THE 2002 OFFICIAL PATIENT’S SOURCEBOOK
on
ALLSTONES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2002 by ICON Group International, Inc. Copyright Ó2002 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Tiffany LaRochelle Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher’s note: The ideas, procedures, and suggestions contained in this book are not intended as a substitute for consultation with your physician. All matters regarding your health require medical supervision. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before taking any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960The 2002 Official Patient’s Sourcebook on Gallstones: A Revised and Updated Directory for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-83276-5 1. Gallstones-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem or as a substitute for consultation with licensed medical professionals. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors or authors. ICON Group International, Inc., the editors, or the authors are not responsible for the content of any Web pages nor publications referenced in this publication.
Copyright Notice If a physician wishes to copy limited passages from this sourcebook for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs or other materials, please contact us to request permission (e-mail:
[email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this sourcebook.
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Dedication To the healthcare professionals dedicating their time and efforts to the study of gallstones.
Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to gallstones. All of the Official Patient’s Sourcebooks draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this sourcebook. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany