, or >5 mm in the body • Type 1 pancreatic-type SOD = (a), (b), (c) • Type 2 pancreatic-type SOD = (a), plus (b) or (c) • Type 3 pancreatic-type SOD = (a) only

Table 14.3 Modified Milwaukee classification for pancreatic-type sphincter of Oddi dysfunction. Adapted from Novak and AlKawas19 by permission of BC Decker Inc.

(a) biliary-type pain (ROME criteria) (b) abnormal AST or alkaline phosphatase >2 X’s normal, on two or more occasions (c) delayed drainage of contrast from the common bile duct on ERCP >45 minutes, and a dilated common bile duct >12 mm • Type 1 biliary-type SOD = (a), (b), (c) • Type 2 biliary-type SOD = (a), plus (b) or (c) • Type 3 biliary-type SOD = (a) only

Table 14.4 Milwaukee classification of biliary-type sphincter of Oddi dysfunction. Adapted from Novak and Al-Kawas19 by permission of BC Decker Inc. tion in pain and clinical episodes of pancreatitis. Type 2 pancreatic SOD may also achieve benefit from a pancreatic sphincterotomy, but most experts prefer to document abnormal pancreatic manometry before undertaking sphincterotomy. In addition, more recent studies have suggested a clinical benefit from pancreatic sphincterotomy in 138

those patients who have persistent pain despite prior biliary sphincterotomy.20

Chronic pancreatitis A pancreatic sphincterotomy alone is frequently used as the primary treatment modality in moderate to severe chronic pancreatitis. The rationale for treating chronic pancreatitis with endoscopic therapy is based on the principle of decreasing pancreatic intraductal pressure. In moderate to severe disease, the development of ductal stones, protein plugs, and ductal strictures may occur. Each of these can cause partial or complete obstruction to the flow of pancreatic juice out into the duodenum, resulting in permanent alterations to the duct morphology (Figs 14.7A–14.7B, 14.8A–14.8B). Ductal obstruction leads to tissue hypertension, and thus tissue ischemia. Karanja et al. demonstrated a reduction of pancreatic blood flow after ligation of the main pancreatic duct (thereby producing intraductal hypertension) in a feline model of pancreatitis.21 The reduction of blood flow was partially reversed after relief of the main duct obstruction. It is strongly believed that the symptom of pain in chronic pancreatitis is directly due to this parenchymal ischemia.1 Another consequence of obstruction of the main pancreatic duct is secondary obstruction of the smaller side branch ducts. This ultimately causes parenchymal atrophy. As the tissue begins to atrophy, the pancreas loses its ability to perform both its endocrine and exocrine functions. A therapeutic intervention that could minimize intraductal pressure might help to prevent this dangerous cascade of events, thus diminishing pain and preserving pancreatic function. This is the basis behind sphincterotomy in chronic pancreatitis. Few studies have specifically examined the role of pancreatic sphincterotomy as the sole endoscopic therapy in chronic pancreati-

Chapter 14 Pancreatic Sphincterotomy

Fig. 14.7 Changes to the ductal morphology seen in moderate severity chronic pancreatitis. (Reproduced by permission of Division of Gastroenterology and Hepatology, Johns Hopkins Hospital.)

Fig. 14.8a–b Changes to the ductal morphology seen in severe chronic pancreatitis. (Reproduced by permission of Division of Gastroenterology and Hepatology, Johns Hopkins Hospital.)

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tis. Most studies that have investigated this topic have done so in the context of additional endoscopic interventions. That is, the sphincterotomy is often performed in conjunction with a further intervention (i.e. stent placement or stricture dilatation). Studies in this area need to be examined closely in order to separate those patients who received a sphincterotomy alone versus those who received a sphincterotomy in concert with an additional endoscopic technique. This is often difficult, especially if the authors have not clearly distinguished between the two groups. Nonetheless, several studies have attempted to evaluate the safety and long-term results of pancreatic sphincterotomy in chronic pancreatitis. Ell et al. described pancreatic sphincterotomy in 118 patients with chronic pancreatitis.22 Eighty percent of the patients underwent a standard pull-type sphincterotomy, while 20% underwent a needleknife technique. Overall, 98% of the sphincterotomies performed were successful, and the complication rate was only 4.2% (four cases of moderate pancreatitis, one case of severe bleeding). The results in terms of pain relief were not examined in this study, however. Okolo et al. retrospectively analyzed 55 patients who had a pancreatic sphincterotomy.23 Forty patients (73%) underwent the procedure for the indication of symptomatic chronic pancreatitis. The goal of the study was to assess the long-term efficacy of sphincterotomy with pain relief being the primary endpoint. After a median followup of 16 months, 60% of all patients reported a significant improvement in their pain scores. Papillary stenosis appears to be a clear-cut indication for pancreatic sphincterotomy alone in those patients with symptomatic chronic pancreatitis. Without significant ductal abnormalities distal to the papilla that require some additional form of intervention, sphincterotomy can be confidently utilized as the primary endoscopic therapy of choice in these patients. Similarly, mucinous ductal ectasia involving the proximal main pancreatic duct for pancreatic sphincterotomy has also been proposed as potentially efficacious in patients with recurrent pancreatitis.4

Pancreatic sphincterotomy as secondary therapy Pancreatic sphincterotomy is commonly performed in concert with other endoscopic techniques such as stent placement or balloon dilatation of the main duct. In this setting, the purpose of the sphincterotomy is to help facilitate the primary therapy (i.e. removal of stones from the duct or dilatation of a ductal stricture). There are several diseases and conditions in which pancreatic sphincterotomy is used in this manner (Table 14.2). The decision to cut the sphincter in these situations is based on sound clinical judgment by the endoscopist, and whether or not he feels that the risk of a sphincterotomy is outweighed by the potential benefit that may be gained by aiding the primary therapy. In moderate to severe chronic pancreatitis, ductal strictures and stones are often times the norm. Frequently, their location within the main duct may be very distal to the papilla. Therefore sphincterotomy alone may not be sufficient. Stone removal or stricture dilatation may therefore be the main goal of ERCP for certain patients. Pancreatic sphincterotomy may be needed before the procedure for better access to the duct (precut), or it can be used simply to help reduce intraductal hypertension and allow for easier flow of juice and calculous debris into the duodenum. This also holds true, for example, when treating pancreatic pseudocysts by means of a transpapillary approach. For those pseudocysts that communicate with the main pancreatic duct, a stent is placed within the duct in order to bridge the fistulous connection.24 A pancreatic sphincterotomy in 140

this setting also helps to reduce intraductal pressures and facilitate flow out towards the papilla. Other clinical scenarios for which sphincterotomy has been proposed as secondary therapy include stent placement prior to surgery for mucinous ductal ectasia, as well as stent placement in the treatment of a pancreatic fistula.4 Pancreatic sphincterotomy may also be used in concert with a pancreatic stent following the resection of an ampullary adenoma. Here, the purpose of the sphincterotomy (and the stent) is to reduce the risk of post-procedural pancreatitis due to periampullary edema. Finally, sphincterotomy is often indicated for the palliative treatment of strictures, stones, and pseudocysts in malignant obstruction of the pancreas.

COMPLICATIONS OF PANCREATIC SPHINCTEROTOMY Although the first endoscopic pancreatic sphincterotomy was performed almost 30 years ago, the technique has not been used nearly as often as biliary sphincterotomy.25 The reason for this is partly due to past uncertainty about its indications, and also concerns over the relatively high likelihood of complications related to this procedure.26 When discussing the complications associated with pancreatic sphincterotomy, it must be remembered that studies which have evaluated this topic are generally small in number and have a small number of participants. They are usually performed at expert referral centers only, and they most often do not have control groups.2 Furthermore, most of the studies report on pancreatic sphincterotomy as it is used to facilitate other endoscopic maneuvers, such as pancreatic stent placement, balloon dilatation, or stone removal. Therefore it is often difficult to decipher which maneuver is truly responsible for the complication. For example, is the resultant pancreatitis due to the stricture dilatation alone, or the sphincterotomy that was first required to access the duct? These are the types of issues that complicate the literature in this area of study. It is on this background in which we discuss the complications that are associated with pancreatic sphincterotomy. In general, there are essentially three different types of complications associated with pancreatic sphincterotomy: early, late, and stent-related complications (Table 14.5).26 Early complications are usually recognized within the first 72 hours after the procedure, but

Early complications (5 mm cutting wire into the orifice and extends the thermal effect into the pancreas, not just the duodenal wall “sphincter zone.” However, a recent database review from our unit showed that >80% of the last 100 minor papilla sphincterotomies were done by the pull technique.

Minor papilla endoscopic sphincterotomy technique—pull type Once a 0.018–0.025 inches guidewire is securely advanced intraductally to at least the mid body of the dorsal duct, the sphincterotome is advanced with the cutting wire oriented toward the 10–11 o’clock position. This is often the unadjusted orientation after sphincterotome passage. Alternatively, this may require the “long scope” position. The pull back “short scope” position tends to cut more toward the 11–12 o’clock position. The latter cut tends to produce more coagulation and probably results in an overall smaller orifice. The papilla is positioned in the lower to mid visual field on the video monitor (Figs 15.6–15.7). This allows for better view of the target tissue. The pull endscopic sphincterotome is then positioned with 3–4 mm of cutting wire into the orifice. The cut is initiated with 2–3 half-second taps on the cautery activation foot pedal. If cutting

Fig. 15.7 Minor papilla sphincterotomy in setting of redundant folds. The cut was in the 11–12 o’clock direction. The upper margin of the papillary mound is less certain.

begins, the foot pedal is continuously activated until the cut is nearly complete. The last 1 mm cut is performed again with 1–2 taps on the cautery activation foot pedal. If no cutting is initiated (only white char) after 2–3 taps followed by 1 second of continuous activation, then all cutting is stopped and the remainder of the sphincterotomy is performed using the needle-knife method. The cut is extended into the 10–11 o’clock direction as directed by the intraductal wire. Pulling back on the bowed sphincterotomy helps expose the available cutting space (Fig. 15.8). The sphincterotome is bowed so as to achieve moderate tension on the tissue. This allows more rapid cutting with less char. Inadequate wire contact results in inadequate cutting and may result in excess coagulation. Precise cutting requires a relatively “dry” field. Repeated fluid aspiration may be required. Excessive bile, pancreatic juice or other fluid in contact with the cutting wire will divert current away from the target tissue (Fig. 15.9). Such a pool of fluid may boil and broadly coagulate the surrounding tissue. This may result in 145

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A

B

Fig. 15.8 A Pulling out (back) on pull sphincterotome helps to better delineate papillary mound and cutting zone. B Pull out view accentuating the minor papilla mound and better defining the safe cutting zone.

Fig. 15.10 Minor papilla sphincterotomy by pull technique sequence. With placement of 5 French stent, our current recommendation is to use small caliber stents, e.g. 3 French.

Fig. 15.9 Minor papilla after ~80% of mound has been cut toward the 10–11 o’clock position. After suctioning bilious fluid, the upper rim of mound was cut.

serious stricture formation. Fluid pooling is especially problematic if secretin was given to aid orifice identification. Pancreatic stent placement with juice diversion and needle-knife sphincterotomy are then recommended. The goal is to cut to the upper rim of the minor papilla mound per se. Alternatively, some of our team members prefer to stop 1 mm short of the minor papilla-flat wall junction (Figs 15.10, 15.11). We attempt to orient the cutting wire perpendicular to the duodenal wall. This helps to limit excessive thermal effect to the intramural portion and avoid ductal injury. If the minor papilla mound is very small, the cut may extend 1–2 mm cephalad to the mound. With a small minor papilla, the “completed cut” minor papilla allows an approximately 1/4–1/3 bowed sphincterotome to pull through the sphincter. For a larger papilla, a 1/3–1/2 bowed 25 mm wire sphincterotome will pull through the sphincterotomy with only mild resistance. To view the ductal lumen per se is usually only possible with “large” papilla cases. After pull endoscopic sphincterotomy, a temporary pancreatic stent is placed in nearly all cases. Occasionally, in advanced chronic pancreatitis, with very dilated dorsal pancreatic duct (>8 mm), stent 146

Fig. 15.11 View of minor papilla 19 months after endoscopic sphincterotomy. Note no papillary mound remains. The cut extended up to the flat wall.

placement is not needed. Over the last 15 years, stent experience has now led to preferred use of very small diameter (3 Fr) 6–8 cm long polyethylene stents with no intraductal barb.5 We prefer a 3/4 pigtail for the duodenal end but double barbs in duodenum are acceptable. The intraductal length serves as a friction anchor (without barb) yet the small diameter causes less “ductitis” than larger diameters. We have abandoned 2–3 cm 5 Fr stents as the intraductal ends cause more focal ductitis (and occasionally strictures). This occurs especially when the firm stent tip abuts the wall perpendicularly at an angulation in the duct.

Chapter 15 Minor Papilla Endoscopic Sphincterotomy

A follow-up plain abdominal x-ray must be obtained in approximately two weeks to confirm spontaneous stent passage. Residual intraductal stents (5–10% of patients) require endoscopy with stent extraction. Patients who refuse follow-up are problematic. For patients who are predicted to be unreliable at follow-up, alternatives include: (1) hospitalization and stent removal 2–3 days later (if not passed spontaneously), or (2) placement of a nasopancreatic catheter for a duration of 2–3 days. The minimal interval for effective post sphincterotomy protective pancreatic stenting has not been defined but we suspect it is 2–3 days.

Needle-knife sphincterotomy over pancreatic duct stent After wire passage deep into the dorsal duct, a pancreatic stent is placed as noted above. Care is taken during final stent delivery (final guidewire withdrawal) to maneuver the pigtail toward the descending duodenum (downward) (Fig. 15.12). This aids minor papilla viewing during cutting and at times lifts the minor papilla up for easier cutting. For cutting, the minor papilla is positioned in the lower to mid visual field on the video screen. This allows better view of the upper rim of the minor papilla. The needle-knife should be maneuvered over the cutting zone of the minor papilla orifice to the upper extent of the minor papilla mound in a “dry run” fashion being sure that the accessory channel

A

B

elevator permits a full extent excursion of this distance. The cut is then initiated (usually start at orifice then cephalad) by lightly hooking (embedding) the terminal 1–2 mm of needle-knife wire into the minor papilla orifice (Fig 15.13). Light, but definite cephalad tension is placed on the wire and current activation done. We generally use continuous foot pedal activation with the ERBE cautery generator while sweeping the needle-knife cephalad over nearly the full extent of the minor papilla mound. This sequence is repeated cutting another 1–2 mm deeper into the mound and exposing more intramural stent. The cut tissue tends to retract exposing the deeper tissue. The cut is extended cephalad until the upper mm of the minor papilla mound is divided. The needle-knife catheter (with needle retracted) is then passed alongside the stent into the pancreatic duct. If the orifice does not permit this, cutting 1–2 mm of the tissue touching the upper rim of the stent is done until cannulation permitted. The above cutting is done in the 10–11 o’clock direction—precisely over the stent. An alternative cutting method is to start at the apex of the anticipated cut and cut downward onto the stent. This more precisely defines the most cephalad extent of the cut. Unintentionally cutting more cephalad than desired can more easily be avoided.

PRECUT SPHINCTEROTOMY TECHNIQUE Precutting refers to cutting the minor papilla without prior deep cannulation, wire passage, or stent placement (Fig. 15.14). Precutting is more risky than the above techniques because if cannulation fails there is no protective pancreatic duct stent. Careful risk:benefit analysis should therefore precede any decision to initiate precut sphincterotomy. Three subcategories exist: (1) minor papilla orifice evident; (2) no minor papilla orifice seen; (3) Santorinicele present.

Precut minor papilla—orifice seen

Fig. 15.12 A Pigtail stent placement with downward placement of pigtail. This facilitates cephalad view of cutting space. B Cutting with needle-knife over stent.

In such cases, the orifice usually can be entered 1–2 mm even if not deeply cannulated. In most cases, Secretin (ChiRhoClin, Inc. Silver Spring, MD) 0.2 mcg/kg IV has already been given to aid orifice identification. The needle-knife cutting wire is extended 1– 2 mm and impacted in the orifice cephalad rim. Cutting is then done toward the 10–11 o’clock direction in identical fashion as to needleknife over stent. We prefer to cut all the way to the rim of the papilla. A second cut is then made 1–2 mm deeper into the base of the first incision or slightly left or right of the first incision. If secretin was

Fig. 15.13 Diagram of needle-knife over pancreatic stent technique.

147

SECTION 2 TECHNIQUES

A

B

C

D

Fig. 15.14 A Minor papilla with orifice seen (arrow) as pink dot in blue background. Secretin was given 10 minutes prior to aid orifice identification. B After precut minor papilla sphincterotomy. C Deep cannulation achieved and sphincterotomy completed by pull technique. D 3 French plastic stent placed after sphincterotomy.

Fig. 15.16 Santorinicele. Dorsal ductogram showing saccular dilation of downstream terminal end of duct.

attempted with a soft tip guidewire (e.g. Metro 0.021–0.025 inches or a blunt tip guidewire such as 0.035 Teflon-coated stainless steel coil wrapped wire (Cook Endoscopy, Winston-Salem, NC)). Gentle probing is mandatory and helps avoid bleeding, which may obscure landmarks. Probing should be toward the 10–11 o’clock direction varying from 45 to 90 degrees (perpendicular) to the wall. If cannulation fails and the precut area maintains a clear view, additional shallow cuts of 3–4 mm length and 1–2 mm depth can be made on each side of the original cut or into the base of the first cuts. Secretin use and gentle probing continue until successful ductal entry or termination of the procedure. With ductal entry, completion sphincterotomy is done with either pull technique or needle-knife over stent technique as needed above. If no ductal entry is achieved, repeat cannulation attempt is best delayed at least 4 weeks until complete healing of the precut area is achieved, if the clinical conditions permit such waiting time.

Precut—no orifice seen When considering precutting and no orifice (and usually no juice flow) can be identified, review carefully whether pancreas divisum or need for minor papilla therapy really exists. If suspicion/need remains high, proceed as follows: Precut identically as above except start on the lower rim of the minor papilla or the point on the minor papilla that the orifice seems most likely. Cut 2–3 mm length, or preferably to the upper rim of the minor papilla. Make 1or 2 cuts, probe gently, administer Secretin if needed, apply methlylene blue, cut 1–2 more shallow incisions, etc. All other aspects are as described in the preceding section above. Occasionally, flaps of tissue between incisions will need removal with small biopsy forceps.

Precut—with Santorinicele Fig. 15.15 Initially minor papilla not found. The duodenum was then washed with a methylene blue solution. Dot of pancreatic juice seen at minor papilla orifice after Secretin stimulation (arrow).

not previously given, or its effect has worn off, repeat dosing is done and the surface of the precut area is washed with a solution of 1 ml methylene blue in 9 ml water with a few drops of simethicone solution (antifoaming properties). Pancreatic juice flow, if present, will be seen as a tiny clear fluid spot or stream amidst the blue stained background mucosa (Fig. 15.15). Deep cannulation is then gently 148

Approximately 15% of minor papillae have saccular dilation of the terminal dorsal duct beneath the duodenal mucosa and papillary mound (Fig. 15.16).8 This has been named a Santorinicele (after the accessory duct of Santorini). In such cases, the mound (bulge) is usually prominent, especially after contrast filling of the dorsal ductal system or after Secretin stimulation. Five to ten minutes after Secretin, the bulge is usually maximal and may have a bluish color. The wall thickness, (distance between the duodenal lumen and saccular lumen) is usually less than 2 mm. Therefore a 2–3 mm long 1–2 mm deep needle-knife incision over the dome (center) of the bulge will usually enter the ductal lumen. Occasionally a second deeper incision is needed. Completion sphincterotomy can be done

Chapter 15 Minor Papilla Endoscopic Sphincterotomy

A

B

Fig. 15.17 A Major and minor papilla orifices two years after sphincterotomies. Slit-like minor papilla orifice (upper arrow) seen with no residual mound. B Due to recurrent pancreatitis episode, a 4 mm balloon dilation done and minimal further cutting done.

Fig. 15.19 Standard 5 Fr triple lumen aspiration type manometry catheter (courtesy of Cook Endoscopy, Winston-Salem, NC) used to measure minor papilla “sphincter” pressure in this re-evaluation case. Prior sphincterotomy was 2 years ago.

pressure9 (Fig. 15.19). The rationale for use of the same cut-off values is that the pancreatic parenchyma probably does not tolerate secretion against a barrier >40 mmHg, whether through the major or minor papilla. Alternatively, the orifice can be probed with a 5, 6, and 7 Fr tapered catheter over a guidewire. If more than minimal resistance to passage is detected (similar to passage of esophageal dilators) by the 6 Fr catheter, the manometry will usually detect >40 mmHg basal sphincter pressure.

OUTCOMES Fig. 15.18 Re-do minor papilla sphincterotomy case. After pull sphincterotome extension of cut to the flat duodenal wall, two 5 French internally unflanged plastic stents placed.

by pull or needle-knife technique. The final sphincterotomy length is often larger (5–8 mm long) if the bulge was large.

Re-do minor papilla sphincterotomy Re-do cases—in which there has been a previous minor papilla sphincterotomy—are more difficult, as the papillary mound has usually been nearly or fully ablated (Fig. 15.11). If residual cutting space is clearly present, we proceed with sphincterotomy—either pull or needle-knife. If there is no obvious residual cutting space seen, we prefer to dilate the orifice using a push dilator to 7 Fr (or larger if the dorsal duct is >4 mm) or with a 4 mm balloon. After dilation, a small cut zone may become evident. If intramural cutting space is then seen, pull or needle-knife sphincterotomy extensions can be done with the cut extending 1–2 mm up onto the flat wall (Fig. 15.17). In re-do cases we commonly place two stents of 3–5 Fr diameter, then cut 2–3 mm further from the upper rim (Fig. 15.18). Care is taken to cut tissue and coagulate minimally. Excess coagulation current probably contributes to scar formation and re-stenosis. The optimal follow-up duration of stenting is unknown. We prefer unflanged stents and check for passage one to two months later using a plain abdominal radiograph. If there is no cutting space, dilation followed by stenting alone is done. Precise methods to detect when the minor papilla orifice is still “too tight” have not been defined. We often use manometry techniques identical to those for the major papilla and use a pressure of 40 mmHg as the cut-off for upper limits of normal for basal sphincter

Efficacy of minor papilla therapy is variable according to the underlying disease state10–15 (Table 15.3). Patients with acute recurrent pancreatitis are most likely to benefit from minor papilla intervention with 77% of 164 patients in Table 15.3 followed up for more than two years having no or fewer hospitalizations from pancreatitis flares. We offer minor papilla therapy to patients with a clinical course of acute recurrent pancreatitis if they have had at least two hospitalizations. Therefore, we usually do not offer minor papilla therapy after a single bout of pancreatitis (unless the CT scan shows evidence of dorsal duct dilation/obstruction/or stones). Long-term (10–20 years) outcomes are awaited. Patients with chronic pain alone (but often with endoscopic ultrasound evidence of chronic pancreatitis) and patients with chronic pancreatitis changes by ERCP or computed tomography have improvement rates of 30–40% (Table 15.3). These latter patients are often disabled and on chronic narcotics. Such “desperate” patients make us more willing to offer trial therapy even if results are suboptimal. Preliminary results from a prospective randomized trial of medical vs endoscopic therapy for “pain only” patients with pancreas divisum has been reported.16 This trial is ongoing.

Complications of minor papilla sphincterotomy Acute complications of minor endoscopic sphincterotomy are similar to major endoscopic sphincterotomy except perforations are less frequent. Pancreatitis rates are similar to other high-risk groups such as idiopathic pancreatitis and sphincter of Oddi dysfunction. Table 15.4 summarizes our large series. Management of complications is nearly identical to that of major papilla sphincterotomy. We have little experience with management of perforations, but would expect most to be small size and easily 149

SECTION 2 TECHNIQUES

Author/year

Therapy

Mean follow-up (mo)

Coleman/1994 Sherman/1994 Kozarek/1995 Heyries/2002 Bierig/2003 Linder/2003 Borak/2005

MiES/stent MiES MiES/stent MiES/stent MiES MiES MiES

23 28 20 39 19 NG (range 1–120) 44

Total

28

ACUTE RECURRENT PANCREATITIS

PAIN ONLY

CHRONIC PANCREATITIS

n

% improved*

n

% improved*

n

% improved*

9 0 15 24 16 38 62

78 — 73 92 94 58 89

5 16 5 0 7 12 29

0 44 20 — 43 0 69

20 0 19 0 16 4 23

60 — 32 — 38 25 43

164

77

74

33

82

41

Table 15.3 Selected series of endoscopic minor papilla therapy for pancreas divisum MiES = Minor papilla sphincterotomy. % of patients improved assessed by overall clinical status. NG = Not given. W:P:MiPaRxPD

Pancreatitis Mild Moderate Severe Bleeding Mild Moderate Severe Perforationc Mild Moderate

Total

13.2%

10.9% 1.9% 0.4% Total

1.0%

.6% .1% .3% Total

.2%

.1% .1%

Table 15.4 Complicationsa of a minor papilla sphincterotomyb in 778 procedures in pancreas divisum (from reference no. 17 with permission) a

Definitions per reference—Cotton et al.17 Database search of 12 year experience at Indiana University Medical Center. c Intraprocedure only (does not include delayed stent induced perforations).

b

managed with pancreatic stent and nasoduodenal decompression. Immediate bleeding during cutting will resolve spontaneously in >80% of cases. If bleeding occurs during needle-knife over stent technique, the pancreatic duct is already stented and protected. This allows use of epinephrine 1 : 10 000 injection (0.5–2 ml/injection) into/around the bleeding site. If bleeding persists, bipolar coaptive cautery is done at setting of 15–20 watts. Care is taken to cauterize focally (not diffusely) in order to limit subsequent scar formation. Persistent bleeding is usually a reflection of a coagulopathy which may then need correction. Pancreatic stenting has decreased (but not eliminated) the frequency and severity of post-ERCP pancreatitis, including for minor papilla settings. If pancreatitis occurs after a stent is placed, pancreatitis is mild and resolves in 1–3 days. More severe pancreatitis warrants a CT scan to exclude simultaneous post-sphincterotomy perforation or stent-related ductal perforation. Such stent perforations may occur at sharp angulations of the main duct or out a side branch. Such stents need urgent endoscopic stent removal or pull back. Pancreatitis may occur with early (>24 hr) spontaneous stent passage. In this situation we do not usually replace the stent but are 150

aware of one center which does so (without published supportive data). The most important long-term complication of minor papilla sphincterotomy is re-stenosis. This occurred in nearly 20% of one tallied series.18 Whether this represents natural healing of a congenitally small orifice or scar formation after cautery and manipulation is unknown. Such re-stenosis can be difficult to manage, as the stenotic zone may extend 2–5 mm outside the duodenal wall and into the head of the pancreas. A randomized trial of steroid injection (20 mg triamcinolone) into the sphincterotomy zone numerically (not statistically significantly) decreased the re-stenosis rate from 23 to 15% over a mean follow-up period of 47 months.18 Cutting space is often not present for either extension of the sphincterotomy or surgical sphincteroplasty. We offer such patients a series of sequential plastic stents or surgical decompression (usually lateral pancreaticojejunostomy).19 Our goal is to progressively dilate the narrowing until at least two 6 French stents can be placed side by side, left in situ for 1–2 months, and subsequently removed (if not passed spontaneously). Outcome from a series of such patients has not yet been tallied. Trials of pure cutting current sphincterotomy to prevent re-stenosis are awaited.

SUMMARY The techniques of minor papilla sphincterotomy have been derived largely from biliary and major papilla pancreatic sphincterotomy. Therapeutic efficacy and complication rates are similar to major papilla techniques. It is recommended that these techniques be performed by endoscopists at referral centers with large ERCP volumes. Long-term outcomes from such intervention and comparative randomized trials with stenting alone20 or surgical sphincteroplasty would be of interest.

Acknowledgement The authors are grateful to Joyce Eggleston for the technical compilation of this document.

Chapter 15 Minor Papilla Endoscopic Sphincterotomy

REFERENCES 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

Fischer M, Fogel EL, McHenry L, et al. ERCP/manometry in 1108 idiopathic pancreatitis patients. Gastrointest Endosc 2005; 61:190A. Park S-H, de Bellis M, McHenry L, et al. Use of methylene blue to identify the minor papilla or its orifice in patients with pancreas divisum. Gastrointest Endosc 2003; 57:358–363. Alsolaiman M, Cotton, P, Hawes R, et al. Techniques for pancreatic sphincterotomy: Lack of expert consensus. Gastrointest Endosc 2004; 59:AB210. Gorelick A, Cannon M, Barnett J, et al. First cut, then blend: an electrocautery technique affecting bleeding at sphincterotomy: Randomized controlled trial. Endoscopy 2001; 33(11):976–980. Rashdan A, Fogel EL, McHenry L, et al. Improved stent characteristics for prophylaxis of post-ERCP pancreatitis. Clin Gastrointest Hepatol 2004; 2:322–329. Smith M, Ikenberry S, Uzer M, et al. Alterations in pancreatic ductal morphology following pancreatic stent therapy. Gastrointest Endosc 1996; 44:268–275. Sherman S, Alvarez C, Robert M, et al. Polyethylene pancreatic duct stent-induced changes in the normal dog pancreas. Gastrointest Endosc 1993; 39:658–664. Eisen G, Schutz S, Metzler D, et al. Santorinicele: new evidence for obstruction in pancreas divisum. Gastrointest Endosc 1994; 40:73–76. Fogel EL, Sherman S, Kalayci C, et al. Manometry in native minor papillae and post minor papilla therapy: experience at a tertiary referral center. Gastrointest Endosc 1999; 49:187A. Coleman SD, Cotton PB. Endoscopic accessory sphincterotomy and stenting in pancreas divisum. Gastrointest Endosc 1993; 39:312.

11. Linder JD, Bukeirat FA, Geenen JE, et al. Long-term response to pancreatic duct stent placement in symptomatic patients with pancreas divisum. Gastrointest Endosc 2003; 57:208A. 12. Lehman GA, Sherman S, Nisi R, et al. Pancreas divisum: results of minor papilla sphincterotomy. Gastrointest Endosc 1993; 39:1–8. 13. Heyries L, Barthet M, Delvasto C, et al. Long-term results of endoscopic management of pancreas divisum with recurrent acute pancreatitis. Gastrointest Endosc 2002; 55:376–381. 14. Bierig L, Chen YK, Shah RJ. Patient outcomes following minor papilla endotherapy (MPE) for pancreas divisum (PD). Gastrointest Endosc 2006; 63:313A. 15. Borak G Alsolaimon M, Holt E, et al. Pancreas divisum: long-term follow up after endoscopic therapy. Gastrointest Endosc 2005; 61:149A. 16. Sherman S, Hawes R, Nisi R, et al. Randomized controlled trial of minor papilla sphincterotomy (MiES) in pancreas divisum (Pdiv) patients with pain only. Gastrointest Endosc 1994; 40:125A. 17. Cotton PB, Lehman GA, Vennes J, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991; 37(3):383–393. 18. Toth TG, Sherman S, Fogel EL, et al. Does intrapapillary steroid injection improve the efficacy of minor sphincterotomy in pancreas divisum? Gastrointest Endosc 2001; 53:60A. 19. Madura JA, Canal DF, Lehman GA. Wall stent-enhanced lateral pancreaticojejunostomy for small-duct pancreatitis. Arch Surg 2003; 138:644–650. 20. Ertan A. Long-term results after endoscopic pancreatic stent placement without pancreatic papillotomy in acute recurrent pancreatitis due to pancreas divisum. Gastrointest Endosc 2000; 52:9–14.

151

SECTION 2

Chapter

16

TECHNIQUES

Plastic Pancreatic and Biliary Stents: Concepts and Insertion Techniques Todd H. Baron and Jeffrey L. Ponsky

INTRODUCTION AND SCIENTIFIC BASIS The use of plastic biliary stents for drainage of the bile duct was described over two decades ago1 and plastic stents are now used in the biliary tree for a variety of therapeutic indications.2 Applications in pancreatic disease have also developed.2 These stents are used for malignant and benign conditions and have proven reliable and safe in decompression of the biliary tree. Palliative insertion of biliary stents relieves distal biliary obstruction as effectively as surgical bypass.3 Plastic stents are available in a variety of configurations and lengths and are composed of Teflon, polyethylene, or polyurethane (Tables 16.1 and 16.2).2 Common configurations are straight, single pigtail, or double pigtail (Fig. 16.1A–16.1B). All plastic stents have limited patency due to occlusion with debris and biofilm (Fig. 16.2)4–6 and require periodic replacement when long-term drainage is required. Nearly all stents of the same diameter have similar patency rates. One 10Fr stent with a unique double layer design (Fig. 16.3) was shown in one study to have prolonged patency as compared to standard stent design.7 Plastic stents have been demonstrated to be easy to insert, effective for decompression, and inexpensive to use. Almost all plastic stents are hollow tubes. Side holes are present to a variable degree, but uniformly present in pancreatic duct stents to allow side branches to drain (Fig. 16.4). Recently, a star-shaped stent with a limited central lumen (Fig. 16.5) has become available for both biliary8 and pancreatic insertion (Viaduct, GI Supply®, Camp Hill, PA).9 The central lumen allows only a guidewire and is inserted without an inner guiding catheter even at 10 Fr diameter (see stent systems below). A new S-shaped pancreatic stent has been introduced which may have less potential for migration and a prolonged patency.10 Finally, a new biliary stent with an antireflux valve (wind-sock) has recently become available to prevent stent occlusion due to food and vegetable material (Cook Endoscopy, WinstonSalem, NC) (Fig. 16.6). This stent may have improved patency over conventional large bore 10 Fr stents.11

STENT SYSTEMS A variety of stent systems are available as discussed in Chapter 4. Stents of less than 8.5 Fr diameter are placed directly over a guidewire using a pusher tube or sphincterotome. Stents of greater than 8.5 Fr diameter typically come with an inner guiding catheter which passes over the guidewire (Fig. 16.7); the stent and pusher tube are then passed over the inner guiding catheter (Fig. 16.8). The inner guiding catheter promotes stability and rigidity which are necessary in passing through tight strictures.

Endoscope requirements For stents of 7 Fr in diameter a diagnostic channel endoscope can be used. However, nearly all modern duodenoscopes are equipped with a therapeutic channel (4.2 mm) which can accommodate stents up to 11.5 Fr in diameter.

Description of technique: biliary Because 10 Fr stents have a patency that is superior to 7 Fr stents, it is recommended that all patients with malignant disease who are undergoing plastic stent placement receive 10 Fr stents, if possible, so as to limit the number of endoscopic procedures required for long-term palliation.

Distal biliary obstruction The approach to distal biliary strictures is slightly more straightforward than for hilar tumors and will be discussed separately. After successful deep cannulation of the biliary tree contrast is introduced to clearly elucidate the margins of the stricture to allow the appropriate stent length to be chosen. The stricture is traversed with a guidewire. It is important to pass the wire well proximal to the stricture to prevent wire loss and to provide mechanical advantage. In general, a biliary sphincterotomy is not required for successful single 10 Fr stent insertion.12 If multiple stents are to be placed, however (for example in patients with benign disease in whom multiple stents are required), a biliary sphincterotomy is required. The guidewire is left in place. For placement of a single 10 Fr stent across a distal biliary stricture it is rarely necessary to dilate the stricture, since the mechanical advantage is great enough to overcome resistance. In cases of uncertainty, a 10 Fr dilating catheter (e.g. Soehendra dilator, Cook Endoscopy, Winston-Salem, NC) can be passed. If it traverses the stricture, then a 10 Fr stent will also traverse the stricture. Otherwise, hydrostatic balloon dilation can be performed. When the insertion of multiple stents is planned, stricture dilation is essential. In this setting, additional guidewires may be placed prior to placement of the first stent or may be passed alongside the first stent after its placement. When multiple stents are placed, it may be useful to place a slightly longer stent first as the friction of the second stent insertion may result in upward movement of the stent. If the first stent is too short it may disappear into the duct. This is usually of no consequence assuming that the stent is still across the stricture. The stent’s length should be selected based upon the distance from the papilla to the proximal edge of the stricture plus an additional 2 cm. Excessively long stents should be avoided as migration tends to occur until the proximal end of the stent impacts the top of the stricture; meanwhile, the distal end of the stent may then 153

SECTION 2 TECHNIQUES

MANUFACTURER/SHAPE ConMed ACS Size (F)a 5 6 7 8.5 10 11.5 12 Length (cm) 1 2.5 3 4 4.5 5 6 6.5 7 8 8.5 9 10 10.5 11 12 12.5 13 14 15 >15 Material Nylon Polyethylene Polyurethane Teflon Two layer Operator centered system Price Stent With delivery system With operator centered system

DP

Hobbs Medicalb ACS DP

√

√

√

√

√

√

√

√

√ √ √ √ √

√

√ √

Microvasive ACS DP

√

√

√

√

√

√

√ √

√

√ √

√

√

√

√

√

√

√

√

√

√

√

√

√

√

√ √ √

√c

√

√ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √

√ √

No 60 115–130 N/A

No 40 86 N/A

Yes 69 119–159 139

DP

√

√

√ √

Olympus ACS

Yes 45–47 117–198 N/A

Cook Endoscopy ACS DP

√ √ √ √

√ √ √ √

√ √ √

√

√

√

√ √ √ √

√

√ √

√

√ √

√ √

√ √

√

√ √ √ √

√

√ √ Yes 57 123 123

Table 16.1 Plastic biliary stents (from reference no. 2 with permission) ACS, Angled, curved, or straight; DP, double pigtail. a Stents >10 Fr require a 4.2 mm channel duodenoscope. b Hobbs Medical did not disclose their stent material for this review. c Covered with hydromer coating.

impact the opposite duodenal wall causing perforation (Figs. 16.9A and 16.9B). As a rule of thumb, most pancreatic cancers producing biliary obstruction will be adequately managed with 5 or 7 cm long stents. Measuring of the stricture can be achieved in several ways. One way is during withdrawal of the initial cannulating catheter. When the catheter is at the proximal end of the stricture, the endoscopist holds the catheter just outside of the biopsy port; the catheter is then withdrawn until it is seen just outside of the papilla. The

154

distance from the endoscopist’s fingers to the biopsy port is measured, which is the minimal length of stent required to cross the lesion. Another way is to use the radiograph to “measure” the length from the top of the stricture to the tip of the endoscope when pressed against the papilla; the diameter of the endoscope serves as the comparison measuring point to account for the magnification factor. The following equation can be used to solve for the unknown (stricture length, Figure 16.10A–16.10B):

Chapter 16 Plastic Pancreatic and Biliary Stents: Concepts and Insertion Techniques

MANUFACTURER/SHAPE

Feature Size (F) 3 4 5 7 Length (cm) 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Material Price ($) (stent/preloaded)

GI Supply S

SP

Hobbs Medical S SP

√ √

√ √

√

√

√

√

√

√

√

√

√

√

√

√

Polyurethane 58

√ √

√

√

√

SP

Cook Endoscopy S SP √ 5, 7, 9

√ √

√ √

Olympus S

Not availablea 40

√ √ √ √ √ √ √

Polyethylene 49

√ 3–15 √

√ √ √ √ √ √ √ √ √ √ √ √ √

√ √ √ √ √ √ √ √ √ √ √ √ √

Polyethylene 57/123

Table 16.2 Pancreatic stents (from reference no. 2 with permission) S, Straight; SP, single pigtail. a Hobbs Medical did not disclose their stent material for this review.

A

B

Fig. 16.2 Endoscopic photo of occluded 10 Fr stent exiting the bile duct.

Fig. 16.1 Various stents: A Straight 10 Fr biliary stent (courtesy of Olympus America Inc., Melville, NY). B Double pigtail 10 Fr stent (courtesy of Cook Endoscopy, Winston-Salem, NC).

155

SECTION 2 TECHNIQUES

Fig. 16.3

Double-layer design (Olympus).

Fig. 16.7 Cook Endoscopy stent system showing typical 10 Fr design. Inner guiding catheter (arrows), stent (blue) and pusher tube (arrowheads) are seen.

Actual stricture length (X) Actual endoscope diameter = Measured stricture length Measured endoscope diameter

Fig. 16.4 Pancreatic duct stent, Cook Endoscopy. Note side holes.

Fig. 16.5 Magnified photograph of a sagittal section of a Viaduct stent. The flow is through the six channels (C) rather than through the central guidewire lumen (L).

Fig. 16.6 Antireflux stent (MarathonTM, Cook Endoscopy). The antireflux wind sock (white) is seen at the end of the stent. 156

Finally, fluoroscopic markers separated by a known distance are available on some catheters and guidewires and used as a reference point to the stricture and papilla. At this point, the stent is placed. The tapered end is the proximal end. Depending on the type of stent system, either the inner guiding catheter alone or the inner guiding catheter with the stent, are advanced over the guidewire. It is important not to allow the wire to pass too proximally into the biliary tree during this advancement, since this could cause hepatic capsule or intrahepatic ductal injury. On the other hand, excessive traction on the wire may result in wire loss. The stent is then advanced over the guide catheter by advancing the pusher tube, which is a somewhat larger bore and stiffer catheter which approximates the diameter of the stent. During advancement, the elevator should remain closed. When the stent impacts the elevator, the elevator is opened slightly to allow it to emerge from the endoscope channel. The elevator is closed to direct the stent upward and into the papilla. It is imperative to maintain a short endoscope position as close as possible to the papilla to maintain maximal mechanical advantage. Using a series of small movements in which the elevator is sequentially lowered to allow advancement of the stent, and then closed to advance the stent in a “ratchet-like” manner, the stent is advanced into the bile duct. Upward tip deflection as well as withdrawing the endoscope to further shorten it also provides forward motion to the stent. It is important to not allow more than a minimal amount of the stent to be advanced out of the endoscope into the duodenum; excessive length between the endoscope tip and papillary orifice decreases the mechanical advantage to forward advancement. To facilitate forward movement of the stent, the endoscopy assistant must provide traction on the inner guiding catheter. Once optimal stent position is achieved, the inner guiding catheter and guidewire are removed while the endoscopist maintains forward pressure with the pusher tube against the stent to prevent distal dislodgement. If additional contrast is needed to assess drainage or intrahepatic anatomy above the stent, the guidewire is removed prior to removing the inner guiding catheter to allow the injection. The guide catheter and pusher tube are then removed as described above. The process is repeated for additional stent placement.

Chapter 16 Plastic Pancreatic and Biliary Stents: Concepts and Insertion Techniques

Fig. 16.8 Illustration of 10 Fr stent system with stent placed for relief of malignant distal biliary obstruction.

A

B

the duct is then cannulated alongside the first stent with the second stent, guidewire, and inner guiding catheter. The process is continued until all stents are deployed. Alternatively, the stents can be placed one by one alongside each stent (Fig. 16.12). Newer stent delivery systems such as the Fusion (Cook Endoscopy) facilitate placement of multiple stents, since they allow intraductal exchange whereby the wire remains across the stricture between stent placements.

Stents for irretrievable bile duct stones Fig. 16.9 Endoscopic photos of distally migrated 11.5 Fr biliary stent impacted against the duodenal wall opposite the major papilla. A Before removal and B after removal, a small defect is seen.

In patients with short, distal bile strictures in whom multiple stents are to be placed (for example chronic pancreatitis with biliary stricture, post-sphincterotomy papillary stenosis) three to four 10 Fr 5 cm stents can be placed at one time on the inner guiding catheter. Once the first stent is in place (Fig. 16.11), the inner guiding catheter and guidewire are withdrawn just enough to release the first stent;

In the absence of a stricture, pigtail stents (Fig. 16.1b) may be preferable to straight stents when placed in a dilated biliary tree because they are less likely to migrate distally and completely out of the bile duct. Pigtail stents are placed slightly differently than straight stents in that if the distal end of the stent is against the papilla, too much stent has been advanced into the duct to allow the pigtail to form in the duodenum. The stent should be advanced until the portion of the stent that is just proximal to the distal pigtail (identified by applying indelible marker prior to placement if a visible marker is not already on the stent) is visible. The stent is then advanced while simultaneously withdrawing the endoscope so that the pigtail is deployed into the duodenum. 157

SECTION 2 TECHNIQUES

B A

Fig. 16.12 Additional stent insertion. Passage of the catheter alongside the initial stents in order to recannulate and place additional stents. Fig. 16.10 Measurement on the radiograph to calculate stent length. A The measurement from the top of the stricture to endoscope tip when positioned at the papilla (bracket) compared to the diameter of the endoscope (arrowheads) was 7 : 1. B Since the diameter of the endoscope was 11.5 mm, a 9 cm stent was placed.

A

B

be adequate to cross the stricture but too short to be “anchored” in the intrahepatic system are more prone to migrate distally. If it is determined that bilateral stents are to be placed, there are two options for guidewire placement. One way is the placement of two wires, one in each intrahepatic system, prior to placing either stent (Fig. 16.1). The other way is to place the first stent, recannulate the bile duct alongside this stent, and pass the guidewire into the opposite intrahepatic system. There are proponents of both methods, with advantages being the lack of friction within the endoscope channel between the first stent (if 10 Fr) and its larger pusher tube and the “second” guidewire within the endoscope channel. This can be overcome by using a 0.025″ guidewire as the “second wire.” It is important to note that it may not be possible to place bilateral 10 Fr stents during the first session. In that case it may be best to place two 7 Fr stents or one 10 Fr and one 7 Fr stent, then upsize one or both at the second session one month later.

Pancreatic duct stent insertion Fig. 16.11 Insertion of Multiple 10 Fr stents. A The first stent (1) is being pushed by the second stent (2) since the actual pusher tube is still well above the multiple stents loaded onto the catheter. B Final result of four 10 Fr stents, all placed with one passage of the stent introducer system.

Hilar biliary obstruction Hilar biliary obstruction differs from distal obstruction in two ways. Although a sphincterotomy is not needed for placement of a unilateral biliary stent, limited data suggest that hilar stent placement for obstruction carries a higher risk of pancreatitis than for distal obstruction, and pancreatitis, which may be prevented by performing a biliary sphincterotomy.13 Secondly, stricture dilation is frequently required because of the loss of mechanical advantage as the resistance of the stricture is away from the tip of the endoscope. Both of these maneuvers become mandatory when bilateral stents are placed (Fig. 16.13A–16.13C). In general, stents used for hilar tumors are 12–15 cm in length, since the average distance to the bifurcation is 9 cm. Stents that may 158

Pancreatic duct stent placement does not usually require the performance of a pancreatic sphincterotomy, especially since these stents have a small caliber (3–7 Fr). Rarely, 10 Fr stents are placed and even then a sphincterotomy for stent placement alone is usually unnecessary. The diameter of the stent chosen is dependent on the indication as well as the size of the main pancreatic duct. As mentioned previously, smaller diameter stents are passed over the guidewire without an inner guiding catheter. Similar to the biliary stenting process, the site of the pathology is identified, a wire passed into the tail and dilation performed, if necessary. The stent is selected and advanced into place with a pusher tube over the guidewire, although most 5, 6, or 7 Fr stents can be pushed into place using a standard 5 Fr catheter or sphincterotome. The wire is removed while keeping the pusher tube in position as mentioned. The pusher tube is then removed, leaving the end of the stent extruding from the papilla. Single pigtail stents with the pigtail in the duodenum are commonly employed in the pancreatic duct to avoid inward migration, which can be difficult to retrieve. Small caliber plastic stents (3–5 Fr) are now typically used for prevention of post-ERCP pancreatitis in patients at high risk (e.g. sphincter of Oddi dysfunction, ampullectomy) and/or the perfor-

Chapter 16 Plastic Pancreatic and Biliary Stents: Concepts and Insertion Techniques

A

B

C

Fig. 16.13 Bilateral stent placement for hilar cholangiocarcinoma. A Malignant stricture involves left (arrowhead) and right hepatic (arrow) ducts. B Balloon dilation is performed of left hepatic duct stricture (arrowhead); note wire is in right intrahe-patic (arrow). C Successful bilateral stent placement.

mance of high-risk interventions (precut biliary sphincterotomy, pancreatic sphincterotomy)14 (Fig. 16.14). These stents are expected to pass spontaneously within 14 days and thereby minimize pancreatic ductal injury.

Drainage of pancreatic fluid collections Double pigtail stents are placed transgastrically or transduodenally when transmural drainage of pancreatic fluid collections is undertaken.15 Usually two stents are placed across the wall into the collection (Fig. 16.15). Although straight stents can be used, they may be

a source of delayed bleeding as the end within the collection impacts the wall as the collection collapses.16 Therefore double pigtail stents are preferred. They are inserted as mentioned above for the biliary tree. It is important to note that the proximal ends of some of the 10 Fr stents are tapered and do not allow an inner guiding catheter to pass. The tapered portion may need to be severed to allow an inner guiding catheter pusher tube to pass through the stent. In addition, one must be especially careful that an excessive length of stent is not passed into a pseudocyst since the entire stent can be “lost” during deployment. 159

SECTION 2 TECHNIQUES

Fig. 16.14 3 Fr pancreatic duct stent placed for prevention of postERCP pancreatitis. Arrows denote ends of stent. Fig. 16.16 Plastic biliary stent (arrowhead) passed through occluded metal biliary stent (arrows) which had been placed for palliation of pancreatic carcinoma.

Fig. 16.15 Two 10 Fr stents placed transduodenally to drain a pancreatic pseudocyst.

Indications and contraindications Biliary indications

Malignant biliary obstruction is the most frequent indication for the use of plastic stents. Distal obstruction is most commonly due to pancreatic carcinoma. Mid to proximal malignant obstruction may be due to primary cancer of the biliary tree (gallbladder or cholangiocarcinoma) or from invasion or obstruction of the duct by adjacent malignant metastatic lymph nodes. Plastic stents may be used to relieve obstruction of previously placed metal stents17 (Fig. 16.16). In general, distal bile duct tumors are more effectively palliated with plastic stents than are hilar tumors. Benign strictures can frequently be managed by the use of plastic stents. Causes of benign obstruction include post-sphincterotomy stenosis, chronic pancreatitis, post-surgical injury, ischemia, and anastomotic strictures after liver transplantation. Indeed, in addition to acute relief of obstruction, serial stenting and dilation with increasing numbers of stents appears to be more effective than single stents for such pathology18–20 (Fig. 16.17). Biliary leaks and fistulae after biliary surgery, cholecystectomy, or trauma are also effectively treated by short-term stent placement across the papilla21 (Fig. 16.18). In most of these latter indications short-length stents are effective and do not need to cross the leak site. The elimination of sphincter pres160

Fig. 16.17 Fluoroscopic image after placement of five stents for treatment of benign distal bile duct stricture.

sure promotes flow away from the leak into the duodenum, promoting closure. For more complex leaks and major leaks of the common bile duct, it may be necessary to traverse the leak site.

Pancreatic indications Plastic stents have been used for relief of pancreatic duct obstruction in the setting of chronic pancreatitis. In this setting there may refractory pain or pancreatic leaks, with resultant pancreatic ascites or pseudocysts.22 Occasionally malignant pancreatic duct obstruction will result in pancreatitis or contribute to disabling pain. Placement of pancreatic stents may be effective in this setting (Fig. 16.19).23 As previously mentioned, temporary stent placement is useful in the prevention of post-ERCP pancreatitis in selected patients. In the setting of severe acute pancreatitis, pancreatic duct leaks and disrup-

Chapter 16 Plastic Pancreatic and Biliary Stents: Concepts and Insertion Techniques

A B

C

Fig. 16.18 Placement of biliary stent for treatment of post-cholecystectomy cystic duct leak. A Active leak is seen. B Fluoroscopic image taken immediately after placement of 10 Fr biliary stent. C Follow-up cholangiogram several weeks later showing closure of leak.

Fig. 16.19 Placement plastic pancreatic stent in patient with unresectable pancreatic cancer, intractable pain, fever, and hyperamylasemia. A Stricture (arrowheads) and dilated main pancreatic duct (arrows). B Immediately after placement of stent. Significant improvement in pain was achieved.

B A

C

A B

Fig. 16.20 Placement of pancreatic stent for treatment of post-splenectomy pancreatic duct leak. A Active leak is seen. B Fluoroscopic image taken immediately after placement of 7 Fr pancreatic stent to tail. C Follow-up pancreatogram several weeks later showing closure of leak.

tions may contribute to the poor outcome of these patients; pancreatic stent placement may improve the clinical course in a subset of these patients.24 In patients with traumatic pancreatic ductal injury, plastic stents may be effective in bridging the injured duct and permitting resolution of the leak. Post surgical pancreatic duct

leaks (distal pancreatectomy, inadvertent surgical injury) can occur and are effectively treated with pancreatic stents (Fig. 16.20).25 Finally, a variety of plastic stent configurations have been useful in transpapillary and transmural drainage of pancreatic fluid collections (see Chapter 45).15 161

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Complications When sphincterotomy is performed to facilitate stent insertion, complications such as hemorrhage (Fig. 16.21) or perforation may occur.26 When placed into the bile duct, problems caused by the stent itself include cholangitis, frequently due to stent occlusion, and cholecystitis as a result of cystic duct obstruction.27 Occlusion of a biliary stent secondary to deposition of bacterial biofilm and/or plant material (Fig. 16.2) is the most commonly encountered complication of plastic stents and occurs in about 30% of cases with resulting jaundice and cholangitis. When placed into the pancreatic duct, stent occlusion may cause pancreatitis. Stent migration, into or out of the bile duct, occurs in up to 5% of cases and may result in recurrent obstruction and cholangitis. Pancreatic stent migration into the duct can be difficult to retrieve due to their small diameter and the small size of the pancreatic duct. If not retrieved, permanent ductal damage can occur. Even when left in for a few weeks in a planned situation, pancreatic duct stents can induce ductal damage similar to chronic pancreatitis.28 (Figs 16.22A–16.22C). Uncommon complications include perforation of the duodenum if distal migration occurs (Fig. 16.9);29 such perforations may be occult until the stent is removed

A

Fig. 16.21 Endoscopically visible vessel (arrow) identified from post-sphincterotomy bleeding following biliary stent placement. Heater probe therapy was applied and no further bleeding ensued.

B C

Fig. 16.22 Pancreatic duct stent-induced ductal damage after treatment of post-tail resection pancreatic duct leak. A Active leak is seen at tail (arrow). B Fluoroscopic image taken immediately after placement of short 7 Fr pancreatic stent. C Follow-up pancreatogram several weeks later showing stricture (arrow) at site where the stent end was in contact with the duct.

and the hole opened. A variety of rare complications have been reported following migration completely out of the bile duct, such as bowel obstruction,30 and intestinal perforation.31

Relative cost Plastic stents provide rapid palliation of biliary obstruction, and shorten hospital stay when compared to surgical bypass. In many cases, stent placement obviates major surgical intervention. The cost of a plastic stent is less than $100 and is far less than an expandable

metal stent, the cost of which may exceed $1800 contingent upon manufacturer and presence or absence of a covering. Metal stents have a significantly longer patency than plastic stents, although if the patient does not survive long enough, this benefit will not be realized. Therefore, in patients with distal malignancy who have an anticipated life expectancy less than three to four months, plastic stents are more cost-effective.3,32 CPT codes and ambulatory payment classifications in the US for placement and/or removal of plastic biliary stents are available in a recent review.2

REFERENCES 1.

Soehendra N, Reynders-Frederix. Palliative bile duct drainage- a new endoscopic method of introducing a transpapillary drain. Endoscopy 1980; 12:8–11. 2. Somogyi L, Chuttani R, Croffie J, et al. Biliary and pancreatic stents. Gastrointest Endosc. 2006 June; 63(7):910–919. 3. Moss AC, Morris E, Mac Mathuna P. Palliative biliary stents for obstructing pancreatic carcinoma. Cochrane Database Syst Rev. 2006 Apr 19(2):CD004200. 162

4. van Berkel AM, van Marle J, Groen AK, et al. Mechanisms of biliary stent clogging: confocal laser scanning and scanning electron microscopy. Endoscopy. 2005 Aug; 37(8):729–734. 5. Farnbacher MJ, Voll RE, Faissner R, et al. Composition of clogging material in pancreatic endoprostheses. Gastrointest Endosc. 2005 June; 61(7):862–866. 6. Weickert U, Venzke T, Konig J, et al. Why do bilioduodenal plastic stents become occluded? A clinical and pathological investigation

Chapter 16 Plastic Pancreatic and Biliary Stents: Concepts and Insertion Techniques

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17. 18.

on 100 consecutive patients. Endoscopy. 2001 Sep; 33(9):786–790. Tringali A, Mutignani M, Perri V, et al. A prospective, randomized multicenter trial comparing DoubleLayer and polyethylene stents for malignant distal common bile duct strictures. Endoscopy. 2003 Dec; 35(12):992–997. Raju GS, Sud R, Elfert AA, et al. Biliary drainage by using stents without a central lumen: a pilot study. Gastrointest Endosc. 2006 Feb; 63(2):317–320. Raju GS, Gomez G, Xiao SY, et al. Effect of a novel pancreatic stent design on short-term pancreatic injury in a canine model. Endoscopy. 2006 Mar; 38(3):260–265. Ishihara T, Yamaguchi T, Seza K, et al. Efficacy of s-type stents for the treatment of the main pancreatic duct stricture in patients with chronic pancreatitis. Scand J Gastroenterol. 2006 June; 41(6):744–750. Reddy DN, Banerjee R, Choung OW. Antireflux biliary stents: are they the solution to stent occlusions? Curr Gastroenterol Rep. 2006 Apr; 8(2):156–160. Giorgio PD, Luca LD. Comparison of treatment outcomes between biliary plastic stent placements with and without endoscopic sphincterotomy for inoperable malignant common bile duct obstruction. World J Gastroenterol. 2004 Apr 15; 10(8):1212–1214. Tarnasky PR, Cunningham JT, Hawes RH, et al. Transpapillary stenting of proximal biliary strictures: does biliary sphincterotomy reduce the risk of postprocedure pancreatitis? Gastrointest Endosc. 1997 Jan; 45(1):46–51. Singh P, Das A, Isenberg G, et al. Does prophylactic pancreatic stent placement reduce the risk of post-ERCP acute pancreatitis? A meta-analysis of controlled trials. Gastrointest Endosc. 2004 Oct; 60(4):544–550. Baron TH. Endoscopic drainage of pancreatic fluid collections and pancreatic necrosis. Gastrointest Endosc Clin N Am. 2003 Oct; 13(4):743–764. Cahen D, Rauws E, Fockens P, et al. Endoscopic drainage of pancreatic pseudocysts: long-term outcome and procedural factors associated with safe and successful treatment. Endoscopy. 2005 Oct; 37(10):977–983. Tham TC, Carr-Locke DL, Vandervoort J, et al. Management of occluded biliary Wallstents.Gut. 1998 May; 42(5):703–707. Baron TH. Endoscopic therapy with multiple plastic stents for benign biliary strictures due to chronic calcific pancreatitis: the good, the bad, and the ugly. J Clin Gastroenterol. 2004 Feb; 38(2):96–98.

19. Pozsar J, Sahin P, Laszlo F, et al. Endoscopic treatment of sphincterotomy-associated distal common bile duct strictures by using sequential insertion of multiple plastic stents. Gastrointest Endosc. 2005 Jul; 62(1):85–91. 20. Kuzela L, Oltman M, Sutka J, et al. Prospective follow-up of patients with bile duct strictures secondary to laparoscopic cholecystectomy, treated endoscopically with multiple stents. Hepatogastroenterology. 2005 Sep–Oct; 52(65): 1357–1361. 21. Kaffes AJ, Hourigan L, De Luca N, et al. Impact of endoscopic intervention in 100 patients with suspected postcholecystectomy bile leak. Gastrointest Endosc. 2005 Feb; 61(2):269–275. 22. Delhaye M, Arvanitakis M, Bali M, et al. Endoscopic therapy for chronic pancreatitis. Scand J Surg. 2005; 94(2): 143–153. 23. Costamagna G, Mutignani M. Pancreatic stenting for malignant ductal obstruction. Dig Liver Dis. 2004 Sep; 36(9):635–638. 24. Lau ST, Simchuk EJ, Kozarek RA, et al. A pancreatic ductal leak should be sought to direct treatment in patients with acute pancreatitis. Am J Surg. 2001 May; 181(5):411–415. 25. Le Moine O, Matos C, Closset J, et al. Endoscopic management of pancreatic fistula after pancreatic and other abdominal surgery. Best Pract Res Clin Gastroenterol. 2004 Oct; 18(5):957–975. 26. Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med. 1996 Sep 26; 335(13):909–918. 27. Dolan R, Pinkas H, Brady PG. Acute cholecystitis after palliative stenting for malignant obstruction of the biliary tree. Gastrointest Endosc. 1993 May–June; 39(3):447–449. 28. Kozarek RA. Pancreatic stents can induce ductal changes consistent with chronic pancreatitis. Gastrointest Endosc. 1990 Mar–Apr; 36(2):93–95. 29. Melita G, Curro G, Iapichino G, et al. Duodenal perforation secondary to biliary stent dislocation: a case report and review of the literature. Chir Ital. 2005 May–June; 57(3):385–388. 30. Simpson D, Cunningham C, Paterson-Brown S. Small bowel obstruction caused by a dislodged biliary stent. J R Coll Surg Edinb. 1998 June; 43(3):203. 31. Storkson RH, Edwin B, Reiertsen O, et al. Gut perforation caused by biliary endoprosthesis. Endoscopy. 2000 Jan; 32(1):87–89. 32. Levy MJ, Baron TH, Gostout CJ, et al. Palliation of malignant extrahepatic biliary obstruction with plastic versus expandable metal stents: An evidence-based approach. Clin Gastroenterol Hepatol. 2004 Apr; 2(4):273–285.

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Chapter

17

TECHNIQUES

Expandable Stent Insertion Ann Marie Joyce and Gregory G. Ginsberg

Introduction Expandable biliary stents are used primarily for the palliation of malignant biliary obstruction. There are two main categories of biliary stents: fixed-diameter plastic stents (FDPS) and self-expanding metallic stents (SEMS). FDPS, introduced in 1980, preceded their SEMS counterparts and are discussed in detail in Chapter 16. While FDPS are a safe and effective means to overcome biliary stenoses, they eventually become occluded.1 Stent occlusion is attributed to biofilm formation such that under even ideal circumstances, FDPS occlusion occurs in 30% and 50% of patients within three and six-months, respectively.2 Bile flow rate is impacted on by the stent lumen diameter. The internal diameter of an FDPS is limited by the accessory channel size of the duodenoscope. Because the diameter of the accessory channel of a “therapeutic” duodenoscope is 3.2 mm, FDPSs are available with internal diameters up to 12 Fr. SEMS were developed to overcome this limitation as they deliver a larger diameter stent (10 mm) via a small diameter (7.5 Fr) delivery device. Because malignant biliary obstruction is typically associated with a survival of less than one year, SEMS are intended to yield “lifelong” palliation of obstructive symptoms.3–5 This chapter reviews the indications for SEMS placement, SEMS selection, types of SEMS available, techniques for SEMS placement, SEMS-related complications, and complication avoidance and management.

INDICATIONS SEMS are indicated for palliation of malignant biliary obstruction. The most common cause of malignant biliary obstruction is pancreatic adenocarcinoma arising in the head or genu region of the pancreas. The management of distal biliary obstruction is discussed in more detail in Chapter 27 by Barkun. Other causes of malignant biliary stenoses are cholangiocarcinoma, ampullary carcinoma, gallbladder cancer, and extrinsic compression associated with lymphadenopathy due to lymphoma and metastatic carcinoma. Patients with malignant biliary obstruction typically present with jaundice. Left unchecked, biliary obstruction may lead to the development of pruritis, pain, cholangitis, hepatic synthetic dysfunction, and malabsorption. Without therapy the mean survival for patients presenting with malignant biliary obstruction is less than 200 days. Because most patients have advanced disease at the time of presentation, operative resection with curative intent is only possible in 10–15% of cases.6,7 Therefore, palliation of symptoms is a major component of management in the majority of patients with malignant biliary obstruction.

Options for palliation of malignant biliary obstruction include operative bypass, percutaneous drainage, and/or endoscopic stenting. In a prospective, randomized trial of endoscopic stenting with FDPSs versus operative bypass the two compared equivalently with respect to alleviation of obstruction and relief of jaundice, and favorably with respect to hospital stay and procedure-related complications and mortality.8 However, late recurrence of jaundice occurred more commonly in the FDPS group owing to stent occlusion. Versus percutaneous drainage, endoscopic stenting compares equivalently for alleviation of jaundice, and superiorly with respect to procedurerelated morbidity and 30-day mortality.9 Both FDPS and SEMS can be used for the palliation of malignant biliary obstruction. FDPSs are safe and effective. They are relatively less expensive compared to SEMS, and can be removed and replaced if they become occluded. To restate, the main drawback of FDPS is their variable rate of occlusion. Symptoms of stent occlusion include recurrence of jaundice and/or ascending cholangitis. Two strategies have been employed related to FDPS occlusion: (1) prophylactic exchange, and (2) expectant management. The former involves elective stent removal and exchange at three-month intervals in order to reduce the risk of cholangitis and need for emergency exchange while the latter relies on watchful waiting and nimble responsiveness should stent occlusion occur. Further discussion on FDPS can be found in Chapter 16 (Baron and Ponsky). SEMS are intended, owing to their larger internal diameter, to extend the duration of patency, thereby reducing the need for and frequency of reintervention. As such, their increased cost may be offset by a reduction in episodes of cholangitis and need for elective and emergency interventions, including hospitalization. A multicenter randomized study that compared a SEMS (Wallstent) to 10 Fr FDPS was performed by the US Wallstent study group10 (Table 17.1). Early stent occlusion occurred in about 3% of the FDPS group as compared to none in the Wallstent group. Early occlusion was attributed to sludge accumulation in the plastic stent groups. During long-term follow-up, the probability of stent occlusion was 2.8 times greater for plastic stents than for Wallstents. Tumor ingrowth or overgrowth contributed to about 14% of the Wallstent occlusions, but this did not affect the plastic stent group. The overall complication rate was significantly lower in the Wallstent group than in the FDPS group (20% vs 31%, p < 0.05). In the plastic stent group there was a higher number of procedures performed which resulted in a higher cost as compared to the Wallstent group. Another prospective, randomized trial was performed to compare the patency and determine the cost-effectiveness of SEMS versus FDPS.4 This study demonstrated that the median period of patency was longer for the metal stent group (33%) after a median of 273 days compared with 54% after a median of 126 days (p = 0.006). Two subsequent prospective, randomized trials11,12 also reported longer duration of patency with Wallstents compared to 165

SECTION 2 TECHNIQUES

Author

No. of patients FDPS SEMS

Drainage (%) FDPS SEMS

Davids (4) Carr-Locke (10) Knyrim (5) Kaassis (11)

49 78 31 59

95 95 100

56 86 31 59

96 98 100

Occlusion on rate (%) FDPS SEMS

Stent patency (days) FDPS SEMS

p value

54 13 36 63

126a 62a 140a 165a

p = 0.006

33 13 22 20

273a 111a 189b Not reached

p = 0.035 p = 0.007

Table 17.1 Randomized trials comparing FDPS versus SEMS for palliation of malignant strictures of the bile duct a

median. mean.

b

COMPLICATIONS Author, year (reference)

No. of pts

Stent occlusion

Smits et al. 1995 (20) Born et al. 1996 (21) Miyayama et al. 1997 (22) Rossi et al. 1997 (23) Hausegger et al. 1998 (24) Shim et al. 1998 (25) Nakamura et al. 2002 (26) Han et al. 2002 (27) Isayama et al. 2002 (28) Schoder et al. 2002 (29) Bezzi et al. 2002 (30) Han et al. 2003 (31) Isayama et al. 2004 (32) Miyayama et al. 2004 (33) Nakai et al. 2005 (34) Kahaleh et al. 2005 (35)

22 10 19 21 30 21 13 10 21 42 26 13 57 22 69 80

2 3 1 7 11 2 1 0 3 6 4 3 8 3 7 12

Tumor in growth 0 0 4 2 2 0 0 0 0 2 0 0

Migration

Cholecystitis

Pancreatitis

Cholangitis

1 1 1

1 (related to tumor)

0

2 4

0 2 3 3 0 2 3 4 3

0 1 1 0 0 5

1 3 0 0 0 1 4 5

4 5

1 5

Table 17.2 Review of available studies of the complications of covered SEMS

FDPS. Along with the extended patency rate with Wallstents there were fewer accumulated hospital days in this group (p < 0.05). Conventionally, the use of SEMS is limited to patients with confirmed, non-operable, malignant biliary obstruction. Our practice, and the practice of many, has been to place FDPS for initial management of suspected malignant biliary obstruction. We have relatively deferred the use of SEMS until there was evidence of occlusion of the initially placed FDPS, a performance status suggesting a greater than 6-month survival, a confirmed tissue diagnosis, and completed staging to confirm non-operability. Our most common application of SEMS has been in patients with biopsy proven, inoperable malignant biliary obstruction that have developed occlusion of a previously placed FDPS with a life-expectancy of greater than 3–6 months. However, recent studies suggest broader application for SEMS. Concerns about the use of SEMS prior to confirming a tissue diagnosis of cancer and affirming unresectability have been contested. In patients with potentially resectable pancreatic cancer, patients have improved survival with neoadjuvant chemotherapy followed by operative resection.13–17 In a small group of patients, Wasan et al. demonstrated that SEMS can be useful for relief of biliary obstruction in resectable pancreatic carcinoma.18 While there had been concern about SEMS complicating operative resection, this 166

has not been borne out in clinical practice. One cost analysis concluded that initial SEMS placement provided equal or superior efficacy and reduced overall costs compared to FDPS placement.19 Covered SEMS share the same indications as their uncovered precursors, though they are not used in hilar or intrahepatic ducts because of blockage to the contralateral intrahepatic system if ipsilateral intrahepatic branches. The anticipated advantage of covered SEMS is the retardation of tissue (malignant or hyperplastic) in-growth contribution to stent occlusion. However, there is considerably less published and unpublished experience with covered SEMS. Limited studies of covered SEMS have raised concerns of higher rates of stent migration, cystic duct obstruction, and pancreatitis (Table 17.2)20–36 Covered stents may be particularly well suited for reconstitution of an occluded indwelling uncovered SEMS. Because they are considered non-removable SEMS have generally been considered contraindicated for management of benign biliary strictures. While SEMS remain patent longer than FDPS, the durability of their biotolerance is not indefinite. Endoscopic removal of occluded uncovered SEMS cannot be reliably achieved as compared with covered SEMS.37 Long-term results from ongoing trials evaluating the application of covered SEMS in the management of benign bile duct disease are awaited with interest.38,39

Chapter 17 Expandable Stent Insertion

TYPES OF SELF-EXPANDING STENTS There are a variety of SEMS used in the palliation of malignant biliary obstruction (Table 17.3). Commercially available SEMS vary moderately in design, delivery, configuration, and sizes. There are few studies comparing the different stents. The available uncovered stents include: Wallstent (Boston Scientific, Natick, MA), Zilver stent (Cook Endoscopy, Winston-Salem, NC), Diamond stent (Boston Scientific, Natick, MA), and Flexxus stent (ConMed, Billerica, MA). Covered stents include the covered Wallstent (Boston Scientific, Natick, MA) and Viabil stent (W.L. Gore, Flagstaff, AZ). To decrease the occlusion of expandable stents by tumor ingrowth covered stents have been introduced. These stents vary slightly but all are deployed through a duodenoscope.

Wallstent The Wallstent is the original SEMS and is considered the industry standard (Fig. 17.1). Most of the published literature on SEMS applies to the biliary Wallstent. It is a braided stainless steel mesh with soft barbed ends. The Wallstent is available in 40, 60 and 80mm lengths. The available diameters of the fully expanded Wallstent are 8 and 10 mm. The delivery device has an outside diameter of 7.5 Fr and consists of an 0.035-inch guidewire compatible introducer catheter, on which the compressed SEMS is constrained by a hydrophilic-coated outer sheath. The delivery device has a tapered

tip to allow ease of passage. The SEMS is deployed by withdrawing the outer sheath releasing the SEMS in the desired location. The Wallstent is radiopaque and there are four radiopaque markers on the delivery device to guide precision deployment. The stent can be recaptured, if need be, and repositioned up until 90% of full stent release. Wallstents can be deployed entirely within the bile duct or in transpapillary position. There is 33% foreshortening of the Wallstent post-deployment. Transpapillary positioned uncovered Wallstents may be reliably removed within 12 to 24 hours after insertion. Subsequently, the stent becomes embedded into the bile duct wall and it is more difficult, if not impossible, to remove.

Diamond Ultraflex stent The Ultraflex Diamond stent is made of nitinol, a nickel-titanium alloy that provides a high degree of flexibility (Fig. 17.2). It is constructed as a laser-welded single knitted wire. The interstices of the lattice work are larger compared to those of the Wallstent. This may more easily permit cannulation of the interstices and dilation for placement of another stent to create a “Y” configuration; this may be potentially helpful in the palliation of hilar strictures. The delivery device is similar to that of the Wallstent. The outer sheath measures 3 mm (8.5 Fr) in diameter. The stent is available in 4, 6, and 8 cm in length and 10 mm in diameter. Once the deployment has commenced the stent cannot be recaptured. There is little foreshortening. There are radiopaque markers to assist with the accurate positioning of the stent, however; the stent itself is less visible

Type

Delivery system (Fr)

Metal

Length (cm)

Diameter (mm)

List price

Wallstent Diamond Ultraflex stent Gianturco-Rosch “Z” stent Spiral Z stent Za stent Zilver stent Flexxus Covered Wallstent Viabil

7.5 9.25 12 8.5 8.5 7 7.5 8 10

Steel Nitinol Stainless steel Stainless steel Nitinol Nitinol Nitinol Steel Nitinol

4,6,8 4,6,8 4,6,8 5.7,7.5 4,6,8 4,6,8 4,6,8,10 4,6,8 4,6,8,10

8,10 10 10 10 10 6,8,10 8,10 8,10 8,10

$1450 $1300 N/A N/A N/A $1250 $1525–$1735 $1650

Table 17.3 Characteristics of SEMS

Fig. 17.1

Wallstent

Fig. 17.2

Diamond Ultraflex stent 167

SECTION 2 TECHNIQUES

radiographically compared to the Wallstent. Radial expansion forces are purportedly similar. Four studies have been published which compared the Ultraflex Diamond stent with Wallstent for palliation of malignant biliary strictures.40–43 While one reported equivalency, three others reported inferior performance of the Ultraflex Diamond as compared to the Wallstent.

Z stent There have been multiple iterations of the Z stent. The original Gianturco-Rosch “Z” stent was a stainless steel wire bent in a continuous Z shaped pattern forming a cylinder. This was modified by stringing together individual cages by adding small eyelets making the stent more flexible and compressible. This is known as the Spiral Z stent The introducer is similar in diameter to the Wallstent but the stent lengths vary. The Spiral Z stent is available in 5.7 cm and 7.5 cm lengths and 10 mm in diameter. There are silver radiopaque markers along the length of the stent. Another iteration of the design, the Za-stent, incorporates nitinol in place of stainless steel making the stent more flexible. The available lengths of the Za-stent are 4, 6 and 8 cm with a diameter of 10 mm. There are gold radiopaque markers in the middle and at the end of the Za-stent for fluoroscopic visualization. The Zilver stent (Fig. 17.3) is one piece of nitinol compared to many pieces of nitinol threaded together (Za). The gold radiopaque markers are at the proximal and distal end of the stents. The introducer diameter is 7 Fr, which is the smallest on the market. The release mechanism is similar to that of the Wallstent. All forms of the Z stent including the newest edition, Zilver stent, are non-shortening facilitating accurate deployment. A multi-center trial comparing the Wallstent with Spiral Z stent was performed by Shah et al. and included 145 patients.44 There were 64 patients in the Z stent group and 68 in the Wallstent group. There was a 100% success in the placement of the stents. There were 8 occlusions in the Z-stent group and 13 in the Wallstent group (p = 0.3). The calculated median patency rates for the Z-stent and the Wallstent were 152 days and 154 days, respectively (p = 0.9). According to this study, the two stents appeared comparable.

Fig. 17.3 168

Zilver stent

Flexxus The Flexxus stent (formerly Memotherm and Luminexx) is a highly flexible nitinol stent with flared ends (Fig. 17.4). The stent is a lasercut single piece of nitinol. Similar to the Diamond stent, the interstices of the lattice work are large enough to permit cannulation of the interstices and dilation for placement of another stent to create a “Y” configuration for palliation of hilar strictures. There are four Tantalum markers on each end to provide improved fluoroscopic imaging. The predeployment delivery diameter is 7.5 Fr and the post-deployment diameters are 8 and 10 mm with lengths of 40 mm, 60 mm, 80 mm, and 100 mm. The release mechanism is unique and employs a pistol-grip handle which withdraws the constraining sheath and allows stepwise, controlled release. During deployment, there is no foreshortening and the stent cannot be re-constrained. There are no studies available to compare the Flexxus with the other stents previously mentioned.

Covered SEMS SEMS have a longer patency rate as compared with plastic stents but they may still eventually become occluded. Plastic stents typically become occluded with sludge and/or biofilm whereas SEMS become occluded with tumor overgrowth or ingrowth, ingrowth of benign epithelial hyperplasia, and/or sludge accumulation. Covered SEMS

Fig. 17.4

Flexxus stent

Chapter 17 Expandable Stent Insertion

were developed to overcome ingrowth through the SEMS interstices. The covered Wallstent has a polyurethane covering (Fig. 17.5). The delivery system and deployment are the same as the uncovered version, though the predeployment diameter is slightly larger at 8 Fr. The initial stents were completely covered but modifications have been made so that 5 mm of each end is uncovered to allow embedding into the tissue to decrease the rate of migration. Published studies of the covered Wallstent have yielded mixed results with respect to improvement in patency rates (Table 17.4).20–36 Furthermore, complications from covered Wallstents included adherent debris, migration (6%) and cholecystitis (12%). Another covered stent for use is the Viabil (Fig. 17.6). The nonporous polytetrafluoroethylene (ePFTE) and fluorinated ethylene propylene (FEP) covering prevents tumor ingrowth. Outside this lining there is a nitinol stent with radiopaque rings on either end. There are anchoring fins along the nitinol stent to prevent migration. The stent is available with or without holes in the covering. The holes are along the proximal end of the stent to prevent occlusion of other duct branches. The stent is available in a variety of sizes with a 10 Fr delivery system and is available through ConMed (Billerica, MA, USA).

TECHNIQUES FOR SEMS PLACEMENT Duodenoscope We preferentially use a therapeutic duodenoscope (accessory channel—4.2mm) for most ERCP. Standard diagnostic duodenoscopes with a 3.2 mm accessory channel do permit insertion of most

Other SEMS Obscure, pirated, and boutique stents have been developed and marketed to limited extents around the globe. However these are not readily available in most markets. The “Y Stent” (Fig. 17.7) is an example, intended for palliation of hilar strictures.

Fig. 17.6 Viabil stents: without holes (top) and with holes (bottom).

Fig. 17.5

Fig. 17.7

Polyurethane covered Wallstent

Author (reference)

No. of pts U

C

Shim et al. 1998 (25) Nakamura et al. 2002 (26) Miyayama et al. 2004 (33) Isayama et al. 2004 (32) Smits et al. 1995 (20)

26 10 19 55 24

21 13 22 57 22

Median stent patency U C 233 >402

267 >470

193a

225a

Stent occlusion U C 6 2 14 21 3

2 1 3 8 2

Y stent

Tumor ingrowth U C 6 2

2 0

16 2

0 0

Migration U C

0 0

1 1 1 1

Cholecystitis U C

Pancreatitis U C

1 1 0

1

0

1

5

0 2 2

Table 17.4 Covered (C) vs uncovered (U) SEMS studies a

mean.

169

SECTION 2 TECHNIQUES

SEMS. In patients with pending or existing gastric outlet or duodenal obstruction, a forward-viewing endoscope may be necessary for initial inspection and stricture dilation. When considering dual enteral and biliary stenting, we place the biliary SEMS first, followed by enteral stent placement.

Cholangiogram A good quality cholangiogram using undiluted contrast will define the length, localization, and configuration of the biliary obstruction and is important for selection of the appropriate stent. MRCP or CT scan with pancreaticobiliary protocol may be valuable in the preERCP evaluation of suspected hilar obstruction when selected unilateral drainage versus bilateral or multisegmental drainage may be indicated, as discussed in Chapter 27.45

Sphincterotomy A biliary sphincterotomy is not obligatory for SEMS placement in either the supra- or transpapillary positions. Assertions that transpapillary SEMS placement without preplacement biliary sphincterotomy increases the risk of pancreatitis are unfounded, and avoidance of sphincterotomy may reduce the risk of procedure-related complications.

Dilation Routine stricture dilation to facilitate SEMS placement is not required. SEMS radial forces are sufficient to permit full or near-full expansion within 48 hours; therefore post-deployment dilation is also not routinely performed. In rare instances the stricture may need to be dilated to allow the passage of the SEMS delivery device.

SEMS shortening needs to be taken into consideration to enhance precision of placement.

Use of guidewire Guidewires are commonly used to traverse malignant bile duct strictures, facilitate catheter insertion, and maintain access during device exchange. The SEMS delivery device is passed over the guidewire and positioned within the stricture. Larger diameter (0.035″), nitinol, hydrophilic coated wires are preferred as they enhance device exchange. If two or more stents are going to be placed to palliate a hilar stricture in a side-by-side fashion, multiple guidewires are used to maintain access to the specific segments.

SEMS positioning Biliary SEMS may be placed in a suprapapillary or transpapillary position. This positioning is at the discretion of the endoscopist. In a suprapapillary position (Fig. 17.8) the sphincter of Oddi remains intact, assuming sphincterotomy was not performed. The potential advantage of this approach is that it prevents free reflux of the duodenal contents into the bile duct which may contribute to stent occlusion. However, there is insufficient data to support this notion for SEMS46 and when this concept was tested with FDPS, no difference in stent occlusion rates was observed. Suprapapillary SEMS placement is most commonly performed for strictures of the hilar region or common hepatic duct with which SEMS length is insufficient to traverse the ampulla. In a study of 59 patients, Liu et al.47 demonstrated that an “inside-stent” was possible in onethird of patients presenting with malignant obstructive jaundice. In

Stent selection The endoscopist and technician should be sufficiently familiar with the delivery and deployment mechanisms and post-deployment performance characteristics of a SEMS when considered for use. This includes guidewire and accessory channel compatibility, device preparation, insertion and deployment mechanisms, radiographic markings, SEMS shortening, recapture and reposition capabilities, and a shared communications terminology. Size matters. While the 10 mm diameter SEMS is used most commonly, SEMS length selection is individualized and dependent on the length and location of the stricture and the intention of supra- or transpapillary placement. Careful measurements best ensure optimal outcomes. Deployed and fully expanded SEMS should extend a minimum of 10 mm beyond the proximal and distal aspects of the stenosis to retard tumor overgrowth. One should prevent placement of the stent where the ends of the SEMS butt up against the bile duct side wall. The SEMS length should be determined at the time of the ERCP cholangiography. Experienced endoscopists commonly estimate the length based on the dimensions of the superimposed duodenoscope diameter (see Chapters 3 and 16). The length of the stricture may also be determined during the out exchange of a catheter or guidewire. The catheter tip is positioned at the desired proximal extent of the stent. Demarcating this position with the fingers on the catheter sheath at the accessory channel port, the catheter is then withdrawn until the tip is positioned at the desired distal extent of the SEMS. The distance is then determined by the length of catheter withdrawn from the accessory channel port. Catheters and guidewires with designated length markings can also be used. The degree of 170

Fig. 17.8

Suprapapillary placement of SEMS

Chapter 17 Expandable Stent Insertion

this patient group there was 2 cm between the papilla and the distal end of the stricture. The potential disadvantage of suprapapillary SEMS placement is that, should it be required for management of SEMS occlusion, recannulation of the stent lumen may prove challenging. Transpapillary SEMS placement (Fig. 17.9) is typically used for common bile duct obstruction. Transpapillary placed SEMS should extend 5–10 mm into the duodenal lumen. This extent permits ease of subsequent recannulation. Transpapillary SEMS that extend much further increase the risk for mechanical trauma to the opposing duodenal wall with potential for development of ulceration, bleeding and perforation. Transpapillary SEMS placement does not promote pancreatic duct obstruction or pancreatitis.

Endoscopic and fluoroscopic guides Once access has been obtained and the appropriate stent selected then the SEMS can be delivered and deployed. One or both ports of the stent introducer (depending on the stent) should be lubricated with a flush of normal saline to ease advancement over the guidewire and withdrawal of the outer sheath. The tip of the duodenoscope should remain in close proximity to the papilla and thus minimal wire is seen endoscopically. This “close” position helps to prevent accidental loss of guidewire access when the rather stiff SEMS introducer catheter is being inserted into the ampullary orifice. The stent is passed over a guidewire into the bile duct and advanced through the stricture. In a coordinated effort between the endoscopist and the assistant, the guidewire is maintained stationary while the introducer catheter is inserted over it. The arrangement and designation

of endoscopic and fluoroscopic marking vary between commercially available SEMS and the endoscopist and assistant must be familiar with these representations. Fluoroscopic markings commonly designate the predeployment and approximate post-deployment proximal and distal ends of the SEMS. If the stent will be placed transpapillary, the distal margin of the SEMS can be seen endoscopically and positioned so as to deploy with the desired length extending from the ampulla. We generally maintain fluoroscopic and endoscopic guidance throughout deployment to ensure accurate SEMS placement. It should be noted that during deployment, SEMS may have a tendency to move upstream. To counter this, during deployment, the endoscopist may need to apply resistance to or graded withdrawal of the introducer catheter in order to achieve precise placement.

Deployment With the SEMS introducer apparatus in the desired position, the outer sheath is incrementally withdrawn by the technician to release the stent. The proximal end (with respect to the liver) of the stent will gradually open as the outer sheath is withdrawn (Fig. 17.10). The stent position may be adjusted distally by withdrawing the entire apparatus. For more proximal position readjustment, the partially released SEMS must be recaptured, if possible, by advancing the outer sheath. The extent of deployment to which the stent may be recaptured varies between products. Withdrawing the outer sheath fully deploys the SEMS. The introducer catheter and guidewire are then removed. Care should be taken to ensure that the obturator tip of the introducer catheter does not catch the SEMS

A

B

Fig. 17.9

Transpapillary SEMS placement 171

SECTION 2 TECHNIQUES

B A

Rendezvous technique When ERCP cannulation of the bile duct cannot be achieved, SEMS placement may be performed in a coordinated effort between the endoscopist and interventional radiologist. A guidewire is placed into the bile duct through the percutaneous transhepatic approach. The guidewire is advanced into the duodenum. The guidewire is grasped in the duodenum by a biopsy forceps or snare and pulled through the accessory channel of the duodenoscope. A catheter or stent introducer is then advanced over the guidewire through the accessory channel and eventually into the bile duct. This combined technique has been successful in 80% of patients with malignant bile duct obstruction.48

Hilar stricture

C

D

Fig. 17.10 Deployment of SEMS. A Cholangiogram demonstrating a markedly dilated proximal bile duct with a distal stricture. B SEMS introducer advanced over the wire with the proximal end of the stent above the proximal end of the stricture. C Initial withdrawal of the outer sheath. D Full deployment of the SEMS.

risking displacement. When using SEMS for palliation of tight stenosis, incomplete radial expansion of the deployed stent is not uncommonly observed. Incomplete expansion may resist withdrawal of the introducer catheter, particularly at the level of the obturator tip, risking dislodgement or malpositioning of the SEMS. To overcome this, the outer sheath may be incrementally re-advanced over the introducer catheter as it is withdrawn. This permits withdrawal of the stent delivery system while applying resistance to the deployed SEMS thereby avoiding unintended dislodgement. The elevator lever should be relaxed during deployment to allow smooth withdrawal of the outer sheath. Post-deployment SEMS cannot be readjusted proximally. A rat-tooth forceps may be used to adjust the position more distally. 172

Management of hilar tumors is also discussed in Chapter 28. Cholangiocarcinoma, gallbladder carcinoma, and portal hepatic lymph nodes can lead to an obstruction of the bile duct at the level of the hilum of the liver. These tumors are associated with poor prognoses and death is usually caused by cholangitis or liver failure. This patient population tends to present with advanced disease; as such, most of the tumors are unresectable. Palliation of hilar obstructions provides a greater challenge than common bile duct lesions. While unilateral stenting is effective for the relief of jaundice, bilateral stenting may be required to palliate cholangitis. In a prospective study of 61 patients with hilar strictures, unilateral stent placement was achieved in 97% of patients.49 Jaundice resolved in 86.9% of patients. Cholangitis developed in three patients within the first week of the stent placement but all of these patients were successfully treated with antibiotics. There was one patient that developed a liver abscess and required percutaneous interventions on the contralateral side.50 It is now generally recommended that both the left and right intrahepatic ducts be drained during the procedure if both sides are opacified during a cholangiogram (Fig. 17.11). A preprocedure MRCP may help to plan selective drainage with metallic stents.45 If there is one dominant side identified by MRCP then selective cannulation with a catheter and a guidewire should be attempted with intentional avoidance of pressure injection of contrast. Once the catheter is in the desired location then measured cholangiography should be performed. If only one side is opacified then single stent can be placed. If there is opacification of both the right and left biliary systems, bilateral stenting should be pursued. Bilateral SEMS may be placed alongside one another or the second SEMS may be deployed through the mesh of the initial SEMS (Fig. 17.12). Two wires are used to maintain access to the right and left biliary systems while placing bilateral stents in a side-by-side fashion. Those wires must remain separated and secure while placing the stents. It can sometimes be difficult to place the second stent beside the first stent. Hookey demonstrated that the placement of a tem-porary plastic stent in the CBD prevents the full expansion of the first stent to facilitate placement of the second SEMS.51 When a second stent is being placed through the interstices of the first stent, sometimes the interstices need to be balloon dilated. If obstructed intrahepatic ducts remain inadequately drained then percutaneous drainage may be required adjunctively.

Duodenal obstruction Up to 10–20% of patients with pancreatic and ampullary tumors develop duodenal or gastric outlet obstruction.52 Enteral stenting is an effective means of palliation of malignant gastroduodenal obstruction symptoms.53–57 Most of these patients have concurrent or

Chapter 17 Expandable Stent Insertion

A

B

D

E

C

Fig. 17.11 Bilateral SEMS for a hilar stricture. A Cholangiogram revealed dilated left and right intrahepatic ducts with a hilar stricture. B Wire placed in the left intrahepatic system. C Catheter placed in right intrahepatic system to facilitate placement of a second wire. D SEMS placed over wire into the right intrahepatic system with a wire in the left intrahepatic system. E Stents placed in both the left and right intrahepatic ducts. The stent in the left intrahepatic duct was placed in a suprapapillary position. A

Fig. 17.12 Positioning of SEMS in hilar strictures. A Side by side placement of stents. B One stent through the interstices of another stent creating a “Y” formation. Redrawn from Ahmad NA, Ginsberg GG. Gastrointestinal Endoscopy 2001;3(2):93– 102 with permission.

B

pending bile duct obstruction and many will already have a bile duct stent in place. Owing to their prolonged patency, a biliary SEMS is recommended prior to placement of an enteral stent. This may be performed at the same setting. While feasible in individual cases, it is apt to be more difficult to place a biliary stent through the interstices of a previously placed enteral stent. Sequential placement of biliary and enteral SEMS was reported on 17 patients. The duodenal stricture was traversed with the duodenoscope after dilation. All patients had resolution of jaundice and 16 of the 17 patients had relief of nausea and vomiting. During the follow-up two patients had recurrence of biliary obstruction and two different patients had recurrence of duodenal obstruction. Three cases were secondary to tumor ingrowth and the fourth case was secondary to migration of the duodenal stent.58

COMPLICATIONS SEMS are generally safe and effective for the palliation of malignant biliary obstruction. The complications related to SEMS include those associated with ERCP and immediate and delayed SEMS malfunction. The generic ERCP associated complications include perforation, pancreatitis, and sedation-related cardiorespiratory compromise and are discussed in more detail in Chapter 6. Immediate causes of SEMS malfunction include device failure, deployment failure, and malpositioning of the stent. Failure to adequately lubricate the delivery device channels may inhibit withdrawal of the outer sheath. Excessive articulation of the elevator lever may similarly retard withdrawal of the outer sheath and has led to separation of the delivery apparatus. 173

SECTION 2 TECHNIQUES

Malpositioning of the SEMS is usually attributable to operator error. If the location of the stent is not satisfactory then a second stent may be placed at the same setting. When in the transpapillary position, another option is to completely remove the stent. Recently placed SEMS may be repositioned more distally or completely removed with a grasping forceps or a snare. For SEMS removal, the stent should be grasped and pulled to the tip of the endoscope, and the endoscope withdrawn under fluoroscopic guidance. The stent should be not pulled into the accessory channel of the duodenoscope because the sharp ends can damage the channel. This is best accomplished within 48 hours of insertion as tissue hyperplasia leads to embedding of the stent within the bile duct wall. Covered SEMS may be more readily removed remote to the time of insertion.37 Other early complications, as defined as occurring within one week of the stent placement, include cholangitis, hemobilia, and perforation. Ineffective drainage of segments opacified during cholangiography increases the risk of cholangitis. Patients with malignant hilar strictures or coexisting primary sclerosing cholangitis are at greatest risk. Administration of prophylactic antibiotics may be beneficial to prevent or manage cholangitis in selected patients. Persistent evidence of cholangitis while on antibiotics requires repeat instrumentation either through a retrograde or antegrade approach. SEMS placement into friable bile duct tumors may induce hemobilia. This bleeding is typically not clinically significant and resolves spontaneously. However, retained clot may result in recurrence of biliary obstruction. The retained blood clot may be cleared with catheter irrigation or a stone retrieval balloon. A malpositioned SEMS may perforate the bile duct wall or produce ulceration, bleeding, and perforation of the opposing duodenal wall. There are reports of using argon beam plasma coagulation to shorten stents of excessive length within the duodenum that have caused complications.59 Studies in animals suggest this is safe to surrounding tissues.60 The most common late complication related to SEMS is stent occlusion. The stent may become occluded by tumor ingrowth or overgrowth, tissue hyperplasia or biliary sludge. Biliary sludge is the most common cause of occlusion of plastic stents but this occurs less commonly with SEMS given their larger diameter. With SEMS, the most common cause of occlusion is tumor ingrowth. The tumor grows through the interstices of the stent. There have been two studies that have investigated the management of an occluded stent. Tham et al.61 performed a multicenter trial that included 38 patients with occluded stents. Occlusions were managed by insertion of another metallic stent in 19, insertion of a plastic stent in 20 and mechanical cleaning in 5. There was no statistical difference in revised stent patency among the different treatment groups. It was noted that it is more cost-effective to place a plastic stent for the management of an occluded metallic stent. A similar single-center

study was performed by Bueno et al.62 In this study, placement of a second Wallstent or plastic stent was equally effective. A covered Wallstent may be chosen for the management of an occluded SEMS. Patient outcome was better if they had a distal bile duct occlusion as opposed to a proximal bile duct occlusion. The means of SEMS revision should be individualized and take into consideration the overall prognosis of the patient. Once deployed, migration of non-covered SEMS is rare. Migration of covered SEMS occurred in 6% of patients in the study by Kahaleh et al.35 Initial iterations of covered stents were 100% covered which appeared to increase the risk of SEMS migration. Subsequent modifications have left the proximal and distal ends of the stent uncovered. This allows some degree of embedding into the bile duct wall to retard migration. Cholecystitis has occurred in 2.9% to 12% of patients with covered biliary SEMS owing to cystic duct obstruction.35

COST SEMS vs Plastic Overall biliary SEMS have longer patency than FDPS. The major limiting factor to SEMS is the higher cost. The cost-effectiveness of the SEMS becomes apparent when multiple FDPS exchanges need to be performed. A randomized, prospective study by Kaassis et al.11 demonstrated that the number of additional days of hospitalization, days of antibiotics and the number of ERCPs performed on the group with the FDPS was higher compared to the group that received the SEMS. Davids et al.4 demonstrated a 28% reduction in ERCPs per patient with the use of SEMS. From those two studies as well as two studies using decision analysis with Markov modeling,63,64 initial SEMS placement is cost-effective in patients with survival of greater than six months. In Kaassis, et al.11 patients with liver metastases had a poorer prognosis with less than six months to live so would be an ideal group for the placement of plastic stents.

CONCLUSION Malignant pancreaticobiliary disease presents at an advanced stage and has a poor prognosis. Endoscopic palliative techniques have largely replaced surgical bypass. SEMS are effective for the palliation of malignant biliary obstruction. SEMS have more durable patency versus FDPS. While the upfront cost is greater for SEMS, compared to FDPS, they require few reinterventions which make SEMS more cost-effective. Covered SEMS have been more recently introduced and have been shown to decrease the rate of tumor ingrowth as compared to uncovered SEMS, however, they have been associated with increased frequency of complications. Covered SEMS are being studied for non-malignant applications.

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Chapter 17 Expandable Stent Insertion

6. Warshaw AL, Fernandez-del Castillo C. Pancreatic carcinoma. N Engl J Med 1992; 326:455–465. 7. Rosewicz S, Wiedenmann B. Pancreatic carcinoma. Lancet 1997; 349:485–489. 8. Smith AC, Dowsett JF, Russell RCG, et al. Randomised trial of endoscopic stenting versus surgical bypass in malignant low bile duct obstruction. Lancet 1994; 344:1655–1660. 9. Speer AG, Cotton PB, Russell RCG, et al. Randomised trial of endoscopic versus percutaneous stent insertion in malignant obstructive jaundice. Lancet 1987; 1:57–62. 10. Carr-Locke DL, Ball TJ, Connors PJ, et al. Multicenter randomized trial of Wallstent biliary endoprosthesis versus plastic stents. Gastrointest Endosc 1993; 39:A310. 11. Kaassis M, Boyer J, Dumas R, et al. Plastic or metal stents for malignant stricture of the common bile duct? Results of a randomized prospective study. Gastrointest Endosc 2003; 57:178–182. 12. Prat F, Chapat O, Ducot B, et al. A randomized trial of endoscopic drainage methods for inoperable malignant strictures of the common bile duct. Gastrointest Endosc 1998; 47:1–7. 13. Pisters PWT, Hudec W, Lee JE, et al. Preoperative chemoradiation for patients with pancreatic cancer: Toxicity of endobiliary stents. J Clin Oncol 2000; 18(4):860–867. 14. Spitz FR, Abbruzzese JL, Lee JE, et al. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol 1997; 15:928–937. 15. Yeo CJ, Abrams RA, Grochow LB, et al. Pancreaticoduodenectomy for pancreatic carcinoma: Postoperative adjuvant chemoradiation improves survival-A prospective, single-institution experience. Ann Surg 1997; 225:621–633. 16. Klinkenbijl JHG, Jeckel J, Sahmoud T, et al. Radiotherapy and 5-FU after curative resection for cancer of the pancreas and periampullary region: A phase III trial of the EORTC Gastrointestinal Tract Cancer Cooperative Group. Ann Surg 1999; 230:776–784. 17. Pendurthi TK, Hoffman JP, Ross E, et al. Preoperative versus postoperative chemoradiation for patients with resected pancreatic adenocarcinoma. Am Surg 1998; 64:686–692. 18. Wasan SM, Ross WA, Staerkel GA, et al. Use of expandable metallic biliary stents in resectable pancreatic cancer. Am J Gastroenterol 2005; 100:2056–2061. 19. Chen VK, Arguedas MR, Baron TH. Expandable metal biliary stents before pancreaticoduodenectomy for pancreatic cancer: A Monte-Carlo decision analysis. Clinical Gastroenterology and Hepatology. 2005; 3:1229–1237. 20. Smits ME, Rauws EAJ, Tytgat GNJ, et al. Preliminary results of a prospective randomized study of partially covered Wallstents vs noncovered Wallstents. Gastrointest Endosc 1995; 41:AB484. 21. Born P, Neuhaus H, Rosch T, et al. Initial experience with a new, partially covered Wallstent for malignant biliary obstruction. Endoscopy 1996; 28:699–702. 22. Miyayama S, Matsui O, Terayama N, et al. Covered Gianturco stents for malignant biliary obstruction: preliminary clinical evaluation. Journal of Vascular and Interventional Radiology. 1997; 8(4):641–648. 23. Rossi P, Bezzi M, Salvatori FM, et al. Clinical experience with covered Wallstents for biliary malignancies: 23-month follow-up. Cardiovasc Intervent Radiol 1997; 20:441–447. 24. Hausegger KA, Thurnher S, Bodendorfer G, et al. Treatment of malignant biliary obstruction with polyurethane-covered Wallstents. Am J Roentgenol. 1998; 170:403–408. 25. Shim CS, Lee YH, Bong HK, et al. Preliminary results of a new covered biliary metal stent for malignant biliary obstruction. Endoscopy 1998; 30:345–350.

26. Nakamura T, Hirai R, Kitagawa M, et al. Treatment of common bile duct obstruction by pancreatic cancer using various stents: single-center experience. Cardiovasc Intervent Radiol 2002; 25:373–380. 27. Han YM, Hwang SB, Lee ST, et al. Polyurethane-covered selfexpandable nitinol stent for malignant biliary obstruction: preliminary results. Cardiovasc Intervent Radiol 2002; 25:381–387. 28. Isayama H, Komatsu Y, Tsujino T, et al. Polyurethane-covered metal stent for management of distal malignant biliary obstruction. Gastrointest Endosc 2002; 55:366–370. 29. Schoder M, Rossi P, Uflacker R, et al. Malignant biliary obstruction: treatment with ePTFE-FEP-covered endoprostheses-initial technical and clinical experiences in a multicenter trial. Radiology 2002; 225(1):35–42. 30. Bezzi M, Zolovkins A, Cantisani V, et al. New ePTFE/FEP-covered stent in the palliative treatment of malignant biliary obstruction. J Vasc Interv Radiol 2002; 13:581–589. 31. Han YM, Jin GY, Lee SO, et al. Flared polyurethane-covered selfexpandable nitinol stent for malignant biliary obstruction. J Vasc Interv Radiol 2003; 14:1291–1301. 32. Isayama H, Komatsu Y, Tsujino T, et al. A prospective randomized study of “covered” versus “uncovered” diamond stents for the management of distal malignant biliary obstruction. Gut 2004; 53:729–734. 33. Miyayama S, Matsui O, Akakura Y, et al. Efficacy of covered metallic stents in the treatment of unresectable malignant biliary obstruction. Cardiovasc Intervent Radiol 2004; 27:349–354. 34. Nakai Y, Isayama H, Komatsu Y, et al. Efficacy and safety of the covered Wallstent in patients with distal malignant biliary obstruction. Gastrointest Endosc 2005; 62:742–748. 35. Kahaleh M, Tokar J, Conaway MR, et al. Efficacy and complications of covered Wallstents in malignant distal biliary obstruction. Gastrointest Endosc 2005; 61:528–533. 36. Yoon WJ, Lee JK, Lee KH, et al.. A comparison of covered and uncovered Wallstents for the management of distal malignant biliary obstruction. Gastrointest Endosc 2006; 63(7):996–1000. 37. Familiari P, Bulajic M, Mutignani M, et al. Endoscopic removal of malfunctioning biliary self-expandable metallic stents. Gastrointest Endosc 2005; 62:903–910. 38. Kahaleh M, Brock A, De La Rue SA, et al. Temporary placement of covered self expandable metal stents (SEMS) in benign biliary strictures: preliminary data. Gastrointest Endosc 2005; 61:AB208. 39. Baron TH, Poterucha JJ. Insertion and removal of covered expandable metal stents for closure of complex biliary leaks. Clin Gastroenterol Hepatol 2006; 4(3):381–386. 40. Dumonceau JM, Cremer M, Auroux J, et al. A comparison of Ultraflex Diamond stents and Wallstents for palliation of distal malignant biliary strictures. Am J Gastroenterol 2000; 95:670–676. 41. Rajiman I, Amin V, Siddique I, et al. The use of the Diamond stent (DS) in the treatment of malignant bile duct stricture. Gastrointest Endosc 1999; 49:AB235. 42. Seecoomar LF, Cohen SA, Kasmin FE, et al. Preliminary experience with the Ultraflex Diamond stent for management of malignant biliary obstruction. Gastrointest Endosc 1999; 49:AB236. 43. Siqueira E, Martin JA, Vargas, et al. Prospective evaluation of a new metal stent for treating malignant biliary obstruction. Gastrointest Endosc 1999; 49:AB236. 44. Shah RJ, Howell DA, Desilets DJ, et al. Multicenter randomized trial of the spiral Z-stent compared with the Wallstent for malignant biliary obstruction. Gastrointest Endosc 2003; 57:830–836. 45. Freeman ML, Overby C. Selective MRCP and CT-targeted drainage of malignant hilar biliary obstruction with self-expanding metallic stents. Gastrointest Endosc 2003; 58:41–49. 46. Pedersen FM, Lassen AT, Schaffalitzky de Muckadell OB. Randomized trial of stent placement above and across the

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47.

48.

49.

50.

51.

52.

53.

54.

55.

176

sphincter of Oddi in malignant bile duct obstruction. Gastrointest Endosc 1998; 48:574–579. Liu Q, Khay G, Cotton PB. Feasibility of stent placement above the sphincter of Oddi (“inside-stent”) for patients with malignant biliary obstruction. Endoscopy 1998; 30:687–690. Dowsett JF, Vaira D, Hatfield AR, et al. Endoscopic biliary therapy using the combined percutaneous and endoscopic technique. Gastroenterol 1989; 96:1180–1186. Deviere J, Baize M, de Toeuf J, et al. Long term follow-up of patients with hilar malignant stricture treated by endoscopic internal biliary drainage. Gastrointest Endosc 1988; 34:95–101. DePalma GD, Pezzullo A, Rega M, et al. Unilateral placement of metallic stents for malignant hilar obstructions: A prospective study. Gastrointest Endosc 2003; 58:50–53. Hookey LC, Le Moine O, Deviere J. Use of a temporary plastic stent to facilitate the placement of multiple self-expanding metal stents in malignant biliary hilar strictures. Gastrointest Endosc 2005; 62(4):605–609. Watanapa P, Williamson RC. Surgical palliation for pancreatic cancer: developments during the past two decades. Br J Surg 1992; 102:608–613. Maetani I, Ogawa S, Hoshi H, et al. Self-expanding metal stents for palliative treatment of malignant biliary and duodenal stenosis. Endoscopy 1994; 26:701–4. Soetikno RM, Carr-Locke DL. Expandable metal stents for gastric outlet, duodenal, and small intestinal obstruction. Gastrointest Endosc Clin North A 1999; 9:447–458. Soetikno RM, Lichtenstein DR, Vadervoort J, et al. Palliation of malignant gastric outlet obstruction using an endoscopically placed Wallstent. Gastrointest Endosc 1998; 47:267–270.

56. Yates III MR, Morgan DE, Baron TH. Palliation of malignant gastric and small intestinal strictures with self-expandable metal stents. Endoscopy 1998; 30:266–272. 57. Yim HB, Jacobson BC, Saltzman JR, et al. Clinical outcome of the use of enteral stents for palliation of patients with malignant upper GI obstruction. Gastrointest Endosc 2001; 53:329–332. 58. Kaw M, Singh S, Gagneja H. Clinical outcome of simultaneous self-expandable metal stents for palliation of malignant biliary and duodenal obstruction. Surgical Endoscopy 2003; 17:457–461. 59. Vanbiervliet G, Piche T, Caroli-Bosc FX, et al. Endoscopic argon plasma trimming of biliary and gastrointestinal metallic stents. Endoscopy 2005; 37(5):434–438. 60. Chen YK, Jakribettuu V, Springer EW, et al. Safety and efficacy of argon plasma coagulation trimming of malpositioned and migrated biliary metal stents: a controlled study in the porcine model. Am J Gastroenterol 2006; 101:1–6. 61. Tham TCK, Carr-Locke DL, Vandervoort J, et al. Management of occluded biliary Wallstents. Gut 1998; 42:703–707. 62. Bueno JT, Gerdes H, Kurtz RC. Endoscopic management of occluded biliary Wallstents: a cancer center experience. Gastrointest Endosc 2003; 58:879–884. 63. Arguedas MR, Heudebert GH, Stinnett AA, et al. Biliary stents in malignant obstructive jaundice due to pancreatic carcinoma: a cost effective anaylsis. Am J Gastroenterol 2002; 97:897–904. 64. Yeoh KG, Zimmerman MJ, Cunningham JT, et al. Comparative costs of metal versus plastic biliary stent strategies of malignant obstructive jaundice by decision analysis. Gastrointest Endosc 1999; 49:466–471.

SECTION 2

Chapter

18

TECHNIQUES

Stent Removal: Migrated and Non-Migrated Tiing Leong Ang, Stefan Seewald and Nib Soehendra

BOX 18.1 SUMMARY OF KEY TECHNIQUES Techniques that do not maintain duct access: • Direct grasping with a basket, rat-tooth forceps or snare • Use of an inflated balloon catheter to provide lateral traction Techniques that maintain duct access: The occluded or proximally migrated stent is first cannulated using a guidewire and catheter. The stent is then retrieved with retrieval devices such as: • Soehendra® stent retriever: The retriever is inserted over the guidewire and pushed into close proximity with the stent. Its screw-tip is then rotated into the distal end of the stent, thus anchoring the stent retriever. The stent is then pulled out through the accessory channel with continued duct access maintained by the guidewire. • Other techniques: 1. A partially opened small snare is passed over the guidewire. The snare is fully opened around the distal tip of the stent which is grasped over the distal flaps. The stent is removed through the accessory channel while the guidewire is maintained in position. 2. A 4 mm diameter, 2.5 cm long dilating balloon is advanced over the guidewire into the stent (size > 10 Fr) and inflated. The stent is withdrawn by pulling the inflated balloon.

INTRODUCTION AND SCIENTIFIC BASIS Plastic endoprostheses have become an established therapy for a variety of biliary and pancreatic disorders (see Chapter 16). Endoscopic biliary stent placement is used for indications such as drainage of malignant or benign biliary obstruction, biliary stricture dilatation and biliary leakage. Pancreatic stents are used for transpapillary drainage of pseudocysts, treatment of pancreatic fistulae, relief of pancreatic duct obstruction from stricture or malignancy, as well as prophylaxis against post-ERCP pancreatitis.1 These stents may be temporary, such as in the case of stricture dilatation or prevention of post-ERCP pancreatitis, or intended for long-term treatment. Stent removal will be required once the therapeutic endpoint is achieved, and when stent occlusion or migration occurs because

of complications such as cholangitis, pancreatitis, duodenal wall injury or perforation. Self-expandable metallic stents (SEMS) are increasingly being used for palliative treatment of malignant biliary obstruction. As compared to plastic stents, the duration of stent patency is longer because of the larger luminal diameter. SEMS have also been shown to be more cost-effective compared to plastic stents for patients who survive more than 4–6 months.2 The placement of uncovered SEMS is generally regarded as permanent due to the fact that they become deeply embedded in the bile duct wall and induce a marked tissue reaction making endoscopic removability difficult, if not impossible. Covered SEMS were developed primarily to extend stent patency by preventing tumor ingrowth. The covering prevents deep embedding of the stent into the biliary wall, which, although increasing the risk of migration, allows them to be potentially endoscopically removable. SEMS are generally only used for palliation of malignant biliary stenosis with intent to remain in place permanently. SEMS placement in benign biliary strictures has been described3 but it is not generally accepted. Although uncovered SEMS are generally not removable, cases of successful extraction have been reported.4 Plastic stents may be removed by directly grasping them with accessories such as rat-tooth forceps, polypectomy snares, or stone retrieval baskets. Other methods of direct removal involve cannulation of the stent lumen with a guidewire followed by insertion of retrieval devices such as the Soehendra® stent retriever or a dilating balloon. Plastic stents can also be removed indirectly by providing lateral traction force, such as with the use of a stone retrieval or dilating balloon. SEMS extraction is more difficult than plastic stents. Covered SEMS can be removed by directly snaring the distal end within the duodenum, whereas uncovered SEMS can be removed by grasping and breaking individual wire filaments in order to unravel the stent, though this is not always technically feasible.

INDICATIONS/CONTRAINDICATIONS OF STENT REMOVAL

BOX 18.2 INDICATIONS AND CONTRAINDICATIONS Indications: • Occluded stents • Migrated stents

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• Therapeutic endpoint achieved • To facilitate duct access for further endoscopic treatment Contraindications: • Presence of severe co-morbid illnesses such that endoscopy cannot be safely performed • In situations such as terminal malignancies where the clinical outcome would not be altered • Uncovered self-expandable metallic stents (relative contraindication)

Indications

1. Occluded stents: Occluded biliary stents need to be removed and replaced in order to facilitate continued biliary drainage. Occluded stents lead to jaundice and cholangitis. If occluded pancreatic duct stents are not replaced, acute pancreatitis may result. If not removed in a timely fashion chronic pancreatic duct changes may also occur. 2. Migrated stents: Completely distally migrated biliary and pancreatic stents usually pass spontaneously and uneventfully out of the gastrointestinal tract into the stool. However, if distal migration of a stent is incomplete, injury to the contra-lateral duodenal wall may arise; duodenal wall perforation has been reported in this context. Usually a distally migrated stent may be simply grasped and removed. Frequently, the distal end is too far to be reached with a snare or basket and can be grasped with a rat-tooth forceps at the point where the stent is exiting the papilla. 7 Fr stents can be grasped with a diagnostic forceps while a therapeutic forceps is required to grasp 10 Fr stents. Grasping the flap is usually not effective, since it usually breaks away from the stent. Proximal migration has been reported to occur at an incidence rate of 4.9% and 5.2% for biliary and pancreatic stents, respectively.5 Unlike distally migrated stents, proximally migrated stents are more difficult to retrieve since they cannot be directly endoscopically visualized; guidance is provided by fluoroscopy which does not provide three-dimensional orientation. 3. Therapeutic purpose achieved: When the treatment endpoint has been achieved, such as after successful dilatation of benign biliary strictures including anastomotic strictures following liver transplantation,6 those due to chronic pancreatitis,7 and after resolution of biliary8 or pancreatic9 fistula, the stent should be removed. Temporary pancreatic stents placed after endoscopic papillectomy or pancreatic duct sphincterotomy require removal if they do not pass spontaneously. 4. To provide access for further endoscopic interventions: In some situations stents are inserted for temporary ductal drainage and require removal before definitive treatment can be carried out. For example, insertion of a temporary biliary stent may be performed if bile duct calculi cannot be extracted. Stents require removal in order to perform additional interventions such as mechanical lithotripsy or electrohydraulic lithotripsy. Temporary stents have also been inserted to facilitate healing of biliary and pancreatic fistulae; if these fistulae are persistent, sealing may be attempted with the help of N-butyl-2-cyanoacrylate.10,11 In these instances, in order to provide adequate duct access for the passage of accessory devices, the temporary stents must first be removed. 178

Contraindications

1. Severe comorbid illnesses: In the presence of severe comorbid medical illnesses, hemodynamic instability, or pulmonary insufficiency, where sedation is hazardous or the patient is unstable, ERCP and stent removal are contraindicated. In terminally ill patients, with a migrated stent but who are asymptomatic, attempted ERCP and stent removal should probably be avoided since it will not be expected to influence the clinical course of the patient. 2. Self-expandable metallic stent: The placement of an uncovered SEMS is generally regarded as permanent. Uncovered SEMS may occlude because of tumor ingrowth and/or tissue hyperplasia. Attempted removal of uncovered SEMS may lead to complications such as bleeding and perforation because they become deeply embedded into the tissue soon after placement. Hence, removal of uncovered SEMS is considered a contraindication, though in certain circumstances the benefits of removal outweigh the potential risks. The presence of a coagulopathy, however, is considered a contraindication to removal of uncovered SEMS.

TECHNIQUES OF STENT REMOVAL Plastic stents

Overview of techniques for plastic stent removal These techniques include direct grasping with an accessory device such as rat-tooth forceps, stone retrieval basket, or polypectomy snare. Indirect techniques utilize traction with an inflated occlusion or dilating balloon that has been advanced alongside the stent followed by withdrawal. Direct traction techniques involve cannulation of the stent lumen with a guidewire followed by insertion of a dilating balloon or screw extractor. These latter methods allow access to the biliary tree to be maintained as the stent is withdrawn facilitating subsequent insertion of a new stent or performance of other therapeutic maneuvers. Maintaining duct access with a guidewire is crucial if the intent is to replace the stent, especially if selective duct cannulation or traversal of a stricture was initially difficult to achieve. Migrated stents are generally more difficult to remove compared to non-migrated stents. With distal migration, the end may be impacted against the contra-lateral duodenal wall or out of reach of the endoscope. Much of the published data on removal of proximally migrated stents consist of case reports. Three larger case series have been reported. In these series successful stent removal was achieved in 85–90% of cases (Table 18.1).12–14 In addition, novel techniques for the removal of migrated stents have also been described.15,16

Common accessories used In general, a therapeutic duodenoscope with a working channel of 4.2 mm diameter is preferred. This allows withdrawal of the retrieved stents (up to 10 Fr) through the accessory channel without having to withdraw the endoscope. Endoscopic accessories that are commonly used for stent removal include the following: polypectomy snare (e.g. ReSnare® (a reusable polypectomy snare), Cook Endoscopy), rat-tooth forceps (e.g. FG-14P-1, FG-8L-1; Olympus Optical Co, Tokyo, Japan), Dormia basket (e.g. FG-22Q-1, Olympus Optical Co, Tokyo, Japan), biliary dilatation balloon (e.g. CRETM wire guided biliary balloon dilators, Boston Scientific, Natick, MA, USA; BB-1, Olympus Optical Co, Tokyo, Japan; QBIDTM, Cook Endoscopy), extraction balloon catheters (e.g. B5-2Q, Olympus Optical Co, Tokyo, Japan; DASH® extraction balloon, Cook Endoscopy), Teflon coated

Chapter 18 Stent Removal: Migrated and Non-Migrated

1st author 12

Tarnasky 1995

Biliary stent

Pancreatic stent

44

0

13

33

26

14

41

0

118

26

Lahoti 1998

Chaurasia 1999

Total

Success rate of endoscopic retrieval

Management of failed retrieval

38/44 (86%)

Radiological Surgery Follow-up

Biliary: 28 (85%) Pancreatic: 21 (80%)

Insertion of 2nd stent Surgery Follow-up

37/41 (90%)

Insertion of 2nd stent

124/144 (86%)

Table 18.1 Results of endoscopic removal of proximally migrated stents

Fig. 18.1 Soehendra® Stent Retriever (courtesy of Cook Endoscopy, Winston-Salem, NC, USA).

Fig. 18.3 basket.

Fig. 18.2 Soehendra® Stent Retriever with extended curved plastic tip facilitating cannulation of the stent (courtesy of Cook Endoscopy, Winston-Salem, NC, USA).

stainless steel and nitinol tracer guidewires (Cook Endoscopy, Winston-Salem, NC, USA), Zebra® wire (Boston Scientific, Natick, MA, USA), Soehendra® universal catheter and Soehendra® stent retriever (Cook Endoscopy, Winston-Salem, NC, USA) (Figs 18.1 and 18.2). Most of these accessories are readily available from a variety of medical device companies (Chapter 4).

SPECIFIC TECHNIQUES 1. Direct grasping of stent The standard method of removing non-migrated or distally migrated stents involves grasping the distal intra-duodenal portion of the stent with a polypectomy snare, stone retrieval basket (Fig. 18.3) or rattooth forceps (Fig. 18.4), followed either by withdrawing the endoscope completely out of the patient or by depositing the stent in the stomach for subsequent removal at the end of the procedure. Alternatively, the stent may be withdrawn through the accessory channel of the endoscope, if the diameter of the stent allows. For example,

Grasping an occluded biliary stent with a Dormia

if a diagnostic duodenoscope with a 2.8 mm accessory channel is used, a 7 Fr stent (2.3 mm diameter) may be extracted through the channel, but a 10 Fr stent (3.3 mm) cannot; similarly, if a therapeutic duodenoscope with a 4.2 mm accessory channel is used, a 10 Fr stent may be extracted through the endoscope if it is captured at its distal end, but if caught in mid-shaft, it tends to fold upon itself, such that the total diameter is 6.6 mm; in this scenario, the duodenoscope would have to be withdrawn. If the distally migrated stent has penetrated the duodenal wall, then neither stone retrieval baskets nor snares are suitable and a rat-tooth forceps would be required. This technique of direct grasping may also be utilized for proximally migrated stents, but in the presence of non-dilated ducts, passage of accessories may be difficult and the forceps may not have enough room to adequately open. A rat-tooth forceps can be used to grasp the distal end of the proximally migrated stent. In addition, a basket or snare can be used to capture the stent from either the proximal or distal end initially, but on removal only the distal end should be grasped in order to avoid perforation.17 If subsequent stent replacement is required, or if the access to the duct needs to be maintained, the biliary or pancreatic duct must be cannulated with a guidewire and the stent removed leaving the wire in place.

2. Indirect technique using balloon traction To retrieve a proximally migrated stent there are two variations of this indirect technique in which either a single or double lumen balloon catheter is passed over a guidewire that has been passed alongside the stent. Either a stone extraction balloon or a dilatation 179

SECTION 2 TECHNIQUES

Fig. 18.4 forceps.

Retrieving an occluded biliary stent with a rat-tooth

balloon may be used. The balloon is advanced so that it is located alongside and at the midpoint of the stent. The balloon is then inflated and gradually withdrawn. The indirect traction provided by the balloon catheter causes the stent to pass distally (Fig. 18.5). An alternative is to pass the balloon catheter to a point just above the proximal end of the stent. The balloon is then inflated and the stent retrieved by gradually pulling the balloon catheter distally. The size of the balloon used depends on the size of the duct; for instance, in a dilated common bile duct, one may be able to use an 8 or 11.5 mm dilating balloon, whereas in a non-dilated pancreatic duct, a smaller size dilatation balloon (4 mm) is used.18

Fig. 18.5 Removal of proximally migrated biliary stent using a dilating balloon. The dilating balloon (arrow) and distal end of the stent (arrowhead) can be seen.

3. Techniques utilizing stent cannulation A variety of techniques which utilize stent cannulation may be used for stent retrieval. The stent lumen is cannulated with a guidewire loaded into a catheter or sphincterotome; the latter allows for upward deflection into the stent. When applying this technique to proximally migrated stents, the lumen can be difficult to cannulate; use of a hydrophilic guidewire may be helpful to access the stent lumen. The Soehendra® stent retriever was developed to maintain duct access during stent removal. This is especially useful when replacing stents in patients in whom the initial cannulation and stent placement were very difficult, such as in the case of perihilar cholangiocarcinoma and multiple stents (Figs 18.6–18.12). It can also be used to retrieve a proximally migrated stent upon initial guidewire cannulation of the stent (Figs 8.13–8.21). It is a wire-guided metal spiral retrieval device 200 cm long with a screw tip 3 to 4 mm long that is rotated into the inner lumen of the stent.19 Exact alignment of the inner lumen of the stent with the retrieval device is needed for this device to self-thread into the stent. Once the stent retriever is securely anchored to the end of the stent, the 180

Fig. 18.6 A patient with perihilar cholangiocarcinoma. Four biliary stents were inserted in order to drain different liver segments; the insertion of two of these stents required a rendezvous procedure after initial unsuccessful ERCP. The figure shows initial cannulation of one of the occluded stents using a 7 Fr universal catheter.

Chapter 18 Stent Removal: Migrated and Non-Migrated

Fig. 18.7 A guidewire had been successfully inserted through the occluded stent.

Fig. 18.8 The catheter was withdrawn and the guidewire left within the stent.

Fig. 18.10 The screw tip of Soehendra® stent retriever was rotated into the distal end of the stent.

Fig. 18.9 Insertion of the Soehendra® stent retriever over the guidewire.

Fig. 18.11 The occluded stent was then removed by the Soehendra® stent retriever. 181

SECTION 2 TECHNIQUES

Fig. 18.12 After the stent had been retrieved, the guidewire was left in place to facilitate subsequent reinsertion of a new stent.

Fig. 18.15 The glidewire was used to direct the tip of the universal catheter into the distal end of the migrated stent.

Fig. 18.13

X-ray picture of a proximally migrated biliary stent.

Fig. 18.16 The glidewire had been withdrawn, and the tip of the universal catheter was inserted in the distal end of the migrated stent.

Fig. 18.14 Cannulation of the proximally migrated biliary stent using Terumo glidewire guided by a universal catheter. 182

Fig. 18.17 A standard guidewire was then inserted through the universal catheter into the lumen of the migrated stent.

Chapter 18 Stent Removal: Migrated and Non-Migrated

Fig. 18.18 The universal catheter was then withdrawn leaving the guidewire in place.

Fig. 18.21 The migrated stent had now been pulled out through the major papilla.

Fig. 18.19 The Soehendra® stent retriever had been inserted over the guidewire and its tip had been rotated into the end of the proximally migrated stent.

Fig. 18.20 X-ray picture of the stent being withdrawn by the Soehendra® stent retriever.

stent is withdrawn through the biopsy channel. The guidewire is maintained during exchange as when any device is exchanged. Depending on the size of the stent, one would need to select an appropriately sized stent retriever. Plastic stents made of polyethylene become softer after a few months and so the tip of the retriever may not anchor firmly into the end of the stent, resulting in failure of stent retrieval. In such a situation, a larger size stent retriever (e.g. 11.5 Fr retriever for a 10 Fr stent) should be used. Newer stents such as the Viaduct (GI Supply®, Camp Hill, PA) and the Marathon antireflux stent (Cook Endoscopy, Winston-Salem, NC) (Chapter 16) are not amenable to this type of removal. Another method of stent removal using the stent cannulation technique is passage of a 4 mm standard biliary dilating balloon into the stent (Fig. 18.22). The balloon is advanced over the guidewire into the stent and inflated. The amount of inflation necessary to provide enough traction is less than for stricture dilatation; 4 atmospheres of pressure is usually adequate. The balloon inflation port is then locked and the stent is withdrawn by withdrawing the balloon while the wire is kept in place. This method can only be used for stents 10 Fr and larger.20 For removal of proximally migrated 5 Fr pancreatic stents, interventional cardiology dilating balloons, such as a 3 mm angioplasty balloon mounted on 2.5 Fr catheter, can be used.15 Yet another technique of removal over the wire utilizes a standard polypectomy snare (Figs 18.23–18.25).21–22 The stent lumen is cannulated with a standard guidewire as mentioned above. A partially opened snare (e.g. 5 Fr mini-snare, snare diameter 5 mm, snare length 1.5 cm, WCMSR-1; Cook Endoscopy, Winston-Salem, NC) is then passed over the guidewire and through the accessory channel. Once in view, the snare is fully opened and advanced to encircle the distal tip of the stent. The snare is closed to grasp the stent and the stent is withdrawn through the biopsy channel while the guidewire position is maintained.22 183

SECTION 2 TECHNIQUES

A

B

Fig. 18.23 This was a patient with pancreas divisum who had been treated with pancreatic stenting due to dorsal duct disruption following pancreatitis. A guidewire had already been inserted through the stent, and a partially opened snare was being advanced over the guidewire toward the stent. 184

Fig. 18.22 Balloon over the guidewire technique. A guidewire was first inserted into the stent. Next a balloon catheter was inserted over the guidewire into the stent. The balloon would then be inflated (either at the proximal end of the stent A or within the stent lumen B) and used to pull the stent down, while keeping the guidewire in place for subsequent stent reinsertion.

Fig. 18.24 The distal end of the pancreatic stent was then captured by the snare.

Chapter 18 Stent Removal: Migrated and Non-Migrated

4. Novel techniques In addition to the use of a rat-tooth forceps, the “lasso” technique had also been reported as a means of retrieving distally migrated plastic stents which have impacted against and perforated the contralateral duodenal wall.23 A 0.035 inch guidewire was passed behind the stent and the tip of the guidewire grasped by a polypectomy snare in front, thus looping the stent. The stent is then winched into close proximity with the endoscope and the entire apparatus retrieved together with the stent (Fig. 18.26). Instead of a snare, a retrieval basket had also been used for this purpose.16 In a case report the removal of proximally migrated 10 Fr biliary stent in which the distal end had become embedded in the wall of the common bile duct was described. A 0.035-inch Glidewire (Boston Scientific Corp, Natick, Mass.) was advanced beyond the proximal end of the stent within the common hepatic duct and then looped at the bifurcation with the tip of the guidewire returning toward the papilla. A snare was inserted through the accessory channel with the wire passing through the loop of the snare. The end of the Glidewire protruding from the papilla was grasped with the snare, tightening the wire and lassoing the stent. With further traction, the stent could be kinked and withdrawn.24 Some patients undergoing liver transplantation have a T-tube inserted across the choledochocholedochostomy to ensure anasto-

motic patency. A stent modified from a 5 Fr latex urinary catheter may be used intraductally to maintain anastomotic patency, and being without flaps, it is intended to pass spontaneously within weeks. A case had been reported in which such a latex stent did not pass spontaneously and was found to be folded back on itself within the bile duct. In this instance, ERC was performed and a guidewire was inserted without performing papillotomy. A rotatable rat-toothed forceps (Olympus America Corp, Lehigh Valley, PA) was inserted through the working channel and manipulated around the guidewire such that the guidewire was entrapped in the notch when the forceps was closed. The forceps was then introduced easily into the common bile duct in tandem with the guidewire, then disengaged, allowing the catheter to be grasped and removed without disrupting the architecture of the papilla.25

Special considerations Newer plastic stents that have become available such as the Viaduct stent and antireflux stent (Chapter 16) may pose special problems for removal. The Viaduct has a small central lumen that only allows passage of a guidewire; thus balloon passage and stent retriever passage into the lumen are not possible. With proximal migration, they may be more difficult to grasp. In patients with the antireflux stent, the wind-sock on the distal end makes it nearly impossible to cannulate the stent lumen. In addition in the event of proximal migration, the wind-sock may tear if grasped with a rat-tooth forceps.

SELF-EXPANDABLE METALLIC STENTS Overview of techniques for metallic stent removal Unlike plastic stents, the techniques used for removal of SEMS involve direct grasping of the stent. For removal of uncovered SEMS embedded into the mucosa, initial fragmentation of the individual wires in order to cause the stent to collapse may be required. Covered stents may be removed by grasping the stent with a snare.

Specific techniques Fig. 18.25 The pancreatic stent was then removed by the snare while the guidewire remained in place.

For an uncovered SEMS which is embedded in the bile duct mucosa, snare removal will be impossible. An option then would be the initial extraction of individual wire filaments from the distal end of the

A

B

Duodenoscope

Snare over stent and guidewire underneath

A lasso is formed as the snare grasps the guidewire, and is used to winch the tip of the stent from the duodenal wall

Fig. 18.26 The “lasso” technique for removing a distally migrated stent that had impacted against the contralateral duodenal wall. A A snare was inserted over the stent while a guidewire was inserted below the stent. B The guidewire was then captured by the snare, creating a “lasso” over the distal end of the stent which was then winched into close proximity with the endoscope, thus freeing the impacted distal end. 185

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SEMS using a “hot” biopsy forceps so that the stent architecture is destroyed, thus allowing the stent to collapse. Once the stent has collapsed, it may then be possible to extract it using a snare. It may be necessary to coagulate the lumen within the stent first before stent extraction in order to reduce the risk of bleeding. If a SEMS has migrated distally and impacted upon the opposite duodenal wall, it may be necessary to attempt cutting the stent with argon plasma coagulation first before extraction with a snare. In one series SEMS removal was successful in 17 out of 18 patients. Among these successfully removed SEMS, 13 were covered and 4 uncovered stents.4 In a larger series, endoscopic removal of 39 SEMS (13 uncovered and 26 covered) was attempted. It was successful in 29 SEMS (74.3%). Covered SEMS were effectively removed more frequently than uncovered ones: 24 of 26 (92.3%) and 5 of 13 (38.4%), respectively (p < 0.05). No major complications were recorded. The presence of a stent covering was the only factor predictive of successful stent extraction. The presence of diffuse and severe ingrowth was the main feature limiting SEMS removal.26 For removal of covered SEMS in which the distal end is lying free in the duodenum beyond the papilla, the distal end is grasped with a polypectomy snare as far proximally as possible based upon the amount of stent remaining within the duodenum. The snare is then closed, such that the distal end of the SEMS becomes compressed, whereupon the SEMS elongates and collapses over a short distance from the point of compression. Either the entire stent can be withdrawn, or the stent can be withdrawn through the accessory channel of the endoscope without injury to the patient or damage to the instrument. In rare situations SEMS can migrate proximally above the stricture and may be “free floating.” Stent retrieval may be possible with either a basket27 or a rat-tooth forceps.28 An interesting method of removal of distally migrated covered Wallstent which had impacted on the contralateral duodenal wall had been reported. A closed biopsy forceps (FB-21K-1, Olympus Optical Co. Ltd, Tokyo, Japan) was advanced through the stent mesh and opened within the stent to form an anchor. The endoscope was then withdrawn together with the opened forceps. During endoscope withdrawal, the stent folded upon itself in the mid-body and was easily transported from the duodenum to the stomach. Once inside the stomach one end of the stent was caught with a snare and the stent was removed by complete withdrawal of the endoscope.29

COMPLICATIONS AND THEIR MANAGEMENT BOX 18.3 COMPLICATIONS AND CONTROVERSIES Complications: • General complications related to endoscopy and ERCP • Duct injury with bleeding or perforation during retrieval of proximally migrated stents • Injury to the cardia and distal esophagus when the unprotected stent is pulled out simultaneously with the endoscope

186

Failure of stent extraction: Options include insertion of another stent to maintain duct drainage, surgical removal of the stent and observation in the context of an asymptomatic patient. Controversies: The placement of a SEMS is generally regarded as permanent. This is due to the metallic mesh being deeply embedded in the biliary wall. Attempted removal may be technically impossible, or may result in bleeding and perforation. Reports of successful endoscopic removal of SEMS have been published, especially of the covered type. Hence the presence of SEMS should no longer be viewed as an absolute contraindication for stent removal.

General complications The usual complications of sedation, cardiopulmonary events, perforation and pancreatitis may occur. Proper patient selection prior to performing the procedure and close clinical monitoring during the procedure are important in reducing the risk of complications.

Complications related specifically to stent removal Although guided by fluoroscopy, the retrieval of a proximally migrated plastic stent is essentially a blind procedure. When accessories such as forceps are used, there is a possibility of accidentally grasping the ductal epithelium instead of the stent which may cause ductal injuries such as bleeding and perforation. In addition, if the stent is grasped at its proximal end instead of its distal end, it may kink and rotate during withdrawal and potentially cause ductal injury. Thus it is important to capture the distal end of the stent before applying traction. In the very rare event of bile duct perforation during stent removal, the insertion of a new biliary stent may allow the perforation to close. One must be careful if the stent and endoscope are withdrawn together because the distal end of the stent may tear the cardia or esophageal wall. The elevator of the working channel must be completely opened. In addition, when using a stone retrieval basket or snare, allowing a sufficient length between the captured end of the stent and the distal tip of the duodenoscope will allow a more flexible and smooth retrieval, as the axis of the snare may be aligned with that of the esophageal lumen. The removal of an uncovered SEMS, if it is possible, is associated with an increased risk of bleeding and perforation. Therefore in patients with uncovered SEMS one should seriously consider whether removal is absolutely necessary. Options to manage the stent include placement of another stent, be it a plastic stent or a SEMS, through the occluded stent. In the event that endoscopic stent removal is not possible, management options include surgical removal, insertion of another stent (if continued duct drainage is required), or observation if the patient remains asymptomatic. Surgical removal should be considered in healthy patients with proximally migrated pancreatic duct stents to minimize the possibility of irreversible ductal injury.

Chapter 18 Stent Removal: Migrated and Non-Migrated

RELATIVE COSTS AND CHOICE OF TECHNIQUE There are no studies that have compared one technique of stent removal to another. In addition, there are no cost-effectiveness studies. It is unlikely that such studies will be done. All of the accessories mentioned in this chapter are likely already available and their use for stent removal should not lead to increased costs. The choice

of a particular technique depends on the specific circumstances requiring stent removal. In patients in whom the goal is to remove and not replace a plastic stent, one should simply grasp the stent with a polypectomy snare, rat-tooth forceps, or stone retrieval basket. If the intent is to replace a stent it is advisable to initially cannulate the stent with a guidewire and remove the stent while maintaining duct access by leaving the guidewire in place.

REFERENCES 1.

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4. 5.

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Soehendra N, Binmoeller KF, Seifert H, et al. Therapeutic endoscopy: color atlas of operative techniques for the gastrointestinal tract. 2nd edn. Stuttgart: Georg Thieme Verlag; 2005:30–155. Arguedas MR, Heudebert GH, Stinnett AA, et al. Biliary stents in malignant obstructive jaundice due to pancreatic carcinoma: a cost-effectiveness analysis. Am J Gastroenterol 2002; 97:898–904. Dumonceau JM, Deviere J, Delhaye M, et al. Plastic and metal stents for postoperative benign bile duct strictures: the best and the worst. Gastrointest Endosc 1998; 47:8–17. Kahaleh M, Tokar J, Le T, et al. Removal of self-expandable metallic Wallstents. Gastrointest Endosc 2004; 60:640–644. Johanson JF, Schmalz MJ, Geenen JE. Incidence and risk factors for biliary and pancreatic stent migration. Gastrointest Endosc 1992; 38:341–346. Shah JN, Ahmad NA, Shetty K, et al. Endoscopic management of biliary complications after adult living donor liver. transplantation. Am J Gastroenterol. 2004; 99:1291–1295. Draganov P, Hoffman B, Marsh W, et al. Long-term outcome in patients with benign biliary strictures treated endoscopically with multiple stents. Gastrointest Endosc. 2002; 55:680–686. Costamagna G, Mutignani M, Ingrosso M, et al. Endoscopic treatment of postsurgical external pancreatic fistulas. Endoscopy. 2001; 33:317–322. Sherman S, Shaked A, Cryer HM, et al. Endoscopic management of biliary fistulas complicating liver transplantation and other hepatobiliary operations. Ann Surg. 1993; 218:167–175. Seewald S, Groth S, Sriram PV, et al. Endoscopic treatment of biliary leakage with N-butyl-2 cyanoacrylate. Gastrointest Endosc. 2002; 56:916–919. Seewald S, Brand B, Groth S, et al. Endoscopic sealing of pancreatic fistula by using N-butyl-2-cyanoacrylate. Gastrointest Endosc. 2004; 59:463–470. Tarnasky PR, Cotton PB, Baillie J; et al. Proximal migration of biliary stents: attempted endoscopic retrieval in forty-one patients. Gastrointest Endosc 1995; 42:513–519. Lahoti S, Catalano MF, Geenen JE, et al. Endoscopic retrieval of proximally mgrated biliary and pancreatic stents: experience of a large referral center. Gastrointest Endosc 1998; 47:486–491. Chaurasia OP, Rauws EAJ, Fockens P, et al. Endoscopic techniques for retrieval of proximally migrated biliary stents: the Amsterdam experience. Gastrointest Endosc 1999; 50:780–785. Baron TH, Dean LS, Morgan DE, et al. Proximal migration of a pancreatic duct stent: endoscopic retrieval using interventional cardiology accessories. Gastrointest Endosc 1999; 50:124–125.

16. Mergener K, Baillie J. Retrieval of distally migrated, impacted biliary endoprostheses using a novel guidewire/basket “lasso” technique. Gastrointest Endosc 1999; 50:93–95. 17. Sharara AI, Leung JW. Endoscopic extraction of proximally migrated biliary endoprostheses using a grasping rat-tooth forceps. Gastrointest Endosc 1995; 41:619–620. 18. Horwhat JD, Jowell P, Branch S, et al. Proximal migration of a 3 French pancreatic stent in a patient with pancreas divisum: suggested technique for successful retrieval. JOP. J Pancreas (Online) 2005; 6:178–184. 19. Soehendra N, Maydeo NA, Eckmann B, et al. A new technique for replacing obstructed biliary endoprostheses. Endoscopy 1990; 22:271–272. 20. Martin DF. Wire-guided balloon assisted endoscopic biliary stent exchange. Gut 1991; 32:1562–1564. 21. Sherman S, Hawes RH, Uzer MF, et al. Endoscopic stent exchange using a guidewire and snare. Gastrointest Endosc 1993; 39:794–799. 22. Bohorfoush AG, Ballinger PJ, Hogan WJ. A new method for exchange of endoprostheses in the biliary and pancreatic ducts. Gastrointest Endosc 1993; 39:799–802. 23. Smith FC, O’Connor HJ, Downing R. An endoscopic technique for stent recovery used after duodenal perforation by a biliary stent. Endoscopy 1991; 23:244–245. 24. Vandervoort J, Carr-Locke DL, Tham TCK, et al. A new technique to retrieve an intrabiliary stent: a case report. Gastrointest Endosc 1999; 49:800–802. 25. Mulcahy HE, Cunningham JT. A guidewire-assisted technique for removing retained biliary stents with rat-toothed forceps during endoscopic retrograde cholangiography. Gastrointest Endosc 2001; 53:386–387. 26. Familiari P, Bulajic M, Mutignani M, et al. Endoscopic removal of malfunctioning biliary self-expandable metallic stents. Gastrointest Endosc. 2005 Dec; 62(6):903–910. 27. Mo LR, Tsai CC, Yueh SK, et al. Endoscopic retrieval of a selfexpanding stainless steel stent from the common bile duct. Endoscopy 1994; 26:562–563. 28. Baron TH, Blackard WG, Morgan DE. Endoscopic removal of a “floating” biliary Gianturco Z stent five years after placement for a benign anastomotic stricture in a liver transplant patient. Gastrointest Endosc 1997; 46:80–82. 29. Matsushita M, Takakuwa H, Nishio A, et al. Open biopsy forceps technique for endoscopic removal of distally migrated and impacted biliary metallic stents. Gastrointest Endosc 2003; 58:924–927.

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Chapter

19

TECHNIQUES

Papillectomy/Ampullectomy Ann M. Chen and Kenneth F. Binmoeller

INTRODUCTION

• Using a duodenoscope, endoscopic ampullectomy is performed in a similar manner to snare polypectomy.

Ampullary tumors Tumors of the ampulla of Vater include adenocarcinomas, lymphomas, neuroendocrine tumors, lipomas, fibromas, leiomyomas, and hamartomas, but adenomas are the most common. Ampullary adenomas are premalignant neoplasms and occur sporadically in about 0.04 to 0.12% of the general population based on autopsy series.1,2 The incidence is increased among patients with hereditary polyposis syndromes, such as familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC). In patients with FAP, 40–100% will develop duodenal adenomas and the relative risk of papillary cancer is over 100 times that of the general population.3

Surgical treatments Surgical treatment of ampullary tumors includes transduodenal local resection (LR) and pancreaticoduodenectomy (PD). For PD, the possible benefit of a low recurrence rate is weighed against a high risk of complications. Surgical-related morbidity of PD can be as high as 50–63% and mortality ranging from 0–9% with the higher rates reported in patients with malignant disease.4–7 Although LR is generally associated with lower morbidity (14–27%)4–6 and mortality rates (0–4%),5–7 recurrence rates can be as high as 17–32%4–8 and thus endoscopic surveillance after surgery is still required.

Endoscopic ampullectomy/papillectomy

Endoscopic ampullectomy was described in 1983 by Suzuki et al.9 and the first large case series was reported in 1993 by Binmoeller et al.10 Over the last decade, many more studies have been published showing high success rates with low morbidity and mortality risks. Endoscopic therapy is therefore gaining increasing acceptance for the treatment of ampullary tumors.

TECHNIQUE

BOX 19.1 SUMMARY OF THE TECHNIQUE • Staging of ampullary tumors and definition of the biliary and pancreatic ductal anatomy are achieved with high accuracy by endoscopic ultrasound. • Endoscopic retrograde cholangiopancreatography prior to ampullectomy is indicated if there is suspicion of intraductal involvement.

• Thermal ablation may be used as adjunctive therapy. • Although not definitive, current data supports prophylactic biliary sphincterotomy and pancreatic stent placement to prevent ductal stenosis, cholangitis, and pancreatitis. • Local tumor recurrences do occur and therefore follow-up surveillance duodenoscopy is essential.

Endoscopic evaluations

1. Conventional endoscopy Evaluation of the ampulla of Vater requires a high degree of suspicion and is best performed with a duodenoscope. Large periampullary diverticula can hinder endoscopic exam (Fig. 19.1). Tumors of the major ampulla can vary in appearance from slight enlargement to granular or polypoid, with or without ulceration (Fig. 19.2). Unfortunately, the presence or absence of malignant transformation cannot be determined by appearance alone and endoscopic biopsies are notorious for missing carcinomatous foci harbored within papillary adenomas.5,11,12 Rattner et al.6 found a sensitivity of only 42% for detection of malignancy by endoscopic biopsies and a specificity of 79% with a poor positive predictive value of 50% and negative predictive value of 73%. Therefore a negative biopsy does not rule out presence of cancer and a minimum of six biopsies to increase histologic yield has been recommended.10,13 It is important to be aware that frequency of malignant foci in an adenoma of the papilla figures around 26–30%.4,14

2. Endoscopic ultrasound Endoscopic ultrasound (EUS) should be performed whenever possible. It is useful in assessing tumor size, depth of invasion relative to the duodenal wall layers, and involvement of the pancreatic or biliary ducts (Fig. 19.3). The radial scanning echoendoscope has been shown to be valuable for identifying patients with disease localized to the muscularis propria in whom endoscopic resection may be appropriate for cure. In one study,6 EUS correctly staged preoperatively 9 of 12 ampullary lesions (3 of 5 villous adenomas, 3 of 3 adenocarcinomas, 1 carcinoid, and 2 of 2 adenocarcinomas arising in a villous adenoma). Size of the lesion did not correlate with the presence of malignancy. Cannon et al.15 reported similar N-stage accuracy by EUS (68%) compared to CT (59%) and MRI (77%) but superior T-stage accuracy (78% for EUS vs 24% and 46% for CT and MRI, respectively). Prior sphincterotomy and the presence of a 189

SECTION 2 TECHNIQUES

transpapillary endobiliary stent, however, can decrease EUS T-stage accuracy. One group16 found intraductal ultrasound to be even better than conventional EUS for T-staging (87% vs 63%) but more studies are needed to confirm these results.

3. Endoscopic retrograde cholangiopancreatography Endoscopic retrograde cholangiopancreatography (ERCP) is helpful in detecting intraductal tumor extension not visualized by computed tomography (CT) scan (Fig. 19.4). Opacification of both the pancreatic and common bile duct should be attempted and surgical referral should be considered if evidence of ductal involvement is found. In addition, pancreatography can define the presence of pancreas divisum and obviate the need for pancreatic stent placement. While EUS is generally performed before resection to increase staging accuracy, ERCP is performed at the time of ampullectomy to exclude intraductal tumor involvement, to perform sphincterotomy, and to place a pancreatic duct stent. If EUS is not available or the findings are equivocal, then ERCP should be performed before ampullectomy to assess for intraductal extension.

Endoscopic ampullectomy There is currently no consensus as to how endoscopic ampullectomy should be performed. Randomized trials are lacking. In general, ampullectomy is accomplished in a manner similar to snare polypectomy using a standard duodenoscope (JF-140, TJF-140; Olympus America, Inc., Leigh Valley, PA). The application of adjuvant thermal therapy, sphincterotomy, and prophylactic stent placement is variable (Table 19.1) and will be discussed further later in this section.

A

B

C A

D

B

Fig. 19.1 Ampullary mass obscured by periampullary diverticulum. Ampullary adenoma hidden in a diverticulum A can be appreciated after eversion of the surrounding mucosa B.

A

B

Fig. 19.2 Endoscopic appearances of tumors of the ampulla of Vater. A Villous adenoma with granular surface. B Bilobed tubular adenoma in a patient with FAP. C T1 submucosal carcinoid tumor seen as a prominent polypoid mass. D Well-differntiated ampullary adenocarcinoma with bleeding and superficial ulcerations. FAP, Familial adenomatous polyposis.

C

Fig. 19.3 EUS examination of ampullary tumors. A Large ampullary mass with tumor extension into a dilated common bile duct. B Hyperechoic stage T2 ampullary mass (black arrow) is seen invading into the wall of the duodenum with extension (white arrow) into the muscularis mucosa (black arrowheads denote intact muscularis). C Large ampullary adenoma. As compared to b, the muscularis is intact (arrowheads). 190

Chapter 19 Papillectomy/Ampullectomy

Although no data exist on prophylactic antibiotics for endoscopic ampullectomy, the procedure is similar to other submucosal resections and we routinely give antibiotics prior to and for three days after the procedure.

1. Snare excision Various types of standard monopolar diathermic polypectomy snares have been used. We prefer a more rigid snare such as the 20 mm oval snare with spiral wires (SnareMaster, Olympus America Inc., Lehigh Valley, PA). In our experience, a stiffer wire can be more easily positioned parallel to the plane of dissection and perpendicular to the catheter for a uniform excision to the level of the muscularis propria (Fig. 19.5). Blended cut is more commonly used than pure cut current to decrease the risks of bleeding. No studies have shown a decreased incidence of tumor recurrence when en bloc (Fig. 19.6) rather than piecemeal endoscopic

A1

ampullectomy is performed. However, as a general rule of oncologic surgery, en bloc resection is preferred because of higher likelihood of complete tumor excision and improved histologic analysis of the resected margins. The downside of en bloc resection is that it can be technically more difficult to perform and may incur higher risks of bleeding and perforation, especially when lesions are large or extremely sessile. Piecemeal excision is therefore sometimes necessary, although complete tumor removal may require several sessions. Vital dye staining with indigocarmine or methylene blue may help to delineate the tumor margins prior to resection (Fig. 19.7).

Common bile duct

Pancreatic duct

A2

Ampulla of Vater

B

Major duodenal papilla

Fig. 19.5 Snare ampullectomy. Schematic drawing showing the ideal plane of dissection during snare ampullectomy.

A

Fig. 19.4 ERCP examination of ampullary tumors. A1 Routine endoscopic visualization of the ampulla after prior sphincterotomy did not reveal obvious residual adenomatous tissue but balloon sweep of the bile duct during ERCP A2 showed intraductal adenomatous growth. B Intraductal filling defect after contrast injection of the common bile duct seen here is consistent with ampullary ductal tumor extension. ERCP, endoscopic retrograde cholangiopancreatography.

Author, y (reference no.)

N

Binmoeller, 1993 (10) Desilets, 2001 (27) Zadorova, 2001 (29) Norton, 2002 (26) Catalano, 2004 (22) Cheng, 2004 (30)

25 13 16 26 103 55

B

Fig. 19.6 En bloc ampullectomy. A Ampullary adenoma ensnared in entirety with gentle pressure on the catheter before snare closure. B Appearance of same lesion after resection.

FAP

Sphincterotomya (biliary, pancreatic)

Thermal therapy, (APC/E/YAG)

Pancreatic stent, size (Fr)

Biliary stent, size (Fr)

NA 7 (54%) 1 (6%) 15 (58%) 31 (30%) 14 (25%)

9 (36%), 0 13 (100%), 13 (100%) 16 (100%), 8 (50%) 26 (100%), 2 (8%) NA 2 (4%), 0

NA 7 (54%), (5/2/0) 3 (19%), (3/0/0) 12 (46%), (2/10/0) 35 (34%), (18/14/3) NA

1 (4%), 7 11 (85%), 5 6 (38%), 7 10 (38%), 5 91 (88%), 5–7 41 (75%), 3–5

0 3 (23%), NA 3 (19%), 10 NA 34 (33%), 7-10 NA

Table 19.1 Techniques of endoscopic ampullectomy in published series

FAP, Familial adenomatous polyposis; NA, not available; APC, argon plasma coagulation; E, electrocautery; YAG, YAG laser. a Pre- or post-ampullectomy.

191

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A1

A2

B1

B2

Fig. 19.7 Vital dye staining. A1 Ampullary adenoma with indistinct borders. A2 Same lesion with well-defined borders after methylene blue staining. B1 A small recurrent adenoma after prior ampullectomy is better visualized with B2 Indigocarmine staining.

The role of submucosal injection with saline or dilute epinephrine prior to ampullectomy remains unclear. Extrapolating from the practice of submucosal injection prior to mucosectomy, there is the theoretical benefit of a reduction in risk of perforation and bleeding. The inability to obtain a cleavage plane with saline injection may be useful in predicting the presence of malignancy in ampullary neoplasia.17 However, ampullary tumors differ from mucosal neoplasms in that the bile and pancreatic ducts are embedded in the tissue. A submucosal injection will fail to raise the tissue at the site of ductal insertion. Furthermore, submucosal injections may increase the risk of procedure-induced pancreatitis. We concur with the findings of Harewood et al.18 that submucosal lifts deter complete resection of ampullary adenomas down to the sphincteric musculature and hinder subsequent access to both pancreatic and biliary ducts. In our practice we do not perform submucosal injection prior to ampullectomy. Recently novel techniques to facilitate endoscopic ampullectomy have been proposed. Aiura et al.19 reported successful en bloc resection of ampullary tumors less than 2 cm in size with the use of an intraductal balloon-catheter for traction. Another group in Korea20 inserted a guidewire into the pancreatic duct preampullectomy to maintain ductal access for stent placement immediately after snare resection. More study is needed to confirm feasibility and safety of these inventive methods. The retrieval of all resected specimens for surgical pathology is essential for detection of small malignant foci. Specimens should be retrieved immediately after resection with a snare, basket, or net (Fig. 19.8). Glucagon administered just before resection may be helpful in preventing loss of tissue downstream due to small bowel peristalsis. While some authors suggest pinning the specimen on polystyrene plates for orientation, our pathologists have not found this to be necessary. 192

Fig. 19.8 Retrieval of specimen with a net after en bloc ampullary resection.

2. Thermal ablation Although thermal ablation was initially used as primary therapy with acceptable success,21 it is now more commonly applied as adjunctive treatment. When used alone, thermal ablation precludes complete histopathologic evaluation and may risk incomplete treatment. Catalano et al.22 reported similar overall success rates among patients who had adjunctive ablation compared with those who did not (81%, 30 of 37 vs 78%, 52 of 66, respectively). However adjunctive thermal ablation has not been addressed consistently in most studies, so its absolute benefit is inconclusive. Thermal modalities to achieve ablation include the Nd:YAG laser,23–25 bipolar and monopolar coagulation,23,25–27 photodynamic therapy,24 and argon plasma coagulation.25–29 We use argon plasma coagulation only when visible residual adenomatous tissue remains after snare excision. Treatment can also be palliative for patients with non-operable neoplasms. We apply a 7 Fr argon plasma probe at a power of 60W and flow rate of 1.2–1.8 L/ml for ablation. For intraductal lesions, a multipolar probe is used at a power of 25–30W. If placement of pancreatic and biliary stents is to be performed, both should be placed before thermal ablation to potentially decrease complications of stenosis by protecting the exposed pancreatic and biliary epithelia (Fig. 19.9).

3. Preresection sphincterotomy There are no data to support any beneficial effect of sphincterotomy, either biliary or pancreatic, prior to ampullectomy. It has been argued that biliary sphincterotomy may allow a more complete excision of the ampulla by facilitating access to tissues in the biliary orifice and thereby increase diagnostic accuracy.24,27 It has also been proposed that biliary and pancreatitic sphincterotomy may decrease the risks of cholangitis and pancreatitis, respectively. Arguments

Chapter 19 Papillectomy/Ampullectomy

A

B

Fig. 19.9 Adjuvant thermal therapy. A Pancreatic and biliary stents placed after endoscopic ampullectomy and before thermal ablation B with APC. APC, argon plasma coagulation.

against preresection sphincterotomy include increased risks of bleeding, perforation, and tumor seeding. The resultant thermal injury from sphincterotomy may impede accurate histopathologic interpretation of the resected specimen. Moreover, if a biliary or pancreatic stent is placed routinely after preresection sphincterotomy, ensuing ampullectomy will likely be in piecemeal fashion rather than en bloc.

4. Postampullectomy sphincterotomy and stent placement After ampullectomy, separate orifices for the biliary and pancreatic ducts can usually be readily identified. Mixing contrast with methylene blue during pancreatography prior to ampullary resection or administering secretin after resection may facilitate the identification of the ductal orifice in cases where localization is difficult. Cholangiopancreatography is performed to define the ductal anatomy as described perviously. The role of prophylactic sphincterotomy to minimize complications such as pancreatitis, cholangitis, and papillary stenosis remains controversial. Sphincterotomy will expose the opening to the distal duct and may thereby allow the detection of intraductal involvement. This benefit will need to be weighed against the risks of bleeding and perforation. Our protocol is to perform a biliary sphincterotomy in all patients, and pancreatic sphincterotomy in patients with any suspicion for pancreatic duct involvement. Pancreatic stent placement after ampullectomy may be performed to minimize the risk of post-ERCP pancreatitis but supportive data is not definitive. A retrospective study by Norton et al.26 found pancreatitis developed in 2 of 10 (20%) patients with pancreatic duct stent placement and 2 of 18 (11%) patients without a stent, but this difference was not statistically significant (p = 0.5). In a larger study using 5–7 Fr pancreatic stents, Catalano et al.22 also found that both acute pancreatitis and papillary stenosis occurred more frequently in patients without stents (17% vs 3% for pancreatitis and 8% vs 3% for stenosis). However, the overall number of patients with pancreatitis (5 of 103) and papillary stenosis (3 of 103) was small and no randomization was done, making interpretation of the results difficult. Similarly, Cheng et al.30 reported 4 of 41 patients (10%) with 3–5 Fr pancreatic stents placed prophylactically developed pancreatitis compared to 1 of 4 (25%) patients without stents. This was again

Fig. 19.10 Prophylactic 5 Fr pancreatic stent placement and biliary sphincterotomy after endoscopic ampullectomy.

not statistically significant (p = 0.33). Furthermore, the only two patients in this study who developed biliary and pancreatic stenosis were among those who had undergone both prophylactic biliary sphincterotomy and pancreatic stent insertions. The only prospective, randomized controlled trial of prophylactic pancreatic stent placement after endoscopic ampullectomy was reported by Harewood et al.18 All patients underwent biliary sphincterotomy, and pancreatic stents were inserted immediately after ampullectomy without pancreatic sphincterotomy. Results showed that single-flanged, 3 or 5 cm long, 5 Fr stents reduced pancreatitis (3 of 19 patients in the unstented group vs 0 of 10 patients in the stented group, p = 0.02). The study was terminated early in response to institutional review board concerns about the risk of pancreatitis in the unstented group. It is important to note that the number of patients enrolled was smaller than the intended 25 patients in each arm for a power of 80% to detect a 25% difference in rates of pancreatitis, hence a single episode of pancreatitis in the stented group would have resulted in a nonsignificant p value.31 Also of interest is that pancreatic stents were endoscopically removed after 24 hours which is much sooner than the general practice of allowing spontaneous stent migration over 1 to 2 weeks and further raises questions regarding the role of stents in these patients. Further larger scale prospective studies are needed to prove prophylactic pancreatic stenting decreases complications of endoscopic ampullectomy, nonetheless current data from difficult or invasive ERCP does support empiric stent placement. In our earlier practice,10 pancreatic stents were inserted only if delayed drainage was noted. We have subsequently changed to routine stenting after observing a high rate of postampullectomy pancreatitis in patients without stenting. Typically a 5 cm long, 5–7 Fr polyethylene stent without an intraductal flange is used (Fig. 19.10). An abdominal x-ray is obtained 1–2 weeks 193

SECTION 2 TECHNIQUES

later to confirm spontaneous stent migration. A stent that remains in situ is removed endoscopically without need for ductography. In contrast to pancreatitis, cholangitis after endoscopic ampullectomy is a rare occurrence and therefore biliary stenting is not routinely performed. One exception is in the event that thermal therapy is required, biliary stent placement should be considered to ensure adequate drainage and to minimize the risk of stenosis of the biliary orifice. We also place a 10 Fr biliary stent if there is evidence of poor bile duct drainage despite biliary sphincterotomy.

• Contraindications to ampullectomy include lesions with advanced intraductal involvement or local metastasis. Patients unwilling to undergo postresection surveillance should also be advised against the procedure. • With improvements in technique and increasing experience, indications for endoscopic ampullectomy will likely expand and continue to be modified.

Postampullectomy surveillance Surveillance duodenoscopy applies predominately to adenomatous tumors, but the same principle can be used to monitor for the recurrence of rare non-adenomatous lesions. Duodenoscopy should be performed with multiple biopsies from the site of the resected ampulla, even in the absence of macroscopic recurrence. There are no standard guidelines regarding appropriate intervals for postampullectomy surveillance. Generally, small (3 cm) sporadic adenomas excised in a piecemeal fashion and for lesions with involved resected margins, repeat ampullectomy with possible thermal ablation as well as ERCP should be performed at 2 to 3 month intervals until ablation is complete.10,22 Subsequently, follow-up duodenoscopy with biopsies and ERCP should be performed every 6 months for a minimum of 2 years. Surgery should be considered if intraductal tumor extension is suspected or if invasive carcinoma is found on biopsies.

Appropriate therapeutic strategy for ampullary tumors is determined by the patient’s general health, tumor characteristics, and experience of the endoscopist. In general, patients with benign ampullary tumors are candidates for endoscopic mucosectomy. Exclusion criteria10,27,30 for endoscopic resection include: 1. histologic documentation of coexistent carcinoma; 2. suspected intraductal tumor extension on EUS or ERCP; 3. tumor size >4 cm; 4. endoscopic findings suspicious for malignancy (i.e. indurated mass, presence of ulceration, excessive friability, or spontaneous bleeding); 5. poor patient compliance with follow-up; 6. absence of endoscopic expertise. It is important to note that the above list of exclusion criteria is not absolute and may be modified as more studies are published. Ampullary adenomas up to 7 cm in diameter29 and lesions with intraductal growth32 have been successfully managed by snare resection. Cases of early T1 ampullary adenocarcinoma have also been treated endoscopically.33 Patients who are poor candidates for surgery or who refuse surgery may also be considered for endoscopic resection and/ or ablation despite unfavorable tumor characteristics.

COMPLICATIONS

INDICATIONS AND CONTRAINDICATIONS BOX 19.3 COMPLICATIONS BOX 19.2 INDICATIONS AND CONTRAINDICATIONS • In general, endoscopic resection is indicated in patients who have benign ampullary lesions less than 4 cm in size without evidence of intraductal involvement. These criteria may be changing, however, as successful resection of larger lesions and lesions with early intraductal invasion and/or malignant transformation is increasingly reported in recent literature.

194

• Complications occur in between 8% and 35% of reported cases but are usually mild and managed endoscopically. These include acute pancreatitis, cholangitis, bleeding, papillary stenosis, and perforation. • Death as a result of endoscopic ampullectomy is very rare.

BOX 19.4 CONTROVERSIES

• Endoscopic therapy may be considered in patients with ampullary malignancies who refuse surgery or are not surgical candidates.

• Controversy exists regarding adequate endoscopic treatment of a lesion with potential for malignant transformation and possible undetected neoplastic foci.

• Endoscopic ampullectomy should be performed by appropriately trained and experienced endoscopists because of potential serious complications.

• Currently, there is no randomized, controlled, prospective study comparing surgery with endoscopic resection for ampullary tumors.

Chapter 19 Papillectomy/Ampullectomy

• The rates of submucosal injection prior to ampullectomy, thermal ablation of resection margins post-ampullectomy, sphincterotomy, and prophylactic stent placement remain debatable.

bringing the elevator down again when deploying or closing the hemoclip (again blindly).

• Optimal strategy for postampullectomy surveillance is also unknown.

Complete tumor eradication is achieved in greater than 85% of endoscopic ampullectomies for benign adenomas, although several treatment sessions may be necessary (Fig. 19.11 and Table 19.3). Recurrences, however, do occur and average around 20% in reported case series. Recurrent lesions are usually benign and most can be retreated endoscopically. Outcome is influenced by tumor histology, size, and genetic disposition. In a retrospective case series, Catalano et al.22 reported higher overall success rates for endoscopic treatment of sporadic lesions compared to genetically determined lesions (86%, 63 of 72 vs 67%, 20 of 31). Age greater than 48 years, lesion size of 24 mm or less, and male gender were also associated with higher rates of successful resection. The presence of intraductal

SUCCESS

Overall complications of endoscopic ampullectomy range between 8 and 35%. Most commonly, mild cases of acute pancreatitis (5–15%) and bleeding (0–16%) are reported (Table 19.2). Perforations26,30 and orifice stenosis26,30 are much less common, and death17,25,34 from ampullary resection is rare. Patients with FAP and those with severe dysplasia or adenocarcinoma may have higher complication rates. In a prospective study35 of 25 patients with FAP and routine pancreatic stenting after ampullectomy, 14% developed pancreatitis. However, all of these patients had adjunctive thermal ablation and some patients had intraductal ablation of adenomatous tissue so that meaningful conclusions can not be made from this data. In most case series, complications were managed without surgical intervention. Pancreatic and biliary stenosis resulting from endoscopic ampullary resections can be treated with sphincterotomy,26 stents,22 and/or balloon dilation.30 Acute pancreatitis usually resolves with conservative therapy while postampullectomy bleeding can be controlled with endoscopic epinephrine injection, electrocautery, or hemoclips and rarely requires blood transfusions or embolizations. Norton et al.26 described one patient with duodenal perforation who was treated endoscopically with a hemoclip. Applying clips through a duodenoscope is technically challenging owing to the angulation at the end of the working channel. The key points to remember are to keep the elevator down when opening the clip (thus opening the clip blindly), lifting the elevator to bring the opened clip into view for proper positioning at the target site, then

Author, y (reference no.)

N

Pancreatitisa

Binmoeller, 1993 (10)

25

Desilets, 2001 (27)

A

B

Fig. 19.11 Eradication with endoscopic ampullectomy. A Large 3.5 cm benign extraductal adenoma. B Same lesion after 4 endoscopic resections. Multiple biopsies of the ampulla resection site revealed benign duodenal tissue. Scarring from previous excisions can be seen near the orifice.

Bleeding; management (n)

Perforation; management (n)

Papillary stenosis; management (n)

3 (12%)

2 (8%); epinephrine injection

0

0

5 (20%)

0%

13

1 (18%)

0

0

0

1 (8%)

0%

Zadorova, 2001 (29)

16

2 (13%)

2 (13%); epinephrine 0 injection

0

4 (25%)

0%

Norton, 2002 (26)

26

4 (15%)

2 (8%); epinephrine injection

1 (4%); hemoclip

2 (8%) sphincterotomy

9 (35%)

0%

Catalano, 2004 (22)

103 5 (5%)

2 (2%) electrocautery (1) and hemoclip (1)

0

3 (3%) sphincterotomy and stent (2), surgery (1)

10 (10%)

0%

Cheng, 2004 (30)

55

9 (16%); nonspecified endoscopic (6) transfusion only (3)

1 (2%); conservative

2 (4%); sphincterotomy and dilation

17 (31%)

0%

5 (9%)

Overall morbidity

mortality

Table 19.2 Complications of endoscopic ampullectomy in published series a

All cases of pancreatitis were mild to moderate and managed.

195

SECTION 2 TECHNIQUES

N

FAP

Mean Mean follow-up procedures Malignant (mos) per patient foci

Binmoeller, 1993 (10)

25

NA

37

1.1

0

2

NA

6/23a (26%)

4/6 (67%)

benign adenomas, 1 with intraductal growth

Desilets, 2001 (27)

13

7 (54%) 19

2.7

0

1

12/13 (92%)

0/12a (0%)

—

—

Zadorova, 2001 (29)

16

1 (6%)

1.4

0

0

16/16 (100%)

3/16 (19%)

2/3 (67%)

benign adenomas, 1 with intraductal growth

Norton, 2002 (26)

26

1.1

1

0

NA

2/20b (10%)

2/2 (100%)

extraductal benign adenomas

Catalano, 2004 (22)

103 31 (30%) 36

1.8

6

0

93/103c (90%)

21/103c (20%)

11/21 (52%)

NA

Cheng, 2004 (30)

55

1.3

7

6

37/39d (95%)

9/27d (33%)

7/7 (100%)

extraductal benign adenomas

Author, y (reference no.)

NA

15 (58%) 9

13 (33%) 30

Intraductal growth

Complete eradication

Recurrences managed by Recurrences endoscopy

Recurrence type

Table 19.3 Outcome of endoscopic ampullectomy in published series

FAP, Familial adenomatous polyposis; NA, not available. a Excludes lesions with ductal (all sent to surg). b Excludes lesion with malignant foci and 5 missing follow-up data. c Includes lesions with malignant foci (n = 6). d Excludes ductal extension, malig foci, and nl histology (n = 3). Recurrence rate also excludes 12 missing follow-up data.

tumor extension also affects outcome. In a prospective study of benign tumors excised endoscopically, Bohnacker et al.32 found comparable recurrence rates between patients with and without intraductal growth (14%, 4 of 31 vs 15%, 11 of 78). However, long-term success rate was significantly higher in the group without ductal involvement (83% vs 46%, p < 0.001).

RELATIVE COST SAVINGS Mean length of hospital stay ranges from 11–13 days following surgical transduodenal LR and 15–23 days following PD.5,6 By comparison, endoscopic ampullectomy is usually performed using conscious sedation alone and on an outpatient basis with two hours of postprocedure observation before discharge. As described earlier, the rates of morbidity and mortality after endoscopic therapy are significantly lower than those of surgical alternatives and recurrence rates are similar to those after LR. Complete eradication after endoscopic resection of ampullary adenomas is eventually successful in greater

than 85% and the number of procedures required range from only 1.1 to 2.7 per patient (Table 19.3) which still translates to significant savings over surgery. Finally, in patients with FAP, recurrence rates are high even after surgical excision36 and these patients will still require lifelong surveillance duodenoscopy for evaluation of duodenal polyps. There is currently no definitive data suggesting improvement in overall survival outcome when small ampullary adenomas in the setting of FAP are aggressively resected. In a study36 of FAP patients surveyed by duodenoscopy with biopsy for >10 years, the histological grade of dysplasia increased in only 3 of 12 subjects who initially had adenoma suggesting that the natural history of these adenomas may be rather static. However, given that endoscopic biopsy surveillance is known for high false-negative detection rates for malignant foci and that there are currently no factors stratifying patients who are likely to progress to ampullary adenocarcinoma, small ampullary adenomas should probably still be resected when found in patients with FAP.

REFERENCES 1.

Baker H, Caldwell D. Lesions of the ampulla of Vater. Surgery 1947; 21:523–531. 2. Shapiro P, Lifvendahl R. Tumors of the extrahepatic bile ducts. Ann Surg 1931; 94:61–79. 3. Offerhaus G, Giardiello F, Krush A, et al. The risk of upper gastrointestinal cancer in familial adenomatous polyposis. Gastroenterology 1992; 102:1980–1982. 196

4. Cahen D, Fockens P, de Wit L, et al. Local resection or pancreaticoduodenectomy for villous adenoma of the ampulla of Vater diagnosed before operation. Br J Surg 1997; 84(7):948–951. 5. de Castro S, van Heek N, Kuhlmann K, et al. Surgical management of neoplasms of the ampulla of Vater: Local resection or pancreatoduodenectomy and prognostic factors for survival. Surgery 2004; 136(5):994–1002.

Chapter 19 Papillectomy/Ampullectomy

6. Rattner D, Fernandez-del Castillo C, Brugge W, et al. Defining the criteria for local resection of ampullary neoplasms. Arch Surg 1996; 131(4):366–371. 7. Beger H, Treitschke F, Gansauge F, et al. Tumor of the ampulla of Vater: Experience with radical resection in 171 consecutively treated patients. Arch Surg 1999; 134(5):526–532. 8. Farnell M, Sakorafas G, Sarr M, et al. Villous tumors of the duodenum: Reappraisal of local versus extended resection. J Gastrointest Surg 2000; 4:13–21. 9. Suzuki K, Kantou U, Murakami Y. Two cases with ampullary cancer who underwent endoscopic excision. Prog Dig Endosc 1983; 23:236–239. 10. Binmoeller K, Boaventura S, Ramsperger K, et al. Endoscopic snare excision of benign adenomas of the papilla of Vater. Gastrointest Endosc 1993; 39:127–131. 11. Seifert B, Schulte F, Stolte M. Adenoma and carcinoma of the duodenum and papilla of Vater: a clinicopathologic study. Am J Gastroenterol 1992; 87:37–42. 12. Yamaguchi K, Enjoji M, Kitamura K. Endoscopic biopsy has limited accuracy in the diagnosis of ampullary tumors. Gastrointest Endosc 1990; 36:588–592. 13. Shemesh E, Nass S, Czerniak A. Endoscopic sphincterotomy and endoscopic fulguration in the management of adenoma of the papilla of Vater. Surg Gynecol Obstet 1989; 169:445–448. 14. Heidecke C, Rosenberg R, Bauer M, et al. Impact of grade of dysplasia in villous adenomas of Vater’s papilla. World J Surg 2002; 26:709–714. 15. Cannon M, Carpenter S, Elta G, et al. EUS compared with CT, magnetic resonance imaging, and angiography and the influence of biliary stenting on staging accuracy of ampullary neoplasms. Gastroentest Endo 1999; 50(1):27–33. 16. Menzel J, Hoepffner N, Sulkowski U, et al. Polypoid tumors of the major duodenal papilla: preoperative staging with intraductal US, EUS, and CT—a prospective, histopathologically controlled study. Gastroentest Endo 1999; 49(3):349–357. 17. Kahaleh M, Shami V, Brock A, et al. Factors predictive of malignancy and endoscopic resectability in ampullary neoplasia. Am J Gastroenterol 2004; 99:2335–2339. 18. Harewood G, Pochron N, Gostout C. Prospective, randomized, controlled trial of prophylactic pancreatic stent placement for endoscopic snare excision of the duodenal ampulla. Gastrointest Endosc 2005; 62(3):367–370. 19. Aiura K, Imaeda H, Kitajima M, et al. Balloon-catheter-assisted endoscopic snare papillectomy for benign tumors of the major duodenal papilla. Gastrointest Endosc 2003; 57(6):743–747. 20. Moon J, Cha S, Cho Y, et al. Wire-guided endoscopic snare papillectomy for tumors of the major duodenal papilla. Gastrointest Endosc 2005; 61(3):461–466.

21. Saurin J, Chavillon A, Napoleon B, et al. Long-term follow-up of patients with endoscopic treatment of sporadic adenomas of the papilla of Vater. Endoscopy 2003; 35:402–406. 22. Catalano M, Linder J, Chak A, et al. Endoscopic management of adenoma of the major duodenal papilla. Gastrointest Endosc 2004; 59(2):225–232. 23. Ponnudurai R, Martin J, Haber G, et al. Endoscopic snare ampullectomy for resection of benign ampullary neoplasm in 25 patients. Gastroentest Endo 2000; 51(4):part 2:AB2213. 24. Ponchon T, Berger F, Chavaillon A, et al. Contribution of endoscopy to diagnosis and treatment of tumors of the ampulla of Vater. Cancer 1989; 64:161–167. 25. Martin J, Haber G, Kortan P, et al. Endoscopic snare ampullectomy for resection of benign ampullary neoplasms [abstract]. Gastrointest Endosc 1997; 45:AB458. 26. Norton I, Gostout C, Baron T, et al. Safety and outcome of endoscopic snare excision of the major duodenal papilla. Gastrointest Endosc 2002; 56:239–243. 27. Desilets D, Dy R, Ku P, et al. Endoscopic management of tumors of the major duodenal papilla: refined techniques to improve outcome and avoid complications. Gastrointest Endosc 2001; 54(2):202–208. 28. Martin J, Haber G. Ampullary adenoma: clinical manifestations, diagnosis, and treatment. Gastrointest Endoscopy Clin N Am 2003; 13:649–669. 29. Zadorova Z, Dvorak M, Hajer J. Endoscopic therapy of benign tumors of the papilla of Vater. Endoscopy 2001; 33:345–347. 30. Cheng C, Sherman S, Fogel E, et al. Endoscopic snare papillectomy for tumors of the duodenal papillae. Gastrointest Endosc 2004; 60:757–764. 31. Baille J. Endoscopic ampullectomy: does pancreatic stent placement make it safer? Gastrointest Endosc 2005; 62(3):371–373. 32. Bohnacker S, Seitz U, Nguyen D, et al. Endoscopic snare resection of benign ampullary tumors of the duodenal papilla without and with intraductal growth. Gastrointest Endosc 2005; 62(4):551–560. 33. Ito K, Fujita N, Noda Y, et al. Case of early ampullary cancer treated by endoscopic papillectomy. Dig Endosc 2004; 16(2):157–161. 34. Churrani R, Cretu D, Pleskow D, et al. Efficacy, safety, and outcome of endoscopic snare ampullectomy for 31 ampullary adenomas. Gastrointest Endosc 2002; 55(5):AB166. 35. DiSario J, Giampaolo A, Samowitz W, et al. Endoscopic management of ampulla of Vater lesions in familial adenomatous polyposis. Gut 2002; 51:A278. 36. Heiskanen I, Kellokumpu I, Jarvinen H. Management of duodenal adenomas in 98 patients with familial adenomatous polyposis. Endoscopy 1999; 31:412–416.

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Chapter

20

TECHNIQUES

Pancreatoscopy Tadashi Kodama, Yoshihide Tatsumi and Tatsuya Koshitani

INTRODUCTION AND SCIENTIFIC BASIS Various techniques imaging the pancreas have recently been developed. Among those methods such as computed tomography (CT), magnetic resonance imaging (MRI) and transabdominal or endoscopic ultrasonography, magnetic resonance cholangiopancreatography (MRCP) has emerged as an alternative diagnostic technology, yielding images at times comparable to endoscopic retrograde cholangiopancreatography (ERCP). Although ERCP is one of the established gold standards for the diagnosis of pancreatic cancer, it, as well as MRCP, may fail to differentiate the origin of a filling defect or a stenosis in the main pancreatic duct, because of inability to directly visualize the duct lumen. This desire of direct vision of the main pancreatic duct gave birth to the idea of direct pancreatoscopy. The pancreatoscope was first developed by the Japanese group of Takekoshi et al. in 1975.1 It was a small caliber fiberscope (baby scope) that could pass through the accessory channel of a duodenoscope (mother scope). Although the idea was very attractive and a few investigators studied its feasibility, pancreatoscopy was unpopular because of instrument fragility and suboptimal visibility as well as its relatively large diameter relative to the duodenal papilla. The description of intraductal papillary mucinous tumor (IPMT) by another Japanese investigator, Ohashi et al.,2 made an impact on pancreatoscopy in the early 1980s. Since then, the pancreatoscope has been reassessed as a useful method to diagnose IPMT by virtue of characteristic endoscopic findings resembling salmon eggs. Initial pancreatoscope prototypes had only optic image fiber bundles without any channel or tip deflection. Subsequent devices of more than 3 or 4 mm in diameter were then developed with oneor two-way tip deflection and with an accessory channel. To insert the scope into a non-dilated pancreatic duct, an ultrathin pancreatoscope (0.8 mm in diameter) was also developed by decreasing the number of optical fibers. These thin or ultrathin fiberoptic scopes had the same problem of low visibility to different degrees, contingent upon the numbers of optical bundles. Recently a peroral electronic pancreatoscope (PEPS), the smallest known electronic endoscope, was developed using the latest high quality television technology. With the above advancements in technology and imaging, peroral pancreatoscopy has been assessed and considered to be a useful technique, although most cases continue to be performed in Advanced Centers of Endoscopic Excellence.

DESCRIPTION OF TECHNIQUE Equipment

Pancreatoscope To date, there are two types of commercially available fiberoptic pancreatoscopes.3 These scopes can be purchased from several endo-

scopic manufactures. Video pancreatoscopes manufactured by Olympus Medical Systems (Tokyo, Japan) are commercially available in Japan. The most commonly used fiberoptic pancreatoscope has an outer diameter of more than 3 mm. It has both tip angulation and an accessory channel (more than 1.2 mm diameter) which allows biopsy and lithotripsy under direct visualization.4–6 Pentax Co. (Tokyo, Japan) offers a 2.7 mm-miniscope with tip angulation, but its small 0.75 mm forceps channel is not large enough to reliably allow biopsy and brush cytology. A much smaller scope lacking an angulation mechanism, with an outer diameter of 1.67 mm and 0.55 mm accessory channel, has also been reported.7 A second type of device is known as the ultrathin pancreatoscope. This fiberscope has an outer diameter of 0.75 or 0.8 mm and contains 3000–6000 bundles of image fibers.4,6,8 Since the ultrathin pancreatoscope can be inserted through the usual ERCP catheter, it can be applied easily at the time of ERCP. Although it has no tip angulation or accessory channel, cytology sampling as well as injection and aspiration of saline are available through the outer cannula (Figs 20.1A, 20.1B).9 Specifications for representative fiberoptic pancreatoscopes in Japan are compared in Table 20.1, although a number of other scopes are available from other manufacturers. The peroral electronic pancreatoscope (PEPS) was first described by Kodama et al. in 1999.10 A new prototype was developed with a newly designed 50 000-pixel interline charge-coupled device (CCD) (about 1 mm square in size) (Matsushita Electronics, Osaka, Japan) in cooperation with Olympus Optical Co. (Tokyo, Japan). The prototype PEPS (XPF-22EY) has an outer diameter of 2.1 mm and a bidirectional angle function without an accessory channel. After its prototype success, Olympus has developed an enhanced version that has an accessory channel (XCHF-BP240).11 At present, Olympus offers two types of commercial electronic pancreatoscopes in Japanese markets. The first type (CHF-BP260) is a commercial model of XCHF-BP240 with a small 0.5 mm accessory channel for a guidewire (Figs 20.2A–20.2E). The second type (CHF-B260) is a larger scope with a larger accessory channel with use for biopsy and lithotripsy under direct visualization. These scopes use a field sequential imaging system. Both types of electronic pancreatoscopes using a simultaneous imaging system have also been developed in the US, but they are not commercially available. The specifications for the prototypes and these new commercial electronic pancreatoscopes are compared in Table 20.2.

Mother scope Direct pancreatoscopy can be safely performed by means of a “mother-baby” method. A “baby scope” with an outer diameter less than 3.1 mm can be inserted through the channel of a standard therapeutic duodenoscope. Since larger baby scopes (e.g. with an 199

SECTION 2 TECHNIQUES

B

A

Fig. 20.1 An ultrathin fiberoptic pancreatoscope, PF-8P (Olympus) and guide catheter. A Overview. a guide catheter inserted through an accessory channel of duodenoscope (TJF-240).

CHF-BP30 PF-8P FCP-9P FCP-8P

B Ultrathin pancreatoscope with

Manufacturer

Tip diameter (mm)

Channel (mm)

Angulation up/down (degrees)

View (degrees)

Olympus Olympus Pentax Pentax

3.1 0.8 (1.8a) 3.0 2.7

1.2 None 1.2 0.75

160/130 none 90/90 90/90

80 80 90 90

Table 20.1 Specifications of representative fiberoptic pancreatoscopes in Japan a

Outer diameter of guide catheter.

XPF-22EY (not commercially available) XCHF-BP240 (not commercially available) CHF-BP260 CHF-B260

Imaging

Tip diameter (mm)

Channel (mm)

Angulation up/down (degrees)

View (degrees)

Simultaneous

2.1

None

120/120

80

Field sequential

2.6

0.5

90/90

90

Field sequential Field sequential

2.6 3.4

0.5 1.2

70/70 70/70

90 90

Table 20.2 Specifications of prototype and commercially available electronic pancreatoscopes PEPS, Peroral electronic pancreatoscope. All electronic pancreatoscopes are manufactured by Olympus Medical Systems Co. at present.

200

outer diameter more than 4 mm) require a special mother scope which proved expensive and hard to control; they are no longer commercialized.

tial color television system that is utilized in another ultrathin video endoscope adapted for upper GI endoscopy (e.g. GIF-N230; Olympus).12

Light source and image processor

Image converter for fiberoptic pancreatoscope

Direct pancreatoscopy requires a second light source for a baby scope as well as one for a mother scope. Video pancreatoscopes also need suitable processors. The prototype (XPF-22EY) works with a processor modified from a CV-140 processor, using a simultaneous color television system. Both new commercial electronic pancreatoscopes (CHF-BP260 and CHF-B260) and XCHF-BP240 work with a CV-240 or CV-260 processor (Fig. 20.3) using a sequen-

Connecting a special video converter (OVC-200) (Fig. 20.4) with a processor (CV-200 or later) to the head of a conventional fiberoptic pancreatoscope facilitates the endoscopic procedure and improves imaging.8 This converter enables viewing the image on a television monitor as a sequential electronic endoscope image, although its image quality is inferior to that of the electronic pancreatoscope. In the US markets, this video converter is also available as OVC-140

Chapter 20 Pancreatoscopy

A

B

C

D

E

Fig. 20.2 Peroral electronic pancreatoscope with a small accessory channel, CHF-BP260 (Olympus). A Overview. B Control section with an up/down angulation control knob and accessory channel port. C Deflection part of pancreatoscope. D Distal chip of pancreatoscope (note channel). E Deflection section of pancreatoscope entirely out of an accessory channel of a duodenosocpe (TJF-240).

201

SECTION 2 TECHNIQUES

with CV-160 (Olympus America), processor using a simultaneous imaging system.

ENDOSCOPIC PROCEDURE Procedure timing In our institutions, MRCP is preferable for the initial diagnostic evaluation of the pancreatic duct. MRCP is usually followed by ERCP and selective pancreatoscopy when a pancreatic lesion is suspected. Enough preparation time for direct pancreatoscopy should be considered if it is undertaken at the time of an initial diagnostic ERCP, since its application requires significant time.

Dilatation of the duodenal papilla prior to insertion When baby scopes with an outer diameter of more than 2.5 mm are utilized, endoscopic sphincterotomy (EST) of the pancreatic sphincter is usually needed. EST may be skipped, if the papilla is dilated in the pathological situation like IPMT (Figs 20.5A, 20.5B). Intravenous administration of a nitric oxide donor such as isosorbide dinitrate (5 mg/hr) can facilitate the insertion of the scope without EST even with some larger pancreatoscopes. With the prototype electronic pancreatoscope (XPF-22EY; outer diameter 2.1 mm) and the enhanced version with an accessory channel (XCHF-BP240; outer diameter 2.6 mm), insertion of the scope has been performed without sphincterotomy with relatively high success rates.10,11 However, the success rate of XCHF-BP240 appears to be inferior to that of XPF-22EY as a consequence of larger outer diameter.

Insertion of the scope Fig. 20.3 CHF-BP260 with a CV-260 processor (Olympus America), using a sequential color television system.

Fig. 20.4 A special video converter, OVC-200 (Olympus) that enables viewing the image of fiberoptic pancreatoscope on a television monitor. OVC-200 connected with the head part of the ultrathin fiberoptic pancreatoscope, PF-8P (Olympus).

202

All pancreatoscopes need a careful insertion procedure because of their fragility. They are easily damaged by acute angulation over the elevator of the duodenoscope. After introduction of a mother scope into the second portion of the duodenum, the main duodenal papilla is viewed and conventional pancreatography performed. Pancreatoscopes without an accessory channel are inserted directly through the papilla, at times alongside of a previously placed guidewire. Cooperation of two experienced endoscopists for the mother and baby scope, using a combination of tip angulation and movement of the duodenoscope, is the key for successful deep insertion (Fig. 20.6).10 Pancreatoscopes which have an accessory channel usually are inserted over a guidewire placed into the main pancreatic duct. However, when using the enhanced PEPS with an accessory channel (XCHF-BP240, CHF-BP260), direct insertion through the papilla is needed, because it cannot be inserted over any available guidewire, to date. However, once inserted into the main pancreatic duct, a thin guidewire through the accessory channel of the instrument can facilitate deep insertion to the targeted point like other scopes with an accessory channel (Fig. 20.7)11 Another type of commercial pancreatoscope, CHF-B260, can be inserted over a 0.035 inch guidewire. An ultrathin pancreatoscope is inserted through the guide cannula. In this setting, a cannula is advanced over a guidewire under fluoroscopy deep into the main pancreatic duct. The guidewire is then removed and an ultrathin pancreatoscope is inserted through the cannula. After the scope has emerged several millimeters from the tip of the cannula, the image of the pancreatic duct is obtained. Observation should be done only during withdrawal of the cannula of the scope from the duct. Pushing the ultrathin pancre-

Chapter 20 Pancreatoscopy

A

B

Fig. 20.5 Observation of intraductal papillary mucinous tumor (IPMT) in the main pancreatic duct by visualized PEPS. A Abundant mucin in dilated papilla. B Filling defects in the dilated main pancreatic duct were observed at ERCP. PEPS was easily inserted without dilatation procedure of papilla.

Fig. 20.6 Electronic pancreatoscopy with a second experienced endoscopist who handles the baby scope.

Fig. 20.7 Endoscopic image obtained with XCHF-BP240 (Olympus) during insertion over a guidewire.

atoscope system may damage both scope and mucosa. If investigation at the distal part of the duct is needed again, the cannula should be advanced again over a guidewire without the scope.8

ability to obtain clear images even with remarkably thick and mucinous pancreatic juice as seen in some cases of IPMT. The XCHF-BP240 pancreatoscope is significantly superior to the XPF22EY when washing under direct visualization (Figs 20.8A–C).11 With any debriding, care must be taken not to use excessive force with irrigation, resulting in acinar rupture and procedural pancreatitis. With an ultrathin pancreatoscope, washing can be also performed under direct visualization through the narrow lumen between the ultrathin scope and the guide catheter. However, saline flow is sometimes too weak to wash out thick mucus. If thick mucus precludes visualization, irrigation through the guide catheter is preferable after temporary removal of the pancreatoscope.

Improving visualization To obtain a clear image, washing with saline is necessary during every procedure. Techniques to wash the pancreatic duct lumina are different for each pancreatoscope mentioned above. When a pancreatoscope without an accessory channel like XPF-22EY is used, washing is needed through an ERCP catheter prior to direct pancreatoscopy, if necessary.10 This method has some limitation when abundant mucus fills the lumen. Secretin (100 clinical units) has also been injected intravenously to stimulate the exocrine function of the pancreas and thus improve visualization with the initial cases utilizing the XPF-22EY miniscope.13 However, this method cannot be utilized in Japan at present, because the drug is currently not available from domestic pharmaceutical companies. When using a pancreatoscope that has an accessory channel, washing with saline in the pancreatic duct can be done through the channel under direct vision. The advantage of this method is the

Biopsy and cytology sampling A sample of pancreatic juice for cytology can be obtained under direct vision when the pancreatoscope has an accessory channel. With an ultrathin pancreatoscope, sampling can be also performed under direct visualization through the narrow lumen between the ultrathin scope and the guide catheter. The diagnosis of in situ carcinoma of the pancreas has been reported by sampling under direct 203

SECTION 2 TECHNIQUES

A

B C

Fig. 20.8 Endoscopic images of intraductal papillary mucinous tumors (IPMT) obtained with XCHF-BP240 (Olympus). Note the effect of washing under direct visualization. Rinsing with saline is sufficient to wash out abundant mucin. After rinsing, an image of egg-shaped tumor of the pancreatic duct was clearly visualized. A Before washing. B During washing. C After washing. Reprinted from Gastrointest Endosc, 59, Kodama T et al., Initial experience with a new peroral electronic pancreatoscope with an accessory channel, 895–900, 2004 with permission from American Society for Gastrointestinal Endoscopy.

vision using the ultrathin scope.9 However, when the juice is extremely turbid or mucinous, it is often impossible to collect a pancreatic juice sample through the narrow lumen of the ultrathin scope system or the 0.5 mm channel of an XCHF-BP240.11 Brush cytology catheters and biopsy forceps can be used if the pancreatoscope has a relatively large accessory channel of 1.2 or 1.7 mm.4,5 When ultrathin pancreatoscopes or other pancreatoscopes with smaller channels are used for examination, transpapillary brush cytology or biopsy is needed under fluoroscopy after baby scope removal. In such cases, the pancreatoscopic findings are referred to decide the target point in the main pancreatic duct.

PROCEDURAL SUCCESS RATES It is important to select a scope prior to examination contingent upon the diameter of the duct and purpose of the study. Most endoscopists will not have access to multiple instruments. With a peroral electronic pancreatoscope (PEPS), a high resolution image is obtained by an ultra-miniature interline charge-coupled device (CCD). Olympus XPF-22EY, XCHF-BP240 and CHF-BP260 electronic baby scopes are designed to be inserted through the papilla without pancreatic duct sphincterotomy. They can be inserted deep into the tail of the non-dilated pancreatic duct unless the duct is too crooked or small in its previously noted diameter. The CHFB260 is designed to function for biopsy and lithotripsy under direct visualization. However, its application requires a pancreatic sphincterotomy and it cannot be inserted into a non-dilated or extremely angulated pancreatic duct. Kodama et al.13 reported the initial use of the XPF-22EY inserted into the pancreatic duct without sphincterotomy. It was successfully inserted into the predetermined target point and the pancreatic duct lesion could be visualized in 42 (75%) of 56 cases. Of the 42 cases, the PEPS reached the pancreatic head in 10 cases, the pancreatic body in 15 cases, and the pancreatic tail in 17 cases. In the 14 remaining cases, 6 failures were related to failure to intubate the papilla and the other 8 to passing the pancreatoscope beyond 204

the genu of the pancreatic duct. In our preliminary experience, the XCHF-BP240 could be inserted successfully into the pancreatic or bile duct without sphincterotomy in 9 of the 11 patients (82%). Observation of a predetermined target and juice collection with direct visualization was successful in 8 of 9 patients (89%).11 With the 3.1 mm fiberoptic pancreatoscope, angulation of the endoscope facilitates the visualization of the pancreatic duct and target biopsy or brush cytology is possible. However, this instrument cannot be inserted into a non-dilated or angulated pancreatic duct. Sphincterotomy of the pancreatic sphincter is usually needed unless the orifice of the papilla is patulous. The 3.1 mm pancreatoscope has been reported to perform successful pancreatoscopy after a pancreatic duct sphincterotomy in 16 (89%) of 18 cases by Riemann et al.4 Two failures occurred because of tight strictures in the setting of calcific pancreatitis. In this study, 5 cases of intraductal cystadenoma and 2 cases of pancreatic adenocarcinoma were all diagnosed by pancreatoscopic images. Histologic confirmation of the above cases was successfully obtained by biopsy under direct visualization. Two cases of segmental pancreatitis were also diagnosed by pancreatoscopic images (smooth strictures in conjunction with negative cytology). With a comparably small sized pancreatoscope, Jung et al.5 also reported that the pancreatic duct lesion could be observed in 15 (83%) of 18 patients with various pancreatic disorders. The author had a comment on the limitation of biopsy with this instrument, specifically, that angulation in a narrow pancreatic duct often precluded passage of a small biopsy forceps. With an ultrathin pancreatoscope, a screening examination is possible for a non-dilated pancreatic duct without sphincterotomy, but lack of angulation of the endoscope limits the visualization of the pancreatic duct. Cytology under direct visualization of the pancreatic duct is possible. Tajiri et al.8 have reported that an ultrathin pancreatoscope was able to reach a predetermined target point and the pancreatic duct lesion noted at ERCP could be observed in 42 (81%) of 52 cases examined. In the 10 inadequate studies, 5 were related to failure to

Chapter 20 Pancreatoscopy

intubate the papilla and the other 5 to failure to pass the pancreatoscope beyond the genu of the pancreatic duct. Yamao, et al.6 also reported with the same type scope that 22 of the 35 pancreatic cancer cases (63%) were observed, although insertion was successful in all cases. The failure to diagnose 13 cases was because of tapering stenosis or obstruction of the main pancreatic duct with asymmetrical deviation. The observation rate was increased to 75% when pancreatic cancers were less than 2 cm. On the other hand, an observation rate of benign stenoses of the pancreatic duct and IPMT were reported to be 16 of 20 (80%) and 57 of 60 (95%), respectively.

ELECTRONIC PANCREATOSCOPIC FINDINGS IN THE VARIOUS TYPES OF PANCREATIC DISEASES With electronic pancreatoscopes, various pancreatic diseases were diagnosed from the endoscopic findings more precisely compared with previous reports using fiberoptic scopes. Furthermore, fine capillary vessels on the surface of the pancreatic duct mucosa was first clearly observed by PEPS.

Fig. 20.9 Endoscopic image of the pancreatic duct of a healthy control subject obtained with PEPS system. Network of fine vessels clearly visualized. Reprinted from Gastrointest Endosc, 49, Kodama T et al., Pancreatoscopy for the next generation: development of the peroral electronic pancreatoscope system, 366–371, 1999 with permission from American Society for Gastrointestinal Endoscopy and Elsevier.

A

B

With PEPS, in normal cases, smooth pancreatic duct walls with white to pink color, and clear confluences of side branches, are observed. Fine capillary vessels are clearly visualized on the surface of the pancreatic duct (Fig. 20.9). In cases with chronic pancreatitis, protein plugs and calcified stones are clearly observed in the main pancreatic duct (Figs 20.10, 20.11A, 20.11B). On the mucosal surface of the pancreatic duct, whitish, rough, scar-like, or erythematous mucosa is observed. Fine capillary vessels on the surface of the pancreatic duct are frequently blurred (Figs 20.12A, 12B). Smooth ductal stenoses with scar formation are also observed (Figs 20.13A, 20.13B). In cases with advanced cancers, friable mucosa with erythema and erosive changes around the stenosis (Fig. 20.14) are observed as diagnostic findings of pancreatic cancer, while in some cases a compressed pancreatic duct wall covered with normal epithelium is observed. In IPMT cases, the characteristic finding of papillary tumors reported by other investigators is visualized with extreme clarity as are mucosal excrescences resembling clustered salmon eggs. Endoscopic findings of IPMT are further discussed in the Indications section of this chapter.

Fig. 20.10 Endoscopic image of the pancreatic duct of a patient with chronic pancreatitis obtained with PEPS system. Fine protein plugs within the pancreatic duct. Reprinted from Gastroenterol Endosc, 44, Kodama T, Present and future of the peroral electronic pancreatoscope (PEPS), 3–10, 2002 with permission from Japan Gastroenterological Endoscopy Society and Elsevier.

Figs. 20.11A, B Endoscopic images of the pancreatic duct of a patient with chronic pancreatitis obtained with PEPS system. A white stone within the pancreatic duct. The fine detail of the texture of the stone is clearly seen. “Reprinted from Gastrointest Endosc, 49, Kodama T et al., Pancreatoscopy for the next generation: development of the peroral electronic pancreatoscope system, 366–371, 1999 with permission from American Society for Gastrointestinal Endoscopy and Elsevier.

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A

Figs. 20.12A, B Endoscopic images of the pancreatic duct in a patient with chronic pancreatitis obtained with PEPS system. Vague network of fine vessels on the rough-surfaced pancreatic duct. Reprinted from Gastrointest Endosc, 49, Kodama T et al., Pancreatoscopy for the next generation: development of the peroral electronic pancreatoscope system, 366–371, 1999 with permission from American Society for Gastrointestinal Endoscopy and Elsevier.

B

Fig. 20.13 Endoscopic image of the pancreatic duct of a patient with chronic pancreatitis obtained with PEPS system. A Remarkable stenosis in the main pancreatic duct was observed in ERCP image. B Smooth stenosis of the main pancreatic duct was noted with the PEPS.

B

A

INDICATIONS Necessary indications

Fig. 20.14 Endoscopic image of the pancreatic duct of a patient with pancreatic cancer obtained with PEPS system. Friable mucosa with erythema and erosive changes around the stenosis of the pancreatic duct clearly visualized. Reprinted from Gastroenterol Endosc, 44, Kodama T, Present and future of the peroral electronic pancreatoscope (PEPS), 3–10, 2002 with permission from Japan Gastroenterological Endoscopy Society and Elsevier. 206

Major indications for direct pancreatoscopy include filling defects on ERCP of uncertain etiology and duct cut-off or stricture of uncertain origin. Direct pancreatoscopy can improve the diagnosis of IPMT from its characteristic endoscopic findings. Direct pancreatoscopy can also differentiate pancreatic cancers from chronic pancreatitis if the cancerous lesion is within the main pancreatic duct. However, final diagnosis should be assured by virtue of directed histology or cytology. Intraoperative pancreatoscopy is very useful in some cases of IPMT to determine the resection line of the pancreas, although frozen section of the margin remains mandatory. The high quality image of PEPS has the potential to improve diagnostic accuracy of IPMT or pancreatic cancer. It also has the potential to improve visual detection of tumor invasion within the pancreatic duct.

Intraductal papillary mucinous tumor (IPMT) The investigation of possible IPMT cases is one of the best indications for pancreatoscopy. IPMT has been recently recognized as a unique pancreatic tumor with an indolent biologic behavior and

Chapter 20 Pancreatoscopy

favorable prognosis. The tumor spreads along the pancreatic duct replacing the normal epithelium and includes a broad spectrum of histopathologic disorders such as hyperplasia, adenoma, and adenocarcinoma. The possible diagnosis of IPMT is usually established by ERCP or MRCP findings.14 They include dilated, mucus-filled papilla, filling defects in the main pancreatic duct, and dilated main and branch pancreatic ducts in the absence of remarkable obstructing ductal strictures. CT and transabdominal or endoscopic ultrasonography are also useful for detecting cystic lesions and tumors within the cysts.15 However, definite diagnosis of IPMT is possible if the characteristic appearance of papillary tumors are observed during pancreatoscopy. A biopsy to differentiate various kinds of histology can be taken from lesions under direct vision when a pancreatoscope with an accessory channel is used. Even without biopsy, pancreatoscopy has been reported to be useful in the differentiation of benign IPMT of the pancreas from more dysplastic lesions. It is often combined with intraductal ultrasonography (IDUS) which can measure the size of papillary lesions and define potential invasion. Hara, et al. classified the endoscopic findings of IPMT into 5 groups and described a fish-egg-like type with prominent vessels, villous type and vegetative type, as often malignant.16,17 Pancreatoscopy also provides valuable information in assessing the extent of the lesion and multicentric lesions. It is helpful at selecting the best surgical procedure in IPMT. Kaneko, et al.18,19 reported that intraoperative pancreatoscopy of IPMT was useful in determining the surgical resection line. These findings were more clearly confirmed by investigators using PEPS.20 With this instrument the characteristic appearance of papillary tumors can be visualized with unsurpassed clarity, even though the distance between each element of the tumor and the distal end of the endoscope varied. PEPS made it possible to make a more detailed morphologic assessment of the tumor and its grade of malignancy. In the case of adenocarcinoma, PEPS revealed a variety of tumors, from granular or nodular tumors to higher villous tumors with dilatation of capillary vessels (Figs 20.15A, 20.15B). Papillary tumors resembling salmon eggs with reddish inner color (venous dilatation) were also observed with adenocarcinoma (Fig. 20.16), while papillary tumors resembling salmon eggs with whitish inner color were recognized in adenomas (Fig. 20.17A). These findings supported the results of the previous studies concerning papillary adenoma or adenocarcinoma in IPMT. PEPS information on the extent of the intraductal growth of the tumor was also reported to be better than conventional pancreatoscopy.20 PEPS clearly visualized even small papillary projections near larger tumors, and the border of the lesion with the normal mucosa was well identified (Figs 20.17A, 20.17B). In a single case of branch-duct type of IPMT, where the main tumor existed in a dilated branch duct off the main pancreatic duct, the PEPS visualized papillary tumors spreading from the orifice of the dilated branch duct.

Differentiation of stenosis of the main pancreatic duct (benign or malignant) From the initial prototype of pancreatoscopy, many trials have been performed to distinguish focal or chronic pancreatitis from pancreatic cancer. Many investigators have described smooth stenoses with or without scar formation or mucosal edema observed in chronic pancreatitis, while lesions with friable erythematous mucosa and erosive changes are more common in pancreatic cancer. Our PEPS findings of pseudotumorous pancreatitis that was differentiated

A

B

Fig. 20.15 Endoscopic images of the pancreatic duct of a patient with intraductal papillary mucinous tumors (IPMT) obtained with PEPS system. Various shapes of tumors were observed inside the dilated pancreatic duct. This case proved to be adenocarcinoma histologically. A numerous tumors with taller villous projections and dilatation of capillary vessels. B granular or nodular tumors. Reprinted from Gastrointest Endosc, 52, Koshitani T et al., Clinical application of the peroral electronic pancreatoscope for the investigation of intraductal mucin-hypersecreting neoplasm, 95–99, 2000 with permission from American Society for Gastrointestinal Endoscopy and Elsevier.

Fig. 20.16 Endoscopic images of the pancreatic duct of a patient with intraductal papillary mucinous tumors (IPMT) obtained with PEPS system. Papillary tumors resembling salmon eggs with dilatation of capillary vessels. This case was proved to be adenocarcinoma. Reprinted from Gastroenterol Endosc, 44, Kodama T, Present and future of the peroral electronic pancreatoscope (PEPS), 3–10, 2002 with permission from Japan Gastroenterological Endoscopy Society and Elsevier.

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A

B

from pancreatic cancer is supportive of this consensus.21 However, smooth stenoses without friable erythematous mucosa and erosive changes do not always imply a benign lesion. Yamao et al.6 reported that the sensitivity and specificity of coarse mucosa or friability for pancreatic cancer were 59% and 88% (coarse mucosa), and 50% and 100% (friability), respectively, in 38 cases that were followed up for more than 2 years. A compressed pancreatic duct wall covered with normal epithelium can be observed with an extrinsic malignancy that does not involve the epithelium of the pancreatic duct at the distal site of the stenosis. Miyakawa et al.22 classified endoscopic cancerous changes into two groups: superficial and compressed. They reported that malignant cells were detected histopathologically in 41% of the superficial type and in none of the compressed type, based on transpapillary biopsy or brush cytology. Although pancreatic duct compression by an extrinsic pancreatic cancer is steeper than compression in chronic pancreatitis, the necessity of surgical treatment cannot be decided from the pancreatoscopic findings alone. Clinical diagnosis of pancreatic cancer should be carefully considered with other multiple imaging modalities if biopsy or cytology is negative.

Appropriate indications Using an ultrathin pancreatoscope, the usefulness of direct pancreatoscopy for the early detection of pancreatic cancer has been reported in small series. Detection of pancreatic cancer using PEPS is being investigated,23 looking for early stages of pancreatic cancer. Direct pancreatoscopy with PEPS image quality may be considered in patients who are suspected of having chronic pancreatitis, equivocal by other imaging modalities including endoscopic ultrasound in this setting. Pancreatoscopic images obtained by PEPS could suggest the clinical diagnosis of chronic pancreatitis from its characteristic endoscopic findings.

Early detection of pancreatic cancer Because most pancreatic cancers are derived from pancreatic duct epithelium, pancreatoscopy can contribute to the diagnosis of early pancreatic cancer if located within the main pancreatic duct. However, reports of in situ carcinoma of the pancreas found by pancreatoscopy are very rare except for that associated with IPMT. 208

Fig. 20.17 Endoscopic images of the pancreatic duct of a patient with intraductal papillary mucinous tumors (IPMT) obtained with PEPS system. A Papillary tumors resembling salmon eggs with whitish inner color. B Small papillary projections near larger tumors. Reprinted from Gastrointest Endosc, 52, Koshitani T et al., Clinical application of the peroral electronic pancreatoscope for the investigation of intraductal mucin-hypersecreting neoplasm, 95–99, 2000 with permission from American Society for Gastrointestinal Endoscopy and Elsevier.

This is partly because the detection of early pancreatic cancer by pancreatoscopy is a limited method for advanced centers of endoscopic excellence. Moreover, it is uncertain how frequently ductal adenocarcinoma begins its growth in the main pancreatic duct. Uehara et al.9 reported diagnosis of in situ carcinoma of the pancreas using the ultrathin peroral pancreatoscope and pancreatoscopic cytology. Out of 11 cases of in situ carcinoma diagnosed in the surgically resected specimen, they observed endoscopic findings of irregular, nodular or papillary mucosa of the main pancreatic duct in 10 cases. They also collected pancreatic juice from abnormal sites of the pancreatic duct seen by peroral pancreatoscopy through the narrow lumen between the scope and the guide catheter. They diagnosed all the 10 cases as carcinoma by this pancreatoscopic cytology. They concluded that pancreatoscopic cytology was useful for locating and diagnosing in situ carcinoma when compared to pancreatic juice cytology obtained by catheter at the time of ERCP. However a more comprehensive study in high-risk patients could reveal the sensitivity and specificity for diagnosing minute pancreatic cancer with pancreatoscopy in the future.

Further investigation of chronic pancreatitis Endoscopic findings of protein plugs and calcified stones floating in turbid pancreatic juice or scar formation on the mucosa have been reported by many investigators in patients with chronic pancreatitis.24 These findings were further studied with PEPS in 36 patients with chronic pancreatitis who were classified as having equivocal to marked ductographic changes by ERP according to the Cambridge criteria.25 With the high quality image of PEPS, these plugs consisted of fine granular or thread-like protein floating in the lumen or coating the epithelium on occasion. In equivocal cases, ductal contents were turbid and calculi co-existing with protein plugs appeared to be relatively soft, while in advanced chronic pancreatitis calculi had a rough surface and were generally calcified. Although the vascular markings in the pancreatic ductal mucosa were clearly observed in normal patients, those in chronic pancreatitis were generally indistinct. However, the vascular markings tended to be visible again in advanced stages of chronic pancreatitis. Normal patients had smooth capillary reticulation markings, whereas changes in the visible vascular net such as disruption, stenosis, irregularity, rearrangement and stretching were observed in chronic pancreatitis.

Chapter 20 Pancreatoscopy

Whitish mucosa co-existing with a rough surface and scar formation of the ductal wall were observed in advanced subjects with vascular changes, while the vascular markings had disappeared and edematous white mucosa was observed in equivocal cases. From these findings, PEPS images appear to be particularly helpful with a patient complaining of symptoms consistent with chronic pancreatitis, whose ERCP image is equivocal relative to the Cambridge criteria of chronic pancreatitis. Further study may establish new diagnostic criteria for chronic pancreatitis by PEPS images.26

Management of complications

Inappropriate indications When the lesion is limited to a side branch of the pancreatic duct, direct pancreatoscopy cannot reach the lesion. Alternative diagnostic modalities in such a case are endoscopic or intraductal ultrasonography (EUS or IDUS) combined with pancreatic juice cytology.27 Multiple molecular biological analyses of the pancreatic juice, including K-ras oncogene mutations and telomerase activity, are being investigated as an adjunct to cytology.28

COMPLICATIONS Acute pancreatitis occurring with or without sphincterotomy is the main complication of pancreatoscopy. Reported complications of pancreatoscopy are relatively low (0–12%), partially because the procedure is usually undertaken at Advanced Centers of Endoscopic Excellence. Moreover, patients with chronic pancreatitis are less susceptible to endoscopic complications than patients with normal pancreatic ducts. Mild pancreatitis after sphincterotomy was reported by Riemann et al.4 in 1 of 16 cases (6%) in one series using the 3.1 mm pancreatoscope. This pancreatitis rapidly improved with standard therapy. In this study, the total complication rate of pancreatoscopy was reported to be 2.6%, including 20 cases studied with an ultrathin pancreatoscope which is probably less invasive. Yamao et al.,6 in turn, reported that using the 3.4 mm pancreatoscope and ultrathin pancreatoscope, mild pancreatitis (lasting 1–2 days) occurred in 4 of 33 patients (12%). In 3 of these 4 patients, transpapillary biopsy specimens or cytology specimens (brushings) were obtained as well as pancreatoscopic investigation. With use of an ultrathin pancreatoscope, Tajiri et al.8 reported that 2 of 52 patients (4%) developed acute pancreatitis. Clinical symptoms and biochemical abnormalities improved completely within 7 days. With use of 3.2 mm or 1.67 mm pancreatoscopes, Hara et al.17 reported that mild to moderate pancreatitis occurred in

CHF-BP30 PF-8P FCP-9P FCP-8P CHF-BP260 CHF-B260 Video Converter CV-140 Processor CV-160

4 of 60 patients (7%). All patients recovered with conservative treatment. Using the XPF-22EY PEPS, 1 of 56 patients developed moderate acute pancreatitis with abdominal pain and elevation of serum amylase after the procedure. Pancreatitis improved with standard therapy, thus giving a total complication rate of 1.8%.13 With the enhanced version, XCHF-BP240, our preliminary experiences in 9 cases, including 2 cases of cholangioscopy, revealed no significant complications.11

To avoid possible complications, patients are usually hospitalized for one day after the procedure and receive peri-procedural intravenous antibiotics. Drugs (gabexate mesilate, nafamostat mesilate, ulinastatin) which inhibit the activation of pancreatic enzymes are also used in Japan to minimize procedurally related pancreatitis.13 A pancreatic duct stent is sometimes placed following endoscopic procedure to prevent acute pancreatitis, especially after sphincterotomy. Standard therapy of intravenous antibiotics and pancreatic enzyme inhibitors is usually enough to treat the mild acute pancreatitis which occasionally occurs after a pancreatoscopy procedure.

RELATIVE COST Pancreatoscopes are relatively expensive instruments for special usage in the pancreatobiliary area. Comparison of prices for pancreatoscopes, video converter and the image processor in US markets are summarized in Table 20.3. CHF-BP30, FCP-9P, FCP-8P, CHFBP260 and CHF-B260 need a therapeutic duodenoscope (channel diameter 4.2 mm) as a mother scope, whereas PF-8P can be used through an ERCP catheter and can be used with a diagnostic duodenoscope. Since all pancreatoscopes are fragile, they require careful insertion procedures. Inspection of the scope before and after the procedure should be performed to find minor damage of the scope as early as possible. In the case of electronic pancreatoscopes, the deflection part is covered with only one layer of very thin rubber to make the diameter small. This is the most fragile part which needs to be checked after each use. It is also important to check that this fragile part is entirely out of the accessory channel of the mother scope when the elevator of the duodenoscope is lifted (Fig. 20.2e). In our experience, the XPF-22EY and XCHF-BP240 needed repairs of the deflection part after about 5 procedures. Even with the most careful procedure, significant maintenance costs can be expected for all miniscopes.

Imaging

Diameter (mm)

Channel (mm)

Price (US dollars)

Fiberoptic Fiberoptic Fiberoptic Fiberoptic Field sequential Field sequential Simultaneous Simultaneous

3.1 0.8 3.0 2.7 2.6 3.4 — —

1.2 None 1.2 0.75 0.5 1.2 — —

20,900 not available 23,700 23,700 not available not available 9,500 19,700

Table 20.3 Comparison of prices of pancreatoscopes and processors in US marketsa a

Prices are based on data, September 2005.

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CONCLUSION Although the problem of suboptimal visualization has finally been resolved by development of electronic pancreatoscopes, other problems such as instrument fragility and relative large diameter remain

problematic in the search for the ideal scope.23,29 Continued research into the design of the pancreatoscope, which could improve durability and success rates, may make this technology more popular in the future.

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Takekoshi T, Maruyama M, Sugiyama N. Retrograde pancreatic cholangioscopy [in Japanese]. Gastroenterol Endosc 1975; 17:678–683. Ohashi K, Murakami Y, Maruyama M, et al. Four cases of “mucous secreting” cancer of the pancreas on specific findings of the papilla Vater [in Japanese]. Prog Dig Endosc 1982; 20:348–351. Technology Committee of American Society for Gastrointestinal Endoscopy. Technology status evaluation: duodenoscope-assisted cholangiopancreatoscopy. Gastrointest Endosc 1999; 50: 943–945. Riemann JF, Kohler B. Endoscopy of the pancreatic duct: value of different endoscope types. Gastrointest Endosc 1993; 39:367–370. Junk M, Zipf A, Schoonbroodt D et al. Is pancreatoscopy of any benefit in clarifying the diagnosis of pancreatic duct lesions? Endoscopy 1998; 30:273–280. Yamao K, Ohashi K, Nakamura T et al. Efficacy of peroral pancreatoscope in the diagnosis of pancreatic diseases. Gastrointest Endosc 2003; 57:205–209. Özkan H, Saisho H, Yamaguchi T et al. Clinical usefulness of a new miniscope in the diagnosis of pancreatic disease. Gastrointest Endosc 1995; 42:480–485. Tajiri H, Kobayashi M, Niwa H, et al. Clinical application of an ultrathin pancreatoscope using a sequential video converter. Gastrointest Endosc 1993; 39:371–374. Uehara H, Nakaizumi A, Tatsuta M. Diagnosis of carcinoma in situ of the pancreas by peroral pancreatoscopy and pancreatoscopic cytology. Cancer 1997; 79:454–461. Kodama T, Sato H, Horii Y, et al. Pancreatoscopy for the next generation: development of the peroral electronic pancreatoscope system. Gastrointest Endosc 1999; 49:366–371. Kodama T, Tatsumi Y, Sato H, et al. Initial experience with a new peroral electronic pancreatoscope with an accessory channel. Gastrointest Endosc 2004; 59:895–900. Technology Committee of American Society for Gastrointestinal Endoscopy. Technology status evaluation: ultrathin endoscopes esophagogastroduodenoscopy. Gastrointest Endosc 2000; 51:786–789. Kodama T, Koshitani T, Sato H, et al. Electronic pancreatoscopy for the diagnosis of pancreatic diseases. Am J Gastroenterol 2002; 97:617–622. Telford JJ, Carr-Locke DL. The role of ERCP and pancreatoscopy in cystic and intraductal tumors. Gastrointest Endosc Clin N Am 2002; 12:747–757.

15. Yamao K, Okubo K, Sawaka A, et al. Endoluminal ultrasonography in the diagnosis of pancreatic diseases. Abdom Imaging 2003; 28:545–555. 16. Yamaguchi T, Hara T, Tsuyuguchi T, et al. Peroral pancreatoscopy in the diagnosis of mucin-producing tumors of the pancreas. Gastrointest Endosc. 2000; 52:67–73. 17. Hara T, Yamaguchi T, Ishihara T, et al. Diagnosis and patient management of intraductal papillary-mucinous tumor of the pancreas by using peroral pancreatoscopy and intraductal ultrasonography. Gastroenterology 2002; 122:34–43. 18. Kaneko T, Nakao A, Nomoto S, et al. Intraoperative pancreatoscopy with the ultrathin pancreatoscope for mucinproducing tumors of the pancreas. Arch Surg 1998; 133:263–267. 19. Kanazumi N, Nakao A, Kaneko T, et al. Surgical treatment of intraductal papillary-mucinous tumors of the pancreas. Hepatogastroenterology 2001; 48:967–971. 20. Koshitani T, Kodama T, Sato H, et al. Clinical application of the peroral electronic pancreatoscope for the investigation of intraductal mucin-hypersecreting neoplasm. Gastrointest Endosc 2000; 52:95–99. 21. Kodama T, Abe M, Sato H, et al. A case of pseudotumorous pancreatitis that presented unique pancreatoscopic findings with the peroral electronic pancreatoscope. J Gastroenterol Hepatol 2003; 18:108–111. 22. Miyakawa H, Suga T, Murashima Y, et al. The role of peroral pancreatoscopy. [in Japanese]. Endosc Dig 1993; 5:943–948. 23. Kozarek RA, Kodama T, Tatsumi Y. Direct cholangioscopy and pancreatoscopy. Gastrointest Endosc Clin N Am 2003; 13:593–607. 24. Kozarek RA. Direct pancreatoscopy in chronic pancreatitis. Dig Endosc 1990; 2:1–5. 25. Kodama T, Imamura Y, Satoh H, et al. Feasibility study using a new small electronic pancreatoscope: description of findings in chronic pancreatitis. Endoscopy 2003; 35:305–310. 26. DiMagno MJ, DiMagno EP. Chronic pancreatitis. Curr Opin Gastroenterol 2003; 19:451–457. 27. Fujita N, Noda Y, Kobayashi G, et al. Endoscopic approach to early diagnosis of pancreatic cancer. Pancreas 2004; 28:279–281. 28. Myung SJ, Kim MH, Kim YS, et al. Telomerase activity in pure pancreatic juice for diagnosis of pancreatic cancer may be complementary to K-ras mutation. Gastrointest Endosc 2000; 51:708–713. 29. Kodama T, Tatsumi Y, Kozarek RA, et al. Direct pancreatoscopy. Endoscopy 2002; 34:653–660.

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Chapter

21

TECHNIQUES

Cholangioscopy Peter B. Kelsey

INTRODUCTION The prospect of visualizing the biliary tree during ERCP has allured gastroenterologists for decades.1 Significant mechanical challenges have resulted in a design evolution of both rigid and flexible endoscopes employing fiberoptic and video technology. The nomenclature has likewise evolved through a spectrum of descriptive terms including cholangioscopy, cholangioscopy, duodenoscope-assisted cholangiopancreatoscopy, and peroral cholangioscopy. The duct can now be accessed through a variety of approaches: percutaneously through a transhepatic route, through a choledochotomy, or the cystic duct created intraoperatively, or through the papilla of Vater via a duodenoscope. This chapter will specifically review the duodenoscope assisted approach to cholangioscopy. In this two endoscope system, the supporting duodenoscope and the cholangioscope are often referred to as the mother and baby scope, respectively.

DESCRIPTION OF THE TECHNIQUE Preprocedure room set-up If cholangioscopy is to become a truly meaningful adjunct for the interventionalist, the equipment needs to be readily available as the indications arise. A giant stone may be encountered that is simply too large to fragment by standard techniques or a stricture suspicious for malignancy may require direct visualization for tissue sampling. Under these circumstances, the ability to perform cholangioscopy as an adjunct to ERCP may both clarify the diagnosis, and facilitate appropriate therapy. The result may both optimize patient care quality and minimize the need for reintervention. For many years, prototype cholangioscopes have been sited in various academic institutions around the world. Currently, in the United States, the limited assortment of cholangioscopes available for purchase is listed in Table 21.1. In general, the smaller the outer diameter of the cholangioscope, the greater the maneuverability within the bile duct. The smaller size, however, leaves less room for important features such as a sufficiently large working channel. The optimal ERCP suite design places the cholangioscope, its power supply, and accessories in close proximity to the endoscopist. Because of the intimate spatial working relationships between the mother and baby scope, the cholangioscope components are set up on or adjacent to the ERCP processor cart. These components include the light generator and image processor as well as the flushing and suctioning equipment. Depending on the manufacturer and the model, the light source, image processing hardware and air/fluid pump are available either as individual components or combined in a single unit (Fig. 21.1).

Likewise strategic placement of the monitors is critical to permit simultaneous viewing of the video images from the mother scope, the baby scope and fluoroscopic unit during cholangioscopy. Ideally, the three monitors are clustered and mounted at eye level in front of the endoscopist. In new unit designs, these three monitors are mounted on articulating arms to maximize the operators’ comfort and ergonomics. Toggle switches or footpedals permit easy switching between other video output sources such as EUS, or a microscopy unit. Extra monitors are positioned for the assisting staff. Digital recording of the cholangioscopic exam provides a permanent record of the exam and most importantly permits post-procedure review of the findings (Box 21.1). A variety of accessories are used during routine cholangioscopy. A special adapter is attached to the opening of the mother scope’s instrument channel through which the cholangioscope is passed. This adapter is designed to prevent crimping of the baby scope as it is maneuvered during the procedure. As copious flushing and suctioning is routine during cholangioscopy, the saline irrigant, connector tubing, stopcocks, and syringes need to be available. Some processors are equipped with irrigation and suctioning components. Finally, there are a variety of accessories specific to cholangioscopy such as cytology brushes, biopsies forceps, snares, and electrohydraulic lithotripsy accessories that need to be organized and readily available.

TECHNIQUE: DIAGNOSTIC The step up from basic interventional ERCP to cholangioscopy requires the development of several new skills. One major challenge of cholangioscopy is the coordination and handling of the twoendoscope system using either the single or the two operator technique. The two person technique requires two experienced endoscopists to be present during the exam, one to handle the mother scope and the other to operate the baby scope with all of its accessories. Alternatively, the single operator technique requires a single interventionalist who manages both endoscopes. The endoscopist’s left hand is used to control the mother duodenoscope scope. The baby scope is secured to the endoscopist by a breast plate (see Fig. 21.2). The endoscopist’s right hand is then free to manage the controls and accessories of both the baby scope as well as the mother scope. The single operator technique has several advantages over the dual operator technique. First, cholangioscopy requires a carefully choreographed coordination of movement between the two endoscopes to both successfully maneuver the baby scope and to minimize the likelihood of damage due to crimping at its insertion into the mother scope. This coordination is more easily performed by a single person than by two trying to synchronize their motions. Second, obligating two physicians to be present during an entire exam is an inefficient use of manpower, especially when the exam can be performed 211

SECTION 2 TECHNIQUES

Feature

Olympus

Pentax

Pentax

Model

CHF BP 30

FCP—9N

FCP—8P

Working Channel

1.2 mm

1.2

0.75

Guidewire size

0.035 in

0.035

0.025

Outer Diameter

3.4 mm

3.1

2.8

“Mother Scope” Channel Diameter

4.2 mm

4.2

3.8

Field of View

90°

90°

90°

Depth of Field

1-50

1-50

1-50

Tip Deflection

160° up/ 130° down

160°/130°

160°/130°

Working Length

187 cm

190

190

Table 21.1 Cholangioscopes available in the US Fig. 21.2 The baby scope secured to the endoscopist by a breast plate.

mother scope and can be immobilized to a breastplate or waistband strapped to the endoscopist.

CANNULATION

Fig. 21.1

Cholangioscopy set-up for routine use.

BOX 21.1 ROOM SET-UP REQUIREMENTS FOR CHOLANGIOSCOPY Cholangioscope Light source and video Processor Breastplate (for single operator technique) Accessories Cytology brush Biopsy forceps Electrohydraulic Lithotripsy EHL power source EHL probes Monitors (2) for cholangioscopic image

efficiently by one physician alone. Finally, since the cholangioscope functions more as a catheter than as a true endoscope, the baby scope handle remains essentially motionless during the cholangioscopy. Most of the steering and maneuvering of the baby scope actually comes from the mother. Since the baby scope is not designed to tolerate torque, its position should remain fixed relative to the 212

There are three considerations when cannulating the ampulla; the need for a papillotomy, the need for guidewire assistance, and the actual maneuvering required to advance the baby scope up the bile duct without injury to the instrument or the patient. First, in almost all cases, the presence of a papillotomy greatly facilitates the ease of the exam. In many instances, however, a papillotomy will have already been performed before the decision has been made to refer the patient for cholangioscopy. The patient with giant, recalcitrant choledocholithiasis has often already undergone one or more failed prior attempts during which a papillotomy has been performed to either remove smaller debris or to permit the use of balloons or lithotripsy catheters. Cholangioscopy has been successfully performed following balloon ampullary dilation without papillotomy.2 Likewise the development of the ultrathin caliber endoscopes permits scope passage through supporting catheters without the need for a sphincterotomy.3 These ultrathin scopes, still not widely used, do not have an instrument channel for tissue sampling or for interventions. The papilla can, however, be dilated using either catheter or balloon dilators to permit passage of the larger cholangioscopes over a guidewire into the biliary tree. Balloon dilation of the papilla carries a defined risk of pancreatitis. Cannulation can be performed either over a guidewire or free hand. The guidewire technique is recommended until the endoscopist becomes experienced with cholangioscopy. Once the guidewire is passed up the bile duct, the cholangioscope is back-loaded over the wire using caution not to damage the channel as it angles and exits near the scope handle. A straw or other similar device can be used to intercept the advancing wire to safely deflect the wire tip out of the scope. The wire now acts as a rail over which the cholangioscope can be passed out from the mother scope and up through the papillotomy. As the cholangioscope approaches the papilla, the assistant provides gentle traction on the guidewire to pull the baby scope upward and into the papillary orifice. This upward deflection minimizes the need to raise the elevator. It is the lifting up of the elevator that causes the most damage to these fragile scopes either by tearing

Chapter 21 Cholangioscopy

the bending rubber at the distal end of the insertion tube or by actually crimping the insertion tube. Once the baby scope tip penetrates the ampullary orifice, it can be further advanced up the bile duct by gently tugging back on the mother scope. There is often a soft pop as the baby scope moves up the biliary tree. The baby scope can then be advanced up the bile duct in one to two centimeter increments followed by a gentle lifting of the elevator. This sequence of motions, similar to the technique used to advance a biliary stent, is repeated until the scope is in a desired and secured position. The free hand cannulation technique can be accomplished, in most cases, by first positioning the mother scope close to the ampulla. The baby scope tip is then advanced through the mother scope elevator. With the tip turned upward, and using the mother scope elevator, the baby scope is lifted up to the papillotomy site. The large dial of the mother scope is turned fully towards the endoscopist which lifts the tip of the mother scope upward and introduces the baby scope into the papilla. Once the tip of the baby scope is fully committed into the papillary orifice, a gentle tugging back on the mother scope, pulling it slightly outward from the patient’s mouth, will often pop the baby scope up through the papillary region and into the free biliary lumen. Fluoroscopy is employed during cannulation to observe both the angle of the cholangioscope’s deflecting tip and the trajectory of its insertion tube as it passes up the bile duct. The cholangioscope’s deflecting tip should not knuckle or bow as it heads up the bile duct. Ideally, the trajectory of the tip and the insertion tube should be straight and should point towards the bifurcation. This will lessen the likelihood of inadvertent cannulation of the pancreatic duct. Fluoroscopic observation is also used to guide the depth of the cholangioscope’s insertion.

Preparing the bile duct for observation With the cholangioscope positioned in the biliary system and the guidewire removed, the lumen of the bile duct comes into view. This view is often obscured by bile, mucus, and debris. Clearing the duct of this debris is necessary for an accurate diagnostic exam and usually requires several minutes of irrigation using a saline lavage. Irrigation with volumes from 5 to 25 cc saline can be used with each flush, depending on the duct diameter. Because of the small caliber of the cholangioscope’s working channel, the viscosity of bile, and the frequent presence of small particles of stone and other debris, suctioning of the irrigant from the duct is a tedious but necessary process. Lavaging the bile duct until it is clear facilitates optimal visualization and is necessary prior to any therapeutic maneuvers. During this cleaning process, fluid and debris tend to accumulate in the intestinal lumen and track up into the stomach. Comparing the amount of lavage fluid instilled to that amount suctioned will help minimize the aspiration risk. When this difference approaches 100 cc, the endoscopist might consider removal of the baby scope and withdrawing the mother scope into the stomach to aspirate the fluid that has accumulated there. Constant suctioning of this fluid from the duodenum should be performed through the mother scope during the procedure. This is a counter-intuitive maneuver for most experienced interventionalists who are trained to constantly insufflate the duodenal lumen with air to maintain good luminal visualization.

Maneuvering the cholangioscope Once positioned in the bile duct and with the guidewire removed, inspection can begin. Optimal visualization occurs under an aqueous

medium and thus saline is constantly pulsed or infused during the procedure. Sterile water can likewise be used safely.4 The amount of irrigant used should be sufficient to permit clear visualization carefully avoiding high pressure injections and excess accumulation of irrigant in the intestinal lumen. The cholangioscope is advanced up the bile duct with the same technique used to advance a biliary stent. With the elevator lowered, the cholangioscope is advanced 2–3 cm. The elevator is raised slightly and the endoscopist’s left thumb turns the mother scope’s large dial towards the endoscopist lifting up the tip of the mother scope towards the ampulla, thus pushing the baby scope up the bile duct. The elevator is then lowered, the large dial turned away, and the process is repeated. The challenge at this point is to keep the baby scope centered in the duct lumen, permitting good visualization. The baby scope tends to slide along the bile duct wall, smearing the mucosa across the viewing lens, thus obscuring the view. The crux of cholangioscopy is the challenge of maintaining a centered position of the baby scope within the bile duct. The insertion tube of the baby scope is not designed to respond to torque, and thus little control actually comes from manipulating the baby scope itself. Most of the baby scope control comes from the handling of the mother scope. Several principles may help the beginner cholangioscopist. Once the cholangioscope is maneuvered up the bile duct, fine tuning of its position lengthwise in the duct is best achieved by slight movements of the mother scope up and down the duodenum past the ampulla. These position changes will similarly move the cholangioscope up and down the bile duct. Lateral movements within the bile duct are more difficult. Rolling and torquing the mother scope and use of the duodenoscope’s small dial will translate into some baby scope lateral movement. Pulling or pushing on the mother scope will affect how straight or curved the baby scope lies within the bile duct and will alter its orientation. The baby scope tip deflection dial offers additional positioning changes.

INDICATIONS FOR CHOLANGIOSCOPY The primary indications for cholangioscopy include the evaluation and management of biliary strictures, filling defects, and difficult choledocholithiasis (Table 21.2).

Evaluation of bile duct lesions Conventional ERCP has an excellent track record in the diagnosis and management of well-defined bile duct abnormalities such as choledocholithiasis and bile leaks. This technique has fared less well in the accurate diagnosis of two, not so well-defined classes of bile duct lesions: biliary strictures and biliary filling defects. Though there is some overlap between these two findings, it may be useful to consider them separately. A filling defect relates to

ERCP Diagnosis

Cholangioscopy offers

Strictures

Improved diagnostic accuracy Tissue acquisition under visualization

Filling defects

Improved diagnostic accuracy Definitive therapy

Stones, refractory

EHL Duct clearance

Table 21.2 Indications for cholangioscopy 213

SECTION 2 TECHNIQUES

Fig. 21.3

Intraluminal filling defects due to stones.

the fluoroscopic appearance of something that actually lies within the bile duct lumen such as a stone or a polypoid tumor. Conversely, a stricture implies a narrowing of the duct lumen due to either thickening of the wall or compression from extrinsic pathology. The increased wall thickening can be intrinsic to the wall such as with a cholangiocarcinoma and might therefore have some associated mucosal defects that could be detected by direct visualization. Compression, on the other hand, due to extrinsic disease, such as nodal metastasis may result in a narrowing of the lumen, but the epithelial lining of the bile duct wall in the region of the stricture may retain a normal appearance. Cholangiocarcinoma, for example, can spread through the biliary tree in the submucosal layers and obstruct by compression. The overlying mucosa, however, may have a completely unremarkable appearance. It has now been clearly established that cholangioscopy can improve the accuracy in the diagnosis of biliary filling defects.5–7 One recent experience examined the impact of cholangioscopy on the diagnostic accuracy of ERCP when there was uncertainty in the ERCP diagnosis.8 Patients were excluded if they had obvious stone disease or classic biliary obstruction due to malignancy in the head of the pancreas. In this study, 91 consecutive patients were evaluated by ERCP supplemented by biopsy/brush cytology when indicated. There were 76 strictures and 21 filling defects in the study group. Of the patients with the 21 filling defects, ERCP with biopsy or brush cytology was able to correctly identify the 8 malignant lesions and the 9 benign tumors. ERCP did not, however, correctly diagnose the four cases of stone disease. In these patients, the stones were adherent to the bile duct wall and had the appearance of a mass. Cholangioscopy, on the other hand was able to make the correct diagnosis using direct visualization alone in all 21 patients. The four patients with stone disease were easily identified and treated with stone removal (Fig. 21.3). While the cholangioscopic differentiation between stone and tissue appears straightforward, the same is not true in the ability to differentiate malignant from benign strictures on the basis of direct visualization alone. Early cholangioscopic experience reported morphologic characteristics that claimed to distinguish malignant from benign tissue with an accuracy that approached 95%.9 Several features were identified as being accurate predictors of malignancy including tumor neovascularization, a dense papillary pattern, and friable nodularity. It was observed that bile duct adenocarcinomas had three patterns: nodular, papillary, and infiltrative. Nodular lesions were bulky and eccentric with an overlying friable mucosa (Fig. 21.4). There was often neovascularization with tissue friability and oozing. The papillary type (Fig. 21.5) was identified by a high density pattern of papilla or fish egg type mucosa. There is often luminal mucin, and blood obscuring the visual field. The third type 214

Fig. 21.4

Nodular lesion with friable mucosa.

Fig. 21.5

Papillary mucinous epithelium.

of bile duct adenocarcinoma is the infiltrating type. This is the most difficult to diagnose because of the paucity of specific cholangioscopic characteristics. The overlying mucosa is bland and whitish with minimal neovascularization. The authors described several other less common bile duct tumors including biliary papillomatosis, mucin-hypersecreting cholangiocarcinoma, and biliary cyst adenocarcinoma. Biliary papillomatosis looks similar to the papillary adenocarcinoma except that it is a multifocal disease with areas of normal intervening mucosa. The mucin-hypersecreting cholangiocarcinoma is similar to the papillary type adenocarcinoma except that according to the authors, the biliary ducts may be dilated and mucin filled. These cholangioscopic criteria for malignancy were tested prospectively on 76 patients with biliary strictures of unknown type and compared to the accuracy of ERCP with biopsy alone. In this study, ERCP with tissue sampling had a sensitivity of 58% and a specificity of 100% (Fig. 21.6). The addition of cholangioscopy to this group of patients did increase the sensitivity to100% but dropped the specificity to 87%. The loss of specificity was due to the incorrect diagnosis of malignancy in 5 patients on the basis of the cholangioscopic appearance of neovascularization and the presence of a tumor vessel. These five false positives were found instead to have chronic pancreatitis in two patients and one patient each with primary sclerosing cholangitis, autoimmune pancreatitis, and a peri-biliary cyst. Another potential advantage of cholangioscopy in the evaluation of biliary strictures is the opportunity to obtain pathologic material under direct observation. Brushings and biopsy forceps can be

Chapter 21 Cholangioscopy

Fig. 21.6

Tissue sampling under direct visualization.

steered directly onto the area of suspicion and the sample obtained under visual guidance. Whether this approach actually increases the yield of correct diagnosis has not been studied. Though it may seem advantageous to obtain tissue in this fashion, there are several recognized difficulties. First, is the issue of access. Negotiating the angulation and turns of the bifurcation and the small biliary radicals remains a challenge given the limitation of maneuverability and steerability of the current cholangioscopes. Once in a tight space, it may not be possible to deflect the scope tip to obtain a specimen from abnormal appearing tissue off to one side. And finally, the cups on the biopsy forceps are quite small, approximately 1 mm in diameter and thus the tissue yield is likewise small and frequently insufficient when biopsying hard or fibrotic tissue. Brush cytology, however, is often feasible. This can be performed by removing the polyethylene sleeve from any inexpensive, disposable brush, and passing the unsheathed brush through the cholangioscope’s channel. After obtaining the specimen, the brush can be withdrawn 1–2 cm inside the baby scope. With the baby scope then removed from the duodenoscope, the brush is advanced out of the cholangioscope’s tip and the specimen swiped on to frosted slides as per routine.

Electrohydraulic lithotripsy Fragmentation of giant or recalcitrant stones is one of the primary indications for interventional cholangioscopy. Candidate stones are usually too large to be trapped in a mechanical lithotripsy basket or are adherent to the bile duct wall and thus can not be easily manipulated. In these circumstances, fragmentation using electrohydraulic lithotripsy (EHL) is an efficient and highly successful technique. Traditionally, endoscopists have been resigned to longterm stenting of large, recalcitrant stones. It has been recently demonstrated, however, that when compared to stone removal using EHL, long-term stenting is associated with higher long-term complications such as cholangitis,10 and thus most patients with such stone burden should be considered for definitive fragmentation therapy. EHL was originally designed as an industrial mining tool. The modification for endoscopy employs a fiber with two embedded electrodes. A power generator delivers a high voltage electrical

current creating a spark across the two electrodes at the tip of the fiber. High frequency discharges cause rapid expansion of the fluidstone interface generating shock waves that fragment the stone. This technique has been successfully applied using percutaneous, surgical and transampullary routes to the bile duct using either cholangioscopic or fluoroscopic guidance. To perform EHL, the cholangioscope must be first positioned in front of the target stone. Achieving a satisfactory position is critical to the safe deployment of the probe. When the EHL probe projects from the cholangioscope, it must hit directly on the target stone and not touch or travel adjacent to the biliary epithelium. In addition, the contact interface between the probe and the stone must be in an aqueous environment for the shock wave to be transmitted and effect fragmentation. In patients with a capacious bile duct and a generous papillotomy, the bile duct may drain too rapidly to perform EHL. The patient must then be rolled to place the biliary tree in a dependent orientation. Before firing, the probe tip should be in close apposition to the stone. The duct is lavaged to sweep away fragmented debris to maintain good visualization. The probe should be aimed at a single target on the stone, chipping away at a focus until the stone cleaves. Often the outer coating of a stone is more durable and requires more EHL pulses. Once chipped, continued firing at the same spot rapidly enlarges the defect and fragments the stone. As the target stone mass is reduced in size, the cholangioscope is advanced up the duct to the next target. Fragmentation is then repeated until all of the target stones are fragmented or the visual field is obscured by debris. It is common to overestimate the degree of fragmentation that has occurred during a round of EHL discharges. With the cholangioscope removed from the bile duct, the stone fragments are swept out using standard balloon and basket techniques. Often, by simply fragmenting the lower stones in a packed duct, the remaining stones can then be more easily removed by standard maneuvers. The second round of EHL, if needed, proceeds more quickly as the duct is less tightly packed and there is more room to maneuver the cholangioscope. Once the bile duct has been cleared of debris and stones, the baby scope can be reintroduced into the bile duct to check for large retained fragments and for unsuspected strictures. The success of EHL has been reported in a number of series.11–13 In one large study, the power generator (Lithotripter Elgin, Il) was configured at settings of 100 watts, a frequency of 6 shots per second and 8 shots per pulse.13 In the management of recalcitrant stone disease that has failed standard ERCP techniques, cholangioscopic directed EHL is 90–100% successful in complete stone eradication.14 While the number of procedures required to achieve this success has ranged broadly from 1 to 13 exams, the experienced cholangioscopists can expect to achieve complete duct clearance in one exam of under 2 hours’ duration in the majority of patients.13

Cholangioscopy without fluoroscopy Occasionally, urgent biliary exploration is indicated when fluoroscopy is either unavailable or not practical. The ability to examine the bile duct without fluoroscopy has proven useful in three clinical situations: in morbidly obese patients whose features may not conform to standard fluoroscopy units, in patients during their first trimester of pregnancy and finally in those patients too critically ill to be transported to a fluoroscopy unit. The technique of cholangioscopy without fluoroscopy requires few modifications from the technique described above. Routine biliary cannulation is performed using a papillotome and a wire. 215

SECTION 2 TECHNIQUES

Once a duct has been deeply cannulated, the guidewire is removed. The observation of bile tracking up the lumen of the papillotome as the guidewire is withdrawn confirms the position of the papillotome in the bile duct. The guidewire is then advanced back up through the papillotome into the biliary system. Sphincterotomy is performed and the papillotome is removed leaving the wire in the biliary tree. The cholangioscope is passed down through the mother scope over the guidewire and a wire-guided cannulation of the bile duct is performed. Once the baby scope is positioned in the region of the bifurcation, the guidewire is removed. Bile and debris can then be flushed from the duct allowing inspection of the biliary tree. Several important interventional manipulations of the biliary tree can be performed without the use of fluoroscopy. Small stones can be removed under direct visualization using either a balloon or a wire-guided basket. Large stones are usually stented, to be more definitively managed at a later date when the patient has stabilized. Cholangioscopic directed EHL without the use of fluoroscopic assistance has not yet been reported, but may become feasible as baby scope technology evolves. Mass lesions encountered during cholangioscopy without fluoroscopy can be brushed or biopsied under direct visualization. Stenting of strictures or obstructing lesions in the common hepatic duct or common bile duct requires a modification from the standard stenting procedure. In determining the appropriate stent length, it is necessary to first pass the baby scope above the level of the obstruction. A guidewire is passed into the free space above the obstruction. The baby scope is slowly withdrawn down the length of the bile duct to the level of the ampulla, carefully measuring this length as it is pulled out of the instrument channel of the mother scope; this defines the appropriate stent length. With the guidewire positioned above the stricture, the cholangioscope is removed, and the plastic biliary stent is passed up the guidewire. Direct visualization of the guidewire is lost as the stent passes out of the working channel of the mother scope. Care must be taken at this point to prevent accident removal of the guidewire to a level below the obstructing lesion. The observation at this point of bile flow through the stent is reassuring of correct stent placement although this finding can also be occasionally observed if the stent has been accidentally placed up the cystic duct (Fig. 21.7).

Therapy of malignant bile duct lesions There is increasing interest in the targeting of therapy against a variety of malignant and pre-malignant bile duct lesions using cholangioscopic assistance. Photodynamic therapy of cholangiocarcinoma has been performed by both the percutaneous15,16 and per-oral route.17 The technique appears safe with minimal complications but its long-term clinical effectiveness remains to be evaluated in multicentered trials. In general, these patients still require stenting to maintain duct patency and the goal of the PDT therapy is likely palliative rather than curative. Biliary papillomatosis is an uncommon condition of multifocal papillary lesions of the bile duct. Patients can present with obstruction and may require transplantation. Transhepatic cholangioscopy using a variety of ablative therapies has been successful in controlling disease progression.18,19

216

Fig. 21.7

Cholangioscopy without fluoroscopy.

CONTRAINDICATIONS TO CHOLANGIOSCOPY Cholangioscopy can be performed in most situations where ERCP is indicated. While there are no absolute contraindications to cholangioscopy, there are several noteworthy areas of caution. Coagulopathic patients may not safely undergo sphincterotomy, thus preventing passage of many of the currently employed cholangioscopes. The risk of bleeding due to EHL induced tissue injury might be increased. In patients with ascending cholangitis, the risk of inducing bacteremia during cholangioscopy might be increased.

COMPLICATIONS The reported complications of cholangioscopy include bacteremia, aspiration, bleeding, and pancreatitis. Bacteremia as determined by serial blood cultures in the minutes following cholangioscopy can be demonstrated to occur in 15% of patients, but cholangitis is clinically relevant in only a minority of these situations.20 Prophylactic antibiotics do not appear to be of benefit following cholangioscopy and stone removal in the surgical setting.21 Bacteremia can result from over-distention of the biliary tree during irrigation. This may be more likely if the ampulla forms a tight seal around the insertion tube of the cholangioscope, preventing the venting of excess irrigant into the duodenum. As a rule, irrigation can be safely performed with a volume equal to or less than that amount of bile aspirated from the obstructed ductal system. Patients suspected of having cholangitis should receive peri-procedure antibiotics. Aspiration occurs as a consequence of the irrigating fluid that accumulates in the stomach.22 Aspiration of these contents can be prevented by frequent suctioning of the gastric contents The reported complications following EHL stone fragmentation during cholangioscopy include cholangitis, bleeding, pancreatitis,23 and perforation. Self-limited bleeding occurs when the EHL pulses are discharged in close apposi-

Chapter 21 Cholangioscopy

tion to the bile duct wall.24 There are no reports of uncontrolled bleeding. Bile duct leaks due to EHL injury have been reported. Perforation can occur at either the papillotomy site or at the site of an errant EHL discharge.

RELATIVE COST There are no published cost comparisons between the technique of cholangioscopy and alternative techniques.

SUMMARY Cholangioscopy is an important adjunct to interventional ERCP. It has been documented to improve the diagnostic accuracy in the assessment of biliary strictures. Cholangioscopy in conjunction with electrohydraulic lithotripsy can fragment and eradicate stones refractory to standard interventional ERCP techniques. There are few complications.

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12.

Kozarek RA. Direct cholangioscopy and pancreatoscopy at time of endoscopic retrograde cholangiopancreatography. Am J Gastroenterol 1988; 83:55–57. Minami A, Nakatsu T, Uchida N, et al. Papillary dilation vs sphincterotomy in endoscopic removal of bile duct stones. A randomized trial with manometric function. Dig Dis Sci 1995; 40:2550–2554. Soda K, Shitou K, Yoshida Y, et al. Peroral cholangioscopy using new fine-caliber flexible scope for detailed examination without papillotomy. Gastrointest Endosc 1996; 43:233–238. Sheen-Chen SM, Chou FF. Is sterile water irrigation safe during postoperative cholangioscopy? A prospective trial. Eur J Surg 1996; 162:801–804. Siddique I, Galati J, Ankoma-Sey V, et al. The role of cholangioscopy in the diagnosis and management of biliary tract diseases. Gastrointest Endosc 1999; 50:67–73. Seo DW, Kim MH, Lee SK, et al. Usefulness of cholangioscopy in patients with focal stricture of the intrahepatic duct unrelated to intrahepatic stones. Gastrointest Endosc 1999; 49:204–209. Seo DW, Lee SK, Yoo KS, et al. Cholangioscopic findings in bile duct tumors. Gastrointest Endosc 2000; 52:630–634. Fukuda Y, Tsuyuguchi T, Sakai Y, et al. Diagnostic utility of peroral cholangioscopy for various bile-duct lesions. Gastrointest Endosc 2005; 62:374–382. Nimura Y, Kamiya J, Hayakawa N, et al. Cholangioscopic differentiation of biliary strictures and polyps. Endoscopy 1989; 21 Suppl 1:351–356. Hui CK, Lai KC, Ng M, et al. Retained common bile duct stones: a comparison between biliary stenting and complete clearance of stones by electrohydraulic lithotripsy. Aliment Pharmacol Ther 2003; 17:289–296. Adamek HE, Maier M, Jakobs R, et al. Management of retained bile duct stones: a prospective open trial comparing extracorporeal and intracorporeal lithotripsy. Gastrointest Endosc 1996; 44:40–47. Binmoeller KF, Bruckner M, Thonke F, et al. Treatment of difficult bile duct stones using mechanical, electrohydraulic and extracorporeal shock wave lithotripsy. Endoscopy 1993; 25:201–206.

13. Farrell JJ, Bounds BC, Al-Shalabi S, et al. Single-operator duodenoscope-assisted cholangioscopy is an effective alternative in the management of choledocholithiasis not removed by conventional methods, including mechanical lithotripsy. Endoscopy 2005; 37:542–547. 14. Arya N, Nelles SE, Haber GB, et al. Electrohydraulic lithotripsy in 111 patients: a safe and effective therapy for difficult bile duct stones. Am J Gastroenterol 2004; 99:2330–2334. 15. Shim CS, Moon JH, Cho YD, et al. The role of extracorporeal shock wave lithotripsy combined with endoscopic management of impacted cystic duct stones in patients with high surgical risk. Hepatogastroenterology 2005; 52:1026–1029. 16. Wiedmann MW, Caca K. General principles of photodynamic therapy (PDT) and gastrointestinal applications. Curr Pharm Biotechnol 2004; 5:397–408. 17. Harewood GC, Baron TH, Rumalla A, et al. Pilot study to assess patient outcomes following endoscopic application of photodynamic therapy for advanced cholangiocarcinoma. J Gastroenterol Hepatol 2005; 20:415–420. 18. Gunven P, Gorsetman J, Ohlsen H, et al. Six-year recurrence free survival after intraluminal iridium-192 therapy of human bilobar biliary papillomatosis. A case report. Cancer 2000; 89:69–73. 19. Meng WC, Lau WY, Choi CL, et al. Laser therapy for multiple biliary papillomatosis via cholangioscopy. Aust N Z J Surg 1997; 67:664–666. 20. Chen MF, Jan YY. Bacteremia following postoperative choledochofiberscopy—a prospective study. Hepatogastroenterology 1996; 43:586–589. 21. Sheen-Chen SM, Chou FF. Postoperative cholangioscopy: is routine antibiotic prophylaxis necessary?—A prospective randomized study. Surgery 1994; 115:170–175. 22. Schebesta AG, Sporr D, O’Leary J, et al. Gastric aspiration associated with operative cholangioscopy. Anaesth Intensive Care 1983; 11:257–258. 23. Sheen-Chen SM, Eng HL. Acute pancreatitis following choledochoscopic stone extraction for hepatolithiasis. Med Sci Monit 2003; 9:CS13–CS15. 24. Fan ST, Choi TK, Wong J. Electrohydraulic lithotripsy for biliary stones. Aust N Z J Surg 1989; 59:217–221.

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ERCP in Children Victor L. Fox

INTRODUCTION Endoscopic retrograde cholangiopancreatography (ERCP) was introduced into pediatric medicine in the mid to late 1970s following initial experience in adult patients. It is now routinely used for the diagnosis and treatment of biliary tract and pancreatic diseases in children who are referred to major medical centers worldwide.1–3 Although expertise remains concentrated among endoscopists with advanced training in adult medicine, pediatric specialists collaborate closely in patient selection, in pre- and post-procedural management, and in the periodic appraisal of the role of ERCP in current pediatric practice.4 In high volume tertiary pediatric referral centers, ERCP is sometimes performed by expert pediatric endoscopists working alone or in consultation with adult medicine colleagues. Major differences between adult and pediatric ERCP relate to alternative approaches to patient preparation and sedation, to technical constraints of equipment that is not optimally designed for small children and infants, and to the rarity of biliary and pancreatic pathology in children.

DESCRIPTION OF TECHNIQUE Procedure setting In modern practice, most patients undergo ERCP with the potential for immediate therapeutic intervention. Therefore, the setting in which the procedure is conducted should include appropriate equipment and staff to proceed with available therapies and support for complications that might arise. Although interventional ERCP can be performed safely on an ambulatory basis in children, overnight hospital admission for observation is often advisable given the risk for post-procedure pancreatitis, and rarer complications of bleeding, infection, or cardiorespiratory compromise. Immediate access to subspecialty consultation by pediatric anesthesiologists, surgeons, and radiologists is essential to provide optimal and comprehensive team management. Ideally, recovery nurses with experience in postoperative recognition and management of complications that occur in children should be available to expedite supportive interventions.

Endoscopist Pediatric ERCP is best performed by an endoscopist with advanced technical skills and sufficient breadth of clinical experience to achieve an optimal outcome for the child. This may require a collaborative effort involving both adult and pediatric medicine specialists. Therapeutic ERCP requires that an endoscopist achieve selective deep cannulation of the desired (biliary or pancreatic) duct with >90% success to enable essential interventions including dilation,

stent placement, sphincterotomy, and stone extraction. Since experience with >200 cases is required by the average trainee to achieve this rate of technical success5 and the volume of pediatric cases is relatively small even in tertiary care facilities, pediatric specialists usually require either supplemental training with adult patients or a very long training period to achieve initial competence. The volume of cases required to maintain competence is less well studied in endoscopists specializing in pediatrics than those specializing in adults. Complication rates in the latter have been shown to correlate with case volume and complexity.6 While advanced endoscopic skills reside most often within adult medicine centers of excellence, technical skill alone does not benefit children in the absence of specialized clinical knowledge and experience, since technical success does not necessarily equate with optimal clinical outcome. Both adult and pediatric medicine trained endoscopists must consider these factors and the availability of alternative management options before embarking on ERCP in pediatric patients.

Sedation Most pediatric gastroenterologists prefer general anesthesia or deep sedation for technically challenging procedures in children. There has also been a trend toward more frequent use of deep sedation in adults undergoing particularly uncomfortable or lengthy endoscopic procedures. Although ERCP may be performed successfully with intravenous (IV) sedation in children, especially in cooperative adolescents, general anesthesia with endotracheal intubation affords safer airway management with assured analgesia and hypnosis for as much time as is necessary to complete a potentially lengthy or difficult procedure.

Fluoroscopy Fluoroscopy for pediatric ERCP may be performed using a fixed table in a dedicated fluoroscopy suite or a portable C-arm in a separate procedure room. The advantages of the C-arm device are portability, lower cost, and easier oblique imaging. Modern digital devices provide excellent image quality. The x-ray equipment should be adjusted to accommodate the smaller body of a young child and reduce the radiation dose rate. Shielding of reproductive organs is important and should be performed in all patients. Good fluoroscopic technique by the examiner can minimize radiation exposure to the child and to personnel (see also Chapter 3). The following rules or principles will help advance this goal: (1) position the child so that the beam takes the shortest distance through the body, i.e. avoid unnecessary oblique projection; (2) position the image intensifier or receptor above the patient; (3) minimize the distance of the intensifier and maximize the distance of the x-ray tube to the child’s body; (4) use the least magnification necessary and utilize field collimators to focus on areas of interest; (5) avoid the use of a grid; (6) minimize beam-on time and use the slowest pulse rates that produce 219

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acceptable imaging for a given task. The assistance of a radiation technologist with pediatric experience for equipment set-up and the availability of a radiologist with pediatric training for consultation can be very important in achieving the goals outlined above. Either low osmolar, non-ionic, or high osmolar water soluble contrast media in the range of 150 to 300 mg per ml may be used.

Supplemental medications Drug dosing for children is usually based on units per kilogram body weight ranging up to maximum adult doses. In addition to endocarditis prophylaxis, antibiotics are generally used in the setting of high-grade biliary or pancreatic duct obstruction, biliary or pancreatic duct disruption, and pancreatic pseudocyst. Ampicillin/sulbactam (100–200 mg/kg/d IV divided every 6 hours, maximum 4 grams sulbactam/d) or a broad spectrum cephalosporin such as cefazolin (50–100 mg/kg/d IV divided every 8 hours, maximum 6 grams/d), or a fluoroquinolone such as ciprofloxacin (20–30 mg/kg/d IV divided every 12 hours, maximum 800 mg/d) are usually adequate. Intravenous glucagon can be used to briefly reduce duodenal contractions during cannulation. A dose of 0.5 mg IV is appropriate for most ages and can be repeated. Intravenous secretin 0.2 mcg/kg may be used to facilitate successful cannulation of the minor papilla.

Endoscopic equipment Children of all ages and sizes, including full-term neonates, can undergo diagnostic and therapeutic ERCP using duodenoscopes that are commercially available. Standard diagnostic duodenoscopes with insertion tube diameters in the range of 11–12 mm can be used effectively in children older than 2 years and with difficulty between 1–2 years of age.7 These endoscopes generally have operating channels that will accommodate catheters and stents up to 7–8 Fr, which is adequate for most interventions. While “therapeutic” duodenoscopes containing operating channels in excess of 4 mm are needed to place 10 Fr stents, such large endoprostheses are rarely needed in young children. These larger endoscopes are easily used in adolescents. Neonates and infants require a small diameter instrument in the range of 7–8 mm that will pass easily through the pylorus and allow effective positioning of the tip adjacent to the major papilla.8 Currently, only two duodenoscopes are available specifically for use in small infants: the PJF 160 (Olympus America, Inc Lehigh Valley, PA) and the ED-2370K (Pentax Medical Company, Montvale, NJ). Both endoscopes have a maximum distal tip diameter of approximately 7.5 mm, an operating channel diameter of approximately 2.0 mm, and an elevator. Most diagnostic and therapeutic maneuvers are possible with these endoscopes, although the repertoire of available accessories that will fit through the small operating channel is quite limited. Sphincterotomy, stone extraction, and temporary stent placement have all been successfully performed in very young infants using these endoscopes9 (Fox, unpublished) (Fig. 22.1). Catheter tips that taper to a diameter of 3–4 Fr are helpful in order to selectively cannulate biliary and pancreatic ducts in infants. Deep advancement of commercially available catheters into these ducts is not always physically possible in young infants with normal anatomy due to the fine caliber of these structures at this age (Fig. 22.2).

Technique The techniques for ERCP in children are the same as for adult patients. The procedure can be conducted with the child either prone or supine on the examining table, although prone positioning is 220

Fig. 22.1 Placement of nasobiliary stent in 4-month-old infant following sphincterotomy for impacted stone.

most comfortable for the endoscopist. The basic endoscopic maneuvers are more technically challenging in children because sideviewing endoscopes and accessories have not been optimally designed to work in a narrow lumen and through a narrow operating channel, respectively. In small children and infants the endoscope tip is forced into a position in close proximity to the papilla, allowing very little of the cannula to extend out into view and increasing the difficulty of achieving optimal position for selective bile duct cannulation. Although pre-curved cannulas tapering to 3 Fr at the tip are available (Glo-Tip, GT-5-4-3, Cook Endoscopy, Winston-Salem, NC), selective biliary cannulation is more easily achieved using a double-lumen tapered tip, pull type sphincterotome with a short, 20 mm cutting wire (Mini-tomeTM pc, MT-20, Cook Endoscopy). Tightening the short cutting wire increases angulation of the catheter tip within a short working distance. Also, by starting the procedure with a sphincterotome, the endoscopist can proceed directly with therapy when indicated. The UTS-15 (Cook Endoscopy), a 5 Fr sphinctertome that tapers to 4 Fr at the tip, accepts a 0.021″ diameter wire guide, and has a 15 mm braided cutting wire, may be used for infants. Wire-guided access, using a soft-tipped, hydrophilic, narrow gauge wire, may be used if free cannulation proves too difficult (Fig. 22.2). Stiff catheters such as those used for stricture dilation or stone retrieval are more likely to require wire-guided entry. Also, in young infants a soft-wire retrieval basket (Memory® Baskets, MSB5-2x4, Cook Endoscopy) will enter the duct more easily if partially opened since the basket wires are more flexible when extending out from the stiffer plastic sheath. Alternatively, the endoscope can be placed in the long position, which may achieve a more favorable position in front of the major papilla, similar to the technique used for cannulation of the minor papilla. Tip control is not optimal, however, with the endoscope in this position. Although ultra thin duodenoscopes have 2.0 mm operating channels that will accept accessory catheters of 5 Fr diameter, the

Chapter 22 ERCP in Children

A

B

C

D

E

F

G

H

I

J

Fig. 22.2 Former 28-week gestation neonate, now a 3-month-old, 3 kg infant with severe cholestasis. A Transabdominal ultrasound showed fusiform distension of the CBD containing debris suggestive of choledochal cyst. B–C Endoscopic views of major and minor papillae. D–F Initial and completed sphincterotomy and emerging sludge. G Tiny normal pancreatic duct. H Wire-guided access for deep bile duct cannulation. I–J Cholangiogram during and after basket extraction of sludge.

catheters tend to bind in the channel when the endoscope is bent. In addition, air and fluid cannot be evacuated easily when an accessory is within the channel. These ultrathin endoscopes are also less apt to maintain a stable scope position due to increased flexibility. Assistance is sometimes needed to maintain torque on the insertion tube.

Another caveat to consider when instrumenting a small child or infant is the fragility of the soft tissues. Repeated impaction of catheters or wire guides against a small papilla in a young infant can render the structure unrecognizable due to traumatic edema. Also, a false tract can be created using surprisingly little force while advancing a catheter or wire into the ampulla of Vater or into the minor papilla. 221

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INDICATIONS AND CONTRAINDICATIONS Diagnostic and therapeutic indications While the necessity of diagnostic ERCP has been diminished by advances in magnetic resonance cholangiopancreatography (MRCP), early or subtle diagnostic findings are still best resolved with direct contrast injection. This is particularly true for young children who cannot cooperate with breath-holding sequences required for MRI or high-resolution CT in the setting of conditions that may require fine spatial resolution such as early sclerosing cholangitis, bile duct paucity syndromes and neonatal biliary atresia, anomalous junction of the biliary and pancreatic ducts, and pancreas divisum. Continued improvement in non-invasive imaging techniques may eventually remove this limitation. The main indication for ERCP in children, as in adults, is for potential therapeutic intervention of known or suspected structural abnormalities in order to relieve obstruction, divert leakage, or drain a collection.

Biliary indications

Neonatal cholestasis Neonatal cholestasis is the only biliary condition unique to pediatrics in which purely diagnostic cholangiography has a role. The most common causes of neonatal cholestasis are idiopathic neonatal hepatitis and total parenteral nutrition, both of which are frequently encountered in neonates compromised by premature birth, congenital abnormalities requiring surgical intervention, or other acute illnesses of the newborn. These conditions are characterized by intrahepatic features of hepatocellular and canalicular dysfunction rather than bile duct obstruction. However, they can sometimes be difficult to distinguish from ductal obstruction due to inspissated bile (seen with cystic fibrosis or idiopathic causes), bile duct paucity (e.g. Alagille’s syndrome), or obliteration of the duct due to biliary atresia (BA). Of these conditions, the correct diagnosis is most urgently needed for BA since surgical intervention by portoenterostomy (Kasai procedure), substantially reduces long-term morbidity and mortality if undertaken early (less than 8 weeks). If left untreated, BA leads to liver failure and organ transplantation or death by 1–2 years of age. The role of ERCP in the diagnosis of BA remains controversial and is most helpful when the diagnosis is thought to be unlikely but cannot be definitely excluded without cholangiography (Fig. 22.3). In this situation, an unnecessary exploratory laparotomy can be avoided. A specialized ultra thin diameter duodenoscope must be used in neonates. The endoscopic findings that suggest BA include: absence of visible bile within the duodenum, partial filling of the bile duct with abnormal termination, and failure to fill the bile duct despite filling of the pancreatic duct (Fig. 22.4).10 A high level of skill and confidence in technical proficiency is required to make this diagnosis with certainty. In the largest neonatal series of suspected biliary atresia, ERCP predicted the correct diagnosis in all but 2 of 147 infants in whom biliary cannulation was successful.11 Complete filling of the bile duct definitely excludes the diagnosis of BA. However, most pediatric gastroenterologists and hepatologists rely on a combination of clinical presentation, serum chemistry profile, ultrasonography, biliary scintigraphy, and liver histology rather than ERCP to select infants with cholestasis for surgical exploration, intraoperative cholangiography, and anticipated portoenterostomy. 222

Fig. 22.3 Normal intrahepatic and extrahepatic bile ducts and small gallbladder in 10-week, 4.3 kg infant who has cholestasis and cystic fibrosis. Biliary atresia was suspected based on nonexcreting biliary scintigraphy and liver biopsy with suggestive histopathology.

Cholelithiasis and choledocholithiasis Choledocholithiasis, usually associated with cholelithiasis, is the predominant indication for ERCP in children. Black pigment bilirubinate material is usually found in infants and young children with cholelithiasis while light-colored cholesterol stones are more typical in adolescent patients without an underlying hemolytic disorder such as sickle cell disease or spherocytosis. Stringer and colleagues recently reported detailed analysis of the chemical composition of gallstones in a series of 20 children ranging in age from 0.3 to 13.9 years.12 Ten had black pigment stones, 2 had cholesterol stones, 1 had brown pigment stones, and 7 (35%) had calcium carbonate stones, a form uniquely found in children. Asymptomatic neonatal cholelithiasis may resolve spontaneously13 and even symptomatic choledocholithiasis can clear without the need for aggressive intervention.14 Therefore, a brief period of supportive care with dietary fasting, IV fluids, and antibiotics can be justified to avoid unnecessary invasive therapy. Otherwise, symptomatic small stones and impacted sludge can be definitively treated endoscopically without resorting to surgical intervention or more involved percutaneous transhepatic techniques. Sphincterotomy with removal of stone and/or sludge material can be undertaken even in very young infants with appropriate equipment9 (Fig. 22.5). Balloon sphincteroplasty rather than sphincterotomy might seem an appealing alternative in young children since the long-term effects of sphincterotomy performed in childhood are unknown. However, there are no data beyond individual case reports on the outcome of balloon sphincteroplasty in children and there is no reason to expect a lower rate of complications from this technique in children compared with adults.15,16

Chapter 22 ERCP in Children

Fig. 22.4 Schematic representation of cholangiographic patterns in infants with biliary atresia. Light green indicates nonopacified or atretic segments (adapted from reference 11 with permission of Taylor and Francis).

Type 1

Type 2

Type 3A

Type 3B

Some pediatric surgeons advocate intraoperative cholangiography and laparoscopic CBD exploration at the time of cholecystectomy for primary therapy of choledocholithiasis, thereby avoiding potential complications of ERCP.17–19 With this approach, therapeutic ERCP is reserved for situations in which intraductal calculi cannot be easily cleared at the time of surgery. However, there are no data to support routine cholecystectomy in young children with choledocholithiasis, especially if there are no residual stones within the gallbladder. Small residual gallstones are expected to pass spontaneously after endoscopic sphincterotomy alone. In this situation, a team approach is needed to offer a thoughtful and coordinated management plan to the family.

Choledochal anomalies Choledochal anomalies include cystic malformations of the bile duct and anomalous junctions between the bile duct and pancreatic duct and these conditions often co-exist. Choledochal cyst (described in more detail in Chapters 36 and 42) is a descriptive term used when there is segmental rounded or fusiform distension of the bile duct. An anatomic classification scheme proposed by Todani20 subcategorizes the condition into types 1 through 5 depending on the shape and location. Distal CBD obstruction in infants due to choledocholithiasis can induce fusiform distension mimicking Type I choledochal cyst (Figs 22.2 and 22.6). ERCP is, therefore, important in

this situation to clarify the diagnosis and render therapy that relieves the obstruction, avoiding unnecessary surgical resection of the bile duct. When anomalous pancreatobiliary union (APBU) accompanies a cystic deformity of the bile duct, stenosis at the junction is often present and surgery becomes a more reasonable treatment option for definitive decompression and to reduce the long-term risk of later onset biliary cancer (Fig. 22.7). APBU may also be found incidentally without associated cystic changes in the bile duct or in association with acute recurrent pancreatitis.

Biliary strictures and leaks Most pediatric biliary strictures are due to sclerosing cholangitis. However, patients with advanced changes of PSC with a dominant stricture that is amenable to therapeutic endoscopic dilation are the exception rather than the rule. The typical picture is one of subtle, diffusely irregular intrahepatic ducts with alternating thin and thick caliber. Since the bile duct epithelium is diffusely inflamed extending to the papilla, there is often minimal dilation of the CBD due to mild functional papillary obstruction (Fig. 22.8). A characteristic observation when PSC is present is underfilling of the intrahepatic ducts despite deep cannulation to the level of the common hepatic duct. Injection through an inflated balloon catheter permits optimal filling of the intrahepatic branches. Sclerosing cholangitis in children is associated with chronic inflammatory bowel disease (ulcer223

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A

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Fig. 22.5 A 4-month-old, 4.8 kg infant presenting with acholic stool and jaundice 6 weeks after surgery for complex congenital heart disease. Endoscopic views of a darkened bulging papilla, cannulation with sphincterotome, removal of impacted soft pigment stone, and retrieval basket within completed sphincterotomy are seen A–D. Cholangiograms showing dilated intra- and extraheptic ducts and small filling defects within common bile duct E, and retrieval basket open within common bile duct F.

ative colitis and Crohn’s disease) and is the most common hepatic complication of primary immunodeficiency disorders.21 Patients with PSC may present with clinical features that are indistinguishable from autoimmune hepatitis and the distinction is identified during cholangiography.22 Although the “double duct sign” is considered ominous for the presence of malignancy when seen in adults, it is usually due to a 224

benign process when seen in children. Imaging with CT or EUS is recommended in order to exclude a rare tumor within the pancreatic head. When the “double duct sign” is present in children, the head of the pancreas appears either normal or slightly swollen due to acute or subacute pancreatitis. Patients present with pain and obstructive jaundice due to extrinsic compression of the distal common bile duct as it traverses the head of the pancreas (Fig. 22.9).

Chapter 22 ERCP in Children

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Fig. 22.6 A Two-year-old child presenting with pancreatitis, obstructive jaundice, and cystic dilation of CBD on ultrasound. B Cholangiogram shows dilation of the CBD extending to the ampulla. Biliary sphincterotomy and stone extraction resolved the problem. Fig. 22.7 Four-year-old child presenting with recurrent pancreatitis and biliary obstruction. Cholangiogram shows an anomalous pancreatobiliary union, distal biliary stricture, and dilated CBD. This was successfully treated with bile duct resection and Roux-en-Y anastomosis.

A

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Fig. 22.8 16-year-old female with Crohn’s disease and PSC confirmed by liver biopsy. A Cholangiogram shows slightly dilated common bile duct and poor filling of intrahepatic ducts despite deep cannulation. B Contrast injected proximal to inflated balloon catheter fills intrahepatic ducts revealing diffusely irregular pattern.

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Fig. 22.9 Stricturing of the CBD and pancreatic duct within the pancreatic head due to subacute pancreatitis in an 11-year-old male with autism who presented with jaundice.

Dilation of the stenosis and placement of one or more temporary 7 Fr stents will relieve the obstruction while awaiting resolution of the pancreatitis. Biliary brush cytology and/or bile duct biopsy may be helpful to assess for malignancy, although the yield is quite low. Biliary strictures following pediatric liver transplantation are frequently inaccessible by endoscopic cholangiography since few children undergo whole organ transplantation with duct-to-duct anastomosis. For example, in the case of biliary atresia, the most common indication for liver transplantation in childhood, a biliary enterostomy is created. Many other children receive a split organ graft due to a shortage of age-matched whole organ donors and the use of living related donor grafts. Strictures at the biliary enteric anastomoses are usually due to ischemia and require radiologic or surgical intervention. Anastomotic strictures after duct-to-duct anastomosis are managed the same as in adult patients using dilation and stent therapy (Fig. 22.10). Strictures near the junction of the main left and right hepatic ducts have been reported rarely in children and are presumed to be congenital in origin (Fig. 22.11).23 These have been successfully managed both surgically and endoscopically. Biliary leaks occur in children with laceration of the liver after blunt abdominal trauma and also after abdominal surgery such as cholecystectomy. ERCP can be used to simultaneously confirm the source and to treat the leak by transpapillary stent placement (Fig. 22.12).24 The diameter of the stent is based upon the ductal diameter.

Fig. 22.10 Choledochal anastomotic stricture and impacted stone in an adolescent male following liver transplantation.

Unusual biliary infections Human immunodeficiency virus (HIV)-associated cholangiopathy has been described in children.25 As in adults, the biliary abnormalities include irregularities of contour and caliber of the intrahepatic and extrahepatic ducts and papillary stenosis. The changes may result from concomitant infection with opportunistic organisms such as cytomegalovirus and Cryptosporidium parvum. Ascariasis infestation may be the most prevalent biliary infection worldwide, although concentrated within tropical climates. Among 214 children admitted to hospital in northern India for management of hepatobiliary and pancreatic ascariasis, 20 (9%) underwent endoscopic and 7 (4%) surgical intervention.26 226

Fig. 22.11 Presumed congenital stricture of the common hepatic duct presenting with advanced cirrhosis and portal hypertension in a 10-year-old child.

Sphincter of Oddi dysmotility Sphincter of Oddi dysmotility is sometimes considered in children with unexplained biliary colic-like pain. Although no normal manometric values have been established for children, some experts apply adult normal data and perform interventions such as

Chapter 22 ERCP in Children

biliary sphincterotomy when basal pressure exceeds 40mm Hg. Improvement following sphincterotomy has been reported in small numbers of patients but no controlled outcome data exist for children.2,27

Pancreatic indications Acute pancreatitis

ERCP is rarely indicated in the setting of acute pancreatitis. As in adults, ERCP is most helpful in the setting of biliary pancreatitis when there is evidence of choledocholithiasis and severe cholangitis.

A

Biliary pancreatitis is a commonly seen but underreported entity in childhood.28–30 Drainage of the bile duct may abruptly improve the child’s condition without necessarily improving the pancreatitis. Another acute indication for ERCP is known or suspected pancreatic trauma, where disruption of the pancreatic duct is questioned. In this case, urgent ERCP is recommended to investigate the integrity of the main duct and attempt to place a transpapillary stent that crosses a site of free duct leakage31 (Fig. 22.13). Endoscopic therapy is not indicated for contained intraparenchymal leaks, which usually heal spontaneously (Fig. 22.14). In tropical countries, parasites,

B

Fig. 22.12 A Contrast leaking from cystic duct stump in 15-year-old female with biliary leak after laparoscopic cholecystectomy. healed after temporary placement of short transpapillary biliary stent.

A

B Leak

B

Fig. 22.13 A Laceration at junction of head and body of the pancreas in 8-year-old boy after fall from a go-cart. B Pancreatogram reveals free extravasation from a disruption that could not be crossed with a wire guide. A distal pancreatectomy was performed after complete pancreatic transection was confirmed during exploratory laparotomy. 227

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Fig. 22.14 Pancreatogram shows faint intraparenchymal extravasation of contrast in head of pancreas in 9-year-old girl after a lap belt injury that occurred during an automobile accident.

Fig. 22.15 Anomalous pancreatobiliary union with long common channel treated with sphincterotomy in 14-year-old girl presenting with recurrent acute pancreatitis. primarily Ascaris lumbricoides, are an important cause of acute pancreatitis in children.26 Endoscopy is indicated to remove obstructing worms that fail to pass after drug therapy.

Persistent, recurrent, and chronic pancreatitis ERCP is an important investigative procedure in children with pancreatitis that is unrelenting after initial onset or recurs without an identifiable cause. However, a careful history and comprehensive medical evaluation along with non-invasive imaging should precede the performance of ERCP in order to avoid unnecessary risk. Occult drug exposures, underlying metabolic and autoimmune disorders, and newly recognized genetic disorders may be revealed and obviate the need for direct pancreatography. Increasingly, children previously labeled with the diagnosis of idiopathic relapsing pancreatitis have been reassigned a specific diagnosis without the need for invasive testing. Complete analysis of the genes for CFTR, SPINK1, and PRSSI, which can identify mutations associated with recurrent and chronic pancreatic disease, has recently become possible using commercially available assays (Ambry Genetics, Aliso Viejo, CA). The finding of mutations in one or more of these genes may call into question formerly assigned diagnoses such as pancreas divisum or sphincter of Oddi dysfunction, for which causality to pancreatitis remains controversial. Developmental anomalies involving the pancreas have been reported in association with recurrent attacks of pancreatitis. These include complete and partial pancreas divisum, anomalous pancreaticobiliary junction (Fig. 22.15), and enteric duplications (Fig. 22.16). Reports of endoscopic therapy with sphincterotomy of the minor and major papillae, respectively for the first two entities in children are limited but indicate potential beneficial outcomes. Communication of the pancreatic duct with cystic duplications may be confirmed endoscopically and help guide surgical intervention.

228

Fig. 22.16 18-month-old infant presenting with recurrent acute pancreatitis and persistent pancreatic cyst. Pancreatogram revealed intestinal duplication cyst in continuity with main pancreatic duct that was surgically excised and histologically confirmed.

Sphincter of Oddi dysfunction has been reported as a cause of recurrent pancreatitis in children, and improves after endoscopic pancreatic sphincterotomy.2,27,32 As with biliary manometry, basal pressures considered normal for adults have been used for normal baseline values in children. There are no controlled studies comparing endoscopic sphincterotomy to sham or placebo therapy in children. The largest series to date2 has not yet reported outcome data. Altered morphology of the main pancreatic duct and its side branches is seen with the progressive disease of chronic pancreatitis from various causes (Fig. 22.17). The range of changes is the same

Chapter 22 ERCP in Children

A

B

Fig. 22.17 Repeat pancreatograms six years apart showing progressive dilation of the main duct in a child with chronic pancreatitis.

as seen in adult patients including ectatic side branches, contour irregularities and dilation of the main duct, and occasional filling defects consisting of protein plugs and stones. Pancreatic sphincterotomy has been advocated in the setting of a dilated main pancreatic duct in symptomatic children who have failed to respond to medical therapy. There are no controlled studies, but short-term improvement following sphincterotomy has been reported. Pseudocysts that are causing clinical symptoms due to compression of adjacent structures may be drained endoscopically using transpapillary, transmural, or combination approaches, as discussed in Chapter 45. Experience in children is limited to case reports and small series.33,34

tion occur rarely in the larger pediatric ERCP series.2,4 Rates of complications after sphincterotomy in children appear comparable to those in adults.37 Cheng et al.2 reported minor acute bleeding treated with epinephrine injection in 5 patients in their series of 245 therapeutic ERCPs in children less than 18 years of age, including 100 selective biliary and 22 dual biliary and pancreatic sphincterotomies. The incidence of delayed complications following sphincterotomy in early childhood has not been reported. Complications of sedation or anesthesia, although relatively rare, especially when administered by an anesthesiologist, must also be considered as part of the total risk to children undergoing ERCP.

COMPLICATIONS

RELATIVE COSTS

Pancreatitis is the most common complication of ERCP in children. Rates have ranged from 3% to 17% with higher rates associated with therapeutic procedures.35,36 The highest rates of post-ERCP pancreatitis in children were reported by Cheng and colleagues2 in patients who underwent sphincterotomy for SOD: 30% with biliary sphincterotomy alone, 25% with biliary sphincterotomy followed by placement of a temporary pancreatic duct stent, and 20% with pancreatic sphincterotomy followed by placement of a pancreatic duct stent. Other complications such as bleeding, perforation, and infec-

There are no published data comparing the cost of ERCP with alternative diagnostic and therapeutic approaches such as percutaneous transhepatic cholangiography and direct surgical exploration. Anesthesia contributes a large fraction of the total cost for each approach. Surgical fees likely exceed those of either endoscopy or interventional radiology. The expense of maintaining costly specialized endoscopes and a reasonable inventory of accessories can be prohibitive for many pediatric facilities. Sharing equipment and accessories with a busy adult medicine service is most cost-effective.

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2.

3.

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6.

7.

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230

Pfau PR, Chelimsky GG, Kinnard MF, et al. Endoscopic retrograde cholangiopancreatography in children and adolescents. J Pediatr Gastroenterol Nutr 2002 Nov; 35(5):619–623. Cheng CL, Fogel EL, Sherman S, et al. Diagnostic and therapeutic endoscopic retrograde cholangiopancreatography in children: a large series report. J Pediatr Gastroenterol Nutr 2005 Oct; 41(4):445–453. Keil R, Snajdauf J, Stuj J, et al. Endoscopic retrograde cholangiopancreatography in infants and children. Indian J Gastroenterol 2000 Oct–Dec; 19(4):175–177. Fox VL, Werlin SL, Heyman MB. Endoscopic retrograde cholangiopancreatography in children. Subcommittee on Endoscopy and Procedures of the Patient Care Committee of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr 2000 Mar; 30(3):335–342. Jowell PS, Baillie J, Branch S, et al. Quantitative assessment of procedural competence: a prospective study of training in retrograde cholangiopancreatography. Ann Intern Med 1996; 125:983–989. Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med 1996; 335:909–918. Teng R, Yokohata K, Utsunomiya N, et al. Endoscopic retrograde cholangiopancreatography in infants and children. J Gastroenterol 2000; 35(1):39–42. Rocca R, Castellino F, Daperno M, et al. Therapeutic ERCP in paediatric patients. Dig Liver Dis 2005 May; 37(5):357–362. Wilkinson ML, Clayton PT. Sphincterotomy for jaundice in a neonate. J Pediatr Gastroenterol Nutr 1996; 23:507–509. Guelrud M, Jaen D, Mendoza S, et al. ERCP in the diagnosis of extrahepatic biliary atresia. Gastrointest Endosc 1991 Sep–Oct; 37(5):522–526. Guelrud M, Carr-Locke DL, Fox VL. ERCP in Pediatric Practice: Diagnosis and Treatment. Oxford: Isis Medical Media Ltd; 1997. Stringer MD, Taylor DR, Soloway RD. Gallstone composition: are children different? Journal of Pediatrics 2003; 142:435–440. Brown DL, Teele RL, Doubilet PM, et al. Echogenic material in the fetal gallbladder: sonographic and clinical observations. Radiology 1992; 182:73–76. St-Vil D, Yazbec S, Luks FI, et al. Cholelithiasis in newborns and infants. Journal of Pediatric Surgery 1992; 27:1305–1307. Baron TH, Harewood GC. Endoscopic balloon dilation of the biliary sphincter compared to endoscopic biliary sphincterotomy for removal of common bile duct stones during ERCP: a metaanalysis of randomized, controlled trials. Am J Gastroenterol 2004 Aug; 99(8):1455–1460. Disario JA, Freeman ML, Bjorkman DJ, et al. Endoscopic balloon dilation compared with sphincterotomy for extraction of bile duct stones. Gastroenterology 2004 Nov; 127(5):1291–1299. Bonnard A, Seguier-Lipszyc E, Liguory C, et al. Laparoscopic approach as primary treatment of common bile duct stones in children. J Pediatr Surg 2005 Sep; 40(9):1459–1463. Mah D, Wales P, Njere I, et al. Management of suspected common bile duct stones in children: role of selective intraoperative cholangiogram and endoscopic retrograde cholangiopancreatography. J Pediatr Surg 2004 June; 39(6):808– 812; discussion -12. Vrochides DV, Sorrells DL, Jr., Kurkchubasche AG, et al. Is there a role for routine preoperative endoscopic retrograde

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33.

34.

35.

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37.

cholangiopancreatography for suspected choledocholithiasis in children? Arch Surg 2005 Apr; 140(4):359–361. Todani T, Watanabe Y, Narusue M, et al. Classification, operative procedures and review of thirty seven cases including cancer arising from choledochal cyst. Am J Surg 1977; 134:263–269. Rodrigues F, Davies EG, Harrison P, et al. Liver disease in children with primary immunodeficiencies. J Pediatr 2004 Sep; 145(3):333–339. Gregorio GV, Portmann B, Karani J, et al. Autoimmune hepatitis/ sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology 2001 Mar; 33(3):544–553. Chapoy PR, Kendall RS, Fonkalsrud E, et al. Congenital stricture of the common hepatic duct: an unusual case without jaundice. Gastroenterology 1981; 80:380–383. Sharpe RP, Nance ML, Stafford PW. Nonoperative management of blunt extrahepatic biliary duct transection in the pediatric patient: case report and review of the literature. J Pediatr Surg 2002 Nov; 37(11):1612–1616. Yabut B, Werlin SL, Havens P, et al. Endoscopic retrograde cholangiopancreatography in children with HIV infection. J Pediatr Gastroenterol Nutr 1996 Dec; 23(5):624–627. Malik AH, Saima BD, Wani MY. Management of hepatobiliary and pancreatic ascariasis in children of an endemic area. Pediatr Surg Int 2006 Feb; 22(2):164–168. Varadarajulu S, Wilcox CM. Endoscopic management of sphincter of Oddi dysfunction in children. J Pediatr Gastroenterol Nutr 2006; 42:526–530. Sutton R, Cheslyn-Curtis S. Acute gallstone pancreatitis in childhood. Ann R Coll Surg Engl 2001 Nov; 83(6):406–408. Akel S, Khalifeh M, Makhlouf Akel M. Gallstone pancreatitis in children: atypical presentation and review. Eur J Pediatr 2005 Aug; 164(8):482–485. Nowak A, Kohut M, Nowakowska-Dulawa E, et al. Acute biliary pancreatitis in a 9-year-old child treated with endoscopic sphincterotomy. Dig Liver Dis 2003 Sep; 35(9):656–659. Canty TG, Sr., Weinman D. Management of major pancreatic duct injuries in children. J Trauma 2001 June; 50(6):1001–1007. Guelrud M, Morera C, Rodriguez M, et al. Sphincter of Oddi dysfunction in children with recurrent pancreatitis and anomalous pancreaticobiliary union: an etiologic concept. Gastrointest Endosc 1999 Aug; 50(2):194–199. Haluszka O, Campbell A, Horvath K. Endoscopic management of pancreatic pseudocyst in children. Gastrointest Endosc 2002 Jan; 55(1):128–131. Cahen D, Rauws E, Fockens P, et al. Endoscopic drainage of pancreatic pseudocysts: long-term outcome and procedural factors associated with safe and successful treatment. Endoscopy 2005 Oct; 37(10):977–983. Brown CW, Werlin SL, Geenen JE, et al. The diagnostic and therapeutic role of endoscopic retrograde cholangiopancreatography in children. J Pediatr Gastroenterol Nutr 1993 Jul; 17(1):19–23. Guelrud M, Mujica C, Jaen D, et al. The role of ERCP in the diagnosis and treatment of idiopathic recurrent pancreatitis in children and adolescents. Gastrointest Endosc 1994 Jul–Aug; 40(4):428–436. Varadarajulu S, Wilcox CM, Hawes RH, et al. Technical outcomes and complications of ERCP in children. Gastrointest Endosc 2004 Sep; 60(3):367–371.

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23

TECHNIQUES

ERCP in Pregnancy William M Outlaw and John Baillie

OVERVIEW Fear of causing fetal and maternal injury or death by procedurerelated pancreatitis delayed the introduction of ERCP for biliary complications of pregnancy until 1990. Since then, there have been seven case series (total of 57 patients) and numerous (>30) single case reports of ERCP in pregnancy. No case of severe ERCP-related pancreatitis (or other severe complication of the procedure) has been reported, and all but one reported case has been successful. PostERCP pancreatitis (PEP) and bleeding were reported in 8% and 4% of the 57 case series patients, while pre-eclampsia, premature birth and spontaneous abortion were observed in 4%, 2% and 2% of these same patients. The physiologic changes of pregnancy have profound implications for many aspects of ERCP, ranging from the type of drugs than can be used for sedation to positioning the patient and shielding the fetus from ionizing radiation. Single cases successfully managed by ERCP during pregnancy include spontaneous bile duct rupture with bile peritonitis and relief of obstructive jaundice from pancreatic adenocarcinoma have been reported. Overall, ERCP with biliary sphincterotomy and clearance of bile duct stones has an acceptably low morbidity in pregnant women, with no reported maternal mortality. It is not clear if one reported spontaneous abortion and two premature labors noted in the case series literature were causally related. ERCP can be recommended for managing the complications of bile duct stones in pregnancy. However, balloon dilation of the papilla (balloon sphincteroplasty) should be avoided due to its tendency to cause pancreatitis.

INTRODUCTION Endoscopic retrograde cholangiopancreatography (ERCP) rapidly advanced as a therapeutic specialty in 1974 with the advent of endoscopic sphincterotomy (ES), reported simultaneously by Kawai1 and Classen.2 However, acceptance of ERCP during pregnancy occurred later than other therapeutic interventions. Based on dated surgical literature which suggested a significant spontaneous abortion rate when laparotomy was performed in the first trimester of pregnancy, endoscopists were frightened to attempt ERCP during pregnancy in any clinical situation. It was felt that a severe attack of pancreatitis following ERCP might result in fetal, and possibly even maternal, death. There was also significant concern about the teratogenicity of fluoroscopy during the first trimester of pregnancy. In 1990, however, a group from Duke University Medical Center (including one of us (JB)) reported its experience of ERCP during pregnancy in five patients. These ERCPs allowed the avoidance of surgery.3 All five procedures were uncomplicated, the pregnancies lasted to full term, and five healthy babies were born. This landmark paper emboldened

other endoscopists to perform ERCP in pregnant women, and this is now considered accepted practice. Moreover, a recent case series4 comparing medical and surgical treatment of biliary stones in pregnancy failed to support the concern about fetal loss following surgery in pregnancy. Cholelithiasis and choledocholithiasis (Fig. 23.1) in pregnancy are common, and their complications, including biliary obstruction, cholangitis and gallstone pancreatitis (Fig. 23.2) are appropriately and safely managed by ERCP with ES. To the best of this author’s knowledge, no pregnant woman has died as a result of ERCP. There have been no studies comparing standard endoscopic sphincterotomy with so-called balloon sphincteroplasty (Fig. 23.3) in pregnant women, nor are there likely to be given the propensity of the latter to cause pancreatitis. It is the authors’ opinion that balloon sphincterotomy should never be used in pregnancy. Biliary obstruction in the setting of uncorrectable coagulopathy in a pregnant woman is more appropriately—and safely—managed by stenting to ensure drainage (Fig. 23.4). Elective sphincterotomy can be performed at a later date, when normal coagulation has been restored.

INDICATION The indication for ERCP during pregnancy must be well-established as necessary and critical to the safety of the mother and fetus: pregnancy is not the appropriate time to be assessing possible Type III sphincter of Oddi dysfunction by biliary manometry. Table 23.1 lists the ASGE’s recommendations regarding Indications for Endoscopy in pregnancy. Table 23.2 lists the ASGE’s Guiding Principles for Endoscopy in Pregnancy. Although choledocholithiasis (Fig. 23.1) is the commonest biliary pathology requiring ERCP in pregnancy, in certain parts of the world parasites (e.g. Fasciola, Clonorchis, Ascaris) can cause biliary obstruction and pancreatitis. These parasites are best treated by a combination of ERCP with ES for duct clearance and specific chemotherapeutic agents5 (see below).

RADIATION PROTECTION Considerable attention has been devoted to shielding the fetus from ionizing radiation during ERCP. Radiation protection is also discussed in Chapter 3. Three types of radiation exposure occur: primary, secondary and “leakage.”6 The primary radiation beam is focused and directed through the area of interest. Personnel (doctors, nurses, technicians) in the procedure room are exposed to secondary (or “scatter”) radiation. “Leakage” is leakage radiation from the radiation source itself. It has been estimated that the typical radiation dose to the fetus during ERCP is 3.1 mGy.7 This compares with 1.75 mGy for an upper GI contrast series, 7.8 mGy for a PET scan, 15.4 mGy for a pelvic CT scan and 37.0 mGy for an intravenous urogram (IVU). Protecting the first and second trimester fetus from irradiation is usually straightforward; a lead apron is applied to the 231

SECTION 2 TECHNIQUES

Fig. 23.1 Endoscopic retrograde common bile duct stones.

cholangiogram

showing

Fig. 23.3 papilla

Dilation (balloon sphincteroplasty) of the duodenal

Fig. 23.4 Plastic stent draining purulent bile from the bile duct in a patient whose severe coagulopathy was a contraindication to endoscopic sphincterotomy

Fig. 23.2 Duodenal papilla obstructed by a stone in a patient with gallstone pancreatitis.

appropriate part, shielding the mother’s abdomen. The endoscopist must confirm which direction the x-rays travel in the fluoroscopy system being employed to ensure that the shielding is appropriately applied; this may dictate placing a lead apron or mat underneath the patient. In the third trimester—especially close to term—it may be impossible to avoid exposing the fetus to a small amount of radiation from screening, but we have no data to suggest that this has caused any detectable harm, especially since the fetus is well-formed by then. As a rule, taking “hard copy” fluoroscopic images should be 232

Significant or continuing GI bleeding Severe or refractory nausea and vomiting or abdominal pain Dysphagia or odynophagia Strong suspicion of a colonic mass Severe diarrhea with negative evaluation Biliary pancreatitis, choledocholithiasis or cholangitis Biliary or pancreatic ductal injury

Table 23.1 Indications for endoscopy in pregnancy (ASGE)

avoided, as this significantly increases radiation exposure. Fluoroscopy time is kept to an absolute minimum; short “bursts” of fluoroscopy are used to confirm the seating of the papillotome in the bile duct and confirmation of the underlying pathology followed by as little contrast injection as possible. Typically, less than 60 seconds

Chapter 23 ERCP in Pregnancy

• Always have a strong indication, particularly in high-risk pregnancy • Defer endoscopy to the second trimester whenever possible • Use the lowest effective dose of sedative medication • Whenever possible, use category A or B drugs • Minimize procedure time • Position pregnant patients in left pelvic tilt or left lateral position to avoid vena caval or aortic compression • The presence of fetal heart sounds should be confirmed before sedation is begun and again at the end of the procedure • Obstetric support should be available in the event of a pregnancy-related complication • Endoscopy is contraindicated in the presence of obstetric complications, such as placental abruption, imminent delivery, ruptured membranes or eclampsia

Table 23.2 General principles guiding endoscopy in pregnancy

of fluoroscopy time are required. However, published reports cite fluoroscopy time ranging from 8 seconds8 to 3.2 minutes.9 A standard radiation dosimeter is applied to the abdominal wall overlying the fundus of the gravid uterus to check that the fetus has been adequately shielded. Radiation doses are typically negligible. Reported measured fetal exposures range from 40 to 310 mrad (4– 31 mGy)—well within established safe limits.9,10 (Note: 1 mGy = 100 mrad.) One novel method of ERCP that avoids radiation exposure altogether was described by Simmons et al.11 This technique involves wire-guided bile duct cannulation without fluoroscopic guidance. Once the wire has passed proximally, the catheter is advanced and entry into the presumed duct is confirmed by aspirating bile into the catheter. After a biliary sphincterotomy is performed stone retrieval is achieved using a stone retrieval balloon. The ballon is passed proximally into the bile duct, inflated, and swept through the sphincterotomy. Using this technique, successful ERCP and stone extraction were described in six cases.11 Neither fluoroscopy nor spot radiographs (“hard copy” images) were used during these procedures. The mean ERCP time was 16 minutes (range 10–25 minutes). Though useful, it is likely that this technique will be used by only the most experienced endoscopists and for straightforward cases.

POSITIONING Positioning the pregnant mother is rarely a problem. However, women in the later stages of pregnancy cannot lie prone, the standard position for ERCP imaging. A semi-prone or left lateral position is acceptable in such circumstances (Fig. 23.5). The endoscopist performing the procedure should be familiar with the altered endoscopic and radiologic appearances when pregnant patients are so positioned. The supine position is not acceptable in the third trimester of pregnancy: the “supine hypotensive syndrome” occurs in 15– 20% of pregnant women at term.12 Uterine blood flow is compromised in the supine position due to inferior vena cava (IVC), and sometimes aortic, compression by the gravid uterus. This phenomenon is exacerbated by the use of vasodilators. As amniotic fluid can conduct electrical current to the fetus,13 it is recommended that the grounding pad for electrocautery should

Fig. 23.5 The patient is lying in the left semi-prone position with lead mats below her and a lead apron draped over the lower abdomen. A dosimeter (not seen) is placed over the fundus of the uterus on the mother’s abdomen to measure fetal radiation exposure.

be placed in such a way as to avoid interposing the uterus on an imaginary line between the electrical device and the pad. Bipolar electrocautery is preferred to minimize the risk of stray currents.

PHYSIOLOGIC CHANGES OF PREGNANCY Although endoscopists rarely consider the physiologic changes of pregnancy, these are important and impact directly on sedation, positioning, fluid balance, prevention of gastroesophageal reflux disease (GERD), etc.14 Pregnancy causes a hypercoagulable state; cardiac output increases 50% during pregnancy; oncotic pressure is reduced, making pulmonary edema more likely in the setting of fluid overload; oxygen consumption increases 60% and functional residual (lung) capacity is reduced 20% at term, due to the presence of the large gravid uterus in the abdomen (this reduction in lung capacity is reduced a further 30% in the supine position); renal blood flow increases 75% (glomerular filtration rate 50%) during pregnancy, which has implications for drug clearance; loss of tone in the lower esophageal sphincter (LES) during pregnancy occurs in 22% of women in the first trimester and increases to nearly 80% in the third trimester. Due to the risk of gastroesophageal reflux and aspiration of gastric contents, it is recommended that pregnant women undergo rapid induction for general anesthesia with cricoid pressure and endotracheal intubation.

SEDATION The sedation used for ERCP in pregnancy is similar to that used for moderate (“conscious”) sedation and general anesthesia, except that benzodiazepines are generally avoided due to their long half-life.15 Sustained use of diazepam in early pregnancy has been associated with cleft palate.16 In later pregnancy, it has been suggested that diazepam use may result in neurobehavioral disorders.17 Midazolam has not been reported to be associated with congenital abnormalities. However, due to concerns about benzodiazepines in general, midazolam is usually avoided, especially in the first trimester. Pro233

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pofolTM (DiprivanTM and others, 2,6-bis(1-methylethyl-phenol)) is considered safe in pregnancy. However, if PropofolTM is used, it should be noted that this agent has no analgesic effect. The fetal heart rate should be assessed before and after ERCP to ensure that the fetus remains viable and undistressed by the procedure. Standard monitoring (i.e. pulse oximetry, automated blood pressure monitoring, and capnography) is employed for the mother. The safety of commonly used medications for endoscopy during pregnancy is covered in more detail in the ASGE Guideline for Endoscopy in Pregnant and Lactating Women.18

OUTCOMES Table 23.3 summarizes the collective outcome of case series consisting of = 3 patients. Reports of one or two cases, and those lumping together ERCP and non-ERCP endoscopy in pregnancy,11,19–24 have been excluded. Seven case series3,9–11,15,19 comprising a total of 57 patients undergoing ERCP during pregnancy have been reported. The median stage of pregnancy in which these patients presented with symptomatic choledocholithiasis (the main indication for ERCP) was mid-to-late second trimester. Complications were postERCP pancreatitis (PEP) 8%, post-sphincterotomy bleeding (4%), and pre-eclampsia (4%). There were two premature births (at 35 weeks, one with severe growth retardation and pulmonary immaturity) (4%) and one spontaneous abortion (2%).

MANAGEMENT OF RELATED BILIARY DISORDERS OF PREGNANCY Thaggard et al.25 reported a rare case of spontaneous bile duct rupture during pregnancy leading to bile peritonitis that was managed endoscopically. Allmedinger et al.26 describe the use of percutaneous cholecystostomy to manage acute cholecystitis in two women during the third trimester of pregnancy. Both delivered normal babies at term and underwent uneventful laparoscopic

cholecystectomy (LC) within 3 months. Sungler at al.,27 and Friedman and Friedman,28 report the combination of ERCP and LC for managing gallstone disease in seven pregnancies, all with successful outcome. Diettrich et al.29 identified 34/1100 pregnant women patients who underwent laparotomy within 6 weeks of delivery. Twenty-six patients had spontaneous vaginal deliveries (SVDs) and eight had Cesarian sections. There were no complications resulting from any of these procedures. Blackbourne et al.30 reported a most unusual case of a patient diagnosed with pancreatic adenocarcinoma at 17 weeks gestation in whom a biliary stent was successfully placed to relieve biliary obstruction. The patient subsequently underwent pancreaticoduodenectomy (Whipple procedure). Hewitt et al.31 described their experience of managing three patients with choledochal cysts (CDC) during pregnancy. One CDC that was conservatively managed ruptured, with fetal loss and a prolonged hospitalization. Based upon this case proactive drainage of CDC should be considered in order to limit the risk of spontaneous rupture in the peripartum period. Routine “worming” of women of childbearing age is recommended in areas where Ascaris is endemic. Despite this, Shah et al.32 describe an interesting experience of 15 cases of symptomatic biliary Ascariasis seen over a 10-year period. Ten of these patients were in their third trimester of pregnancy. The condition was most reliably diagnosed by transabdominal ultrasound. Nine of the 15(60%) patients responded to conservative treatment. Among the remaining six cases, endoscopic extraction of Ascaris worms was successful in four cases and open biliary surgery was required in two cases. Of the pregnant patients, one suffered a spontaneous abortion at 12 weeks and another went into premature labor. In summary, ERCP is a safe and effective modality primarily for the management of choledocholithiasis.33–36

Acknowledgement The authors are grateful to Dr Dick Kozarek (Seattle, WA) for his helpful critique of the first draft of this manuscript.

Author

Number of pts

Mean gestation (weeks)

Complications/outcomes

Kaleleh (ref 12)

17

18.6

PEP-1, Bleed-1 Pre-eclampsia-2

Gupta (ref 10)

18

17

PEP-1, Bleed-1 Preterm delivery-1

Jamidar (ref 16)

23 (6 centers; total of 29 ERCPs)

15-1st trimester 8-2nd trimester 6-3rd trimester

PEP-1 Spontaneous abortion 3 months after ERCP

Tham (ref 11)

15

28.9

None

Baillie (ref 6)

5

1-1st trimester 4-2nd trimester

None

Barthel (ref 20)

3

n/a

PEP-1

Simmons (ref 21)

6

6-30 weeks

2 premature births

Total

57

mid-late 2nd trimester

PEP-4 (8%) Bleed-2 (4%) Pre-eclampsia-2 (4%) Spontaneous abortion 1 (2%) Premature birth 2 (4%)

Table 23.3 ERCP during pregnancy: series of ≥2 patients PEP-post-ERCP pancreatitis.

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Kawai K, Akasaka Y, Murakami K, et al. Endoscopic sphincterotomy of the ampulla of Vater. Gastrointest Endosc 1974; 20:148–151. Classen M, Demling L. Endoscopic sphincterotomy of the papilla of Vater and extraction of stones from the choledochal duct. Dtsch Med Wochenschr 1974; 99(11):496–497. Baillie J, Cairns SR, Putnam WS, et al. Endoscopic management of choledocholithiasis during pregnancy. Surg Gynecol Obstet 1990; 171(1):1–4. Lu EJ, Curet MJ, El-Sayed YY, et al. Medical versus surgical management of biliary tract disease in pregnancy. Am J Surg 2004; 188(6):755–759. Shah OJ, Robanni I, Khan F, et al. Management of biliary Ascariasis in pregnancy. World J Surg 2005; 29(10):1294–1298. http://www.sgna.org/resources/guidelines/guideline2_print.html. http://brighamrad.harvard.edu/education/fetaldose/diagexposure.html. Gupta R, Tandan M, Lakhtakia S, et al. Safety of therapeutic ERCP in pregnancy—an Indian experience. Indian J Gastroenterol 2005; 24(4):161–163. Tham TC, Vandervoort J, Wong RC, et al. Safety of ERCP during pregnancy, Am J Gastroenterol 2003; 98(2):308–311. Kahaleh M, Hartwell GD, Arseneau KO, et al. Safety and efficacy of ERCP in pregnancy. Gastrointest Endosc 2004; 60(2):287–292. Simmons DC, Tarnasky PR, Rivera-Alsina ME, et al. Endoscopic retrograde cholangiopancreatography (ERCP) in pregnancy without the use of radiation. Am J Obstet Gynecol 2004; 190(5):1467–1469. Holmes F. Incidence of supine hypotensive syndrome in late pregnancy. A clinical study of 500 subjects. J Obstet Gynaecol Br Emp 1960; 67:254–258. Einarson A, Bailey B, Inocencion G, et al. Accidental electric shock in pregnancy: a prospective cohort study. Am J Obstst Gynecol 1997; 176:678–681. Cappell MS. Sedation and analgesia for gastrointestinal endoscopy during pregnancy. Gastrointest Endosc Clin N Am 2006; 16(1):1–31. Jamidar PA, Beck GJ, Hoffman BJ, et al. Endoscopic retrograde cholangiopancreatography in pregnancy. Am J Gastroenterol 1995; 90(8):1263–1267. Ornoy A, Arnon J, Shectman S, et al. Is benzodiazepine use during pregnancy really teratogenic? Reprod Toxicol 1998; 12:511–515. Laegreid L, Olegard R, Wahlstrom J, et al. Teratogenic effects of benzodiazepine use during pregnancy. J Pediatr 1989; 114:126–131. ASGE Standards of Practice Committee. Guidelines for endoscopy in pregnant and lactating women. Gastrointest Endosc 2005; 61(3):357–362. Barthel JS, Chowdhury T, Miedema BW. Endoscopic sphincterotomy for the treatment of gallstone pancreatitis in pregnancy. Surg Endosc 1998; 12(5):394–399.

20. Rahmin MG, Hitscherich R, Jacobson IM. ERCP for symptomatic choledocholithiasis in pregnancy. Am J Gastroenterol 1994; 89(9):1601–1602. 21. Uomo G, Manes G, Picciotto FP, et al. Endoscopic treatment of acute biliary pancreatitis in pregnancy. J Clin Gastroenterol 1994; 18(3):250–252. 22. Cohen SA, Kasmin FE, Siegel JH. ERCP during pregnancy. Am J Gastroenterol 2003; 98(2):237–238. 23. Goldschmidt M, Wolf L, Shires T. Treatment of symptomatic choledocholithiasis during pregnancy. Gastrointest Endosc 1993; 39(6):812–814. 24. Quan WL, Chia CK, Yim HB. Safety of endoscopical procedures during pregnancy. Singapore Med J 2006; 47(6):525–528. 25. Thaggard WG, Johnson PN, Baron TH. Endoscopic management of spontaneous bile duct perforation and bile peritonitis complicating term pregnancy (case report). Am J Gastroenterol 1995; 90(11):2054–2055 (case report). 26. Allmendinger N, Hallisey MJ, Okhi SK, et al. Percutaneous cholecystostomy of acute cholecystitis of pregnancy. Obstet Gynecol 1995; 86(4 pt 2):653–654. 27. Sungler P, Heinerman PM, Steiner H, et al. Laparoscopic cholecystectomy and interventional endoscopy for gallstone complications of pregnancy. Surg Endosc 2000; 14(3):267–271. 28. Friedman RL, Friedman IH. Acute cholecystitis with calculous biliary obstruction in the gravid patient. Management by ERCP, papillotomy, stone extraction and laparoscopic cholecystectomy. Surg Endosc 1995; 9(8):910–913. 29. Diettrich NA, Kaplan G. Surgical considerations in the contemporary management of biliary tract disease in the postpartum period. Am J Surg 1998; 176(3):251–253. 30. Blackbourne LH, Jones RS, Catalano CJ, et al. Pancreatic adenocarcinoma in the pregnant patient: case report and review of the literature. Cancer 1997; 79(9):1776–1779. 31. Hewitt PM, Krige JE, Bornmann PC, et al. Choledochal cyst in pregnancy: a therapeutic dilemma. J Am Coll Surg 1995; 181(3):237–240. 32. Shah OJ, Robanni I, Khan F, et al. Management of biliary ascariasis in pregnancy. World J Surg 2005; 29(10):1294–1298. 33. Axelrad AM, Fleischer DE, Strack LL, et al. Performance of ERCP for symptomatic choledocholithiasis during pregnancy: techniques to increase safety and improve patient management. Am J Gastroenterol 1994; 89(1):109–112. 34. Baillie J. ERCP during pregnancy. Am J Gastroenterol 2003; 98(2):237–238. 35. Menees S, Elta G. Endoscopic retrograde cholangiopancreatography during pregnancy. Gastrointest Endosc Clin N Am 2006; 16(1):41–57. 36. Cappell MS. The fetal safety and clinical efficacy of gastrointestinal endoscopy during pregnancy (review). Gastrointest Endosc Clin North Am 2003; 32(1):123–179 (review).

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ERCP in Surgically Altered Anatomy Simon K. Lo

ERCP is generally considered the technically most difficult endoscopic procedure. But it can be made more challenging if the gastrointestinal or pancreaticobiliary anatomy is modified. A thorough understanding of a surgically altered anatomy is essential to minimize complications and to enhance the chance of a successful outcome. In virtually all these cases, careful preprocedure planning is mandatory (Table 24.1).

SURGERY THAT MAY IMPACT THE PERFORMANCE OR INTERPRETATION OF ERCP Many operations reroute the upper gastrointestinal tract and may require a special equipment or extreme familiarity in order to reach the pancreatic and biliary systems. Some surgery removes or alters a portion of the bile duct or pancreas but does not create any hardship to performing ERCP. Conversely, there are those improbable surgical consequences that would not allow any endoscopic access of the biliary tract regardless of experience, skill and equipment. We will explain most of these operations and attempt to bring up relevant points pertaining to ERCP.

ESOPHAGEAL RESECTION Mostly done for esophageal neoplasm or pre-malignant conditions, up to 22% of esophageal resections may be accompanied by high esophageal anastomosis strictures.1 Additionally, small diverticuli can form proximal to these anastomoses. In passing a duodenoscope, care must be taken to avoid forcing it through a diverticulum or an anastomotic stricture. If resistance is encountered, an end-viewing upper endoscope should be used to inspect the esophageal anatomy carefully. Esophageal resections also result in the stomach being brought up above the diaphragm and turned into a tubular sack that ends with a pyloroplasty. Once the duodenoscope has passed through the pylorus, the approach to the major papilla requires slightly more clockwise rotation or a longer insertion of the endoscope than usual. This is because of the more proximal location of the duodenum and the lack of a competent pylorus to hold the endoscope in place.

GASTRIC RESECTION There are many forms of gastric resection, ranging from a Billroth I where there is very little loss of the volume of the stomach to a total gastrectomy. As a result, the impact of gastric resection on ERCP can be either minimal or profound.

Billroth I In a Billroth I surgery, only the antrum and pylorus are removed and the stomach is attached to the duodenum along its greater

curvature (Fig. 24.1). Scope passage into the duodenum is typically easier than usual, but the papilla is harder to visualize. As expected, both the major and minor papillae are more proximally located than usual. In the short-scope position, the papilla is seen following an exaggerated clockwise rotation of the endoscope. However, anchoring of the endoscope is difficult without the pylorus and achieving a stable scope position for deliberate cannulation can be quite difficult. In this situation, working in the long-scope position may be more desirable for bile duct cannulation because the papillary orifice is better visualized and the scope is more stably situated.

Billroth II Before proton pump inhibitors were introduced, peptic ulcer surgery was common. A Billroth II operation involves an antrectomy and creation of a gastrojejunostomy. The result is an end (stomach)-toside (jejunum) anastomosis with an afferent and an efferent limb (Figs 24.2A, 24.2B) next to each other beyond the line of anastomosis. The afferent limb travels proximally and ends at the duodenal stump whereas the efferent limb restores continuity with the rest of the gastrointestinal tract. The major papilla is obviously located near the duodenal stump and is seen with the papillary orifice facing the endoscope. There are several challenges that the endoscopist has to deal with when performing ERCP in a patient with Billroth II anatomy. It begins with the choice of endoscope. Once it was believed that end-viewing endoscopes were best used to navigate the small bowel and pass cannulas into the biliary orifice. Many experienced biliary endoscopists switched to using the side-viewing duodenoscopes to take advantage of the elevator and better viewing of the papilla. But in a prospective randomized study of 45 patients in Korea, no difference was noted between the side-viewing and endviewing endoscopes in success of cannulation and sphincterotomy.2 In fact, the end-viewing endoscopes were safer to use. Regardless of what endoscope to use, Billroth II ERCP is one of the more difficult procedures. In a study involving 185 Billroth II ERCP procedures, the failure rate was 34%.3 The afferent lumen cannot be identified by visual inspection alone, though it is commonly believed that it is the more awkwardly located orifice. The afferent limb can be attached to the stomach along either the lesser (antiperistaltic) (Fig. 24.2A) or greater (isoperistaltic) curvature (Fig. 24.2B). Scope passage with an end-viewing device is rather intuitive, and the major challenge is in visualizing and cannulating the papilla. Even though data suggests there is no difference in technical success between side-viewing and endviewing, endoscopies, in reality it is far easier to perform cannulation and therapies using a duodenoscope. When using a duodenoscope, the difficulty starts with gaining entry into the afferent lumen. It is even more difficult if the afferent limb is sutured to the lesser curvature after it has exited the 237

SECTION 2 TECHNIQUES

Understand the prior surgery thoroughly Choose the proper endoscope Standard therapeutic duodenoscope Thin-caliber diagnostic duodenoscope Pediatric duodenoscope Diagnostic upper endoscope Therapeutic upper endoscope Pediatric (variable stiffness) colonoscope Therapeutic colonoscope Push enteroscope Double balloon enteroscope Linear EUS scope Position the patient properly Prone Supine Left lateral Left oblique Prepare accessories Standard accessories Non-precurved catheters Nasobiliary drains Specialty accessories (e.g. for Billroth II) Long-length accessories Anesthesia Conscious sedation Propofol anesthesia General anesthesia

Table 24.1 Pre-procedure planning in situations that involve surgically altered anatomy A

Fig. 24.1 Billroth I gastrectomy. Antrectomy is followed by connection of the stomach to the duodenum in the end-to-end fashion. The lesser curvature side of the cut end of the stomach is closed to allow creation of the gastroduodenostomy.

B

Fig. 24.2 A Billroth II gastrectomy with an antiperistaltic gastrojejunostomy anastomosis. In this case, the afferent limb is accessed through the stomal orifice located near the lesser curvature. B Billroth II gastrectomy with an isoperistaltic anastomosis, where the afferent limb is attached to the greater curvature. 238

Chapter 24 ERCP in Surgically Altered Anatomy

gastrojejunostomy, as this form of operation creates a fixed and significantly angulated point of entry4 (Figs 24.3A, 24.3B). When a duodenoscope is used, the technique to enter the orifice is the same as for the pylorus. When the lumen can only be visualized in the retroflexed position, gliding the scope along gently toward it rarely works. Suctioning out excess gastric air may make the gliding a little easier. Once the tip of the scope has reached the orifice, the scope should be gradually pulled back and straightened in order to advance further. There is the technique of entering the lumen by rotating the scope 180 degrees at the orifice and pointing the tip of the scope down until the small bowel lumen is clearly in sight. This technique A

can theoretically be done with the scope facing the opening rather than “backing in.” However, the endoscope would be blinded by mucosal lining and visual inspection during the maneuvering would become impossible. Hand compression of the mid-abdomen or extending a polypectomy snare into the intended lumen has been reported to add to the success of intubation of a difficult intestinal orifice.5 Even in a tertiary biliary center, failure to enter the afferent limb has been reported to be as high as 10%.3 Once the side-viewing duodenoscope has securely engaged in a jejunal lumen, passage forward is safe and effective by constantly orientating the bowel in the 6 o’clock position (Figs 24.4A). This

B

Fig. 24.3 A Endoscopic appearance of a typical Billroth II gastrojejunostomy. Viewing from the stomach, the two jejunal limbs are located at the extreme right and left of this image. B Billroth II gastrectomy with the greater curvature side of the stomach attached to the jejunum in an end-to-side fashion. The lesser curvature side of the stomach is closed surgically. Some surgeons choose to suture the jejunum onto this area to protect the suture line. If the afferent limb is tagged down in this manner, then endoscope entry into this limb may be quite difficult. A

B

Fig. 24.4 A The typical view of the jejunal lumen when a side-viewing duodenoscope is being advanced. Note the upper half of the lumen should always be kept in the 6 o’clock position. B A similar duodenoscopic view of the distal lumen in the 6 o’clock position. Note the upper lumen always represents a retroflexed view. An attempt to pass the scope toward the 12 o’clock direction would cause either perforation or the scope to fold backward.

239

SECTION 2 TECHNIQUES

would simulate the view of driving a car in a long tunnel. It is common to see two lumens when a duodenoscope is partially retroflexed and it creates confusion regarding where to advance the endoscope. A good rule of thumb is to orientate the two lumens along the vertical midline and the lower lumen is the one that the endoscope should enter (Fig. 24.4B). Natural intestinal redundancy and tortuosity rarely allow unimpeded forward advancement. Rather, successful passages require a combination of gentle rotation, dial redirection, pulling and pushing. Care must be taken to minimize sudden or forceful manipulations, as perforation may result. In one series, perforation occurred in 5% and was mainly from manipulations in the afferent limb.3 In another study, 18% of the cases were complicated by jejunal perforation.2 Usage of a small caliber and soft, older duodenoscope may reduce the chance of traumatizing the intestinal wall. Minimizing air insufflation helps keep the lumen straight and the bowel wall soft and stretchable. Rotating the patient is occasionally effective in getting around seemingly improbable turns. These measures all may contribute to a safe and successful procedure. With experience and special care, an acceptable risk of perforation can be achieved.6 After passing some distance, it is wise to take a fluoroscopic picture to confirm that the scope has passed or is passing though the transverse duodenum (Fig. 24.5). If the scope is in the pelvis, then it is likely to be in the efferent limb and should be withdrawn to search for the other intestinal orifice. Some afferent limbs seem to be longer and more tortuous to reach the papilla than others. This impression is indeed correct, as the afferent loop may be created in the antecolic fashion over the transverse colon (Figs 24.6A, 24.6B). On the way to the proximal duodenum, an anastomosis that connects the afferent to the efferent limbs may be encountered. This Braun procedure is a modification of the Billroth II operation to reduce bile reflux into the stomach or to lessen the chance of duo-

Fig. 24.5 Fluoroscopy shows the duodenoscope is facing the right direction and crossing the transverse duodenum. 240

A

B

Fig. 24.6 A Retrocolic construction of the Billroth II gastrojejunostomy. The afferent limb is relatively short in this case. B Antecolic Billroth II gastrojejunostomy. The afferent limb is significantly longer than that in 24.6a.

Chapter 24 ERCP in Surgically Altered Anatomy

denal obstruction (Fig. 24.7). It should not influence the endoscopic passage other than by creating confusion to the endoscopist. On some occasions the duodenal stump appears as a blind sac with a distinctly flat and smooth mucosa and is reached without the major papilla being noticed. The minor and then major papilla should be readily identified upon gradual withdrawal of the endoscope (Figs 24.8A–24.8C). The major papilla is almost always found near the 12 o’clock position of the duodenum when a duodenoscope is used (Fig. 24.8C). If the intestinal lumen is kept in view ahead of the endoscope, then the bile duct leads away from the endoscope straight ahead or slightly to the right (Figs 24.9A, 24.10). In order to keep the cannulating catheter or guidewire tangentially to the duodenal wall for biliary access, the papilla should not be approached up close (Fig. 24.8C). Rather, the scope should be pulled back slightly with its elevator partially lowered for catheter passage. Conversely, the pancreatic duct is easier to cannulate by advancing the scope close to the papilla and keeping the elevator in a lifted position (Fig. 24.8B). Some endoscopists prefer to use straight-tip catheters for biliary cannulation,5 while others like to use straight guidewires. However, perhaps the most effective way in entering the bile duct is to use a catheter that has been bent in an S-shape (Fig. 24.9B). A cap-assisted approach has been described to improve cannulation of a Billroth II papilla when an end-viewing endoscope is used7 (Fig. 24.11). On some occasions when pancreas divisum is suspected, the minor papilla should be correctly identified for cannulation. As a general rule, it is located slightly further away from (cephalad to) and to the left of the major papilla (Figs 24.8A, 24.10). Biliary sphincterotomy is accomplished either by the use of a Billroth II sphincterotome or a needle-knife to cut over a biliary stent. A Billroth II push sphincterotome is designed virtually opposite to a conventional traction sphincterotome. The cutting wire is loosened to form a half loop over a straight sphincterotome catheter. The wire loop is then pushed forward to cut the papilla hood along the 12 o’clock position. Sphincterotomy done in this manner is slightly less well controlled than in the normal setting because of the pushing motion and suboptimal visualization of the proximal edge of the papillary mound. A modified sphincterotome that forces its tip into an S-shape when the cutting wire tightens may also be used to

A

B

perform sphincterotomy in this setting.8 However, most endoscopists seem to prefer needle-knife sphincterotomy over a biliary stent because it avoids injury to the pancreatic sphincter and allows gradual, unhurried tissue cutting.4,9 Balloon sphincter dilation, commonly done with an 8 mm balloon, is technically easy to perform. A randomized study showed balloon sphincter dilation was as effective as sphincterotomy to facilitate stone extraction and had fewer com-

Fig. 24.7 A Braun modification of a Billroth II operation. Here the afferent and efferent limbs are connected via a side-to-side anastomosis.

C

Fig. 24.8 A The minor papilla, which is quite prominent in this case, is located more cephalad to and to the left side of the major papilla. Further up the afferent lumen is the duodenal stump. B As the scope is pulled back from the duodenal stump, the major papilla is seen up close and perpendicular to the duodenoscope. This position favors cannulation of the pancreatic duct. C The duodenoscope is pulled back further and farther away from the major papilla. This position favors cannulation of the bile duct. 241

SECTION 2 TECHNIQUES

A

Fig. 24.9 A The major papilla is usually located at the 12 o’clock position. Here the guidewire points in the direction of the bile duct. B This S-shaped biliary cannula is best used for intubating the bile duct.

B

Minor papilla

Major papilla

Fig. 24.10 A schematic illustration of the relationship of the major and minor papillae and the directions of the bile duct (yellow arrow) and pancreatic duct (blue arrow).

Fig. 24.12

A typical Roux-en-Y gastrojejunostomy.

plications.9 Additionally, there was no more pancreatitis with this treatment than sphincterotomy.

Roux-en-Y gastrectomy Fig. 24.11 A balloon dilator is being used to perform sphincteroplasty using an end-viewing endoscope. Note a short, soft cap has been fitted to the tip of the scope. This cap is believed to improve the ability to cannulate the papilla. 242

Created to reduce reflux of pancreatic and biliary fluids into the stomach following a partial gastrectomy, the gastric outlet is constructed similar to that of a Billroth II surgery. However, this endto-side anastomosis leads to a very short blind stump and a long, efferent limb (Fig. 24.12). The jejunum of the efferent limb extends

Chapter 24 ERCP in Surgically Altered Anatomy

around 40 cm before a jejunojejunostomy anastomosis is found. At this point two or three lumens (Figs 24.13A, 24.13B) will be identified, depending on whether the two jejunal limbs are connected end-to-side (Fig. 24.13C) or side-to-side (Fig. 24.13D). If done sideto-side, one of the three outlets is a short, blind stump. If the afferent limb is correctly entered, the endoscope will travel up the proximal jejunum, the ligament of Treitz, transverse duodenum and finally the descending duodenum. This long distance to travel makes it nearly impossible for a 125 cm-long duodenoscope to reach the major papilla. Many longer-length endoscopes have been used to perform ERCP in this setting, including pediatric or adult versions of colonoscopes and push enteroscopes.10 A special oblique-viewing endoscope has been reported to be potentially useful for this purpose.11 Double-balloon enteroscopes can reach as far as the cecum per-orally and were introduced in the United States in 2004 (Figs 24.14A–D). ERCP, including therapeutic maneuvers, has been reported to be successful in 5 of 6 patients when using this new form of enteroscope.12 The challenge of performing ERCP in a Roux-en-Y gastrectomy lies not just in traveling a great length and recognizing the proper intestinal lumen but also in selectively cannulating the bile duct and pancreatic duct. All end-viewing endoscopes have the inherent difficulty in identifying the major papilla because of its location along

A

C

B

the interior aspect of the duodenal C-loop. Even when it is seen, cannulation is extraordinarily difficult because of awkward orientations and unstable positioning for cannulation (Figs 24.15A–C). In the hands of ERCP experts, the success rate is a mere 67%.13 Yamamoto and colleagues reported the success of performing diagnostic and therapeutic ERCP with a double-balloon enteroscope in five patients.12 Interestingly, the authors fitted a small plastic cap on the tip of the enteroscope to enable cannulation. It is uncertain if and how this plastic cap helps with the procedure. Given the difficulty and frequent failure of performing ERCP in this postoperative anatomy, it is best to refer this type of cases to a tertiary biliary center or choose an alternative method such as a transhepatic study. Performing ERCP with the intent to evaluate and treat a pancreatic condition is particularly problematic as a transhepatic procedure is ineffective. An intraoperative transjejunal ERCP method has been reported to overcome this difficulty. At laparotomy, an enterotomy is made at 20 cm distal to the ligament of Treitz to allow passage of a gas-sterilized duodenoscope to advance up the afferent limb.14

Total gastrectomy Done usually for treatment of gastric cancer, a total gastrectomy leads to the creation of an end-to-side esophagojejunostomy. One

Fig. 24.13 A A schematic illustration of 3 lumens at the point of a jejunojejunostomy anastomosis. The single distal lumen on the same side of the anastomosis is either the efferent or a blind limb. One of the two lumens on the other side of the anastomosis is a blind stump or the efferent limb while the other is the afferent limb. In either case, the afferent limb has to cross the line of anastomosis. B Endoscopic picture of the two lumens seen beyond an anastomosis. One of these two orifices should lead to the afferent limb. C Illustration of an end-toside jejunojejunostomy anastomosis. D Illustration of a side-to-side jejunojejunostomy anastomosis.

D

243

SECTION 2 TECHNIQUES

B A

D

C

Fig. 24.14 The double-balloon system consists of a balloon on the tip of a thin endoscope A and a balloon on an overtube B. C Both balloons are inflated. D Balloon inflation device that controls air insufflation, deflation, pressure reading, and an alarm with a yellow-light indicator of excessive pressure.

A

B

C

Fig. 24.15 A The major papilla seen with an end-viewing endoscope. Note it is a very tangential view with an awkward position for cannulation. B After rotating the end-viewing endoscope, the major papilla appears to be optimally positioned for cannulation. The papilla is still tangentially located and it is difficult to maintain this view for long. C A catheter has been successfully inserted into the bile duct with this end-viewing endoscope. 244

Chapter 24 ERCP in Surgically Altered Anatomy

Fig. 24.16 A total gastrectomy with a Roux-en-Y esophagojejunostomy. In spite of the significant distance, a side-viewing duodenoscope is usually long enough to reach the papilla.

lumen of the esophagojejunostomy is a blind end, whereas the other is the efferent jejunal limb (Fig. 24.16). In a short distance down this limb is a side-to-side or end-to-side jejunojejunostomy to receive pancreatic and biliary contents. Similar to the Roux-en-Y gastrectomy, the endoscope has to enter the afferent limb and pass through the proximal jejunum and most of the duodenum. But unlike Rouxen-Y partial gastrectomy, a duodenoscope actually can reach the major papilla on a more regular basis. Once the major papilla is identified with the duodenoscope, the approach to ERCP cannulation and therapy is quite similar to that for a Billroth II anatomy. But if a duodenoscope is too short to reach the descending duodenum, then an end-viewing long endoscope has to be used. In that case, the challenge lies in cannulating and treating disease processes without the benefits of an elevator and the side-viewing capability.

tomy is usually located along the dependent portion of the stomach. However, it may be slightly off to the anterior or posterior wall along the greater curvature (Figs 24.17A, 24.17B). While most anastomoses for bypass of obstructive diseases are expected to be large, some of these gastrojejunostomy openings appear to be quite small. Immediately through the rim of anastomosis two jejunal orifices will be found, and either opening can be the one that leads to the afferent limb. If it is the more distal orifice, then it is an antiperistaltic connection and the afferent limb is relatively short. But this distance becomes longer if the surgery is done in the antecolic fashion because the intestine has to drape over the transverse colon. This limb may become even longer if the gastrojejunostomy is created in the isoperistaltic manner. On some occasions a second anastomosis is noted beyond the gastrojejunostomy. This Braun procedure (Fig. 24.17B) is done to add further bypass of contents between the afferent and efferent limbs to reduce alkaline biliary reflux into the stomach or to provide a safety net to minimize the chance of an afferent limb obstruction. If the scope passes through a Braun anastomosis, it has a 50% chance of returning to the stomach via the other limb of the gastrojejunostomy. Since the major papilla is intact in this setting, a duodenoscope is preferred for ease of inspection and cannulation unless it is proven to be too short. In practice, reaching the descending duodenum is often not the key issue. Instead, inspection and cannulation is a bigger challenge because most of these cases have a highly stenotic duodenum that has led to the gastrojejunostomy. Fortunately, duodenal obstruction from pancreatic head cancer is frequently located proximal to the major papilla leaving sufficient room to carry out an ERCP. In the event of an inadequate space, balloon dilation of the duodenal stricture can be perform but the resultant mucosal trauma and hemorrhage may add even more obstacles to the procedure. A transhepatic approach to biliary drainage is frequently necessary in this situation. Alternatively a rendezvous procedure, in which a transhepatic catheter or guidewire is passed across the biliary sphincter, can be done for endoscopic access. There are occasions when the bypass surgery is done for gastroparesis and performing an ERCP in the usual antegrade fashion is preferred. In this situation the duodenoscope has to be slightly rotated, when gliding along the greater curvature, to skip around the gastrojejunostomy to reach the pylorus.

Duodenal bypass

UPPER GI BYPASS SURGERY WITHOUT RESECTION

Duodenal perforations are occasionally treated by a duodenojejunostomy. Even though this form of operation is uncommon, the finding of two or more intestinal lumens beyond the pylorus or at the descending duodenum may create confusion to the endoscopist. If there is no associated duodenal narrowing, the procedure is straightforward and the key is to carefully inspect each lumen until the major papilla is found. If a mildly to moderately stenotic duodenal lumen is found, gentle balloon dilation may be attempted to ease the scope passage. Alternatively, a pediatric ERCP scope with a 7.5 mm outer diameter and 2.0 mm instrument channel can be used. But the small endoscope channel allows only limited therapeutic possibilities such as sphincterotomy, basket stone extraction and placement of a 5-French stent.

Gastrojejunostomy

BARIATRIC SURGERY

The indications for gastrojejunostomy without resection of any part of the stomach include large pancreatic head mass, benign chronic duodenal obstruction and unresectable malignant duodenal stricture. When inspecting the stomach during ERCP, the gastrojejunos-

There are many forms of bariatric operations to induce weight reduction, but about 70% of them in the US are Roux-en-Y gastric bypass. Biliopancreatic diversion (12%), vertical banded gastroplasty (7%) 245

SECTION 2 TECHNIQUES

A

B

Fig. 24.17 A Gastric bypass with an anteriorly located gastrojejunostomy. B Gastric bypass with a posteriorly located gastrojejunostomy. Note a Braun procedure that connects the afferent and efferent jejunal limbs.

and gastric banding (5%) constitute the remaining practices of bariatric surgery today.15 Interestingly, morbidly obese patients are most likely to have bariatric surgery done in the northeastern United States than the rest of the country.16 As obesity affects more Americans, more weight-reduction operations are being performed. Since gallstone disease and abdominal pain are common issues in obese individuals, biliary and pancreatic evaluations are in increasing demand. At the same time, this group of patients are the most difficult to perform ERCP on because of the need to pass through the extremely long intestine to get to the proximal duodenum. Variation of techniques and surgeons’ preferences add further confusion to this difficult ERCP arena.

Malabsorptive-jejunoileal bypass This form of weight-reduction surgery is mentioned here primarily for the historical purpose. It is neither practiced today nor does it affect the performance of ERCP. Rarely, a consultation for ERCP may be requested for a patient with a prior jejunoileal bypass surgery because of jaundice. In this case, the cause of jaundice is more likely due to hepatic failure rather than biliary tract disease. This operation, popular prior to 1980, consists of transecting and connecting a large jejunoileal segment to the distal colon. Alternatively, the proximal jejunum is transected and connected to the distal ileum in an endto-side manner, excluding a long jejunum and ileum from contact 246

with intestinal nutrients (Fig. 24.18). The result of this form of operation is a very short functioning small bowel that causes weight loss by malabsorption and maldigestion. Chronic diarrhea, stone diseases and fatal liver dysfunction are reasons why all patients who have undergone this surgery should have a jejunoileal bypass reversed.17

Biliopancreatic diversion and duodenal switch There are two other forms of malabsorptive operations that are still practiced today. Metabolic complications are reportedly less often seen than in jejunoileal bypass. Both operations require resection of most of the stomach and connection of either the duodenum or the stomach remnant to the distal ileum (250 cm proximal to the ileocecal valve) (Figs 24.19A, 24.19B). The excluded block of duodenumjejunum-ileum is then hooked up to the distal ileum at around 100 cm proximal to the ileocecal valve. ERCP is not a possibility whether it is biliopancreatic bypass or duodenal switch because the descending duodenum can only be reached by passing through most of the small intestine.

Restrictive surgery There are two forms of this operation that aim to restrict food intake by creating a mere 15 ml proximal gastric pouch and a small pouch outlet of roughly 1 cm in diameter. Vertical band gastroplasty,

Chapter 24 ERCP in Surgically Altered Anatomy

Fig. 24.18 Jejunoileal bypass. This surgery does not interfere with the performance of ERCP.

popular in 1980s, consists of cutting off the fundus with staples and limiting the pouch outlet with a 5 cm circumferential Marlex band17 (Fig. 24.20A). A more modern alternative is the laparoscopic adjustable gastric banding procedure, done with placement of a silicone band that wraps around the gastric cardia (Fig. 24.20B). Tightness of this band can be modified following surgery by inserting a needle into a reservoir embedded in the abdominal wall. Restrictive gastric surgery is easily recognized endoscopically because of the tiny gastric pouch that leads to a small firm outlet that barely allows the passage of an upper endoscope. The channel length is usually only 1–2 cm. If this surgery is suspected in advance of the ERCP, it is best to start the procedure with a standard upper endoscope to inspect the tightness of the outlet. If difficulty passing a duodenoscope is anticipated, then dilating the ring outlet with a 13.5 mm balloon can be safely done. Once the duodenoscope has reached the distal stomach, no special technique is needed to accomplish an ERCP procedure. In patients who have regained their weight after a vertical band gastro-

plasty, their stomachs may appear normal with minimal evidence of any restriction or have two outlets from the pouch that lead to the rest of the stomach. This loss of physical restriction is either due to breakage of the gastric band or development of a gastric pouchgastric fundus fistula.

Gastric bypass This is the most commonly done surgical procedure to induce weight reduction today. It works by both restricting food intake with a small (9 mm and >10 mm at 5 years postcholecystectomy.16 Though most patients have minor if any dilation post-cholecystectomy, there are clearly those that may manifest a more profound asymptomatic dilation of the ducts. Variation of normal extrahepatic bile duct size due to extrinsic factors such as time of day, respiration, or patient positioning, have all been shown to affect the caliber of the CBD.18–20 Given all the possible circumstances that may affect the measurement of the extrahepatic biliary system, it is difficult to define an absolute measurement that will by itself yield satisfactory predictive values for obstruction as a cause of duct dilation. Instead, the duct diameter should be interpreted in the context of potential causes of obstructive biliary dilation so that any pertinent findings from the clinical 263

SECTION 3 APPROACH TO CLINICAL PROBLEMS

Fig. 25.1 Transabdominal ultrasound examination demonstrating intrahepatic ductal dilation (arrowheads).

Fig. 25.3 Abdominal CT demonstrating a dilated CBD (arrow) in a patient with choledocholithiasis.

without evidence of an obstructing lesion (Fig. 25.4).23 These numbers are similar to other studies that have demonstrated the general results in order of decreasing prevalence: choledocholithiasis, pancreatic cancer, ampullary carcinoma, and cholangiocarcinoma as causes of biliary dilation.6 Assessing the a priori likelihood of a particular disease given the clinical scenario should influence the choice of the subsequent diagnostic evaluation.

EVALUATION

Fig. 25.2 Transabdominal ultrasound examination demonstrating a dilated CBD (arrowheads) and dilated CHD (arrows).

presentation or biochemical tests may be considered in the decision to pursue further diagnostic evaluation.

ETIOLOGY Identifying the level of biliary obstruction is important in developing a differential diagnosis. Common causes of obstruction include both neoplastic and benign causes such as choledocholithiasis (Table 25.1).1,21,22 Less common in the United States, but more common worldwide would be infectious etiologies such as parasitic disease. A study on the use of EUS in the evaluation of a dilated biliary tree in 90 patients with an unrevealing abdominal US found 40 patients with choledocholithiasis, 13 with tumor, 8 with benign stricture, 2 choledochal cysts, 1 with infection with ascaris, and 24 dilated ducts 264

Though there is a strong correlation between a dilated bile duct and the presence of an obstruction, as previously discussed, there is a broad interpretation of what is considered dilated. Many of the techniques used for biliary imaging are based on anatomic measurements and are not a functional demonstration of flow within the ducts as may be evident on cholangiography or scintigraphy. It is therefore important that decisions to proceed with further evaluation include both a clinical and biochemical assessment for obstruction in addition to consideration of the initial imaging results (Fig. 25.5).

Clinical evaluation The clinical presentation should be assessed for any signs or symptoms relating to biliary obstruction or its cause. For example, the history should elicit any symptoms such as abdominal pain, fever, weight loss, jaundice, pruritus, acholic stools, dark urine, or steatorrhea. The physical exam may be limited in its utility, but special attention should be paid to the presence of an abdominal tenderness or mass, hepatomegaly, jaundice, or lymphadenopathy. A positive history or physical examination may serve to lower the threshold for further diagnostic evaluation in those patients with an equivocal duct size on initial imaging. In the era of laparoscopic cholecystectomy, studies have attempted to develop models of these clinical

Chapter 25 Dilated Bile Duct

SITES OF BILIARY OBSTRUCTION Intrahepatic

Porta hepatis

Suprapancreatic

Intrapancreatic

Primary sclerosing cholangitis Space occupying liver lesion

Cholangiocarcinoma

Pancreatic carcinoma

Pancreatic carcinoma

Primary sclerosing cholangitis Gallbladder carcinoma Hepatocellular carcinoma

Cholangiocarcinoma Metastatic disease Direct extension of gastric/colon/ gallbladder Carcinoma Pancreatitis

Pancreatitis Choledocholithiasis Ampullary stenosis/carcinoma

Malignant lymph nodes Liver metastases

Duodenal carcinoma Cholangiocarcinoma

Table 25.1 Common obstructive causes of biliary dilation

Fig. 25.4 Radial EUS examination demonstrating a longitudinal view of a dilated CBD (arrows).

features in addition to biochemical values to predict choledocholithiasis prior to surgery. Some of these studies have demonstrated an increased likelihood for choledocholithiasis with jaundice or fever at presentation, acholic stools, dark urine, or an older patient age.24–27 However, it is difficult to draw a clear conclusion from these studies as they differ in methodology and results.

Biochemical evaluation Integral to the biochemical evaluation of obstruction are the bilirubin and liver associated enzymes (LAEs), commonly referred to as liver function tests. These generally include alkaline phosphatase (AP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). The principal markers of cholestasis are bilirubin and AP.28–30 The total bilirubin present in the serum represents a balance between input from production and hepatobiliary removal. In obstructive jaundice, the serum bilirubin is principally in the conjugated form (water soluble). Hepatobiliary AP is present on the apical membrane of the hepatocyte and in the luminal bile duct epithelium. Increases in AP result from increased synthesis and release into the serum. As a result, levels may not rise until one to two days after biliary obstruction occurs. In addition, the enzyme has a half-life of a week and the

level may therefore remain elevated for several days even after the resolution of biliary obstruction. Levels of AP up to three times normal are relatively nonspecific and occur in a variety of liver diseases. However, higher elevations are more specific for biliary obstruction (intra- or extrahepatic) and infiltrating liver diseases. As AP can be produced in sources outside of the liver, it may be necessary in certain instances to use other biochemical tests such as the AP isoenzymes or the gamma-glutamyl transpeptidase or 5’-nucleotidase to confirm the hepatobiliary etiology of an elevated AP. The serum aminotransferases include AST and ALT. Transient elevations occurring rapidly (within one to two days) and with levels into the thousands may occur in acute CBD obstruction, from trauma or more commonly from choledocholithiasis, Subsequent levels rapidly decline.28–30 Aminotransferase levels may also rise from other subacute or chronic obstructions but typically remain less than 500 IU/dl. It is difficult to interpret the predictive models using these markers in evaluating obstruction from choledocholithiasis as the results vary among studies.24–27 In general, there is increased likelihood for stones with abnormalities in bilirubin, AP, and transaminase levels. With these studies in mind, one can predict that it would be unusual for a lesion to cause biliary obstruction and dilation without clinical or biochemical abnormality. This is not universal, however, and there have been case reports of patients with normal LAEs despite having dilated ducts and choledocholithiasis.31

Imaging Imaging of the biliary tract continues to evolve with the enhancement of non-invasive techniques for cross-sectional evaluation and biliary reconstruction. There are numerous radiographic and invasive modalities now available to the clinician to image the anatomy of the biliary system. These include US, CT and CT cholangiography, magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP), EUS, and ERCP. Each has advantages and disadvantages as well as limitations in the evaluation of the biliary system. The goal of any radiologic procedure evaluating the dilated bile duct is to confirm the presence of obstruction and to define its location, extent, and cause.

Ultrasound US is often the first line imaging technique in the evaluation of the bile ducts, gallbladder and right upper quadrant and is usually the test initially demonstrating dilation of the bile ducts. US is noninvasive, inexpensive and is a quick procedure that may be done at the bedside. It does, however, require experience in technique and interpretation and may be limited due to interference from gas 265

SECTION 3 APPROACH TO CLINICAL PROBLEMS

External bile duct diameter

Initial imaging

Ultrasound MRI

CT/Cholangiogram

Bile duct measurement 10 mm

Biochemical/ clinical assessment (–) No further evaluation indicated.

Fig. 25.5

(+) Indeterminate, obstruction possible. Follow labs and imaging.

(–) Indeterminate, consider patient characteristics such as age or cholecystectomy.

(+) Further evaluation indicated.

No further evaluation indicated.

(+) Indeterminate, obstruction possible. Follow labs and imaging.

(–) Indeterminate, consider patient characteristics such as age or cholecystectomy.

(+) Further evaluation indicated.

Algorithm for assessment of the external bile ducts for obstruction.

within the surrounding bowel. US has been shown to be one of the most accurate imaging studies in the evaluation of cholelithiasis with both a sensitivity and specificity of up to 99%.4,32–34 It is also highly sensitive for detecting dilation of the biliary tree as a whole with a sensitivity greater than 90%.4,35 The ability of ultrasound to define the site and cause of biliary obstruction is slightly less reliable. A review of the literature with more than 700 patients demonstrated that ultrasound has a sensitivity of 71% in delineating the level of obstruction, a sensitivity of 57% in defining the etiology, and a sensitivity for choledocholithiasis of 32%.32 However, there is great variation with sensitivities ranging from 27% to 95% for the correct level of obstruction and 23–81% for the correct cause of obstruction.36–39 Some of this limitation may result from a relative inability to image the distal CBD due to bowel gas. This area is well visualized in only 40–50% of patients.4 Clearly the ease of use, widespread availability, and few contraindications place US early on the algorithm for evaluation of the biliary tract or abdominal pain, but it typically leads to further studies as it is often inconclusive and does not provide adequate staging or surgical information in the setting of suspected neoplasms.

Computed tomography Similar to ultrasound, abdominal CT may be the initial test demonstrating dilation of the bile ducts or can also be considered as a test to further evaluate suspected biliary pathology. Multidetector CT can obtain images at thin 1.25–2.5 mm intervals that can be reformatted with high resolution into views to reproduce the biliary tree.1,40,41 This, in conjunction with careful review of axial images, can provide a complete evaluation of the bile ducts. Infusion of intravenous contrast agents is necessary to provide vascular landmarks and organ opacification maximizing the visualization of the bile ducts.40 Unenhanced scans can highlight the presence of calcifications and aid in visualization of choledocholi266

(–)

thiasis. Water is often used as an oral contrast agent when biliary tract abnormalities are suspected so as not to obscure potential pathology at the level of the ampulla of Vater.40 CT cholangiography has been evaluated in the United States and is used extensively in Asia and Europe. This employs the administration of IV contrast material to highlight the biliary tree. The fact that obstruction limits contrast excretion into the bile ducts and the higher incidence of adverse reactions to the contrast agents has limited the role of CT cholangiography.42 However, with new contrast agents and multidetector CT this may be the preferred imaging technique in the future. In a study evaluating the presence of biliary obstruction, defined as extrahepatic bile duct diameter >8 mm, the sensitivity and specificity of CT for diagnosing dilated ducts was 96% and 91% respectively.40 CT is also accurate at defining the level of obstruction in 88–97% of cases as well as the cause of obstruction in 70–95% of cases.39,40,43,44 Though CT is a readily available test that can accurately identify a dilated CBD as well as provide important details as to the level and cause of obstruction, there are limitations as well. It requires intravenous contrast to optimize the images, which may lead to adverse reactions including potential nephrotoxicity. CT also lacks sensitivity for a common cause of obstruction, choledocholithiasis, which is likely responsible for the lower rates of detection of the etiology of obstruction; approximately 20–25% of biliary stones are isoattenuating with bile making them difficult to detect on CT.1,40 Sensitivity of CT for choledocholithiasis ranges from 70% to 94% depending on the use of indirect signs of obstruction that typically coincide with choledocholithiasis.1,45,46

Magnetic resonance imaging Since it was first introduced in 1991, MRCP has gained popularity as a non-invasive imaging modality of the biliary system. MRCP

Chapter 25 Dilated Bile Duct

Fig. 25.6 MRCP image demonstrating markedly dilated bile ducts proximal to a Klatskin-type bile duct tumor.

Fig. 25.7

exploits the differences between fluid filled structures in the abdomen and adjacent soft tissues. The static or slow-moving fluid within the pancreatic and biliary system produces a different signal than solid tissue.21,22 Images can be obtained without use of IV contrast and are routinely performed in the axial and coronal planes. MRCP has a high accuracy in detecting the level and cause of biliary obstruction (Fig. 25.6). It has been shown to have a sensitivity of 91–97% and specificity of up to 99% for the diagnosis of biliary obstruction.47–49 Unlike US and CT, which can be limited in their ability to correctly identify the level and etiology of an obstructed biliary system, MRCP can more accurately define these parameters, similar to the use of direct cholangiography. The level of obstruction can be determined with MRCP in 87–98% of cases.47,48,50,51 The etiology of obstruction was determined in roughly 84% of cases with a malignant process and 94% in cases of a benign process.47,48 This was corroborated by a large meta-analysis demonstrating a sensitivity and specificity of MRCP of 92% and 97% respectively for cholelithiasis and 88% and 95% respectively for malignant causes (Fig. 25.7).47 However, the reported accuracy in discerning benign from malignant obstruction has varied from 30% to 98% across studies, with a mean accuracy of 88% reported in the meta-analysis. Addition of conventional T1 and T2 weighted images to MRCP allows for evaluation of extraductal soft tissue increasing the diagnostic accuracy by demonstrating tumor extension, lymph nodes, or metastatic disease.51,52 In one study, this increased the sensitivity, specificity, and accuracy 17–20% for differentiation of benign and malignant causes of biliary obstruction.53 This, however, comes with increased cost and time of exam. The major advantages of MRCP over other imaging techniques include the avoidance of invasive procedures, IV contrast, ionizing radiation, and the ability to visualize the biliary system above and below an obstruction. MRCP does have limitations. Its non-invasive nature means an inability to perform therapeutic intervention. Tech-

nical and interpretive difficulties can simulate or miss pathologic conditions of the biliary system. Static images demonstrating a contraction on the distal CBD can simulate a stenosis for example.54 Other drawbacks include the high cost of the test, extended time to perform an exam leading to patient intolerance, and contraindications such as magnetic objects.

MRCP demonstrating choledocholithiasis (arrow).

Endoscopic ultrasound EUS has emerged as a significant advance in gastrointestinal endoscopy since its introduction in 1987. It allows for both diagnostic evaluation of the pancreaticobiliary system with high resolution images as well as for therapeutic procedures. EUS is performed utilizing a specialized endoscope with a radial or linear ultrasound transducer at the tip.55,56 Images of the biliary system are obtained from transgastric or transduodenal locations. Unlike transabdominal ultrasound, EUS allows for better visualization of the extrahepatic biliary tree without interference of bowel gas as the CBD passes posterior to the duodenal bulb. Additionally, EUS offers accurate and systematic visualization of the wall of the duodenum including the papillary region (Fig. 25.8). EUS has been studied extensively in a variety of disorders that can lead to dilation of the CBD. In the setting of choledocholithiasis, EUS has consistently demonstrated sensitivities of >90% and specificities up to 100%.57–59 EUS may be particularly useful for detecting microlithiasis (stones 2.0 cm and for ampullary neuroendocrine

Carcinoma Carcinoma of the ampulla can be classified histopathologically and immunohistochemically as either an intestinal or pancreaticobiliary

FAP HNPCC Neurofibromatosis type 1 Muir-Torre syndrome

Table 26.2 Cancer syndromes associated with ampullary carcinoma • Hereditary nonpolyposis colorectal carcinoma (HNPCC) is weakly associated with ampullary carcinoma. • Neurofibromatosis seems to be a predisposition of both somatostatinomas and carcinomas of the ampulla of Vater. • Muir-Torre syndrome is a condition characterized by the association of multiple sebaceous tumors and kerato-acanthomas with internal malignancies, including ampullary carcinomas.

Fig. 26.6

Carcinoid at the papilla. 277

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A

B

C

D

A

B

Fig. 26.8 Metastasis of a melanoma to Vater’s ampulla. A Patient with a history of a melanoma was admitted because of cholangitis. ERCP showed a bulging papilla. B Easy bleeding during cannulation. Endoscopic ultrasound-guided fine-needle aspiration biopsy confirmed the suspicion of a metastasis of melanoma.

Benign disease

Fig. 26.7 Periampullary gangliocytic paraganglioma. A Large, stalked polyp. B Indentification of the orifice of the papilla. C Cannulation. D Snare resection just under the papilla, after placing an “endoloop.”

carcinomas.40 Local surgical, or endoscopic resection can be considered for smaller carcinoids without evidence of metastases. Generally, the prognosis of ampullary carcinoids after resection is good, with a five-year survival period of 90%.40 Poorly differentiated neuroendocrine carcinomas have an aggressive clinical behaviour, however, with early metastases, and often, a fatal outcome.

Lymphoma

Lymphomas of the biliary system are rare, but should be considered in the differential diagnosis of malignant strictures of the common bile duct. The ampulla is even more rarely the site of origin of these tumors. Four types of primary lymphomas of the ampulla of Vater have been described: • Primary ampullary MALT lymphoma arise from the mucosaassociated lymphoid tissue of the duodenum. Similar to MALT lymphomas in the stomach, ampullary MALT lymphomas are sometimes controlled by eradication of Helicobacter pylori. In other cases, tumor regression is accomplished only with more aggressive forms of therapy, such as radio- or chemotherapy.41 • Diffuse largeB-cell lymphoma. Together with MALT lymphomas, diffuse large B-cell lymphomas seem to be the most prevalent lymphomas in the periampullary region. Their absolute incidence is low, however.42 • Follicular lymphomas are infrequently limited to the ampulla. Surgery can be avoided, if a proper diagnosis is made before operation, as chemotherapy is reported to be effective.43 • T-cell lymphomas very rarely infiltrate the sphincter of Oddi and cause jaundice.44 Association with celiac sprue has been described. 278

Adenoma Carcinoid GIST Lipoma Leiomyoma Hamartoma (Peutz-Jeghers polyp) Schwannoma Lymphangioma Hemangioma Fibroma Neurofibroma Granular cell tumor Adenomyoma Eosinophilic gastroenteritis Duodenal duplication Choledochocele Heterotopic pancreas Heterotopic gastric mucosa Brunner’s gland hyperplasia Inflammatory nonneoplastic lesions: odditis/papillitis (e.g. due to lithiasis) Large, but normal variant ampulla

Table 26.3 Differential diagnosis of tumors and pseudotumors of the ampulla of Vater

Gastrointestinal stromal tumor (GIST) There are few reports of gastrointestinal stromal tumors of the ampulla. Most patients have been treated with a pancreaticoduodenectomy. Treatment with imatinib mesylate has shown to improve outcome in unresectable, metastatic or recurrent disease.45,46

Metastasis Metastasis to the ampulla is extremely unusual. It may arise from a variety of primary lesions including renal cell carcinomas, melanomas, and ovarian-, breast-, esophagus- and larynx cancer (Fig. 26.8).47

Miscellaneous The ampulla of Vater can harbour a variety of other neoplasms, and an extended overview is given in Tables 26.3 and 26.4.

Chapter 26 Ampullary Neoplasm

Malignant disease (Adeno)carcinomaa Neuroendocrine carcinoma Malignant GIST Lymphoma Pancreatoblastoma Leiomyosarcoma Neurofibrosarcoma Kaposi sarcoma Angiosarcoma Malignant schwannoma Rhabdomyosarcoma (only described in children) Metastasis to the ampulla

Table 26.4 Differential diagnosis of malignant tumors and pseudotumors of the ampulla of Vater a

• Mixed cellular populations of carcinoma have been described, such as: ° Sarcomatoid carcinomas, an intermixture of carcinomatous and sarcomatous elements. ° Adenocarcinoid tumors, an intermixture of adenocarcinoma and carcinoid tumor • Ampullary carcinomas with unusual patterns of differentiation, such as papillary carcinomas, Paneth cell carcinomas and signet-ring cell carcinomas are also included.

Points

1

2

3

Polyp number Polyp size (mm) Histology Dysplasia

1–4 1–4 Tubular Mild

5–20 5–10 Tubulovillous Moderate

>20 >10 Villous Severe

Table 26.5 Staging system for the severity of duodenal polyposis in FAP: the Spigelman classification (Reproduced from reference no. 49 with permission.)

effectively prevents cancer, it is questionable whether all stage IV patients should be exposed to this procedure in view of its considerable morbidity, and mortality.52 An alternative would be to follow these patients regularly with upper endoscopy. Unfortunately, endoscopic surveillance seems not to detect all carcinomas, as has been shown in the study by Björk et al.51 This was potentially related to the use of forward-viewing, rather than forward- and side-viewing endoscopes. Alternatively, endoscopic biopsies may not have been sensitive enough, or disease may have progressed rapidly between screening intervals. In spite of these limitations, upper gastrointestinal endoscopic surveillance is recommended for all FAP patients, with special attention for the periampullary region. Adenomas of the major duodenal papilla are more likely to undergo malignant transformation than an adenoma arising elsewhere in the duodenum, reflecting the fact that the occurrence of dyplasia in the periampullary region has been reported to be as high as 66–74%.27,34,49 Surveillance intervals of 3 years are recommended by experts for less severe disease; those with stage IV disease should be examined every 6 months to 1 year.53 Biopsies should be taken routinely, also from normal appearing papillae, as a normal appearing papilla can harbour an adenoma in more than 50% of cases (Fig. 26.2A).34 The role of endoscopic treatment of ampullary lesions in FAP is not yet clearly defined. Randomized trials of the different surgical and endoscopic modalities are lacking. Endoscopic therapy has not been studied in large prospective studies yet, but the available literature on this subject seems promising.13,54 Endoscopic treatment of (peri) ampullary lesions in FAP does not differ from therapy for “sporadic” ampullary lesions, although one should take into account that recurrence of adenomas is more common in FAP patients.13

TREATMENT

0 points = Stage 0; 1–4 = Stage I; 5–6 = Stage II; 7–8 = Stage III; 9–12 = Stage IV

Familial adenomatous polyposis (FAP) FAP syndrome and its variants (Gardner’s syndrome and Turcot syndrome) afflict approximately 1 in 20 000 people (data from Denmark).48 Duodenal cancer, mainly in a (peri) ampullary location, is the leading cause of cancer death in patients with FAP who have undergone prophylactic colectomy.48 Patients with FAP have a cumulative lifetime risk of over 90% for developing duodenal adenomas, and a lifetime risk of 4–10% for developing periampullary or duodenal adenocarcinoma.48–51 The risk of adenocarcinoma of the major duodenal papilla has been estimated to be greater than 100 times that of the general population.50 In an attempt to prevent cancer, screening programmes have been developed using a welldefined staging system to detect those patients most at risk, as shown in Table 26.5. Patients with stage IV disease have a 10–30 times higher chance of developing carcinoma, as compared to patients at a lower stage.51,52 How to treat patients with Spigelman stage IV remains controversial. Around 25% of patients with stage IV periampullary adenomas developed cancer in a large Scandinavian study.51 It is our impression however, that the use of current high resolution endoscopes and chromoendoscopy leads to upstaging of patients in the Spigelman classification. This upstaging will probably diminish the cancer risk in stage Spigelman IV. Although (pancreatico) duodenectomy

Optimal therapy results in a radical excision of all neoplastic tissue, minimizes the chance of recurrence, and has an acceptable procedure-related morbidity and mortality.

Adenomas Pancreaticoduodenotomy has been the traditional treatment of ampullary adenomas for years. This procedure effectively eliminates all adenomatous tissue, but has been associated with considerable morbidity (25–65%), and with mortality (0–10%). Two strategies have been developed to diminish complications: transduodenal local surgical resection (surgical ampullectomy) and endoscopic therapy. Postoperative morbidity is definitely lower with local surgical resection (0–25%), and mortality is low to absent (0–5%), but recurrence of adenomas occurs in 5–30% of operated patients. Endoscopic surveillance is therefore indicated after this type of surgery.12,55,56 Since 1983, reports have been published on the endoscopic treatment of ampullary adenomas, using snare resection and laser photocoagulation.57–59 Later, with the results of snare removal of the entire ampulla as a single specimen, described by Binmoeller, it became clear that endoscopic snare resection in selected patients provides an excellent alternative to traditional surgery (Figs 26.9 and 26.10) (for indications, see Chapter 19).60 Controlled studies comparing endoscopic and surgical strategies have not (yet) been conducted. The published reports on this subject are case series from surgical and endoscopic centers, and vary considerably in 279

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A

B

A

B

C

D

C

D

Fig. 26.9 En bloc resection of a tubulovillous adenoma. A Periampullary polypoid mass. B Indentification and cannulation of the papilla. C Snare resection. D Result after ampullectomy, and sphincterotomy of the common bile duct.

Fig. 26.10 Piecemeal resection of a large tubulovillous adenoma. A Large polyp with orifice of the papilla on top. B Twisted stalk. C Piecemeal resection. D Result after two months.

100 90 80 70 Survival (%)

patient selection and demographics, thus making comparison difficult. Table 26.6 summarizes the literature on endoscopic therapy. The choice on how to treat ampullary adenomas is highly dependent on local expertise. In our opinion, because of its favourable outcome, its low morbidity and absent mortality in most case series, endoscopic snare resection as the initial treatment is justified in centers with experience in this type of endoscopic interventions. An additional advantage is that this treatment can be performed on an outpatient basis.

Carcinomas Standard surgical management of invasive ampullary carcinoma is resection by pancreaticoduodenectomy. Local surgical therapy for pT1 carcinoma is questionable, as the resection is often limited,61 and a reduced survival has been reported compared to pancreaticoduodenectomy.62 Conversion to pancreaticoduodenectomy is indicated when pathological examination of an ampullectomy specimen identifies invasive carcinoma. The subsequent operation does not seem to increase morbidity when compared to initial pancreaticoduodenectomy.63 For high grade dyplasia/carcinoma in situ, radically removed endoscopically or with local surgical excision, there is insufficient evidence that a subsequent operation (i.e. lymphadenectomy) is beneficial. Lymph node metastasis in such cases seems to be absent.64 A “wait and see” policy may be justified, but opinions are divided on this issue. Survival after resection in a relatively recent, large, single center study is summarized in Figure 26.11. Operative mortality has diminished over time, with no postoperative death in this and in other studies.2 Factors predictive of improved survival in ampullary carci280

60 50 40 30 20

T1 T2 T3

10 0

No. at risk T1 T2 T3

0

24 30 12 18 Time after resection (months)

6

18 32 20

17 30 17

17 28 12

15 24 11

13 23 11

12 18 8

36

11 16 5

42

10 18

Fig. 26.11 Survival curves for 70 patients after resection of ampullary carcinoma, stratified by tumor stage. Patients with T3 tumors had poorer survival than those with T1 or T2 disease (P = 0.05). (Redrawn from reference no. 2 with the permission of John Wiley & Sons Ltd on behalf of the British Journal of Surgery Society Ltd.)

2005

2005

2005

Harewood

Bohnacker

Han

Retrospective Prospective

Prospective

Retrospective

n = 14

n = 19

n = 106 (109 lesionsb)

n = 22

0

0

Intraductal growth

Snare excision

0

Snare excision 31 and/or electrocoagulation

Snare excision (RCT of prophylactic pancreatic stent placement)

Snare excision

Retrospective/ Prospective Technique

b

Median number of 3 therapeutic sessions to achieve complete destruction of adenomatous tissue. Synchronous tumors of the major and minor papillae.

a

Table 26.6 Summary of the literature on endoscopic resection of ampullary tumors

2006

Number of Year of patients publication included

Katsinelos

First author

NR: Not reported

Bleeding 5%, perforation 5%, papillary stenosis 5%, cholangitis 5%, cholestasis 5%

Pancreatitis 12%, bleeding 3%

Pancreatitis 33% without pd stent, vs 0% with pd stent. Cholestasis 5%

Pancreatitis 7%, bleeding 7%

Complications

NR

NR

28 79% months

15 adenoma 8 86% (3 with months HGD), 2 carcinoma, 1 carcinoid, 3 inflammatory lesion, 1 lymphangioma

NR

19%

NR

21%

5%

18%

NR

18%

Complete Follow- endoscopic up resection Surgery Recurrence

92 adenoma 43 73% (18 with months HGD), 4 carcinoma, 12 inflammatory lesion, 1 lymphangioma

NR

11 adenoma, 3 carcinoma

Histology

Recurrence: recurrence of adenoma (or adenocarcinoma) after complete endoscopic resection (patients lost to follow-up are excluded).

Surgery (percentage per total number of patients) includes the need of surgery for malignant disease, for persistent adenoma, for complications, and for recurrences that could not be treated endoscopically.

Complete endoscopic resection (percentage per total number of patients): total clearance of adenoma in one or more treatment sessions, without the need for surgery (this includes recurrences that could be treated endoscopically).

Complication rate (percentage per total number of patients): Only clinically evident bleeding that occurred after completion of the procedure was regarded as a complication. Pancreatitis and perforation were managed conservatively in the majority of patients.

Inclusion: Studies published from 1990, and with more than 5 patients included, on endoscopic treatment of ampullary tumors with benign features.

Chapter 26 Ampullary Neoplasm

281

282

2004

2004

2003

2002

2001

2001

2000

2000

1993

Cheng

Catalano

Saurin

Norton

Desilets

Zádarová

Vogt

Park

Binmoeller

Table 26.6 Continued

2005

Moon

Prospective

Retrospective

Retrospective

Retrospective

Retrospective

Retrospective Retrospective Retrospective Retrospective Prospective

n=6

n = 55

n = 103

n = 24

n = 26 (28 lesionsb)

n = 13

n = 16

n = 18

n=6

n = 25 Snare excision

Snare excision

Snare excision

Snare excision

Snare excision (piecemeal)a

Snare excision

Mainly laser photodestructiona

Snare excision

Snare excision (wire-guided endoscopic papillectomy).

2

NR

NR

NR

0

0

0

0

6

0

13 adenoma (1 with HGD)

25 adenoma, 1 carcinoma, 1 inflammatory lesion, 1 normal histology

Pancreatitis 12%, bleeding 8%

25 adenoma (1 with HGD)

4 adenoma, 2 carcinoma

Pancreatitis 11%, bleeding 11%, 18 adenoma stent dysfunction 6% Pancreatitis 33%

36 80% months

30 74% months

7 100% months

100%

37 92% months

21 67% months

75 100% months

NR

19 92% months

9 96% months

Forcepsbiopsies: 81 67% 24 months adenoma (10 with HGD)

97 adenoma (14 with HGD), 6 carcinoma

45 adenoma (7 with HGD), 5 carcinoma, 2 carcinoid, 1 gastric heterotopia, 2 normal histology

6 adenoma (1 with HGD)

Pancreatitis 13%, bleeding 13% 16 adenoma

Pancreatitis 8%

Pancreatitis 15%, perforation 4%, pancreatic duct stenosis 8%

Pancreatitis 17%, bleeding 13%, perforation 4%

Pancreatitis 5%, bleeding 2%, papillary stenosis 3%

Pancreatitis 9%, bleeding 7%, perforation 2%

Late onset pancreatitis 17%, cholangitis 17%

12%

17%

17%

6%

8%

4%

17%

16%

13%

0%

26%

0%

44%

19%

0%

10%

6%

20%

33%

0%

SECTION 3 APPROACH TO CLINICAL PROBLEMS

Chapter 26 Ampullary Neoplasm

noma vary per study, and include resectability, negative margins (R0 resection), negative lymph nodes, differentiation of the tumor, and absence of pancreatic, vascular and perineural invasion.2,61 Palliative treatment for ampullary carcinoma can consist of a local resection in very frail patients with a small, pT1 tumor.64 Literature on endoscopic resection of this kind of tumor is only anecdotal.65 Furthermore, biliary- or pancreatic drainage can be achieved with ERCP by placing an endoprosthesis or by papillotomy. In case of duodenal obstruction an expandable metal stent can be placed endoscopically to palliate the gastric outlet obstruction.

varies between a local endoscopic resection in case of a benign lesion, and a radical surgical pancreaticoduodenectomy for malignant disease. The diagnostic work-up of ampullary lesions is challenging. A high index of suspicion together with careful endoscopic examination of the papilla are crucial for early detection. CT-scan and endoscopic ultrasonography are usually necessary to decide on the optimal treatment for the individual patient. Ampullary tumors are typically lesions that require close cooperation of a multidisciplinary team consisting of a gastroenterologist, radiologist, surgeon and pathologist.

CONCLUSIONS Ampullary tumors are rare lesions, but of interest. Their prognosis is generally better than that of pancreatic tumors and their treatment

REFERENCES 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

Urbach DR, Swanstrom LL, Khajanchee YS, et al. Incidence of cancer of the pancreas, extrahepatic bile duct and ampulla of Vater in the United States, before and after the introduction of laparoscopic cholecystectomy. Am J Surg 2001; 181(6): 526–528. Bettschart V, Rahman MQ, Engelken FJ, et al. Presentation, treatment and outcome in patients with ampullary tumours. Br J Surg 2004; 91(12):1600–1607. Cheng CL, Sherman S, Fogel EL, et al. Endoscopic snare papillectomy for tumors of the duodenal papillae. Gastrointest Endosc 2004; 60(5):757–764. Nowak A, Botdys H, Marek T, et al. Unusual cause of severe upper gastrointestinal hemorrhage treated using a simple endoloop technique. Endoscopy 2001; 33(8):733. Kau SY, Shyr YM, Su CH, et al. Diagnostic and prognostic values of CA 19-9 and CEA in periampullary cancers. J Am Coll Surg 1999; 188(4):415–420. Van Heek NT, Maitra A, Koopmann J, et al. Gene expression profiling identifies markers of ampullary adenocarcinoma. Cancer Biol Ther 2004; 3(7):651–656. Ponchon T, Berger F, Chavaillon A, et al. Contribution of endoscopy to diagnosis and treatment of tumors of the ampulla of Vater. Cancer 1989; 64(1):161–167. Kahaleh M, Shami VM, Brock A, et al. Factors predictive of malignancy and endoscopic resectability in ampullary neoplasia. Am J Gastroenterol 2004; 99(12):2335–2339. Napoléon B, Pialat J, Saurin JC, et al. Adenomas and adenocarcinomas of the ampulla of Vater: endoscopic therapy. Gastroenterol Clin Biol 2004; 28(4):385–392. Bohnacker S, Seitz U, Nguyen D, et al. Endoscopic resection of benign tumors of the duodenal papilla without and with intraductal growth. Gastrointest Endosc 2005; 62(4):551–560. Yamaguchi K, Enjoji M, Kitamura K. Endoscopic biopsy has limited accuracy in diagnosis of ampullary tumors. Gastrointest Endosc 1990; 36(6):588–592. Cahen DL, Fockens P, de Wit LT, et al. Local resection or pancreaticoduodenectomy for villous adenoma of the ampulla of Vater diagnosed before operation. Br J Surg 1997; 84(7):948–951.

13. Catalano MF, Linder JD, Chak A, et al. Endoscopic management of adenoma of the major duodenal papilla. Gastrointest Endosc 2004; 59(2):225–232. 14. Bourgeois N, Dunham F, Verhest A, et al. Endoscopic biopsies of the papilla of Vater at the time of endoscopic sphincterotomy: difficulties in interpretation. Gastrointest Endosc 1984; 30(3):163–166. 15. Defrain C, Chang CY, Srikureja W, et al. Cytologic features and diagnostic pitfalls of primary ampullary tumors by endoscopic ultrasound-guided fine-needle aspiration biopsy. Cancer 2005; 105(5):289–297. 16. Skordilis P, Mouzas IA, Dimoulios PD, et al. Is endosonography an effective method for detection and local staging of the ampullary carcinoma? A prospective study. BMC Surg 2002; 25; 2:1. 17. Menzel J, Hoepffner N, Sulkowski U, et al. Polypoid tumors of the major duodenal papilla: preoperative staging with intraductal US, EUS, and CT—a prospective, histopathologically controlled study. Gastrointest Endosc 1999; 49(3):349–357. 18. Chen CH, Tseng LJ, Yang CC, et al. The accuracy of endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, computed tomography, and transabdominal ultrasound in the detection and staging of primary ampullary tumors. Hepatogastroenterology 2001; 48(42):1750–1753. 19. Schwarz M, Pauls S, Sokiranski R, et al. Is a preoperative multidiagnostic approach to predict surgical resectability of periampullary tumors still effective? Am J Surg 2001; 182(3):243–249. 20. Andersson M, Kostic S, Johansson M, et al. MRI combined with MR cholangiopancreatography versus helical CT in the evaluation of patients with suspected periampullary tumors: a prospective comparative study. Acta Radiol 2005; 46(1): 16–27. 21. Will U, Meyer F, Erhardt C, et al. Correlation of differential diagnosis between inflammatory and malignant lesions of the papilla of Vater using endosonography with results of histologic investigation [Abstract]. Gastroenterology 2003; 124 (suppl 1) A 440. 283

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22. Cannon ME, Carpenter SL, Elta GH, et al. EUS compared with CT, magnetic resonance imaging, and angiography and the influence of biliary stenting on staging accuracy of ampullary neoplasms. Gastrointest Endosc 1999; 50(1):27–33. 23. Kubo H, Chijiiwa Y, Akahoshi K, et al. Pre-operative staging of ampullary tumours by endoscopic ultrasound. Br J Radiol; 72(857):443–447. 24. Mukai H, Nakajima M, Yasuda K, et al. Evaluation of endoscopic ultrasonography in the pre-operative staging of carcinoma of the ampulla of Vater and common bile duct. Gastrointest Endosc 1992; 38(6):676–683. 25. Tierney WM, Francis IR, Eckhauser F, et al. The accuracy of EUS and helical CT in the assessment of vascular invasion by peripapillary malignancy. Gastrointest Endosc 2001; 53(2): 182–188. 26. Itoh A, Goto H, Naitoh Y, et al. Intraductal ultrasonography in diagnosing tumor extension of cancer of the papilla of Vater. Gastrointest Endosc 1997; 45(3):251–260. 27. Seifert E, Schulte F, Stolte M. Adenoma and carcinoma of the duodenum and papilla of Vater: a clinicopathologic study. Am J Gastroenterol 1992; 87(1):37–42. 28. Schneider AR, Seifert H, Trojan J, et al. Frequency of colorectal polyps in patients with sporadic adenomas or adenocarcinomas of the papilla of vater–an age-matched, controlled study. Z Gastroenterol 2005; 43(10):1123–1127. 29. Zádorová Z, Dvorák M, Hajer J. Endoscopic therapy of benign tumors of the papilla of Vater. Endoscopy 2001; 33(4):345–347. 30. Saurin JC, Chavaillon A, Napoléon B, et al. Long-term follow-up of patients with endoscopic treatment of sporadic adenomas of the papilla of Vater. Endoscopy 2003; 35(5):402–406. 31. Kimura W, Futakawa N, Zhao B. Neoplastic diseases of the papilla of Vater. J Hepatobiliary Pancreat Surg 2004; 11(4):223–231. 32. Fischer HP, Zhou H. Pathogenesis of carcinoma of the papilla of Vater. J Hepatobiliary Pancreat Surg 2004; 11(5):301–309. 33. Spigelman AD, Talbot IC, Penna C, et al. Evidence for adenomacarcinoma sequence in the duodenum of patients with familial adenomatous polyposis. The Leeds Castle Polyposis Group (Upper Gastrointestinal Committee). J Clin Pathol 1994; 47(8):709–710. 34. Burke CA, Beck GJ, Church JM, et al. The natural history of untreated duodenal and ampullary adenomas in patients with familial adenomatous polyposis followed in an endoscopic surveillance program. Gastrointest Endosc 1999; 49(3):358–364. 35. Takashima M, Ueki T, Nagai E, et al. Carcinoma of the ampulla of Vater associated with or without adenoma: a clinicopathologic analysis of 198 cases with reference to p53 and Ki-67 immunohistochemical expressions. Mod Pathol 2000; 13(12):1300–1307. 36. Kimura W, Futakawa N, Yamagata S, et al. Different clinicopathologic findings in two histologic types of carcinoma of papilla of Vater. Jpn J Cancer Res 1994; 85(2):161–166. 37. Zhao B, Kimura W, Futakawa N, et al. p53 and p21/Waf1 protein expression and K-ras codon 12 mutation in carcinoma of the papilla of Vater. Am J Gastroenterol 1999; 94(8):2128–2134. 38. Hoffmann KM, Furukawa M, Jensen RT. Duodenal neuroendocrine tumors: Classification, functional syndromes, diagnosis and medical treatment. Best Pract Res Clin Gastroenterol 2005; 19(5):675–697. 39. Makhlouf HR, Burke AP, Sobin LH. Carcinoid tumors of the ampulla of Vater: a comparison with duodenal carcinoid tumors. Cancer 1999; 85(6):1241–1249. 40. Hatzitheoklitos E, Buchler MW, Friess H, et al. Carcinoid of the ampulla of Vater. Clinical characteristics and morphologic features. Cancer 1994; 73(6):1580–1588.

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41. Toyoda H, Yamaguchi M, Nakamura S, et al. Regression of primary lymphoma of the ampulla of Vater after eradication of Helicobacter pylori. Gastrointest Endosc 2001; 54(1):92–96. 42. Yildirim N, Oksuzoglu B, Budakoglu B, et al. Primary duodenal diffuse large cell non-hodgkin lymphoma with involvement of ampulla of Vater: report of 3 cases. Hematology 2005; 10(5):371–374. 43. Nadal E, Martinez A, Jimenez M, et al. Primary follicular lymphoma arising in the ampulla of Vater. Ann Hematol 2002; 81(4):228–231. 44. Weinstock LB, Swanson PE, Bennett KJ, et al. Jaundice caused by a clinically undetectable T-cell lymphoma infiltrating the sphincter of Oddi. Am J Gastroenterol 2001; 96(11):3186–3189. 45. Matsushita M, Kobayashi Y, Kobayashi H, et al. A case of gastrointestinal stromal tumour of the ampulla of Vater. Dig Liver Dis 2005; 37(4):275–277. 46. Schubert ML, Moghimi R. Gastrointestinal Stromal Tumor (GIST). Curr Treat Options Gastroenterol 2006; 9(2):181–188. 47. Le Borgne J, Partensky C, Glemain P, et al. Pancreaticoduodenectomy for metastatic ampullary and pancreatic tumors. Hepatogastroenterology 2000; 47(32):540–544. 48. Bülow S. Results of national registration of familial adenomatous polyposis. Gut 2003; 52(5):742–746. 49. Spigelman AD, Williams CB, Talbot IC, et al. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet 1989; 2(8666):783–785. 50. Offerhaus GJ, Giardiello FM, Krush AJ, et al. The risk of upper gastrointestinal cancer in familial adenomatous polyposis. Gastroenterology 1992; 102(6):1980–1982. 51. Björk J, Åkerbrant H, Iselius L, et al. Periampullary adenomas and adenocarcinomas in familial adenomatous polyposis: cumulative risks and APC gene mutations. Gastroenterology 2001; 121(5):1127–1135. 52. Bülow S, Björk J, Christensen IJ, et al. Duodenal adenomatosis in familial adenomatous polyposis. Gut 2004; 53(3):381–386. 53. Burke C. Risk stratification for periampullary carcinoma in patients with familial adenomatous polyposis: does theodore know what to do now? Gastroenterology 2001; 121(5):1246–1248. 54. Norton ID, Gostout CJ. Management of periampullary adenoma. Dig Dis 1998; 16(5):266–273. 55. Martin JA, Haber GB. Ampullary adenoma: clinical manifestations, diagnosis, and treatment. Gastrointest Endosc Clin N Am 2003; 13(4):649–669. 56. Farnell MB, Sakorafas GH, Sarr MG, et al. Villous tumors of the duodenum: reappraisal of local vs. extended resection. J Gastrointest Surg 2000; 4(1):13–23. 57. Shemesh E, Nass S, Czerniak A. Endoscopic sphincterotomy and endoscopic fulguration in the management of adenoma of the papilla of Vater. Surg Gynecol Obstet 1989; 169(5): 445–448. 58. Lambert R, Ponchon T, Chavaillon A, et al. Laser treatment of tumors of the papilla of Vater. Endoscopy 1988; 20 Suppl 1:227–231. 59. Suzuki K, Kantou U, Murakami Y. Two cases with ampullary cancer who underwent endoscopic excision. Prog Dig Endosc 1983; 23:236–239. 60. Binmoeller KF, Boaventura S, Ramsperger K, et al. Endoscopic snare excision of benign adenomas of the papilla of Vater. Gastrointest Endosc 1993; 39(2):127–131. 61. Beger HG, Treitschke F, Gansauge F, et al. Tumor of the ampulla of Vater: experience with local or radical resection in 171 consecutively treated patients. Arch Surg 1999; 134(5):526–532.

Chapter 26 Ampullary Neoplasm

62. Roggin KK, Yeh JJ, Ferrone CR, et al. Limitations of ampullectomy in the treatment of nonfamilial ampullary neoplasms. Ann Surg Oncol 2005; 12(12):971–980. 63. de Castro SM, van Heek NT, Kuhlmann KF, et al. Surgical management of neoplasms of the ampulla of Vater: local resection or pancreatoduodenectomy and prognostic factors for survival. Surgery 2004; 136(5):994–1002.

64. Yoon YS, Kim SW, Park SJ, et al. Clinicopathologic analysis of early ampullary cancers with a focus on the feasibility of ampullectomy. Ann Surg 2005; 242(1):92–100. 65. Jung S, Kim MH, Seo DW, et al. Endoscopic snare papillectomy of adenocarcinoma of the major duodenal papilla. Gastrointest Endosc 2001; 54(5):622.

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27

APPROACH TO CLINICAL PROBLEMS

Malignant Biliary Obstruction: Distal Raed M. Alsulaiman and Alan Barkun

INTRODUCTION Malignant biliary obstruction is most frequently encountered in the setting of pancreatic adenocarcinoma, but can also be due to cholangiocarcinomas, gallbladder, and ampullary neoplasms. The approach and management of distal biliary obstruction, including the role of endoscopic retrograde cholangiopancreatography (ERCP), will be discussed in this chapter. For discussions on the approach to managing patients with proximal biliary obstruction and the practical aspects of biliary stenting, readers are referred to Chapters 17 and 28.

EPIDEMIOLOGY Malignancies of the biliary and pancreatic systems are not uncommon; together they represent two of the 10 most incident cancers in North America and Europe. While the incidence of pancreatic cancer has remained stable over the last 25 years, the epidemiology of cholangiocarcinoma has changed. The incidence of intrahepatic cholangiocarcinomas seems to be rising while that of extrahepatic biliary tumors is decreasing, even though the reasons for such a change in pattern are not known.1 Because these cancers are usually diagnosed at advanced stages, when the probability of cure is very low, the mortality rate is very high. Consequently pancreatic cancer ranks as the fifth most lethal cancer in the US, and second as a cause of digestive cancer-related deaths, behind colon cancer. The incidence of pancreatic and biliary malignancies increases with age and, in fact, these tumors are rarely seen before the age of 45. Epidemiological surveys have shown that the median age of diagnosis approximates 70 years. Exceptions include genetically predisposed individuals, and those with chronic pre-malignant conditions such as primary sclerosing cholangitis.2 Pancreatic cancer is more common in males, people of Jewish and Afro-American descent. Diabetes, chronic pancreatitis, pernicious anemia, inherited disorders such as familial adenomatous polyposis, and high fat and meat intake have been cited as risk factors for pancreatic cancer.3 Although rare and confined to clusters of families, genetic disorders such as hereditary pancreatitis and familial pancreatic cancer have also been linked to pancreatic cancer; individuals with these conditions appear to have up to a 40% lifetime risk of malignant transformation.4 The majority of cases of cholangiocarcinoma have no identifiable underlying etiology. However, a number of risk factors have been implicated in its development; most factors exhibit long-standing inflammation and chronic injury of the biliary epithelium. Primary sclerosing cholangitis is an uncommon disease, more commonly seen in middle-aged males. It is characterized by stricturing, fibrosis and inflammation of the biliary tree, and is closely associated with inflammatory bowel disease, particularly ulcerative colitis. Approximately 10–20% of patients with primary sclerosing cholangitis will

develop cholangiocarcinoma. The rare congenital fibropolycystic diseases of the biliary system are associated with increased risks of cholangiocarcinoma, particularly choledochal cysts and Caroli’s disease. Choledochal cysts are associated with a 10% lifetime incidence of cholangiocarcinoma: there is a 1% per year risk which plateaus after 15–20 years.5 In the Far East, other forms of chronic inflammation associated with cholangiocarcinoma include infestation with the liver flukes Clonorchis sinensis and Opisthorchis viverinni. Cholangiocarcinoma is also rarely seen in association with cirrhosis and has been weakly linked to hepatitis C infection. Among neoplasms involving the biliary tree, carcinoma of the gallbladder has the poorest prognosis with a 5-year survival ranging between 0% and 10% in most reported series.6 Gallbladder cancer is the most incident malignant lesion of the biliary tract, and the fifth most common among malignant neoplasms of the digestive tract. It affects women two to six times more often than men, and the incidence increases with age. Although its etiology is unknown, cholelithiasis is thought to be an important risk factor for gallbladder cancer. Other risks factors such as the presence of a porcelain gallbladder, gallbladder polyps, an anomalous pancreaticobiliary junction and obesity have also been suggested in epidemiological studies.7

NATURAL HISTORY Although not always present, obstruction of the distal common bile duct (CBD) occurs during the natural evolution of most of these tumors, depending on their location and behavior. The most common malignancy causing distal biliary malignant obstruction is pancreatic cancer accounting for more than 90% of cases (2), followed by gallbladder cancer, malignant lymphadenopathy and cholangiocarcinoma, the latter being relatively uncommon in Western countries. Carcinoma of the ampulla of Vater can also obstruct the distal CBD and although rarely seen in otherwise healthy individuals, it is particularly common in patients with familial adenomatous polyposis. In fact, it is a leading cause of death in this population. Gallbladder cancer and cholangiocarcinoma involving the distal CBD may also obstruct, but represent just a small fraction of all such patients. The overall prognosis of malignancies that cause biliary obstruction is dismal. Except for extrinsic compressions caused by enlarged lymph nodes in the case of hematological malignancies such as nonHodgkin’s lymphomas and for ampullary tumors, the majority of patients found with unresectable disease have a median survival of 3–5 months.8

CLINICAL FEATURES The most common presenting symptoms of pancreaticobiliary malignancies are painless jaundice, anorexia and weight loss, and are seen in most patients. If pain occurs it is often located in the 287

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Demographic Age Gender Race Symptoms and signs Abdominal pain Jaundice Weight loss Nausea/vomiting Back pain

Palliated (N = 256)

Resected (N = 512)

64.0 ± 0.7 years 57% male 91% white

65.8 ± 0.5 years 55% male 91% white

64% 57% 48% 30% 26%

36%a 72%a 43% 18%a 2%

Ampullary adenocarcinoma Pancreatic adenocarcinoma Head Body/tail Gallbladder adenocarcinoma Cholangiocarcinoma Non-hilar Metastatic disease

Table 27.2 Most prevalent distal pancreaticobiliary malignancies

Table 27.1 Presenting symptoms and signs in patients with resectable and unresectable pancreatic cancer a P < 0.001 vs. Palliated group With permission from Sohn TA, Lillemoe KD, Cameron JL, et al. Surgical palliation of unresectable periampullary adenocarcinoma in the 1990, J Am Coll Surg 1999; 188:658–666. © 1999 The American College of Surgeons.

epigastric region or right upper quadrant, and may radiate to the back. Back pain usually indicates retroperitoneal infiltration by the tumor, and therefore, probable unresectability (Table 27.1). Other symptoms may include dark urine, pale stools and pruritus. As many as 80% of patients with pancreatic cancer will present with impaired glucose tolerance or frank diabetes mellitus. Carcinoma of the body and tail of the pancreas presents with similar features, although jaundice is usually absent or develops very late in the course of the disease. A history of inflammatory bowel disease or previously diagnosed malignancies should be sought. A complete physical examination, including assessment for abnormal lymph nodes, jaundice, hepatomegaly, palpable gallbladder, or mass should be performed. A chest radiograph may be appropriate to exclude pulmonary metastases. Obtaining serum tumor markers such as CA19-9 and CEA may be appropriate. Once there is a clinical suspicion of a pancreaticobiliary malignancy, further investigation with abdominal imaging studies is appropriate.

DIFFERENTIAL DIAGNOSIS OF DISTAL BILIARY MALIGNANCIES AND IMAGING TECHNIQUES The differential diagnosis of distal biliary malignancies is shown in Table 27.2.

Ampullary carcinoma Ampullary carcinoma is suspected based upon the demonstration of obstructive jaundice, often with dilation of the pancreatic and biliary ducts seen on abdominal imaging studies. A discrete mass may or may not be identifiable by using standard transabdominal US (TUS) or helical computerized tomography (CT) scanning. ERCP allows for direct identification and biopsy confirmation, although the diagnostic accuracy of biopsy is not 100%. MRCP may allow identification of the lesion and obviate diagnostic ERCP. Endoscopic ultrasound (EUS) allows for more accurate diagnosis and staging of these lesions than CT, and also allows for fine needle aspirate (FNA) tissue sampling.9 EUS also may facilitate the selection of patients who can undergo local resection instead of pancreaticoduodenectomy (Whipple operation). Once the lesion is identified and staged, the choice of operative resection for cure or some form of jaundice palliation are similar to treatment options for carcinoma of the pancreatic head. 288

Fig. 27.1 CT demonstrating a pancreatic carcinoma causing biliary obstruction: enlarged head of the pancreas with an irregular area of low attenuation of the tumor.

Pancreatic malignancies The approach to the patient with pancreatic carcinoma involving the pancreatic head is different than in the patient with body/tail lesions in terms of accessibility, curative potential, and palliation. Most patients with cancer of the pancreatic head present with obstructive jaundice. Radiological imaging studies are performed allowing for (a) detection of the tumor, (b) determination of tumor resectability, and (c) tissue acquisition under imaging guidance. TUS will suggest biliary obstruction by the demonstration of biliary ductal dilation. It may also identify the presence of obvious liver metastases. However, standard TUS is operator dependent and has a poor sensitivity for detecting small neoplasms of the pancreatic head. Recent advances in TUS, such as color-power Doppler US, US angiography, harmonic imaging (tissue harmonic imaging and contrast harmonic imaging), and three-dimensional US, may improve the usefulness of this modality in the staging of pancreatic cancer. Nonetheless, more information regarding staging and extent of disease, and possible nodal or vascular involvement is obtainable with other imaging modalities. Helical CT of the abdomen with fine cuts through the pancreas during the arterial and portal phases of contrast enhancement has a high sensitivity and specificity for the detection of pancreatic carcinoma (Fig. 27.1). It allows for the determination of tumor extension, liver metastases, and invasion of vascular structures, and thus, resectability. Multislice (multidetector) CT has been introduced and

Chapter 27 Malignant Biliary Obstruction: Distal

may improve on the accuracy of helical CT. If the CT findings are found to be highly suggestive of a resectable pancreatic carcinoma in the appropriate clinical setting, and the patient is felt to be an operative candidate, a reasonable approach is to then refer the patient directly for an attempt at surgical resection (pancreaticoduodenectomy) with or without further imaging (depending on local availability and expertise) or diagnostic testing. Transabdominal or CT-guided biopsy of the pancreatic mass rarely may result in tumor seeding at the needle track or within the peritoneum and has been reported to increase the risk of postoperative recurrence.10 If the CT scan reveals overt evidence of unresectable pancreatic cancer or the patient is a not an operative candidate because of co-morbid medical conditions, non-operative palliation of obstructive jaundice should be performed at ERCP. If a definitive tissue diagnosis is required for the administration of chemotherapy and/or radiation therapy, tissue acquisition can be performed at the time of the palliative ERCP. If a tissue diagnosis cannot be made at that time, then transabdominal biopsy (CT-guided or US) of the mass or metastatic disease sites (i.e. liver lesions), or EUS-guided FNA of the mass or metastatic sites should be performed. Magnetic resonance imaging (MRI) of the pancreas may include MRI, MR cholangiopancreatography (MRCP), or magnetic resonance angiography. Standard abdominal MRI appears to be an accurate modality for staging pancreatic carcinoma, though it does not appear to be more specific or sensitive than helical CT. In addition, it is more expensive and more time consuming to perform than CT11 (Fig. 27.2). If expertise in EUS is readily available, it should be used as a preoperative staging modality in patients with suspected pancreatic cancer (Fig. 27.3). This is particularly important in patients with equivocal findings on CT or those with co-morbidities and, therefore, at higher risk for intra-operative or postoperative complications. EUS allows identification of vascular invasion as well as sampling of suspicious-appearing lymph nodes, which, if positive, may change the treatment approach as it alters prognosis. EUS appears to be complementary to helical CT, with EUS better at detecting small (3 cm) or liver metastases, both of which are poor predictors of survival, as plastic stents are cost-saving in patients surviving less than 3–4 months while SEMS are more cost-effective in patients expected to survive longer than 6 months.50,51 Direct cost measurements from a randomized controlled trial demonstrated similar results.52 Despite these considerations, there are no strict criteria for selecting between plastic stents and SEMS for the palliation of unresectable malignant biliary obstruction. Indeed, the decision must be individualized as patient factors must also be considered. For example, SEMS may be preferred in a patient who is non-compliant or resides in a remote area without medical access, despite an anticipated short life expectancy. Patients with difficult endoscopic biliary access from associated duodenal stenosis may benefit from early SEMS placement, and may even be candidates for endoscopic double bypass where a biliary and an enteric metallic stents are placed.52a

Fig. 27.10 Plain abdominal radiograph showing a plastic stent inserted within a blocked SEMS.

The optimal stenting strategy In addition to deciding on the optimal stent technology (plastic versus SEMS), an endoscopist must also consider the optimal stenting strategy. For example, if a plastic stent is initially inserted, should it be replaced at regular intervals to prevent stent blockage, or is it best to change the plastic stent on demand during the life of the patient? In a randomized trial, routine exchanges every 3 months were associated with longer symptom-free intervals for patients than exchanges at signs of stent occlusion, but there was no difference in overall survival.52 An extensive cost-effectiveness model suggested, in order of the most to the least cost-effective approaches, the following approaches: initial insertion of a covered SEMS, or of an uncovered metal stent, and a plastic stent with its subsequent on demand replacement (when the patient developed symptoms suggesting stent occlusion). Least cost-effective was the routine threemonthly replacement of a plastic stent.53 As discussed previously, a cost-minimization analysis suggested that the preoperative insertion of a short covered SEMS is cost saving.27 Occluded SEMS are managed by a variety of methods. The most commonly used techniques include insertion of a plastic stent within the occluded SEMS (Fig. 27.10), insertion of a second SEMS (Fig 27.11) and mechanical cleaning of the occluded stent lumen. Overall success rates for re-establishing biliary drainage are over 80%. Mechanical cleaning methods, such as catheter irrigation or the use of stone-extraction balloons, may be less successful and are associated with decreased duration of patency than repeat stenting. Given the typical short median survival at the time of the first SEMS occlusion, treatment with a plastic prosthesis seems to be the most costeffective method. Other techniques for SEMS recanalization include application of thermal energy and intaductal brachytherapy but are not widely used.

294

Percutaneous approach

Fig. 27.11 Plain abdominal radiograph showing a second SEMS inserted within an initially placed, now occluded SEMS.

Percutaneous insertion of plastic stents and SEMS is an acceptable alternative for management of distal biliary malignant obstruction not successfully treated by an endoscopic approach. Percutaneous drainage was the preferred palliative method in patients with malignant obstruction until several years ago. This procedure entails sterile catheterization of a peripheral biliary radical after percutaneous puncture. External drainage is accomplished by percutaneous transhepatic insertion of a catheter, manipulation of a guidewire and insertion of a drainage catheter through the obstructing lesion that

allows both internal and external bile flow. The technique has evolved over the years and currently insertion of an indwelling catheter without external drainage is possible; furthermore, the advent of SEMS has obviated in many cases the need for serial tract dilation. Prior to the era of metallic expandable stents, the percutaneous approach had permitted the insertion of plastic stents with larger diameters when compared to endoscopic drainage. The consequent

Chapter 27 Malignant Biliary Obstruction: Distal

benefit of a longer stent patency represented a significant advantage over the prosthesis inserted by ERCP which was historically limited by the size of the accessory channel of duodenoscopes. Also, percutaneous drainage appeared to be as effective as biliary bypass and had other inherent advantages. Bornman et al. found the overall survival to be similar in both surgical and percutaneous groups, whereas percutaneous drainage was associated with a lower procedure-related complication and 30-day mortality rate.54 The disadvantages of external biliary drainage include the risk of spontaneous catheter dislodgment, inflammation and pain around the puncture site, leak of ascitic fluid and bile around the catheter, and loss of fluid and electrolytes. The complication rate for transhepatic biliary drainage can be substantial and varies with the patient status prior to the procedure as well as the diagnosis. The presence of coagulopathy, cholangitis, stone, malignant obstruction or intrahepatic lesions are all associated with high complication rates. The advent of self-expandable metal endoprostheses, larger size accessory channels in duodenoscopes, and the complication rate observed with percutaneous drainage have changed the standard of practice. Speer and colleagues conducted a prospective, randomised study comparing percutaneous and endoscopic drainage. While overall survival was not different between either arm, 30-day mortality, both by intention-to-treat and per-protocol analysis, was significantly lower in the endoscopy group and justified the early termination of the study.55 The authors found that complications associated with the percutaneous procedure accounted for the difference in mortality and that endoscopic insertion of a stent was safer and more likely to succeed.55 In contradistinction, a recent RCT showed that patients undergoing percutaneous drainage had a longer survival than those in the endoscopy group.56 However, a number of possible confounders of outcome need to be examined: First, the authors selected not only patients with unresectable distal biliary obstruction but also subjects with more proximal obstruction including hilar tumors. The latter may be more amenable to percutaneous management. These inclusion criteria could explain the low success rate of PE stent insertion by endoscopy (58%) which, in turn, accounted for the suboptimal efficacy observed in this group. Secondly, the authors used SEMS in the percutaneous group and PE stents in the endoscopic drainage group, which biases against the endoscopic approach even though it may represent that institution’s practice. The economic evaluation of this study is also difficult to interpret as it did not include procedural costs, and may thereby have further disadvantaged the endoscopic treatment arm. At present, there is insufficient evidence in the literature to advocate the routine use of percutaneous drainage as the preferred approach in the palliation of patients with distal biliary obstruction other than for reasons of institutional expertise or availability.

Surgical palliation Historically, surgery was the favored method of palliation, but has been replaced by percutaneous and endoscopic insertion of stents.57 The 30-day mortality after surgical palliation for pancreatic cancer and cholangiocarcinoma is significant, especially in the face of advancing age and metastatic disease. Surgical biliary and gastrointestinal bypass have been advocated for patients who also suffer from chronic pain, since celiac nerve block can also be performed at the time of surgery. Whether prophylactic gastrointestinal bypass should be offered to patients with malignant obstructive jaundice, and if so, when, remains unclear. Recent studies have shown that gastrojejunostomy, in addition to biliary bypass may decrease the inci-

dence of late gastric outlet obstruction without higher morbidity or mortality.58 Surgery has the advantage of precluding multiple reinterventions, associated with less invasive procedures, namely endoscopic stenting. Three prospective randomized trials have compared open surgery to endoscopic stenting.59–61 Smith and colleagues randomized 203 patients to 10 French (Fr) plastic stents or biliary bypass (choledochoduodenostomy and choledochojejunostomy). Patients who underwent stent placement had lower procedurerelated and major complication rates as well as a shorter hospital stay than the surgical group. Most complications occurred in the first 30 days in the surgical group. In contrast to the endoscopy group, therefore numerically fewer late complications due to cholangitis or gastric obstruction. Shepherd and Andersen conducted smaller studies that have shown similar results. While overall survival did not differ between treatments, they demonstrated that endoscopic stenting had a lower rate of short-term complications than surgical treatment. Although patients in the endoscopy group had more obstructions and needed more re-interventions, the total number of days in hospital was higher in the surgical group. A meta-analysis performed with these three studies confirmed a higher likelihood of intervention in the stent group.62 The recent Cochrane systematic review by Moss et al. suggested a lower recurrent biliary obstruction rate attributable to surgery, with a higher overall complication rate, and no difference in mortality when compared to plastic biliary stenting.49a Although performed more than 10 years ago, before the advent of newer stent technologies and less invasive surgical procedures, these studies suggest that endoscopic prostheses are effective and less costly than surgery. A recent, single-center, retrospective cost-analysis in the US also revealed a striking difference between endoscopic palliation and surgery despite the need for repetitive interventions and readmissions in the endoscopic group.63 However, surgical bypass remains an excellent alternative and may be favored in patients with unresectable disease at the time of laparotomy, and for those requiring concomitant gastrointestinal bypass and/or celiac nerve block for management of chronic pain.

Adjuvant therapy While the cases of biliary obstruction due to lymphomas can be managed with stent insertion or surgical bypass, cure can only be achieved with remission of the underlying disease. Responsiveness to chemotherapy is the main predictor for outcome in these patients. In contrast, cure of tumors of epithelial origin can only be achieved with surgical resection, even though adjuvant chemotherapy has been shown to improve 1- and 5-year survival after resection of pancreatic adenocarcinoma.64 The role of chemotherapy in patients with unresectable disease is still limited. Studies have shown that 5-Fluoracil (5-FU) based regimens are superior to observation or supportive treatment in patients with unresectable adenocarcinoma of the pancreas. Unfortunately, the combination of other chemotherapeutic agents such as cisplatin with 5-FU is no better than 5-FU alone.65 In fact, this combination is associated with an increased rate of systemic toxicity, which seems to be unrelated to the biliary obstruction and inability to excrete the drug metabolites. An important breakthrough in the management of advanced pancreatic cancer occurred with the introduction of gemcitabine and other cytotoxic drugs which have been shown to improve major symptoms such as pain and weight loss, clinical benefit response, time to progression, and length of survival, but maintain an acceptable toxicity profile.66 295

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The effect of chemotherapy in the management of malignant biliary obstruction is unknown. Because tumor invasion into the biliary tree is unlikely to be relieved by chemotherapy alone, a procedure to palliate the obstruction is still necessary regardless of the administration and response to adjuvant therapy, and may in fact be required to improve liver tests and function prior to the initiation of this treatment. In contrast, addition of a chemotherapeutic regimen for the treatment of patients with unresectable disease could potentially result in an improvement in survival and influence the choice of palliation. There are no studies evaluating the effect of chemotherapy on the patency of stents. While chemotherapeutic agents are unlikely to affect the mechanisms involved in plastic stent occlusion, reduction of the tumor mass could diminish the probability of tumor ingrowth and prolong patency of SEMS. It is unknown if adjuvant chemotherapy can increase the risk of stent migration and malfunctioning as has been suggested for esophageal malignancies.67

SUMMARY Distal malignant biliary obstruction is a commonly encountered problem facing endoscopists that requires a multidisciplinary approach involving surgeons, radiologists and gastroenterologists. The optimal approach to manage this complex medical problem depends more on available expertise and resources than the evidence in the literature. Endoscopic techniques have advanced significantly over the past two decades and maintain a central role in the palliation of distal pancreaticobiliary malignancy.

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27. Chen VK, Arguedas MR, Baron TH. Expandable metal biliary stents before pancreaticoduodenectomy for pancreatic cancer: a Monte-Carlo decision analysis. Clin Gastroenterol Hepatol 2005; 3:1229–1237. 28. Scheeres D, O’Brien W, Ponsky L, et al. Endoscopic stent configuration and bile flow rates in a variable diameter bile duct model. Surg Endosc 1990; 4:91–93. 29. van Berkel AM, van Marle J, Groen AK, et al. Mechanisms of biliary stent clogging: confocal laser scanning and scanning electron microscopy. Endoscopy 2005; 37:729–734. 30. Libby ED, Leung JW. Prevention of biliary stent clogging: a clinical review. Am J Gastroenterol 1996; 91:1301–1308. 31. Speer AG, Cotton PB, MacRae KD. Endoscopic management of malignant biliary obstruction: stents of 10 French gauge are preferable to stents of 8 French gauge. Gastrointest Endosc 1988; 34:412–417. 32. Kadakia SC, Starnes E. Comparison of 10 French gauge stent with 11.5 French gauge stent in patients with biliary tract diseases. Gastrointest Endosc 1992; 38:454–459. 33. Catalano MF, Geenen JE, Lehman GA, et al. “Tannenbaum” Teflon stents versus traditional polyethylene stents for treatment of malignant biliary stricture. Gastrointest Endosc 2002; 55: 354–358. 34. van Berkel AM, Huibregtse IL, Bergman JJ, et al. A prospective randomized trial of Tannenbaum-type Teflon-coated stents versus polyethylene stents for distal malignant biliary obstruction. Eur J Gastroenterol Hepatol 2004; 16:213–217. 35. Pedersen FM, Lassen AT. Response. Gastrointest Endosc 2000; 51:117. 36. De Ledinghen V, Person B, Legoux JL, et al. Prevention of biliary stent occlusion by ursodeoxycholic acid plus norfloxacin: a multicenter randomized trial. Dig Dis Sci 2000; 45:145–150. 37. Halm U, Schiefke, Fleig WE, et al. Ofloxacin and ursodeoxycholic acid versus ursodeoxycholic acid alone to prevent occlusion of biliary stents: a prospective, randomized trial. Endoscopy 2001; 33:491–494. 38. Waschke K, da Silveira E, Toubouti Y, et al. The role of plastic stents, adjuvant therapy and metal stents in distal malignant biliary obstruction. a systematic review and series of metal-analyses. American Journal of Gastroenterology 2004; 99:AB 74. 39. Chan G, Barkun J, Barkun AN, et al. The role of ciprofloxacin in prolonging polyethylene biliary stent patency: a multicenter, double-blinded effectiveness study. J Gastrointest Surg 2005; 9:481–488. 40. Tringali A, Mutignani M, Perri V, et al. A prospective, randomized multicenter trial comparing DoubleLayer and polyethylene stents for malignant distal common bile duct strictures. Endoscopy 2003; 35:992–997. 41. Raju GS, Sud R, Elfert AA, et al. Biliary drainage by using stents without a central lumen: a pilot study. Gastrointest Endosc 2006; 63:317–320. 42. Huibregtse K, Carr-Locke DL, Cremer M, et al. Biliary stent occlusion—a problem solved with self-expanding metal stents? European Wallstent Study Group. Endoscopy 1992; 24:391–394. 43. Dumonceau JM, Cremer M, Auroux J, et al. A comparison of Ultraflex Diamond stents and Wallstents for palliation of distal malignant biliary strictures. Am J Gastroenterol 2000; 95: 670–676. 44. Shim CS, Lee YH, Cho YD, et al. Preliminary results of a new covered biliary metal stent for malignant biliary obstruction. Endoscopy 1998; 30:345–350. 44a. Shah RJ, Howell DA, Desilets DJ, Sheth SG, Parsons WG, Okolo P 3rd, Lehman GA, Sherman S, Baillie J, Branch MS, Pleskow D,

Chuttani R, Bosco JJ. Multicenter randomized trial of the spiral Z-stent compared with the wallstent for malignant biliary obstruction. Gastrointest Endosc 2003; 57(7):830–836. 45. Isayama H, Komatsu Y, Tsujino T, et al. A prospective randomised study of “covered” versus “uncovered” diamond stents for the management of distal malignant biliary obstruction. Gut 2004; 53:729–734. 45a. Park do H, Kim MH, Choi JS, Lee SS, Seo DW, Kim JH, Han J, Kim JC, Choi EK, Lee SK. Covered versus uncovered wallstent for malignant extrahepatic biliary obstruction: a cohort comparative analysis. Clin Gastroenterol Hepatol. 2006; 4(6):790–796. 45b. Yoon WJ, Lee JK, Lee KH, Lee WJ, Ryu JK, Kim YT, Yoon YB. A comparison of covered and uncovered wallstents for the management of distal malignant biliary obstruction. Gastrointest Endosc 2006; 63(7):996–1000. 46. Nakai Y, Isayama H, Komatsu Y, et al. Efficacy and safety of the covered Wallstent in patients with distal malignant biliary obstruction. Gastrointest Endosc 2005; 62:742–748. 46a. Suk KT, Kim HS, Kim JW, Baik SK, Kwon SO, Kim HG, Lee DH, Yoo BM, Kim JH, Moon YS, Lee DK. Risk factors for cholecystitis after metal stent placement in malignant biliary obstruction. Gastrointest Endosc 2006; 64(4):522–529. 47. Baron T, Poterucha J. Insertion and removal of covered expandable metal stents for closure of complex biliary leaks. Clinical gastroenterology and hepatology 2006; 4:381–386. 48. Davids PH, Groen AK, Rauws EA, et al. Randomised trial of selfexpanding metal stents versus polyethylene stents for distal malignant biliary obstruction. Lancet 1992; 340:1488–1492. 49. Kaassis M, Boyer J, Dumas R, et al. Plastic or metal stents for malignant stricture of the common bile duct? Results of a randomized prospective study. Gastrointest Endosc 2003; 57:178–182. 49a. Moss AC, Morris E, Leyden J, MacMathuna P. Malignant distal biliary obstruction: a systematic review and meta-analysis of endoscopic and surgical bypass results. Cancer Treat Rev 2007; 33(2):213–221. 49b. Soderlund C, Linder S. Covered metal versus plastic stents for malignant common bile duct stenosis: a prospective, randomized, controlled trial. Gastrointest Endosc 2006; 63(7):986–895. 49c. Waschke K, da Silveira E, Toubouti Y, Rahme E, Barkun A. Selfexpandable metal stents confer a survival advantage in palliation of distal malignant biliary obstruction. Gastrointest Endosc 2005; 61(5):T1322. 50. Arguedas MR, Heudebert GH, Stinnett AA, et al. Biliary stents in malignant obstructive jaundice due to pancreatic carcinoma: a cost-effectiveness analysis. Am J Gastroenterol 2002; 97:898–904. 51. Yeoh KG, Zimmerman MJ, Cunningham JT, et al. Comparative costs of metal versus plastic biliary stent strategies for malignant obstructive jaundice by decision analysis. Gastrointest Endosc 1999; 49:466–471. 52. Prat F, Chapat O, Ducot B, et al. A randomized trial of endoscopic drainage methods for inoperable malignant strictures of the common bile duct. Gastrointest Endosc 1998; 47:1–7. 52a. Maire F, Hammel P, Ponsot P, Aubert A, O’Toole D, Hentic O, Levy P, Ruszniewski P. Long-term outcome of biliary and duodenal stents in palliative treatment of patients with unresectable adenocarcinoma of the head of pancreas. Am J Gastroenterol 2006; 101(4):735–742. 53. da Silveira E, Waschke K, Barkun A, et al. Cost-effectiveness decision analysis comparing covered to uncovered selfexpandable metal stents to elective or on-demand polyethylene stent changes in patients with distal biliary malignant obstruction. Gastrointest Endosc 2005; 61:AB 203.

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54. Bornman PC, Harries-Jones EP, Tobias R, et al. Prospective controlled trial of transhepatic biliary endoprosthesis versus bypass surgery for incurable carcinoma of head of pancreas. Lancet 1986; 1:69–71. 55. Speer AG, Cotton PB, Russell RC, et al. Randomised trial of endoscopic versus percutaneous stent insertion in malignant obstructive jaundice. Lancet 1987; 2:57–62. 56. Pinol V, Castells A, Bordas JM, et al. Percutaneous self-expanding metal stents versus endoscopic polyethylene endoprostheses for treating malignant biliary obstruction: randomized clinical trial. Radiology 2002; 225:27–34. 57. Sharma D, Bhansali M, Raina VK. Surgical bypass is still relevant in the palliation of malignant obstructive jaundice. Trop Doct 2002; 32:216–219. 58. Lillemoe KD, Grosfeld JL. Addition of prophylactic gastrojejunostomy to hepaticojejunostomy significantly reduces gastric outlet obstruction in people with unresectable periampullary cancer. Cancer Treat Rev 2004; 30:389–393. 59. Andersen JR, Sorensen SM, Kruse A, et al. Randomised trial of endoscopic endoprosthesis versus operative bypass in malignant obstructive jaundice. Gut 1989; 30:1132–1135. 60. Shepherd HA, Royle G, Ross AP, et al. Endoscopic biliary endoprosthesis in the palliation of malignant obstruction of the

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distal common bile duct: a randomized trial. Br J Surg 1988; 75:1166–1168. Smith AC, Dowsett JF, Russell RC, et al. Randomised trial of endoscopic stenting versus surgical bypass in malignant low bileduct obstruction. Lancet 1994; 344:1655–1660. Taylor MC, McLeod RS, Langer B. Biliary stenting versus bypass surgery for the palliation of malignant distal bile duct obstruction: a meta-analysis. Liver Transpl 2000; 6:302–308. Martin RC, 2nd, Vitale GC, Reed DN, et al. Cost comparison of endoscopic stenting vs surgical treatment for unresectable cholangiocarcinoma. Surg Endosc 2002; 16:667–670. Shore S, Raraty MG, Ghaneh P, et al. Review article: chemotherapy for pancreatic cancer. Aliment Pharmacol Ther 2003; 18:1049–1069. Ducreux M, Rougier P, Pignon JP, et al. A randomised trial comparing 5-FU with 5-FU plus cisplatin in advanced pancreatic carcinoma. Ann Oncol 2002; 13:1185–1191. Heinemann V. Gemcitabine in the treatment of advanced pancreatic cancer: a comparative analysis of randomized trials. Semin Oncol 2002; 29:9–16. Siersema PD, Hop WC, Dees J, et al. Coated self-expanding metal stents versus latex prostheses for esophagogastric cancer with special reference to prior radiation and chemotherapy: a controlled, prospective study. Gastrointest Endosc 1998; 47:113–120.

SECTION 3

Chapter

28

APPROACH TO CLINICAL PROBLEMS

Malignant Biliary Obstruction: Hilar Giovanni D. De Palma

INTRODUCTION BOX 28.1 KEY POINTS 1. Review of epidemiology of malignant bile duct obstruction at the hepatic hilum. 2. Review of anatomical classification.

Epidemiology of malignant bile duct obstruction Malignant biliary obstruction at the liver hilum is caused by a heterogeneous group of tumors that includes primary bile duct cancer (the so-called Klatskin tumor), cancers that involve the confluence by direct extension (e.g., gallbladder and liver cancer), and metastatic cancer to hilar lymphatic nodes or to the liver (Table 28.1). Primary cholangiocarcinoma of the hepatic hilus affecting either the right or left main hepatic ducts or the biliary confluence was first described in 1957 by Altemeier et al. Other investigators have also documented the existence of this tumor, but it was not until 1965 that Klatskin1 reported the first comprehensive examination of the pathology, diagnosis, and management of the tumor that now bears his name. Cholangiocarcinoma is an uncommon malignancy comprising less than 2% of all cancer diagnoses. The overall rate of occurrence of cholangiocarcinoma is 1.2/100 000 individuals, with two-thirds of all cases occurring in patients more than 65 years old, and a near tenfold increased rate of occurrence in patients more than 80 years of age.2 In recent years, there has been a worldwide trend towards decreased mortality from extrahepatic tumors, particularly for females. In contrast to the observations in intrahepatic cholangiocarcinoma, the estimated annual percentage change in mortality for extrahepatic biliary tract cancers decreased in most countries, with the exception of the United Kingdom.3 Chronic biliary tract inflammation represents a major risk factor for the development of cholangiocarcinoma. The association between chronic parasitic infection of the biliary tract and cholangiocarcinoma is obvious in regions of high endemicity, such as in certain Far Eastern nations. In Western nations, primary sclerosing cholangitis is the most common risk factor identified with the development of cholangiocarcinoma.4 Extrahepatic cholangiocarcinoma has traditionally been separated into three groups, based on anatomical location. Upper third or hilar

tumors are those located in the common hepatic duct and/or the right and left hepatic ducts including their confluence. Middle third tumors occur in the region bounded by the upper border of the duodenum and extending to the common bile duct. Lower third or distal bile duct tumors arise between the ampulla of Vater and the upper border of the duodenum. Tumors at the biliary confluence of the liver are the most common and comprise 40–60% of the total. Middle third and distal third tumors comprise 17–20%, and 18–27%, respectively. A small percentage of patients (1/4) always remain undrained (Fig. 28.6). In the absence of intractable symptoms, these patients should not undergo further endoscopic measures, as the risk of inducing cholangitis outweighs any benefits realized from the establishment of endoscopic drainage. 304

Patient preparation The patients should have an intravenous line for administration of sedatives, antibiotics and hydration. Antibiotic coverage is mandatory, particularly in those patients with more complex strictures (Bismuth type III and IV). Prophylaxis can be given as a single, adequate dose shortly before the procedure and should be continued for 4–5 days after the procedure. Escherichia coli, and to a lesser extent, Klebsiella spp. (gram-negative bacteria) and gram-positive Enterococcus spp. are the most common organisms in bile. Therefore, antibiotics should be aimed mainly at gram-negative bacteria with good penetration in liver tissue and bile. Ciprofloxacin is

Chapter 28 Malignant Biliary Obstruction: Hilar

the guidewire passes through the stricture in the desired direction, it is advanced as deeply as possible into that lobe. Then a catheter is advanced over the guidewire and through the stricture as far as possible, the guidewire is removed, and as much bile as possible is aspirated to decompress the accessed duct. Contrast is injected with the catheter and the unilateral cholangiogram is completed. Subsequently, a stiff guidewire is substituted for the initial guidewire and the catheter removed, leaving the guidewire in that duct for the remainder of the procedure until final stent deployment. Thereafter, if necessary, dilation of the malignant stenosis is performed using either balloon catheters or bouginages. If histological diagnosis is not already established, sampling is performed with a biopsy forceps and cytology brush. Finally a plastic or a metal stent is inserted to decompress the proximal ductal system. If bilateral stent placement was planned, immediately after insertion of the first guidewire a second guidewire is inserted into the contralateral side, stents are placed sequentially into the left and then the right hepatic ducts over dual guidewires.

Fig. 28.6 strictures

ERCP showing patient with multiple intrahepatic

currently the first choice of antibiotic. In case of cholangitis, the addition of amoxicillin or a switch to piperacillin/tazobactam is advisable, Patients should be routinely sedated with diazepam or midazolam, sometimes combined with fentanyl or pethidine. The patients should be monitored by an assistant and by mechanical methods including pulse oximetry. Supervision by an anesthetist may be required.

MRCP and CT-guided stent implantation (Fig. 28.7) Recent reports describe the utility of MRCP or CT imaging to guide selection of the target lobe for subsequent endoscopic stenting, often without use of contrast.37,39 MRCP or CT images are used to confirm the diagnosis of Klatskin tumor to exclude other biliary diseases (Fig. 28.1) and to demonstrate the stenoses as well as dilation of proximal liver segments. The left or right main hepatic duct is chosen for stent insertion, depending on the number of drainable liver segments. Subsequent to MRCP selective endoscopic retrograde contrast injection is deliberately limited to the distal end of the malignant tumor stenosis. Thereafter, sphincterotomy is generally performed, the papillotome or a catheter is advanced to the distal margin of the stricture and a guidewire (hybrid or hydrophilic, with a torquable angle-tip if necessary) is advanced, under fluoroscopic guidance, in the direction of the duct preselected for drainage based on prior imaging. Once

Unilateral random stent implantation (Figs 28.8–28.9) MRCP images are used to confirm the diagnosis of Klatskin’s tumor, to exclude other biliary diseases, and to demonstrate the stenoses, as well as dilation of proximal liver segments. Contrast injection at ERCP is deliberately limited to the extrahepatic bile duct distal to the tumor. Then, sphincterotomy is performed in all cases, and a guidewire is subsequently advanced through the malignant stenosis into the duct that is technically easiest to access. A catheter is then passed over the guidewire and through the stenosis, and, after removal of the guidewire, a unilateral cholangiogram is completed. Finally, a single plastic or metallic stent is deployed.36,38

Contrast-free stent implantation (Fig. 28.10) Stents are placed in these patients under fluoroscopic guidance as follows: the stent assembly is passed over the guidewire above the suspected site of stricture (Fig. 28.10A) and the stent is deployed at the desired site.40

Rendezvous technique An interventional radiologist passes a guidewire transhepatically down the bile duct and into the duodenum; this wire is then grasped by the endoscopist to place stents in the bile duct. The combined percutaneous-endoscopic approach has been reported by many groups. The rationale is that the complications should be lower than those with a purely percutaneous approach, since only small catheters are passed through the liver, and rather briefly. However, the complication rates are not negligible. The overall morbidity, including the initial failed endoscopic attempts, proved to be 62% and 27% in one series of 74 patients.

Plastic versus metal stents Theoretically, a metal stent should result in better drainage than plastic stent in hilar strictures. Metal stents have two advantages over the plastic stents: they do not occlude side branches because of the mesh; furthermore, because most hilar tumors are firm and scirrhous, tumor ingrowth probably occurs less frequently. Metallic stents offer longer but still limited stent patency duration of about 4–6 months compared with a patency duration of 2–4 months for plastic stents (Table 28.4). 305

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A

B

C

D

E

Fig. 28.7 MRCP-targeted unilateral implantation of SEMS. A Contrast enhanced MR showing hilar cholangiocarcinoma causing marked dilation of the bile ducts in the lateral segments of the right lobe. B MRCP image showing tumor occluding the common hepatic duct and the right (IIIa) hepatic duct (same patients as in Fig. 28.5A). (A and B courtesy of Mainenti P, MD, and Maurea S, MD. Dipartimento di Scienze Biomorfologiche e Funzionali; University of Naples Federico II, School of Medicine.) C The stent is advanced over the guidewire into dilated right hepatic duct as planned. D The SEMS has been deployed. E Post-ERCP x-ray image showing SEMS in place providing drainage.

306

Chapter 28 Malignant Biliary Obstruction: Hilar

A

B

C

Fig. 28.8 Retrograde cholangiograms illustrating unilateral contrast injection and unilateral stent deployment. A Contrast injected into distal common duct distal to stenosis. Stenosis itself and the more proximal bile duct regions are deliberately not opacified. B Guidewire is advanced through tumor stenosis toward left hepatic duct under fluoroscopic control. A minimal contrast injection into dilated left hepatic ductal system shows correct position of the guidewire and guiding catheter. Injection of contrast into right hepatic duct system has been avoided. C Stent advanced through stenosis into dilated left hepatic duct.

A B

C

Fig. 28.9 Retrograde cholangiograms illustrating unilateral stent deployment in a patient with type IV Bismuth hilar stricture. A ERCP showing dilated biliary tree with high-grade stricture affecting the distal common bile duct, caused by carcinoma of the pancreas. Narrowed common hepatic duct and dilation of proximal biliary tree are compatible with metastatic disease producing obstruction at the bifurcation. B A guidewire and a guide-catheter advanced through the stricture in the left hepatic duct. C Single 10 Fr plastic stent advanced through stenosis.

In contrast to plastic stents, metallic stents are not removable after the first few days of deployment, as the stent becomes embedded in the tumor tissue which may grow into each individual mesh opening. Thus, metallic stents should be used in patients with proven unresectable malignancies, because initial insertion of an expandable metal stent makes subsequent surgery more difficult as these stents cannot readily be removed surgically. The main disadvantage is the cost of the metallic stent (US$ 900–1200), and identification of patients who are likely to outlive their first plastic stent, and warrant a metal stent, is a major challenge for the managing clinician. Cost analysis showed that metallic stents were advantageous versus plastic stents in patients surviving more than six months and very costly when patients survived less

than three months. Therefore, the use of metal stents should be restricted to those patients with unresectable tumors who will, in all probability, live longer than three months. Unfortunately there is no a good way to predict life expectancy at this time. Tumor size (>3 cm), evidence of diffuse liver metastases, and general condition of the patient could guide the choice of stent. An additional indication for the use of metal stents is the small group of patients who suffer rapid and repeated obstruction of plastic stents. These patients have not been well studied and presently cannot be identified at the start. This group constitutes patients who will also benefit from a metal stent. All patients, who need a stent exchange because of clogging of a plastic stent within 1 month after insertion are good candidates for metal stent insertion. 307

SECTION 3 APPROACH TO CLINICAL PROBLEMS

30-days Patients Drainage mortality Occlusion (N) (%) (%) (%)

A

Davids (1992) Metal 49 Plastic 56 Carr-Locke (1993) Metal 86 Plastic 78 Knyrim (1993) Metal 31 Plastic 31

Patency (days)

96 95

14 4

33 54

372 126

98 95

5 5

13 13

111 62

100 100

13 9

22 43

— —

Table 28.4 Treatment outcomes: comparison of plastic versus metal stents for low bile duct obstruction (randomized controlled trials)

B

Fig. 28.11 Duonenal perforation by guidewire in a patient with high-grade stricture affecting common hepatic duct and dilation of proximal biliary tree.

Fig. 28.10 Contrast-free deployment of stent. A A guidewire is passed above the suspected site of stricture, deeply in the left hepatic duct. B Stent is passed over the guidewire above the stricture.

COMPLICATIONS BOX 28.4 KEY POINTS 1. Review of the complications of the endoscopic approach. 2. Identifying strategies to reduce complications and their management.

308

Early and late complications of stent insertion Immediate complications of attempted and successful stent placement are similar to those of other ERCP procedures. Pancreatitis can be provoked. A small sphincterotomy, when performed, rarely results in direct complications, such as bleeding or perforation (Fig. 28.11). In contrast, post-ERC bacterial cholangitis in patients with Klatskin tumors occurs in 17–49%.5,23 Bacterial cholangitis is caused by infected bile and inflammation of ductal epithelium. In animal studies bacterial reflux from bile to blood is enhanced by increased intrabiliary pressure.16 This suggests that increased intrabiliary pressure during ERC is the main reason for increased bacterial access to the blood. The major late complication is clogging of the prosthesis, occurring in 21–36% of cases. Much higher rates of 21–54%

Chapter 28 Malignant Biliary Obstruction: Hilar

are reported in prospective randomized studies, with an overall incidence of 42%. Stents placed for hilar obstruction appear to occlude faster than stents placed for more distal obstruction.41 The problem with stent occlusion has been studied intensively but attempts at altering bile composition using choleretic agents, reducing bacterial load with antibiotics, or influencing mucin production with aspirin have failed to prolong stent patency. Prophylactic stent changes have been advocated by many authorities: However, nearly 50% of patients undergoing stenting with 10 or 11.5 French plastic stents die prior to stent occlusion. Thus, not all patients will require stent changes and a watchful waiting remains a reasonable option if a good follow-up system is in place. Other late complications are unusual and include migration into the more proximal bile duct or bowel, duodenal or bile duct perforation and acute cholecystitis.

How to reduce the risk of acute cholangitis All patients undergoing evaluation and therapy should receive antibiotics before and after ERCP. The antibiotic chosen should penetrate an obstructed biliary tree (see patient preparation). For Bismuth type II and III strictures, good endoscopic techniques are paramount. Minimal contrast medium should be injected only into the duct to be drained. Once access is obtained to the obstructed segment, the pressure in the system should be reduced before more complete filling, by aspirating bile. If possible, manipulation of ducts that will not be drained should be avoided. A single stent into an obstructed segment that drains at least 25% of the liver should be placed. There does not seem to be any advantage to choosing one lobe of the liver over the other. If cholangitis occurs, ERCP or a percutaneous approach to drain the obstructed lobe of the liver should be performed promptly.36,38,42

Complications specific to metal stents Incomplete removal of the covering membrane, failure of stent expansion and inability to remove the inner catheter after stent release are rare technical problems. About 10–15% of metal stents eventually get occluded because of tumor ingrowth through the wire mesh or tumor overgrowth above or below the stent. The problem can be solved by inserting another stent, either plastic or metal, through the occluded stent (Figs 28.12–28.13).

A

B

Fig. 28.12 Tumor ingrowth: endoscopic treatment. A ERCP showing a case of tumor ingrowth in a SEMS. B A plastic stent inserted through the SEMS.

A

B

Fig. 28.13 Stent clogging: endoscopic treatment. A Endoscopic view showing the distal end of stent completely occluded. B Insertion of new SEMS through the occluded stent.

COSTS There are no economic analyses which compare various palliative options in patients with malignant biliary obstruction of the hepatic hilum. A “cost-effectiveness” study previous reported a tabulation of hospital charges comparing surgical bypass with endoscopic stenting in patients with distal malignant biliary obstruction. The study reported total costs per patients of 25 000 US$ for patients treated with surgical bypass, and 5000 US$ per patient treated with endoscopic stent.43 The cost-effectiveness of palliation with endoscopic stent is enhanced when metal stents are used. Studies have demonstrated that the cost for both treatment strategies are different only because of stent price. Cost analysis has concentrated on patency rates, repeat ERCPs, and total length of hospital stays. Of critical importance in determining cost-efficiency is the length of survival of each patient. Because occlusion rates are dependent on survival, the longer a patient survives, the more likely a metal stent will be beneficial (as plastic stents occlude earlier than metal). Despite the initial heavy cost of expandable metal stents (30–40 times that of the plastic stents), in patients surviving over than 4–6 months, metal stents ultimately (because of longer patency periods) prove to be the least expensive method of relieving biliary obstruction.44,45

SUMMARY 1. The evaluation of patients with suspected malignancy of the hepatic hilum should include helical or multislice CT of the abdomen. An MRCP should be obtained to assess for resectability. 2. If the disease is resectable and the patient is fit, surgical resection of the lesion should be performed. 3. Preoperative ERCP should be avoided unless there is cholangitis or significant delay in surgery and the patient is symptomatic. 4. If the lesion is unresectable or the patient is unfit for surgery, then endoscopic palliation of jaundice should be performed by using MRCP as a guide for unilateral drainage to minimize cholangitis. 309

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5. If cholangitis occurs, ERCP or a percutaneous approach to drain the obstructed lobe of the liver should be performed promptly. 6. The use of metal stents should be restricted to those patients who will, in all probability, live longer than 3 months.

Acknowledgments I thank Francesca Salvatori, MD, for the English text revision and Pietro Addeo, MD, for the bibliographic research.

REFERENCES 1.

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Klatskin G. Adenocarcinoma of the hepatic duct at its bifurcation within the porta hepatis: an unusual tumor with distinctive clinical and pathological features. Am J Med 1965; 38:241–256. De Groen PC, Gores GJ, LaRusso NF, et al. Biliary tract cancers. N Engl J Med 1998, 341; 18:1368–1378. Patel T. Worldwide trends in mortality from biliary tract malignancies. BMC Cancer 2002; 2(10):1–5. Chamberlain SS, Blumgart RH. Hilar cholangiocarcinoma: a review and commentary. Annals of Surgical Oncology, 2000; 7:55–66. Michaud DS. The epidemiology of pancreatic, gallbladder, and other biliary tract cancers. Gastrointest Endosc 2002; 56(6): S195–S200. Bismuth H, Corlette MB. Intrahepatic cholangioenteric anastomosis in carcinoma of the hilus of the liver. Surg. Gynecol. Obstet. 1975; 140:170–176. Gerhards MF, van Gulik TM, de Wit LT, et al. Evaluation of morbidity and mortality after resection for hilar cholangiocarcinoma-a single center experience. Surgery 2000; 127:395–404. Han JK, Choi BJ, Kim AY, et al. Cholangiocarcinoma: pictorial essay of ct and cholangiographic findings. RadioGraphics 2002; 22:173–187. Yeh T, Jan YY, Tseng JH, et al. Malignant perihilar biliary obstruction: magnetic resonance cholangiopancreatographic findings. Am J Gastroent 2000; 95:432–440. Mortele KJ, Ji H, Ros PR. CT and magnetic resonance imaging in pancreatic and biliary tract malignancies. Gastrointest Endosc 2002; 56:S206–S212. Lee WJ, Lim HK, Jang KM, et al. Radiologic spectrum of cholangiocarcinoma: emphasis on unusual manifestations and differential diagnoses RadioGraphics 2001; 21:S97–S116. Fritscher-Ravens A, Broering DC, Sriram PVJ, et al. EUS-guided fine-needle aspiration cytodiagnosis of hilar cholangiocarcinoma: a case series. Gastrointest Endosc 2000; 52:534–540. Anderson CS, Pinson CV, Berlin J, et al. Diagnosis and treatment of cholangiocarcinoma The Oncologist 2004; 9:43–57. Gerhards MF, van Gulik TM, de Wit LT, et al. Evaluation of morbidity and mortality after resection for hilar cholangiocarcinoma—a single center experience. Surgery 2000; 127:395–404. De Bellis M, Sherman S, Fogel EL, et al. Tissue sampling at ERCP in suspected malignant biliary strictures (Part 1). Gastrointestinal Endosc 2002; 56:552–561. De Bellis M, Sherman S, Fogel EL, et al. Tissue sampling at ERCP in suspected malignant biliary strictures (Part 2). Gastrointestinal Endosc 2002; 56:720–730. Sugiura Y, Nakamura S, Iida S, et al. Extensive resection of the bile ducts combined with liver resection for cancer of the main hepatic duct junction: a cooperative study of the Keio Bile Duct Cancer Study Group. Surgery 1994; 115:445–451.

18. Smimada K, Sano T, Sakamoto Y, et al. Safety and effectiveness of left hepatic trisegmentectomy for hilar cholangiocarcinoma. World J. Surg. 2005; 29:723–727. 19. Capussotti L, Muratore A, Polastri R, et al. Liver resection for hilar cholangiocarcinoma: in-hospital mortality and longterm survival. J Am Coll Surg 2002; 195:641–647. 20. Meyer CG, Penn I, James L. Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation 2000; 69:1633–1637. 21. De Vreede I, Steers JL, Burch PA, et al. Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma. Liver Transpl 2000; 6:309–316. 22. Zoepf T, Jakobs R, Rosenbaum A, et al. Photodynamic therapy with 5-aminolevulinic acid is not effective in bile duct cancer Gatrointest Endosc 2001; 54:763–766. 23. Ortner MEJ, Caca K, Berr F, et al. Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study. Gastroenterology 2003; 125:1355–1363. 24. Wiedmann M, Berr F, Schiefke I, et al. Photodynamic therapy in patients with non-resectable hilar cholangiocarcinoma: 5-year follow-up of a prospective phase II study Gastrointest Endosc 2004; 60:68–75. 25. Hawes RH. Diagnostic and therapeutic uses of ERCP in pancreatic and biliary tract malignancies. Gastrointest Endosc 2002; 56: S201–S205. 26. Strasberg SM. ERCP and surgical intervention in pancreatic and biliary malignancies Gastrointest Endosc 2002; 56:S213–S217. 27. Flamm CR, Mark DH, Aronson N. Evidence-based assessment of ERCP approaches to managing pancreaticobiliary malignancies Gastrointest Endosc 2002; 56:S218–S225. 28. Rey JF, Dumas R, Canard JM, et al. Guidelines of the French Society of Digestive Endoscopy: Biliary Stenting. Endoscopy 2002; 34:169–173. 29. ASGE Guidelines. The role of endoscopy in the evaluation and treatment of patients with pancreaticobiliary malignancy. Gastrointest Endosc 2003; 58:643–649. 30. ASGE guideline: the role of ERCP in diseases of the biliary tract and the pancreas. Gastrointest Endosc 2005; 62:1–8. 31. Chang W, Kortan P, Haber G. Outcome in patients with bifurcation tumors who undergo unilateral versus bilateral hepatic duct drainage. Gastrointest Endosc 1998; 47:354–362. 32. Abraham NS, Barkun JS, Barkun A. Palliation of malignant biliary obstruction: a prospective trial examining impact on quality of life Gastrointest Endosc 2002; 56:835–841. 33. Raiker GV, Melin MM, Ress A, et al. Cost-effective analysis of surgical palliation versus endoscopic stenting in the management of unresectable pancreatic cancer. Ann Surg Oncol 1996; 3:470–475. 34. Brandabur JJ, Kozarek RA, Ball TJ, et al. Non-operative versus operative treatment of obstructive jaundice in pancreatic cancer: cost and survival analysis. Am J Gastroenterol 1988; 83:1132–1139.

Chapter 28 Malignant Biliary Obstruction: Hilar

35. Taylor MC, McLeod RS, Langer B. Biliary stenting versus bypass surgery for the palliation of malignant distal bile duct obstruction; a meta-analysis. Liver Transpl 2000; 6:302–308. 36. Speer AG, Cotton PB, Russell RCG. Randomized trial of endoscopic versus percutaneous stent insertion in malignant obstructive jaundice. Lancet 1987; 2:57–62. 37. De Palma GD, Galloro G, Iovino P, et al. Unilateral versus bilateral endoscopic hepatic duct drainage in patients with malignant hilar biliary obstruction. Results of a prospective, randomized, and controlled study. Gastrointest Endosc 2001; 53:547–553. 38. Hintze RE, Abou-Rebyeh H, Adler A, et al. Magnetic resonance cholangiopancreatography—guided unilateral endoscopic stent placement for Klatskin tumors. Gastrointest Endosc 2001; 53:40–46. 39. De Palma GD, Pezzullo A, Rega M, et al. Unilateral placement of metallic stents for malignant hilar obstruction: a prospective study. Gastrointest Endosc 2003; 58:50–53. 40. Freeman ML, Overby C. Selective MRCP and CT-targeted drainage of malignant hilar biliary obstruction with self-expanding metallic stents Gastrointest Endosc 2003; 58:41–49.

41. Singh V, Sigh G, Verma GR, et al. Contrast-free unilateral endoscopic palliation in malignant hilar biliary obstruction: New method Journal of Gastroenterology and Hepatology 2004; 19:589–592. 42. Shermann S, Lehman G, Earle D. Are the patency rates for 10French, 11.5-French stents different for common duct obstruction and hilar obstruction? Randomized, prospective study. Gastrointest Endosc 1996; 43:396. 43. Shermann S. Endoscopic drainage of malignant hilar obstruction: Is one biliary stent enough or should we work to place two? (Editorial) Gastrointest Endosc 2001; 53:681–684. 44. Raikar GV, Melin MM, Ress A, et al. cost-effective analysis of surgical palliation versus endoscopic stenting in the management of unresectable pancreatic cancer. Ann Surg Onc 1996; 3:470–475. 45. Schmassmann A, Von Gunten E, Knuchel J, et al. Wallstents versus plastic stents in malignant biliary obstruction: effects of stent patency of the first and second stent on patient compliance and survival. Am J Gastroenterol 1996; 91:654–659.

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29

APPROACH TO CLINICAL PROBLEMS

Indeterminate Biliary Stricture Bret T. Petersen

Biliary obstruction results from diverse benign and malignant processes and patients can present acutely or chronically with signs and symptoms ranging in severity. The nature of an obstruction is often immediately clear at the time of initial investigation, while at other times obstruction is readily apparent but the nature of the pathologic process remains uncertain. No single definition exists for the term “indeterminate stricture,” but it commonly refers to biliary strictures in patients in whom cross-sectional imaging is unrevealing, i.e. without an associated mass lesion, and without pathologic confirmation. Recent experience with inflammatory pancreatic masses might prompt expansion to include all strictures, including those with associated mass lesions, prior to histological characterization. When biliary obstruction is identified, an efficient approach to early diagnostic testing and management is important for reduction of morbidity and guidance of definitive therapy. Untreated obstructive cholestasis of even moderate degree can culminate in secondary biliary cirrhosis within several months.1,2 Patients with inadequately treated strictures also risk development of acute or chronic cholangitis, particularly following invasive testing. Key steps in the assessment and management of patients with indeterminate biliary strictures include characterization of the pathogenesis of the stricture, relief of biliary obstruction and/or definitive treatment of the pathologic process—employing medical, endoscopic, percutaneous, or surgical means. Stricture characterization and relief of obstruction are not independent pursuits but are typically accomplished in unison. Stricture characterization is based upon historical features, laboratory testing, non-invasive and invasive imaging, and by the use of various tissue sampling methods (Fig. 29.1).3

HISTORICAL FEATURES Historical features may contribute to both the correct diagnosis and the management strategy for newly identified biliary strictures (Table 29.1). Prior history of ulcerative colitis, complicated biliary surgery, or chronic pancreatitis suggest PSC, postoperative strictures, and pancreatic compression of the CBD, respectively. An acute presentation in the early postoperative period or during an episode of pancreatitis suggests significant operative injury or stonerelated obstruction whereas sub-acute but early (3 mm was 79% sensitive and 79% specific for malignancy. The sensitivity of FNA was 47%, with 100% specificity and positive predictive value but only 50% negative predictive value.10 In a comparative study of several modalities, EUS sensitivity and specificity (79% and 62%) were less than ERCP or MRCP but complementary to them.8 In contrast, a study evaluating EUS with FNA in 28 patients with non-diagnostic sampling of biliary strictures obtained during ERCP, PTC, or CT demonstrated 86% sensitivity, 100% specificity, 100% positive predictive value, 57% negative predictive value, and 88% accuracy for malignant lesions.11 Importantly, management B

Fig. 29.4 Cross-sectional imaging with MRCP or CT provides guidance to the preferred lobe for palliative biliary drainage during ERCP in patients with proximal biliary obstruction. A MRCP suggests access should be pursued toward the dominant right lobe. B CT in the same patient demonstrates left lobe atrophy, also suggesting access should be to the right lobe. 316

Chapter 29 Indeterminate Biliary Stricture

was influenced in 84% of patients. Some but not all studies note a greater sensitivity of EUS/FNA for pancreatic lesions than for extrahepatic cholangiocarcinoma.12 EUS and CT are complementary studies for staging and determination of resectability for distal biliary strictures due to pancreatic mass lesions.13 Hence, while not a primary imaging modality for biliary strictures, EUS with FNA is an important ancillary technique when diagnosis remains elusive and when staging for determination of resectability is sought. Cholangiography is the mainstay for diagnosis and characterization of extrahepatic biliary lesions of all types. Endoscopic and percutaneous approaches to cholangiography are complementary studies and, on occasion, both will be necessary to characterize and treat difficult biliary lesions (Table 29.2). In general, proximal lesions that appear to involve the hilar region are best investigated initially with non-invasive MRCP, as this study provides directional guidance for subsequent invasive imaging and palliation7 and avoids the risk of cholangitis that occurs with ERCP when contrast is injected into areas which may not be drainable. However, preoperative planning for hilar lesions may still require the clarity of contrast-based cholangiography (ERCP or PTC). The cholangiographic appearance of the stricture is generally inadequate for interpretation of malignancy and many strictures that are interpreted as benign prove to be malignant.14 Features suggestive of malignancy include progressive focal stricturing over time, abrupt shelf-like borders, length greater than 14 mm, intrahepatic duct dilation, and presence of intraductal polypoid or nodular areas.14,15 In the setting of background sclerosing cholangitis with dominant strictures, malignant lesions are more likely to exceed 1 cm in length, be located at the bifurcation as opposed to the common bile duct, and have irregular margins.16 Despite these criteria, cholangiography alone correctly identified only 8 of 12 (66% sensitivity) malignant lesions and 21 of 41 (51% specificity) benign lesions.16 Endoscopic retrograde cholangio-pancreatography (ERCP) has become the primary non-operative modality for both investigation and palliation of biliary strictures because it provides high quality contrast-based images of the ductal systems, access for tissue sampling, and means of therapy via internal drainage. ERCP is preferred if there is a likely need for stone extraction or stent placement in the extrahepatic ducts, when coagulopathy or ascites is present, when

the bile ducts are not dilated, and when percutaneous approaches fail. It should be undertaken only by endoscopists with the experience and ability to proceed with appropriate imaging, tissue sampling, and therapies. In inexperienced hands initial studies often yield poor stricture definition, inadequate drainage, or procedural complications. Endoscopic cholangiography in the setting of obstructive jaundice should be performed with peri-procedural antibiotic coverage and anticipation of continuing antibiotics for a brief interval, particularly if complete drainage cannot be achieved. Stent placement should be performed whenever significant contrast is instilled above a lesion that prevents spontaneous drainage. In the setting of hilar strictures intrahepatic filling of contrast should be avoided until wire access is accomplished, to ensure the ability to provide subsequent palliative drainage of the imaged segments. As noted, prior highquality CT or MRCP imaging can guide selection of optimal intrahepatic systems for wire access and stent placement. Optimal characterization and successful access for sampling and treatment require attention to imaging principles that are often not appreciated by non-radiologists. The following points apply equally to imaging of benign or malignant strictures (Table 29.3): (1) Strictures, unlike large dilated systems, are best imaged with full-strength contrast. (2) Multiple early films should be taken as contrast is first crossing the lesion, continuing the injection until the image has been obtained (Fig. 29.5). This allows later reference back to the minute details of angles or bifurcations, which may not be evident when the ducts are completely filled. (3) Coning down on an area of interest will sharpen the detail seen on hard copy. This requires at least some larger views to maintain anatomic reference. (4) Tissue sampling and therapy should be performed with the least contrast filling required to adequately demonstrate the anatomy. Excessive filling of intrahepatic ducts often obscures the bifurcation. (5) The proximal extent of duct involvement must be well demonstrated for surgical or endoscopic decision making. Following wire access,

1. 2. 3. 4. 5.

Settings favoring endoscopic approach (ERCP) Preferred in most settings Intact upper gut anatomy Anticipated need for therapeutic stenting or stone removal Need for luminal exam Ascites Coagulopathy Small caliber ducts Failed percutaneous approaches Settings favoring percutaneous approach (PTC) Altered upper gut anatomy, especially Roux-en-Y gastric bypass, +/− Whipple anatomy Complete biliary obstruction Failed endoscopic access for cholangiography or stent placement Need to better image and stage proximal end of stricture for surgical planning

Table 29.2 Indications and favored settings for endoscopic vs percutaneous cholangiographic approach to biliary strictures

6.

7.

8.

8.

9.

Use pre-procedure antibiotics and full strength contrast. Obtain multiple early images during contrast injection. Obtain selected broad views to maintain anatomic reference. Cone down on the area of interest to sharpen radiographic detail. Use the least contrast filling required to adequately demonstrate anatomy. Employ prior CT or MRCP for hilar lesions to guide intrahepatic duct selection for contrast filling and decompression. When wire access is confirmed the proximal extent of duct involvement must be well demonstrated for surgical or endoscopic decision making. Head-up and head-down positions on a tilt table can facilitate imaging of stricture extent by inducing contrast flow to the area of interest. An open hilar view is best obtained with a 20 degree oblique position using a C-arm or by rolling the prone patient rightward toward the endoscopist. After demonstrating a distal stricture, the bifurcation and central intrahepatic ducts should be filled to exclude secondary proximal obstruction (e.g. adenopathy). Some lesions can only be well characterized by percutaneous cholangiography.

Table 29.3 Pointers for stricture characterization during cholangiography 317

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A

B

C

Fig. 29.5 Early A vs later B images acquired during ERCP. Note detail evident on early image is obscured by intrahepatic filling overlapping the area of interest in the subsequent view. Note improved view C with oblique imaging.

A

B

A

B

Fig. 29.6 A and B Overlapping and open views of the ducts at the hilum. B is obtained by rolling the patient rightward 15–20 degrees or by leftward rotation of a C-arm.

marked filling may be required to delineate the proximal end of the stricture. (6) Head-up and head-down positions on a tilt table can facilitate imaging of stricture extent by employing gravity to shift contrast to the area of interest. (7) An open view of the hilum, without overlapping ducts, is best seen in an oblique position, which is achieved with use of a C-arm or by rolling the prone patient rightward toward the endoscopist (Fig. 29.6). (8) After demonstrating a distal extrahepatic stricture, the central intrahepatic ducts and hepatic confluence should be filled to exclude additional proximal strictures (e.g. adenopathy) within reach of endoscopic management. (9) Some lesions can only be well characterized by percutaneous cholangiography (Fig. 29.7). (10) Limited pancreatography may aid in demonstrating or excluding a pancreatic primary lesion when biliary strictures involve the distal third of the duct. Stricture access with guidewires and subsequently other over-thewire accessories is required to accomplish cytology brushing, dilation, and palliative stenting or definitive endoscopic management. Access is usually gained with multipurpose plastic-coated guidewires or specialty hydrophilic wires that are extremely slippery, flexible, and torqueable.17 Manipulation of angled wires using simultaneous torque and advancement can be performed by the assistant, or by the endoscopist using any of several recently designed short318

Fig. 29.7 Benefit of percutaneous trans-hepatic cholangiography (PTC) for proximal evaluation of selected duct lesions. A Partial endoscopic cholangiogram demonstrating complete duct obstruction following laparoscopic cholecystectomy. B PTC-placed hepatic drain demonstrating intrahepatic ducts, confirming complete duct disruption.

wire systems. This is best done with two hands to facilitate fine wire control and maintenance of position (Fig. 29.8). Stricture dilation should be performed prior to passage of larger caliber devices. In the case of benign lesions this constitutes the first step in their therapy. For the tightest strictures that will not accept anything beyond 0.035″ guidewires, initial dilation can be accomplished with angioplasty balloons that traverse 0.018″ wires and expand up to 4 mm from their deflated 0.035″ caliber (Fig. 29.9). Rigid 4–5–7 F dilators can be passed over a 0.025 guidewire. Standard balloon dilators can then be used to expand to larger calibers. Balloon selection is based upon the size of the non-obstructed duct just distal to the stricture. Most often this calls for 4, 6, or 8 mm diameter balloons. Tight chronic strictures carry some risk for rupture or tear during dilation. Should this occur, adequate

Chapter 29 Indeterminate Biliary Stricture

stenting for drainage is mandatory and addition of a nasobiliary drain may be useful during a several-day hospital stay for parenteral antibiotics. Percutaneous transhepatic cholangiography (PTC) has similar capabilities of duct imaging, access, and palliative drainage as does ERCP; however, it is performed through a sterile prepped cutaneous field and hence cholangitis risks are lessened and drainage of filled

segments is less critical. PTC is only indicated when the proximal end of a stricture has not been adequately characterized by MRCP or retrograde methods (if this information will change management), when endoscopy fails to access and decompress an obstructed system, or altered anatomy dictates that percutaneous routes be used. When an extrahepatic stricture cannot be accessed from below, a guidewire can be advanced via PTC for subsequent retrograde access. Use of this so-called “combined procedure” to enable stent placement and decompression should have less morbidity than conversion of the entire management plan to a percutaneous approach.

TISSUE ACQUISITION AND PATHOLOGIC INVESTIGATIONS

Fig. 29.8 A view of the endoscopist’s hands during manipulation of a slippery guidewire through difficult strictures. Note that two hands are used to hold and move the wire, while the base of one hand holds the control section of the endoscope.

A

Methods of tissue acquisition and analysis for cholangiography include performance of fine needle aspiration and mucosal brushing for thin preparation cytologic exam, mucosal biopsy for standard histological analysis, and evaluation of both cytology and biopsy specimens using a variety of specialized tests for nucleic abnormalities or by-products of neoplasia. Tissue acquisition is a key element of each of these techniques. In a recent review, all available sampling techniques during ERCP were evaluated.18 Overall, the results for pathologic examination of tissues acquired at ERCP remain frustratingly low. This is due to several factors, including the scirrhous nature of many tumors, the small tissue samples acquired, difficulty in targeting the abnormality in question, and time constraints in procedures geared primarily toward palliation and less so to tissue acquisition. During cholangiography, spot film radiographic documentation should be obtained of all sampling techniques and locations.

B

C

Fig. 29.9 Dilation of a web-like anastomotic stricture with an angioplasty balloon passed over a 0.018” guidewire. This balloon dilates from an outer diameter of 0.035” to 4 mm, allowing subsequent passage of standard 5 Fr balloon catheters for dilation to 6 or 8 mm. 319

SECTION 3 APPROACH TO CLINICAL PROBLEMS

A

Fig. 29.10 Various cytology brush designs include: A metal tip brush; B brush with flexible wire leader in single lumen catheter; C brush with leader and guidewire in dual lumen catheter; and (d) large caliber brush. (With permission, from Clinical Gastrointestinal Endoscopy, Elsevier Saunders.)

B

Fig. 29.11 A Cholangiogram demonstrating an indeterminate biliary stricture. B Wire-guided brush cytology device within the stricture.

A

B

Brush cytology The yield of brush cytology for the diagnosis of strictures varies widely, with confirmation of malignancy in 15–65% of biliary strictures secondary to pancreatic cancer and in 44–80% of strictures due to cholangiocarcinoma.18,19 Combined results in over 800 patients reported sensitivity of 42%, specificity of 98% and positive predictive value (PPV) of 98% among patients with confirmed cancer.18 Studies pertaining to sampling technique note that cellular yield is improved by using a minimum of five brush passes through the stricture, removal of the catheter and brushing together while avoiding brush withdrawal through the length of the catheter, and flushing residual cells from within the catheter into the sample vial after removal of the brush.20 It is unclear whether stricture dilation improves sample cellularity. Inclusion of washings from the barb or lumen of removed plastic stents may also enhance cytology yield. A variety of brushes are available but few comparative data exist among them. One major design variant is incorporation of a leading flexible wire guide for maintenance of position both within the stricture and within the duct (Fig. 29.10). One study showed no difference between traditional biliary brushes and a new design with longer, stiffer, angled bristles.19 Both brushes yielded adequate specimens in over 80% of cases, suggesting cytologic technology itself is suboptimal for all varieties of malignant biliary lesions. Today biliary cytology brushing is most commonly employed using wire-guided devices (Fig. 29.11). The technique involves first establishing wire-access through the stricture, advancement of the cytology device over the guidewire until through the stricture, advancement of the brush beyond the end of the sheath, and withdrawal of the two together until the brush is within the stricture. The brush is then passed up and down through the stricture at least five times, using either combined movement of the sheath and the brush by the endoscopist, or movement of the brush itself by the assistant as the sheath is held in place. Those devices with a flexible wire leader ahead of the brush can be withdrawn through most of the length of the stricture and safely advanced without risking loss of access or perforation. Some tight or angled strictures can only be brushed with a downward movement or brush withdrawal, requiring repeated access with the entire assembly for each brush pass. 320

Fig. 29.12 A An indeterminate biliary stricture with a neighboring pancreatic stricture representing a double duct sign, suspicious for pancreatic carcinoma. B Forceps biopsy being performed parallel to a guidewire.

Intraductal transmucosal fine needle aspiration This FNA method was reported to yield positive or suspicious cytology in 67% of cancers in the hands of one proponent21 but cumulative data from over 220 patients in five series yielded a sensitivity of only 34%, with 100% specificity and 100% PPV.18 The technique has not gained favor as it is difficult and is optimally performed with a cytopathologist in the room.

Intraductal forceps biopsies Intraductal biopsies provide the greatest yield for detection of malignancy among the ERCP-based modalities, with a cumulative sensitivity of 56%, specificity of 97% and positive predictive value of 97% based upon 500 patients in five cumulative studies.18,20 A variety of straight, angled, and malleable forceps are available in adult (7 F) and pediatric (5–6 French) calibers for intraductal use. Passage of these devices may require performance of a biliary sphincterotomy. However, passing the forceps alongside of a guidewire without sphincterotomy is possible.22 Trocars or sheaths for transpapillary passage of biopsy cables are also available. There are limited data comparing the different biopsy devices. The technique of passing a biopsy forceps into the bile duct involves impacting the rigid leading end of the biopsy cable into the papillary os or the sphincterotomy opening from a short scope position, then advancing the endoscope several centimeters while simultaneously flexing the large ratchet backward to look upward from below the papilla, followed by upward advancement of the cable (Fig. 29.12). Alternatively one can occasionally advance the biopsy

Chapter 29 Indeterminate Biliary Stricture

A B

Fig. 29.13 Fluorescent in-situ hybridization demonstrates a single microscopic field with fluorescent probes of different colors attached to specific chromosomal loci. Two copies of each probe should be present. Presence of more than two copies represents aneuploidy in a cell. A a normal cell. B a cell from a malignant stricture in a patient with PSC.

cable directly into the papilla from a slightly longer flexed position, looking upward from below the papilla. The highest diagnostic yield for tissue sampling during ERCP is obtained when two or more of the standard modalities are combined at the same procedure. Ponchon increased the cumulative yield to 63% by combining brush cytology (43% sensitivity) and intraductal biopsy (30%).23 Combined biopsy, brushing, FNA, and stent cytology yielded positive diagnosis in 82% of patients in one study.23a Given the suboptimal diagnostic yield from standard analyses of brush cytology and tissue biopsy samples, a variety of advanced analytic techniques have been investigated. They include flow cytometry, digital image analysis (DIA), and fluorescent in-situ hybridization (FISH). In a limited number of studies, flow cytometry for DNA assessment of large cellular populations yielded improved sensitivity at the expense of significantly reduced specificity.24 Digital image analysis uses a computerized assessment of cellular DNA ploidy within a smaller number of individual cells identified on a cytology slide to estimate the relative proportion with aneuploidy, which serves as a marker of malignancy. In a recent prospective study of 100 patients with mixed benign and malignant strictures the sensitivity, specificity, and accuracy of DIA of biliary brush cytology samples was 39.3%, 77.3%, and 56%, compared to 17.9%, 97.7%, and 53% for standard cytology.25 False positive results from DIA (10 of 44, 22.7%) occurred only in patients with primary sclerosing cholangitis (PSC). The only false positive for routine cytology (1/44, 2.3%) was also in a patient with PSC. Fluorescent in-situ hybridization employs fluorescent probes that label specific portions of selected chromosomes, allowing for determination of cellular ploidy via fluorescent microscopy of specific cellular samples (Fig. 29.13). Recent studies have employed chromosomal probes that were originally designed for identification of urothelial cancers (centromeres to chromosomes 3, 7, and 17 plus chromosomal band 9p21).26 Detection of more than five cells with polysomy is considered evidence for malignancy. In preliminary

studies, the FISH technique increased the sensitivity of brush sampling for detection of malignancy from 15% to 34% (p < 0.01), with corollary non-significant reduction in specificity from 98% to 91% (p = 0.06).26 Concerns about specificity persist and confirmatory series are needed. Studies designed to identify products of other genetic mutations (p-53, k-ras) in bile or tissues have not yielded adequate sensitivity and specificity to be of clinical use for diagnosis.

ANCILLARY TECHNIQUES Intraductal ultrasonography (IDUS) employs a 20 mHz radial ultrasound probe on the leading end of a 7 French catheter that can be passed over a guidewire into the biliary and pancreatic ducts during ERCP (Fig. 29.14). IDUS has been employed for identification of residual duct stones, characterization of strictures, and staging of local cancer involvement. Following performance of cholangiography, a 0.035″ guidewire is left in the duct and the ultrasound probe is advanced over the wire with the radial crystal stationary. Imaging is then performed primarily during catheter withdrawal, to limit mechanical trauma to the mechanical drive of the probe. Acquisition of IDUS skills is less involved than acquisition of EUS skills and most experienced endoscopists should be able to adopt IDUS for the management of stone disease with limited training, and for stricture assessment with slightly greater experience. Ultrasonographic features of malignant strictures include hypoechoic asymmetric wall thickening, poorly demarcated borders and abrupt shoulders (Fig. 29.15). Benign lesions tend to be hyperechoic, have less asymmetry, sharper demarcation with surrounding tissues, preserved tissue planes, and smooth edges. IDUS interpretation is more difficult in the setting of primary sclerosing cholangitis, where widespread background inflammation and duct thickening are present. Similarly, prolonged stenting can induce more widespread duct abnormalities than were originally present at the level of the index stricture. 321

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A

B

C

Fig. 29.14 A Leading end of 5 F wire-guided intraductal ultrasound (IDUS) probe. The mechanical radial ultrasound crystal is noted with an arrow. B IDUS catheter exiting from the duodenoscope. C IDUS probe within stricture in Figure 29.11.

Fig. 29.15 IDUS images from an extrahepatic cholangiocarcinoma. Note the asymmetry of wall thickening and its irregular outer boundary.

Several studies have demonstrated the superior sensitivity and accuracy of IDUS for characterization of strictures as malignant (sensitivity >90%; accuracy 88–92%) compared to standard cholangiography, with or without cytology and biopsy sampling (sensitivity 48–57%; accuracy 73–78%).27–29 In a recent prospective study in 87 patients, elevated serum CA 19-9 (>100 units), routine cytology and 322

intraductal biopsy were compared to advanced cytologic assessment with DIA, FISH and stricture assessment with IDUS. IDUS showed the greatest sensitivity (87%) and accuracy (90%), and the combination of IDUS, DIA, and FISH allowed diagnosis of malignancy in 87% of those with falsely negative routine cytology.30 Studies of IDUS for tumor staging also report utility for defining longitudinal extent as well as the extent of invasion to the pancreatic parenchyma, portal vein, and right hepatic artery.31 Periductal, nodal, and distant spread is not adequately assessed by IDUS. Cholangioscopy, or direct visual evaluation of the biliary tree, is increasingly used for visually directed sampling of indeterminate strictures and for electrohydraulic lithotripsy therapy of intractable stones. Cholangioscopy is also discussed in Chapter 21 (Fig. 29.16). It usually employs 8–10 French mini-endoscopes that are passed through the working channel of a therapeutic duodenoscope, with or without guidewire assistance. Fiberoptic cholangioscopes are commercially available; digital video-chip versions are in use but not widely available. Cholangioscopy is usually performed with the assistance of a second endoscopist to manipulate the cholangioscope controls and biopsy cables while the primary endoscopist controls the duodenoscope and the insertion of the cholangioscope. Some centers employ custom endoscope holders for the cholangioscope to enable studies by a single operating physician.32 During cholangioscopy attention must be paid to frequent or continuous flushing to clear the field of bile or debris. Fluid run-off to the stomach requires frequent aspiration, use of a nasogastric tube, or endotracheal intubation. Cholangioscopes are relatively fragile and care must be taken to avoid excessive angulation or force, particularly at the level of the elevator on the duodenoscope. Recent series demonstrate improved sensitivity and accuracy for diagnosis of malignant obstruction when cholangioscopy is employed33,34 In one study, ERCP with fluoroscopically guided tissue sampling had a sensitivity of 58% and accuracy of 78% for malignancy while addition of cholangioscopy raised these values to 100%

Chapter 29 Indeterminate Biliary Stricture

A

B

Fig. 29.16 A Radiograph of a cholangioscope advanced to the level of the proximal extrahepatic duct. B Cholangioscopic view of hepatic confluence with open left hepatic duct and tumor occluding right hepatic duct.

and 94% respectively.33 Cholangioscopy may be particularly useful in differentiating benign from malignant strictures in the setting of primary sclerosing cholangitis. One study demonstrated improved sensitivity (92% vs 66%, p = 0.25), specificity (93% vs 51%, p < 0.001), and accuracy (93% vs 55%, p < 0.001) for cholangioscopic characterization compared to radiographic characterization.16 The criteria for suspicion of malignancy in this study were the presence of an associated polypoid or villous mass or irregularly shaped ulceration. A recently developed technology employs a single-use 10 Fr multi-channeled sheath (SpyglassTM Direct Visualization System; Boston Scientific, Marlboro, MA) that attaches to the head of the duodenoscope just below the biopsy port and advances through the accessory channel for insertion into the duct (Fig. 29.17). The sheath provides 4-way steering of the tip, illumination, water flushing, a channel for passage of a 0.035” caliber fiberoptic probe for visualization of the duct (SpyScope), and another for either wire guidance or passage of therapeutic or sampling devices such as the electrohydraulic probe, biopsy cables (SpyBite), or cytology brushes. Preliminary data demonstrate utility in 18 of 20 cases for directed biopsy, stone therapy, or clarification of anatomy or pathology.35 Stent placement for biliary decompression is the major therapeutic modality used for patients with indeterminate strictures. Stenting as definitive therapy for benign lesions or as palliative therapy for malignant obstruction is discussed in Chapters 16 and 17. Plastic stents are usually employed for palliation of indeterminate strictures to ensure the ability to remove them at a later endoscopic or surgical procedure and to limit the cost of potentially brief duration stenting. When diagnosis remains indeterminate, serial procedures and repeated tissue sampling are often performed; hence shorter intervals of drainage and smaller caliber 7 and 8.5 French stents may suffice. If subsequent diagnostic investigations are chosen that employ EUS rather than ERCP or if the patient is not a surgical candidate regardless of the diagnosis, it is preferable to palliate the indeterminate lesion with larger caliber 10 French stents that remain patent longer and may minimize the number of

A

B

C

D

Fig. 29.17 The SpyGlass Direct Visualization System attached to the duodenoscope and advanced into the accessory channel. Close-up demonstrates ratchets for steering and ports for passage of guidewire, biopsy forceps, and 0.035” SpyGlass fiberoptic probe. 323

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subsequent procedures. In the patient with an indeterminate stricture self-expandable metal stents (SEMS) are typically avoided due to both their permanence and their expense. Partially coated SEMS are generally removable when they are left extending into the duodenum, and fully coated variants designed specifically for removal are under investigation.36,37 Their use can be entertained in the indeterminate lesion if prolonged stenting for either treatment of benign stricture or palliation of cancer is desirable. Plastic stents

remain preferable for the patient with a mass lesion and high likelihood of resectability. Modern imaging and new analytical techniques have advanced our ability to characterize indeterminate biliary strictures. Nevertheless, in some patients with indeterminate strictures a definitive diagnosis cannot be made via minimally invasive approaches. In these instances, surgical exploration with a goal of diagnosis and resection should be considered in operable patients.

REFERENCES 1. Afroudakis A, Kaplowitz N. Liver histopathology in chronic common bile duct stenosis due to chronic alcoholic pancreatitis. Hepatology 1981; 1:65–72. 2. Lesur G, Levy P, Flejou JF, et al. Factors predictive of liver histopathological appearance in chronic alcoholic pancreatitis with CBD stenosis and increased serum alkaline phosphatase. Hepatology 1993; 18:10781–1081. 3. ASGE Standards of Practice Committee. An annotated algorithmic approach to malignant biliary obstruction. Gastrointest Endosc 2001; 53:849–852. 4. Torok N, Gores GJ. Cholangiocarcinoma. Seminars in Gastrointestinal Disease 2001; 12:125–132. 5. Klimstra DS, Adsay NV. Lymphoplasmacytic sclerosing (autoimmune) pancreatitis. Seminars in Diagnostic Pathology 2004; 21:237–246. 6. Chari ST, Smyrk TC, Levy MJ, et al. Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience. Clin Gastroenterol Hepatol 2006 Aug; 4(8):1010–1016. 7. De Palma GD, Pezzullo A, Rega M, et al. Unilateral placement of metallic stents for malignant hilar obstruction: A prospective study. Gastrointestinal Endoscopy 2003; 58:50–53. 8. Rosch T, Meining A, Fruhmorgen S, et al. A prospective comparison of the diagnostic accuracy of ERCP, MRCP, CT, and EUS in biliary strictures. Gastrointestinal Endoscopy 2002; 55:870–876. 9. Domagk D, Wessling J, Reimer P, et al. Endoscopic retrograde cholangio-pancreatography, intraductal ultrasonography, and magnetic resonance cholangio-pancreatography in bile duct strictures: A prospective comparison of imaging diagnostics with histopathological correlation. American Journal of Gastroenterology 2004; 99:1684–1689. 10. Lee JH, Salem R, Aslanian H, et al. Endoscopic ultrasound and fine-needle aspiration of unexplained bile duct strictures. American Journal of Gastroenterology 2004; 99:1069–1073. 11. Eloubeidi MA, Chen VK, Jhala NC, et al. Endoscopic ultrasoundguided aspiration biopsy of suspected cholangiocarcinoma. Clinical Gastroenterology and Hepatology 2004; 2:209–213. 12. Rosch T, Hofrichter K, Fringberger E, et al. ERCP or EUS for tissue diagnosis of biliary strictures? A prospective comparative study. Gastrointestinal Endoscopy 2004; 60:390–396. 13. Wiersema MJ, Fletcher JG, Jondal ML, et al. Prospective evaluation of triple phase multidetector computed tomography, dynamic gadolinium-enhanced magnetic resonance imaging and endosonography in potentially resectable pancreatic adenocarcinoma. Gastrointestinal Endoscopy 2002 Oct; 56(4 Suppl):S123. 14. Bain VG, Abraham N, Jhangri GS, et al. Prospective study of biliary strictures to determine the predictors of malignancy. Endoscopy 2000; 14:397–402. 15. MacCarty RL, LaRusso NF, May GR, et al. Cholangiocarcinoma complicating primary sclerosing cholangitis: cholangiographic appearances. Radiology 1985; 156:43–46. 324

16. Tischendorf JJW, Kruger M, Trautwein C, et al. Cholangioscopic characterization of dominant bile duct stenosis in patients with sprimary sclerosing cholangitis. Endoscopy 2006; 38:665–669. 17. ASGE Technology Committee. Technology assessment status evaluation: guidewires in gastrointestinal endoscopy. Gastrointestinal Endoscopy 1998; 47:579–583. 18. De Bellis M, Sherman S, Fogel EL, et al. Tissue sampling at ERCP in suspected malignant biliary strictures (Part 2). Gastrointestinal Endoscopy 2002; 56:720–730. 19. Fogel EL, deBellis M, McHenry L. Effectiveness of a new long cytology brush in the evaluation of malignant biliary obstruction: a prospective study. Gastrointest Endosc 2006; 63:71–77. 20. Barkun A, Liu J, Carpenter S, et al. Update on endoscopic tissue sampling devices. Gastrointestinal Endoscopy 2006; 63:741–745. 21. Howell DA, Beveridge RP, Bosco J, et al. Endoscopic needle aspiration biopsy at ERCP in the diagnosis of biliary strictures. Gastrointestinal Endoscopy 1992; 38:531–535. 22. Lin LF, Siauw CP, Ho KS, et al. Guidewire technique for endoscopic transpapillary procurement of bile duct biopsy specimens without endoscopic sphincterotomy.Gastrointest Endosc 2003 Aug; 58(2):272–274. 23. Ponchon T, Gagnon P, Berger F, et al. Value of endobiliary brush cytology and biopsies for the diagnosis of malignant bile duct stenosis: results of a prospective study, Gastrointestinal Endoscopy 1995; 42:565–572. 23a. Jailwala J, Fogel EL, Sherman S, et al. Triple-tissue sampling at ERCP in malignant biliary obstruction. Gastrointest Endosc 2000; 51:383–390. 24. Ryan ME, Baldauf MC. Comparison of flow cytometry for DNA content and brush cytology for detection of malignancy in pancreaticobiliary strictures. Gastrointest Endosc 1994; 40: 133–139. 25. Baron TH, Harewood GC, Rumalla A, et al. A prospective comparison of digital image analysis and routine cytology for the identification of malignancy in biliary tract strictures. Clinical Gastroenterology and Hepatology 2004; 2:214–219. 26. Kipp BR, Stadheim LM, Halling SA, et al. A comparison of routine cytology and fluorescence in situ hybridization for the detection of malignant bile duct strictures. Am Journal of Gastroenterology 2004; 99:1675–1681. 27. Farrell RJ, Agarwal B, Brandwein SL, et al. Intraductal US is a useful adjunct to ERCP for distinguishing malignant from benign biliary strictures. Gastrointest Endoscopy 2002; 56:681–687. 28. Vazquez-Sequeiros E, Baron TH, Clain JE, et al. Evaluation of indeterminate bile duct strictures by intraductal US. Gastrointestinal Endoscopy 2002; 56:372–379. 29. Inui K, Miyoshi H. Cholangiocarcinoma and intraductal sonography. Gastrointestinal Endoscopy Clinics of NA 2005; 15:143–155. 30. Levy MJ, Rumalla A, Baron TH, et al. Prospective Evaluation of Intraductal Ultrasound (IDUS), Digital Image Analysis (DIA), Fluorescence in Situ Hybridization (FISH), CA 19-9, and ERCP with routine

Chapter 29 Indeterminate Biliary Stricture

cytology and intraductal biopsy in the evaluation of indeterminate bile duct strictures. Gastrointestinal Endoscopy 2006; 63:AB88. 31. Tamada K, Ido K, Ueno N, et al. Preoperative staging of extrahepatic bile duct cancer with intraductal ultrasonography. American Journal of Gastroenterology 1995; 90:239–246. 32. Farrell JJ, Bounds BC, Al-Shalabi S, et al. Single-operator duodenoscope-assisted cholangioscopy is an effective alternative in the management of choledocholithiasis not removed by conventional methods, including mechanical lithotripsy. Endoscopy 2005; 37:542–547. 33. Fukuda Y, Tsuyuguchi T, Sakai Y, et al. Diagnostic utility of peroral cholangioscopy for various bile-duct lesions. Gastrointestinal Endoscopy 2005; 62:374–382.

34. Shah RJ, Langer DA, Antillon MR, et al. Cholangioscopy and cholangioscopic forcepts biopspy in patients with indeterminate pancreaticobiliary pathology. Clinical Gastroenterology and Hepatology 2006; 4:219–225. 35. Chen YK. Results from the first human use clinical series utilizing a new peroral cholangiopancreatoscopy system (Spyglass(tm) Direct Visualization System). Gastrointestinal Endoscopy 2006; 63: AB86. 36. Familiari P, Bulajic M, Mutignani M, et al. Endoscopic removal of malfunctioning biliary self-expandable metallic stents. Gastrointestinal Endoscopy 2005; 62:903–910. 37. Petersen BT. SEMS removal: salvage technique or new paradigms. Gastrointestinal Endoscopy 2005; 62:911–913.

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30

APPROACH TO CLINICAL PROBLEMS

Benign Biliary Strictures Guido Costamagna, Syed G. Shah and Lalit Shimpi

BOX 30.1 KEY POINTS • There are a variety of causes of benign biliary strictures • Postoperative biliary strictures are the most common benign biliary stricture • Endoscopic therapy for benign biliary strictures consists of dilation and stent placement using multiple, large-bore plastic stents • Chronic pancreatitis strictures are less responsive to endoscopic therapy • The short-term outcome following endoscopic treatment of benign strictures is excellent • Successful long-term outcome following endoscopic therapy of benign biliary strictures is comparable to surgery, and does not preclude subsequent surgical therapy in cases that fail or recur

The majority of benign bile duct strictures occur as a result of postoperative iatrogenic injury, most commonly following cholecystectomy, or occur at the site of biliary anastomosis after hepatic resection or liver transplantation. Benign strictures may also result from a variety of other causes (Table 30.1). The endoscopic management of benign biliary strictures is also covered in Chapters 31, 35, and 43. Bile duct injuries are reported to be higher during laparoscopic cholecystectomy than open surgery.1 The estimated overall incidence of biliary injuries following laparoscopic cholecystectomy has been reported to be between 0.2% and 1.7%.2,3 Misidentification of anatomic structures during dissection, presence of acute inflammation or fibrous adhesions in the gallbladder fossa, excessive use of electrocautery to control bleeding, inaccurate placement of clips or sutures, and excessive traction on the gallbladder neck are major causes.2 Bergman et al.4 described four types of postoperative bile duct injuries: Type A-cystic duct leaks or leakage from aberrant or peripheral hepatic radicles, Type B-major bile duct leaks with or without concomitant biliary strictures, Type C-bile duct strictures without bile leakage, and Type D-complete transection of the duct with or without excision of some portion of the biliary tree. Postoperative biliary strictures occur in 0.2–0.5% of patients and usually occur as a result of partial or complete transection by clipping or ligation of the bile duct, or less frequently as a result of vascular injury during dissection or cauterization. Injury to sectorial or

segmental branches may occur in patients with anatomic anomalies of the biliary tree. Approximately 10–30% of patients with chronic pancreatitis develop symptomatic biliary stenosis.5 Biliary obstruction due to compression by an edematous pancreatic head or pseudocyst usually resolves when the inflammation subsides or after resolution of the pseudocyst. However, obstruction caused by a fibrotic stricture does not resolve spontaneously and requires therapeutic intervention.

CLINICAL FEATURES Approximately 10% of postoperative bile duct strictures present within 1 week of surgery. These usually occur as a result of inadvertent clipping or ligation of the common bile duct and may or may not be associated with biliary leaks. Patients may present with abdominal pain, fever, pruritus, jaundice or biliary fistula. However, in the majority of cases presentation is delayed and 70–80% present within 6–12 months of surgery.6 The presentation is symptomatic or asymptomatic cholestasis, recurrent cholangitis, stone formation, or secondary biliary cirrhosis. Bismuth7 classified benign strictures into five types: Type 1-Low common hepatic duct (CHD) or bile duct (CHD >2 cm), Type 2-Mid common hepatic duct (CHD 2cm

2 cm), biliary mechanical lithotripsy (BML) allows successful ductal clearance in 80–90% of cases. Stone impaction in the bile duct is a significant predictive factor of endoscopic failure.27 Electrohydraulic lithotripsy (EHL) via peroral endoscopic choledochoscopy is a safe technique that allows successful management of difficult CBD and intrahepatic ductal stones in a high percentage of patients (Figs 33.7–33.8). The fragmentation rate is as high as 96% and complete stone clearance as high as 90%.28 In a cohort of 313 patients with difficult CBD stones, 90% achieved ductal clearance with the use of high-energy extracorporeal shock wave lithotripsy (ESWL). The success of ESWL was not influenced by stone location, size, or presence of bile duct stricture.29 The selection of specific treatment methods depends on the availability of the equipment and local expertise. If this equipment is not available the temporary insertion of a biliary stent may fragment the stone and aid in future endoscopic treatment (Fig. 33.9).30

SURVEILLANCE AFTER TREATMENT OF CHOLEDOCHOLITHIASIS Recurrence of biliary complications after endoscopic and surgical treatment of choledocholithiasis ranges from 3.7% to 32%. Higher rates of recurrent choledocholithiasis are seen in patients with an

A

362

B

intact gallbladder, dilated CBD, periampullary diverticula, history of primary bile duct stone, and use of T-tube drainage at the time of cholecystectomy.31 Patients with a history of recurrent cholangitis may have a shortened period of remission.32 Therefore, in high-risk patients it is logical to perform surveillance. In one study of patients who underwent a follow-up program of serum liver enzymes testing and US examination every 3–6 months, recurrent stones were detected when asymptomatic.33 Therefore, in patients with risk factors of recurrent choledocholithiasis, multiple episodes of cholangitis, and presence of major systemic diseases, a regular surveillance program should be considered. Repeat ERCP and endoscopic sphincterotomy in patients with prior sphincterotomy may be safe in expert hands but does not eliminate the risk of recurrent choledocholithiasis.32

PERI-OPERATIVE MANAGEMENT OF CHOLEDOCHOLITHIASIS The management of bile duct stone in the era of laparoscopic cholecystectomy (LC) has been a subject of much debate. The current options available include preoperative ERCP, intraoperative ERCP, postoperative ERCP, laparoscopic exploration of the CBD (LECBD) through a transcystic route or laparoscopic choledochotomy, and open CBD exploration. In patients who are at high risk of choledocholithiasis (history of cholangitis, pancreatitis, deranged liver function, dilated CBD) preoperative ERCP should be performed prior to LC. From a retrospective audit of 1139 patients, 227 (20%) patients were selected for ERCP examinations based on the above criteria. 53% of the patients had choledocholithiasis; among them, 97% had successful endoscopic stone extraction.34 In a prospective study, 427 patients were assessed for ERCP before surgery based on the same criteria. Forty-

Fig. 33.7 A Multiple intrahepatic CBD stones. B Photograph of a mother and “baby scope” (choledochoscope) seen passing through the duodenoscope. A forceps is pictured exiting the baby scope working channel which allows extraction of stone fragments after intraductal lithotripsy.

Chapter 33 Choledocholithiasis

A

Fig. 33.8 A Endoscopic view from the baby scope shows the detail of the bile duct and the presence of pigment stones. B The extracted pigment stone.

B

one patients (9.6%) met the criteria and among them 22 patients (53.7%) were found to have choledocholithiasis. The strongest predictive factor for CBD stones on ERCP was a dilated CBD in association with abnormal serum liver chemistries. During follow-up, 28 patients (6.6%) were found to have recurrent or residual CBD stones.35 These studies demonstrated that selective use of ERCP before LC reduces the routine use of time-consuming laparoscopic cholangiography or LCBDE. However, there are drawbacks in employing these selection criteria since only half of the patients selected were confirmed to have choledocholithiasis and hence up to 50% of patients were subjected to an unnecessary invasive procedure. Thus better methods of selecting patients for ERCP are needed. Studies have shown that MRCP36 and EUS37 are both useful in selecting patients for ERCP before LC. Recently, a decision analysis model suggested that when the risk of bile duct stones is less than 10% (low risk), expectant management with postoperative ERCP for recurrent symptoms is less costly. When the risk of stones is greater than approximately 55% (high risk), preoperative ERCP is most costeffective. When the risk is intermediate (10–55%), preoperative testing with either EUS or MRCP, or intraoperative cholangiography is the best approach.38

Occasionally bile duct stones are discovered during LC. A recent study shows that by using intraoperative ERCP, one can avoid LCBDE which is technically more demanding. In a two-year prospective study of 674 patients, 34 (5.7%) patients were found to have a CBD stone detected during laparoscopic cholangiography and required intraoperative ERCP.39 Cannulation of the CBD was aided by surgical passage of a guidewire through the cystic duct and across the papilla. Successful cannulation was reported in 100% and no pancreatitis occurred. CBD stones were successfully extracted in 93.5% of patients. The operating time was prolonged but the length of hospitalization was not increased. This combined procedure may actually reduce the cost and hospital stay for patients by preventing two separate procedures. If the stones cannot be cleared during the intraoperative ERCP the operation can be converted to LECBD or even open bile duct exploration.40 Postoperative ERCP and stone removal allows successful clearance in 93–100% of patients.3,41 Should the stone be removed during the operation or postoperatively at ERCP? In a prospective randomized trial, 471 patents underwent LC and 80 (17%) patients were found to have CBD stones by cholangiogram.41 Half of the patients were randomized to receive LECBD and the other half randomized to postoperative ERCP and stone 363

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A

B

C

D

Fig. 33.9 The use of biliary stent in the treatment of difficult CBD stone. A Fluoroscopic image of large CBD stone impacted in the CBD; there was no room in which to open the biliary mechanical lithotripter (BML). B A biliary stent was inserted. C Three months later the stone had reduced in size to allow entrapment and crushing using the BML. D Only small fragments remained in the CBD which were subsequently removed using standard retrieval techniques.

extraction. The ductal clearance after first intervention was 75% in both groups. There was no difference in clinical outcome but the postoperative hospital stay was significantly shorter in the laparoscopic group than the ERCP group (median 1 day versus 3–5 days). The advantage of one-stage laparoscopic approach is also supported

364

by a decision analysis model.42 It showed LCBDE is a cost-effective method of managing CBD stones found on LC. If expertise in LECBD is unavailable, then postoperative ERCP should be offered. These conclusions from the above studies should be considered with caution. Despite the reported high success rate of postoperative ERCP, there are still about 5% of cases in whom complete stone clearance is not achieved. The patient may then need to undergo another operation for stone removal. Therefore, patient selection for preoperative stone extraction is very important. If endoscopic stone extraction fails, CBD exploration is deemed inevitable. Findings of large stone size (>25 mm diameter), presence of intrahepatic stones or multiple tightly packed CBD stones, CBD stricture, duodenal diverticulum, and history of Bilroth II or Roux-en-Y operation during LC predicts failure of postoperative ERCP.3 In these situations, open or laparoscopic CBDE for stone removal seems to be a better choice. An algorithm for the management of choledocholithiasis incorporating endoscopic and laparoscopic treatment had been proposed.43

CHOLECYSTECTOMY AFTER ENDOSCOPIC SPHINCTEROTOMY Endoscopic sphincterotomy and stone extraction have gained wide acceptance in the management of choledocholithiasis. However, following the endoscopic removal of bile duct stones, the need for cholecystectomy in patients with concomitant gallstone is less clear. Various studies had shown that further biliary complications occur in 4–24% of patients after varying periods of follow-up and the rate of subsequent cholecystectomy ranges from 6% to 18%.44,45 The age and presence of comorbidity of the patients also factors into the equation. A randomized, prospective study of 120 patients (mean age 62 years) who underwent ERCP with CBD stone removal followed by either LC or expectant management showed that recurrent biliary symptoms, mainly biliary pain and acute cholecystitis, occurred in 2% of patients in the LC group as compared with 47% of patients in the expectant group.46 In the expectant group, 37% of the patients subsequently required cholecystectomy and in over half of them conversion to open surgery was required. In contrast, in an Oriental non-randomized study of 140 patients (mean age 67 years) there were no significant differences in the incidence of recurrent bile duct stones, biliary symptoms and complications between those who received elective LC or were managed expectantly.47 The discrepancy in outcome arises from the origin of choledocholithiasis which is gallstone predominantly from the gallbladder in the West and pigment stone from the bile ducts in the East. In a recent study from Hong Kong 178 patients (mean age 71 years) were randomized to LC or expectant management after endoscopic sphincterotomy and stone extraction.48 During 5 years of follow-up, 6 patients in the cholecystectomy group returned with biliary events (cholangitis 5, epigastric pain 1); whereas in those with gallbladders in situ, 21 patients developed further biliary events including recurrent choledocholithiasis with cholangitis in 13, epigastric pain in 2, obstructive jaundice in 1, and acute cholecystitis in 5. The cumulative probability of recurrent biliary events in the cholecystectomy group and gallbladders in situ group was

Chapter 33 Choledocholithiasis

5.8% and 25.4%. It is concluded that after endoscopic sphincterotomy and removal of bile duct stones, even in Asian patients, cholecystectomy should be performed to reduce the risk of recurrent biliary events.

CONCLUSION

treatment of choledocholithiasis. Advances in therapeutic ERCP have resulted in successful clearance rates of choledocholithiasis and improved patient outcome. Endoscopic and laparoscopic treatments of bile duct stones should be considered complementary approaches to the management of choledocholithiasis.

Advances in recent imaging techniques have replaced diagnostic ERCP for choledocholithiasis. ERCP remains the mainstay for

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Ralls PW, Jeffrey Jr. RB, Kane RA, et al. Ultrasonography. In: Yamada T, Alpers DH, eds. Textbook of gastroenterology, 4th edn. Philadelphia: Lippincott Williams & Wilkins; 2003:3124. Greenberger NJ, Paumgartner G. Diseases of the gallbladder and bile duct. In: Braunwald E, Fauci AS, Kasper DL, eds. Harrison’s principles of internal medicine, 15th edn. New York: McGraw-Hill; 2001:1785. Park AE, Mastrangelo MJ Jr. Endoscopic retrograde cholangiopancreatography in the management of choledocholithiasis. Surg Endosc 2000; 14(3):219–226. Frossard JL, Hadengue A, Amouyal G, et al. Choledocholithiasis: a prospective study of spontaneous common bile duct stone migration. Gastrointest Endosc 2000; 51(2):175–179. Das A, Isenberg G, Wong RC, et al. Wire-guided intraductal US: an adjunct to ERCP in the management of bile duct stones. Gastrointest Endosc. 2001; 54(2):31–36. Siddique I, Mohan K, Khajah A, et al. Sphincterotomy in patients with gallstones, elevated LFTs and a normal CBD on ERCP. Hepatogastroenterology 2003; 50(53):1242–1245. Soto JA, Alvarez O, Munera F, et al. Diagnosing bile duct stones: comparison of unenhanced helical CT, oral contrast-enhanced CT cholangiography, and MR cholangiography. AJR Am J Roentgenol 2000; 175(4):1127–1134. Romagnuolo J, Bardou M, Rahme E, et al. Magnetic resonance cholangiopancreatography: a meta-analysis of test performance in suspected biliary disease. Ann Intern Med 2003; 139(7):547–557. Kaltenthaler E, Vergel YB, Chilcott J, et al. A systematic review and economic evaluation of magnetic resonance cholangiopancreatography compared with diagnostic endoscopic retrograde cholangiopancreatography. Health Technol Assess 2004; 8(10):iii,1–89. Aube C, Delorme B, Yzet T, et al. MR cholangiopancreatography versus endoscopic sonography in suspected common bile duct lithiasis: a prospective, comparative study. AJR Am J Roentgenol 2005; 184(1):55–62. Romagnuolo J, Currie G. Calgary Advanced Therapeutic Endoscopy Center study group. Noninvasive vs. selective invasive biliary imaging for acute biliary pancreatitis: an economic evaluation by using decision tree analysis. Gastrointest Endosc 2005; 61(1):86–97. Buscarini E, Tansini P, Vallisa D, et al. EUS for suspected choledocholithiasis: do benefits outweigh costs? A prospective, controlled study. Gastrointest Endosc 2003; 57(4):510–518. Sung JY, Shaffer EA, Olson ME, et al. Bacterial invasion of the biliary system by way of the portal-venous system. Hepatology 1991; 14(2):313–317. Sung JJ, Lyon DJ, Suen R, et al. Intravenous ciprofloxacin as treatment for patients with acute suppurative cholangitis: a

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randomized, controlled clinical trial. J Antimicrob Chemother 1995; 35(6):855–864. Lau JY, Chung SC, Leung JW, et al. Endoscopic drainage aborts endotoxaemia in acute cholangitis. Br J Surg 1996; 83(2):181–184. Leung JW, Chung SC, Sung JJ, et al. Urgent endoscopic drainage for acute suppurative cholangitis. Lancet 1989; 1(8650):1307–1309. Lai EC, Mok FP, Tan ES, et al. Endoscopic biliary drainage for severe acute cholangitis. N Engl J Med 1992; 326(24):1582–1586. García-Cano J. Success rate for complete choledocholithiasis extraction by means of endoscopic retrograde cholangiopancreatography. Surg Endosc 2004; 18(11):1681–1682. Sugiyama M, Atomi Y. The benefits of endoscopic nasobiliary drainage without sphincterotomy for acute cholangitis. Am J Gastroenterol 1998; 93(11):2065–2068. Hui CK, Lai KC, Yuen MF, et al. Does the addition of endoscopic sphincterotomy to stent insertion improve drainage of the bile duct in acute suppurative cholangitis? Gastrointest Endosc 2003; 58(4):500–504. Lee DW, Chan AC, Lam YH, et al. Biliary decompression by nasobiliary catheter or biliary stent in acute suppurative cholangitis: a prospective randomized trial. Gastrointest Endosc 2002; 56(3):361–365. Sharma BC, Kumar R, Agarwal N, et al. Endoscopic biliary drainage by nasobiliary drain or by stent placement in patients with acute cholangitis. Endoscopy 2005; 37(5):439–443. Chopra KB, Peters RA, O’Toole PA, et al. Randomised study of endoscopic biliary endoprosthesis versus duct clearance for bileduct stones in high-risk patients. Lancet 1996; 348(9030):791–793. Hui CK, Lai KC, Ng M, et al. Retained common bile duct stones: a comparison between biliary stenting and complete clearance of stones by electrohydraulic lithotripsy. Aliment Pharmacol Ther 2003; 17(2):289–296. Rodriguez-Gonzalez FJ, Naranjo-Rodriguez A, Mata-Tapia I, et al. ERCP in patients 90 years of age and older. Gastrointest Endosc 2003; 58(2):220–225. Hui CK, Lai KC, Wong WM, et al. A randomised controlled trial of endoscopic sphincterotomy in acute cholangitis without common bile duct stones. Gut 2002; 51(2):245–247. Garg PK, Tandon RK, Ahuja V, et al. Predictors of unsuccessful mechanical lithotripsy and endoscopic clearance of large bile duct stones. Gastrointest Endosc 2004; 59(6):601–605. Arya N, Nelles SE, Haber GB, et al. Electrohydraulic lithotripsy in 111 patients: a safe and effective therapy for difficult bile duct stones. Am J Gastroenterol 2004; 99(12):2330–2334. Sackmann M, Holl J, Sauter GH, et al. Extracorporeal shock wave lithotripsy for clearance of bile duct stones resistant to endoscopic extraction. Gastrointest Endosc 2001; 53(1):27–32.

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30. Chan AC, Ng EK, Chung SC, et al. Common bile duct stones become smaller after endoscopic biliary stenting. Endoscopy 1998; 30(4):356–359. 31. Uchiyama K, Onishi H, Tani M, et al. Long-term prognosis after treatment of patients with choledocholithiasis. Ann Surg 2003; 238(1):97–102. 32. Sugiyama M, Suzuki Y, Abe N, et al. Endoscopic retreatment of recurrent choledocholithiasis after sphincterotomy. Gut 2004; 53(12):1856–1859. 33. Lai KH, Lo GH, Lin CK, et al. Do patients with recurrent choledocholithiasis after endoscopic sphincterotomy benefit from regular follow-up? Gastrointest Endosc 2002; 55(4):523–526. 34. Coppola R, Riccioni ME, Ciletti S, et al. Selective use of endoscopic retrograde cholangiopancreatography to facilitate laparoscopic cholecystectomy without cholangiography. A review of 1139 consecutive cases. Surg Endosc 2001; 15(10):1213–1216. 35. Katz D, Nikfarjam M, Sfakiotaki A, et al. Selective endoscopic cholangiography for the detection of common bile duct stones in patients with cholelithiasis. Endoscopy 2004; 36(12):1045–1049. 36. Laokpessi A, Bouillet P, Sautereau D, et al. Value of magnetic resonance cholangiography in the preoperative diagnosis of common bile duct stones. Am J Gastroenterol 2001; 96(8):2354–2359. 37. Palazzo L, O’Toole D. EUS in common bile duct stones. Gastrointest Endosc 2002; 56(4 Suppl):S49–S57. 38. Sahai AV, Mauldin PD, Marsi V, et al. Bile duct stones and laparoscopic cholecystectomy: a decision analysis to assess the roles of intraoperative cholangiography, EUS, and ERCP. Gastrointest Endosc 1999; 49(3 Pt 1):334–343. 39. Enochsson L, Lindberg B, Swahn F, et al. Intraoperative endoscopic retrograde cholangiopancreatography (ERCP) to remove common bile duct stones during routine laparoscopic

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SECTION 3

Chapter

34

APPROACH TO CLINICAL PROBLEMS

Pancreaticobiliary Pain and Suspected SOD Paul R. Tarnasky and Robert H. Hawes

INTRODUCTION The diagnosis and treatment of suspected sphincter of Oddi dysfunction (SOD) presents a significant challenge for physicians who care for patients with digestive diseases. This chapter is intended to provide readers with a practical guide to the evaluation and management of patients with pancreaticobiliary type pain and suspected SOD. The overall goals of this chapter include identifying the challenges which these patients present and offering a pragmatic approach to the clinical evaluation and decisions regarding treatment. The specific goals are: (1) describe pain patterns that are consistent and not consistent with SOD; (2) define SOD and the clinical scenarios where SOD might be considered; (3) describe a rational initial evaluation for patients with suspected SOD; (4) provide guidance for patient and physician decisions regarding management of SOD; (5) describe techniques of sphincter of Oddi manometry (SOM) and endoscopic treatment of SOD; and (6) reinforce the risks inherent to the endoscopic evaluation of SOD and how they can be minimized. It should be emphasized that there is a paucity of good data to guide clinicians in this arena. When data is available, recommendations will be evidence based but much of the following information is derived from anecdotal experience of which the authors have a considerable amount. Clinical syndromes which may be attributed to SOD range from functional disorders with purely subjective symptomatology to structural disorders having objective pathologic features. Functional and structural SOD diagnoses are widely divergent with regard to their presentation and management. Unexplained upper abdominal pain and acute pancreatitis represent the two most important examples at each end of this spectrum and will be the focus of this review. Other clinical scenarios that may be associated with SOD include chronic acalculous cholecystitis, early chronic pancreatitis, biliary pancreatitis, postoperative bile leak, and pancreatic fistula.

DEFINITIONS Confusing terminology and varied clinical presentations explain part of the complexity regarding SOD. Biliary dyskinesia is the encompassing term for a group of disorders with acalculous biliary-type pain. Subgroup diagnoses include chronic acalculous cholecystitis, gallbladder dyskinesia, cystic duct syndrome, and SOD. Sphincter of Oddi dysfunction may occur in patients with or without a gallbladder but is most commonly diagnosed in patients with postcholecystectomy symptoms. Attempts have been made to develop consensus on defining the signs and symptoms of SOD culminating in what are called the

“Rome criteria.”1 Definitions established for post cholecystectomy patients and those with gallbladder in situ are listed in Tables 34.1 and 34.2. Revisions in the Rome criteria for SOD were recently published.2 The Rome criteria are meant to provide a general framework for clinicians but obviously do not describe all patients. A unifying symptom, present in all patients with SOD, is pain. There may be associated symptoms such as nausea with or without vomiting but the hallmark symptom is pain—located in the epigastrium and/ or right upper quadrant (RUQ). When evaluating a patient with possible SOD, the most important aspect of the evaluation is the history. It is imperative that the clinician gain a clear understanding of the nature, location and timing of pain. The Rome criteria specify that the pain should be intermittent with pain-free intervals. This is a very controversial point. While biliary pain is typically intermittent, in some cases, patients will have a constant, low-grade discomfort with exacerbations. This can be seen particularly in those with pancreatic sphincter hypertension who typically have exacerbations after eating. These patients should undergo careful review and extensive evaluation for other causes of pain (Table 34.3) but should not be excluded from evaluation for SOD based solely on there being a constant component to their pain. However, if associated symptoms such as nausea, vomiting, abdominal distention or bowel dysfunction are dominant, then the patient likely does not have SOD as the predominant explanation for their symptoms. Based on observations and after developing correlations between patients’ presentation and outcomes after endoscopic sphincterotomy, Joseph Geenen, Walter Hogan, and Wylie Dodds published what have become to be known as “The Geenen-Hogan Criteria” (Table 34.4).3 These have been modified over the years but still serve as a very good “compass” to clinicians to direct them in their evaluation and therapeutic decision making. The original criteria were applied to patients who had previously undergone cholecystectomy and were based on three factors which could be assessed without ERCP-presence of “typical” pancreatic or biliary type pain, the presence or absence of elevated liver or pancreatic tests during or shortly following an episode of pain, and the presence or absence of bile and/or pancreatic duct dilation. The original criteria also included measurement of pancreatic and biliary drainage times. Drainage times are very imprecise, require instillation of contrast into the respective duct and in the case of biliary drainage times, the endoscope must be withdrawn, the patient placed in the supine position and an abdominal film obtained at 45 minutes. Studies have shown that drainage times do not correlate with SOM4 and delayed drainage is common in asymptomatic postcholecystectomy volunteers.5 As a result, drainage times are no longer performed and are not part of the current Geenen-Hogan (G-H) criteria. 367

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Post cholecystectomy Episodes of severe steady pain located in the epigastrium and right upper quadrant and all of the following: 1. Episodes lasting 30 minutes or longer 2. Recurrent symptoms occurring at different intervals and not daily 3. The pain is steady, interrupts daily activity and/or leads to medical encounter 4. The pain is not relieved by bowel movements, postural change, or antacids 5. Structural diseases that could explain symptoms are excluded

Table 34.1 Rome criteria for sphincter of Oddi dysfunction Gallbladder in situ Episodes of severe steady pain located in the epigastrium and right upper quadrant and all of above criteria plus: Normal liver and pancreas chemistries Absence of gallbladder stones, sludge, or microlithiasis Abnormal gallbladder emptying

Table 34.2 Rome criteria for sphincter of Oddi dysfunction Esophageal Spasm or other motility disorder Esophagitis Gastric Gastroparesis Ulcer Hiatal hernia Volvulus Pyloric stenosis Duodenal Stricture Ulcer Diverticulitis Ampullary neoplasm Biliary Stone Benign stricture Sump syndrome Neoplasm Pancreatic Chronic pancreatitis Neoplasm Abdominal Wall Neuroma Myopathy/myositis Irritable bowel syndrome

LFT > 2X Normal × 2

BD diam > 10 mm

+ + +

+ + −

+ + −

or

Table 34.4 Geenen-Hogan classification for SOD

368

The first step is a detailed review of prior health care encounters pertinent to the clinical presentation with a focus on questions of when, where, and what (Table 34.5). A complete history and thorough review of records will define the clinical symptoms, reveal what tests have been done, what treatments (surgical, endoscopic, medical) have been tried, and what the impact has been on the patient. Patients with unexplained symptoms that may be attributed to SOD often end up undergoing a massive assault with both diagnostic and therapeutic fronts. It can be helpful to organize objective data with regards to prior laboratory testing, imaging and treatments (Table 34.6).

Table 34.5 Important history questions for suspected SOD

Typical pain

LFT = Liver function tests. BD = Bile duct.

CLINICAL EVALUATION

When did the attacks begin? When do the attacks occur? Where is the pain? Where does the pain radiate? What is associated with the attacks? What has been done to investigate the cause? What has been done to treat the attacks? What are the consequences of the attacks?

Table 34.3 Diagnoses to consider (other than SOD) for unexplained upper abdominal pain

Type I Type II Type III

The G-H criteria are important because they represent a framework around which a clinician can plan patient evaluation. If one obtains an appropriate history of pain, bile duct imaging should be obtained and the patient should be given a prescription directing health care providers (in an emergency room, hospital lab or clinic) to obtain liver and pancreatic tests (amylase and lipase) during or shortly after a pain episode. These data then can be used to stratify patients as to their likelihood of having SOD.

Laboratory and pathology Serum liver and pancreas chemistries Serum fasting triglyceride Gallbladder pathology Imaging Transabdominal ultrasound Computed tomography Magnetic resonance with MRCP Biliary scintigraphy Endoscopic ultrasound Intraoperative cholangiography Previous Treatment Surgical Cholecystectomy Biliary bypass Pseudocyst drainage Pancreatic bypass or resection Partial gastrectomy Gastric bypass Endoscopic Biliary sphincterotomy Pancreatic sphincterotomy Stenting

Table 34.6 Clinical details pertinent to sphincter of Oddi dysfunction

Chapter 34 Pancreaticobiliary Pain and Suspected SOD

Type

I

II

III

Definition Baseline pressure >40 mmHg Benefit from sphincterotomy

Pain + 3 criteria* 70–100% 55–91%

Pain + 1 or 2 criteria* 40–86% p > 40 mmHg: 80–90% p < 40 mmHg: 30–35%

Pain only 20–55% p > 40 mmHg: 8–56%

Table 34.7 Correlation between Geenen/Hogan Criteria, results of SOM and outcome with sphincterotomy The criteria used were the following: 1. ALT and alkaline phosphatase over twice upper limit of normal. 2. Dilated bile duct on sonography. 3. Delayed drainage of contrast material at ERCP.

Some historical details may indicate that SOD is likely. It is not uncommon for SOD patients to have undergone cholecystectomy because of a “diseased” or dysfunctional gallbladder. Patients with a history of chronic narcotic analgesic use who then develop pancreaticobiliary pain often have SOD. Symptomatic patients who have a history of common bile duct exploration, postoperative bile leak and/or post-ERCP pancreatitis are often discovered to have SOD. Pain is a subjective complaint. Nevertheless, considerable information can be obtained. There are a number of “classic” descriptors that can help guide whether or not SOD is a likely cause for pain. Typical pancreatic/biliary pain occurs intermittently, begins after meals, and lasts minutes to hours. It is located in the epigastric or right upper quadrant areas and may radiate to the back, chest or right shoulder. Occasionally, the pain is perceived first in the back or chest. Daily pain that is constant is not typical for SOD unless associated with chronic pancreatitis. Patients may be awakened from sleep because of pain. It is not uncommon for patients to describe their symptoms as “my gallbladder pain” and even describe symptoms that are “worse than my gallbladder attack.” Transient elevations of serum liver and/or pancreas enzymes drawn hours after pain onset may suggest SOD. The possibility of more common and potentially more treatable diagnoses should be considered before proceeding with an evaluation for possible SOD. Symptom history and diagnostic testing should be directed at evaluation for the potential diagnoses listed in Table 34.3. For example, bile duct dilation should raise a suspicion for neoplasia or bile duct stones if associated with abnormal liver tests. Alternatively, a dilated bile duct with normal liver tests in a patient with intermittent pain should raise suspicion for SOD. Evaluation for possible common bile duct stones deserves careful consideration. Bile duct stones are very rarely found when routine imaging tests such as transabdominal ultrasound and laboratory testing are normal. Therefore, unless there are objective indicators to suggest bile duct pathology, ERCP should be avoided when purely used to “rule out bile duct stones.” Additional imaging such as MRCP or EUS can be helpful in this setting. It is most reasonable to consider ERCP when SOM and/or definitive endoscopic therapy is planned. Ideally, patients with unexplained upper abdominal pain can be categorized as to the likelihood for SOD and a favorable response to endoscopic treatment. The Geenen-Hogan classification (Table 34.4) is the standard in this regard. Type I SOD patients have objective evidence of impaired drainage and are more likely to have structural obstruction (papillary stenosis). In addition to characteristic pain, they have dilated duct(s) and abnormal liver tests during episodes of pain. Patients with Type II SOD will have characteristic pain and either a dilated duct or abnormal laboratory tests with pain. Type III SOD

patients have typical biliary or pancreatic pain but no objective evidence of impaired drainage. Such patients likely have a purely functional disorder. The reason that this categorization of patients is important is that it predicts, to a certain extent, the chance of finding an abnormal SOM and having a favorable outcome following sphincterotomy (Table 34.7).6 Remarkably, disease and/or interventions of such a small structure may lead to a tremendous burden on behalf of the patient and their physician. From the patient standpoint, SOD may present a wide spectrum of physical and emotional symptoms ranging from nuisance to total disability. Much of the emotional burden is derived from uncertainty. Patients become desperate when not knowing the cause of their symptoms; whether and when they will have future attacks, and if there are safe and effective treatments. Diverse challenges which face physicians include substantial time-requirements, potential legal ramifications, and the broad range of necessary skills such as history taking, record-keeping, radiology interpretation, and psychological assessment. Moreover, physicians who decide on doing ERCP in this setting need to possess appropriate technical skills such as sphincter manometry, selective cannulation, sphincterotomy (perhaps precut), and pancreatic therapy. Compassion and judgment are the intangible physician qualities that are more important than knowing how to cut a sphincter or place a stent. These qualities are tested when faced with the often asked question: “What would you do if I was your mother or daughter or . . .?” Once a clinical impression of SOD is established, ideally a noninvasive test would be available to confirm one’s clinical impression before proceeding to ERCP. Several tests have been studied and individual centers have reported good correlation with SOM and/or sphincterotomy. The problem is that when these tests are evaluated on a broader scale, their accuracy does not match previous, single center reports. The Hopkins group first reported on the accuracy of dynamic (quantitative) biliary scintigraphy.7–8 The test was designed to measure delayed bile flow through the ampulla by assessing the time it takes for the radionuclide to reach the duodenum. These authors found a good correlation with SOM. Their results were supported by Corazziari, et al.9 This prompted the Hopkins group to suggest that this test could substitute for SOM.10 However, when this test was evaluated in normal volunteers, we found it had very poor specificity and it had little value in excluding SOD in patients suspected to suffer from this disorder.11 Another test hypothesized to detect SOD is fatty meal ultrasound (FMS). An abnormal test is defined by a >2 mm dilation of the bile duct 45 minutes after ingestion of a standardized “fatty meal.” Rosenblatt et al. compared SOM, FMS and hepatobiliary scintigraphy (HBS) in a retrospective comparative study.12 Poor correlation was observed between FMS and HBS with SOM. However, of the patients with abnormal SOM who had a good long-term response to 369

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sphincterotomy, 85% (11/13) had an abnormal FMS and HBS. This raises an interesting point; perhaps non-invasive tests should be evaluated as to whether they predict response to sphincterotomy rather than whether they correlate with SOM. What a clinician really wants to know from a non-invasive test is whether or not the patient will respond to endoscopic sphincterotomy.

UPPER ABDOMINAL PAIN WITH GALLBLADDER IN SITU Management of patients with biliary-type pain without evidence of gallstones on standard imaging represents a challenge. Physicians (including surgeons) and patients usually prefer to identify some proof of gallbladder pathology before considering cholecystectomy. Biliary crystal analysis can be performed on bile collected from the duodenum or bile duct after cholecystokinin (CCK) stimulation. Endoscopic ultrasound is more sensitive for discovering biliary sludge13–14 and can also be used to assess for evidence of pancreatitis. If EUS and CCK stimulated biliary drainage are performed and biliary crystals or gallbladder sludge are found, >90% of patients will have resolution of pain with cholecystectomy.15 Biliary scintigraphy may reveal evidence of chronic acalculous cholecystitis (gallbladder ejection fraction 18,000/mm3 Serum glucose > 200 mg/dl (11.1 mmol/L) a Serum LDH > 400 IU/L Serum AST > 250 IU/L Within 48 hours of hospital admission Hematocrit fall > 10 percentage points a BUN rise > 2 mg/dl (0.7 mmol/L) a Base deficit > 5 meq/L (5 mol/L) a Fluid sequestration > 4 L Serum calcium < 8 mg/dl (2 mmol/L) Arterial PaO2 < 60 mm Hg

Table 39.3 Ranson’s criteria of pancreatitis severity for biliary pancreatitis Modified from Table 4, Reference 24. a Denotes changes from original Ranson criteria for all other causes of acute pancreatitis.

the presence of local complications such as pancreatic necrosis, abscess or fluid collection by cross-sectional imaging. With these parameters, the Atlanta Classification of 1992 standardized the definition of SAP as the presence of local complications and/or organ failure (Table 39.1), or an Acute Physiology and Chronic Health Evaluation II (APACHE II) (Table 39.2) score greater than 8 or greater than three Ranson’s criteria.21 It is important to note that a modification of Ranson’s original criteria is used for biliary pancreatitis (Table 39.3).22 Organ failure, particularly persistent or worsening organ failure, is a strong determinant of mortality in patients with SAP.23,24 Though many definitions of organ failure have been used, more recent studies utilize the multiple organ dysfunction syndrome (MODS) score or the systemic inflammatory response syndrome (SIRS) score to ensure that findings can be generalized. Mortality in the setting of AP with organ failure can range from 20% to as high as 50% and is dependent upon the duration, severity and number of organ systems in failure.20,21,25 Prognostic indices have been formulated to predict which patients are more likely to develop severe AGP and to direct appropriate care toward that group. These include Ranson’s criteria (biliary version), modified Glasgow criteria and APACHE II score. Radiologic scores such as the Balthazar score and the modified CT severity index which are based on the extent of pancreatic necrosis and fluid collections, have been shown to correlate with mortality.26,27 Several biochemical markers of inflammation have been studied to predict SAP, but serum C-reactive protein level of greater than 150 mg/L at 48–72 hours after symptom onset remains the standard.28 Recent data suggest that a genetic polymorphism that confers an enhanced chemokine response to an inflammatory stimulus is a risk factor for progression to SAP.29 The search continues for a biochemical marker that can be easily measured in the first 24 hours of AP and reliably predicts progression to severe disease.

ENDOSCOPIC THERAPY FOR ACUTE GALLSTONE PANCREATITIS The mainstay of therapy for all forms of SAP remains supportive care including aggressive hydration, adequate nutritional support, pain control and often an intensive care unit (ICU).30 With regard to severe AGP in particular, early endoscopic therapy has become

Chapter 39 Biliary Intervention in Acute Gallstone Pancreatitis

an integral management strategy, supported by anecdotal reports31 and evidence from randomized clinical trials (RCTs).3,7,20 An additional RCT from Germany brought into question the benefit of early ERCP with ES in a subgroup of patients without signs of biliary obstruction.6 These studies differ on the assessment of pancreatitis severity, timing to ERCP, exclusion criteria and possibly endoscopic expertise. The four RCTs designed to assess the safety and benefit of early ERCP in AGP are described below and summarized in Table 39.4.

Neoptolemos et al. 1988 This landmark study comparing ERCP and ES against conservative management of AGP was performed by Neoptolemos and colleagues from 1983 through 1987 and published in 1998.7 The investigators randomized 121 of 146 consecutive patients who presented to a single institution with suspected AGP to receive either conservative management or ERCP within 72 hours of admission. The diagnosis of AGP was established by ultrasound and laboratory data. The severity of pancreatitis was predicted within 48 hours of admission using the modified Glasgow criteria.32 If choledocholithiasis was found on ERCP, an ES with stone extraction was performed. Outcome measures included mortality, length of stay, local complications and organ failure. Predicted severe AP was present in 44% of all patients enrolled (25 of 59 in the ERCP group and 28 of 62 in the conservative management group). ERCP was successful in 94% of mild disease and 80% of severe disease. One ERCP-related complication was cited, a case of vertebral osteomyelitis. There were no cases of ERCP-related hemorrhage, cholangitis or perforation. The overall mortality was not significantly different in the two patient groups (ERCP group: 2% vs conservative management group: 8%; p = 0.23). However, the overall morbidity was significantly lower in the group that underwent ERCP within 72 hours of admission (17% vs 34%; p = 0.03). Sub-group analysis demonstrated that the morbidity difference was limited to the group of patients with predicted SAP. In patients with predicted SAP who were randomized to urgent ERCP, the complication rate was 24%, in comparison to 61% in patients with predicted SAP managed conservatively (p < 0.01). Accordingly, the length of hospitalization was shorter in

Study

No. treated patients

No. control patients

the patients with SAP who underwent urgent ERCP (9.5 days vs 17 days; p < 0.035). The investigators acknowledged the concern that the benefit of early ERCP +/− ES might be a result of treating cholangitis and not pancreatitis. They controlled for this possible confounding factor by excluding the patients who presented with cholangitis and analyzing the remaining patients separately. The complication rate remained significantly lower in the group of patients without cholangitis who underwent urgent ERCP (11% vs 33%; p = 0.02). Again, the majority of this difference occurred in the sub-group of patients with predicted SAP. In summary, this study by Neoptolemos and colleagues demonstrated that it is safe to perform ERCP in patients with AGP admitted to an expert center and early ERCP is associated with significantly decreased morbidity and hospital stay in patients with predicted severe AGP in comparison to conservative management.

Fan et al. 1993 The investigators of this trial from Hong Kong randomized 195 patients with acute pancreatitis of all etiologies to undergo urgent ERCP within 24 hours of hospital admission or conservative management followed by selective ERCP for clinical deterioration. The authors utilized this approach of selecting all patients with pancreatitis in order to minimize selection bias. Analysis of the subgroup of patients with AGP, revealed that 127 of the 195 randomized patients (65%) had biliary stones. Sixty-four of the 97 patients randomized to early ERCP were found to have biliary stones and 38 of these required ES for CBD or ampullary stones. Of the 98 patients in the conservative therapy group, 63 had biliary stones and 27 of these patients required ERCP for clinical deterioration. Ten of these patients were found to have CBD or ampullary stones. The severity of pancreatitis was graded by serum urea concentration and plasma glucose concentration and Ranson’s score. Patients were categorized as having SAP if serum urea concentration was greater than 45 mg/dL or if plasma glucose concentration was greater than 198 mg/dL at admission. Predicted SAP was diagnosed in 41.5% of the patient population, distributed evenly between the treatment groups. The overall morbidity (urgent ERCP group: 18%

Study design

Outcomes

Neoptolemos

59

62

Single center Consecutive patients with suspected AGP

Significant morbidity reduction in severe AGP Significant length of stay reduction in severe AGP

Fan

97

98

Single center Consecutive patients with AP, regardless of etiology AGP analyzed separately

Significant morbidity reduction in AGP Significant reduction in biliary sepsis in severe AGP

Fölsch

126

112

Multi-center Patients with suspected AGP, excluded those with bilirubin > 5 mg/dL

Similar morbidity rates between study groups Significantly higher incidence of respiratory insufficiency in ERCP group

Nowak

178

102

Single center Consecutive patients with suspected AGP All underwent duodenoscopy, immediate ES if obstructed, randomized if not

Significant reduction in both morbidity and mortality in the early ERCP + ES group

Table 39.4 Summary of randomized controlled trials 413

SECTION 3 APPROACH TO CLINICAL PROBLEMS

vs conservative management group: 29%; p = 0.07) and mortality (5% vs 9%; p = 0.4) were not significantly different in the two patient groups. When considering only those patients with biliary stones, the morbidity rate in the urgent ERCP group was significantly lower than in the conservative management group (16% vs 33%, p = 0.03) and there was a trend toward lower mortality (2% vs 8%; p = 0.09). These findings were driven by the significant morbidity advantage of urgent ERCP in the sub-group of patients with predicted SAP. In particular, the incidence of biliary sepsis among those patients predicted to have SAP was significantly lower in the urgent ERCP group than in the conservative management group (0% vs 20%; p = 0.008). In contrast, among patients with mild pancreatitis, there was no difference in the incidence of biliary sepsis between the two study groups. In summary, this trial demonstrated a morbidity benefit in patients with predicted severe AGP who underwent urgent ERCP +/− ES as compared to those managed conservatively. Despite the high prevalence of cholelithiasis in the study population, this trial corroborates the findings of the earlier study from the UK.

Fölsch et al. 1997 In this German multi-center study, 126 patients with AGP were randomly assigned to early ERCP within 72 hours of the onset of symptoms and 112 patients with AGP were assigned to conservative management. The inclusion criteria in this study were distinct from the previous studies in that patients with obstructive jaundice (total bilirubin >5 mg/dL) were excluded. In doing so, the investigators sought to determine the effect of early ERCP upon AGP independent of its known benefit in patients with cholangitis.33 In these patients with acute pancreatitis, the diagnosis of AGP was made if gallstones were seen on imaging or if two of three serum liver chemistry values (ALT, alkaline phosphatase and/or total bilirubin) were abnormal. The severity of pancreatitis was predicted by the modified Glasgow criteria. Early ERCP was successful in 96% of the treatment group and 46% of patients in this group were found to have choledocholithiasis. Elective ERCP was required in 20% of the conservative treatment group and 59% of those patients were found to have bile duct stones. Predicted SAP was seen in 19.3% of patients overall and similarly distributed between the treatment groups. Complications directly attributable to ERCP were minimal, with post-sphincterotomy hemorrhage seen in 2.8% and no duodenal wall perforations reported. Overall complications were similar in the early ERCP and control groups (46% vs 51%) and mortality rates were also similar (11% vs 6%; p = 0.10). Stratification of patients by predicted severity of pancreatitis did not alter these findings. Though systemic complications overall were not significantly different, the patients in the early ERCP group had a higher rate of respiratory insufficiency, as defined by pO2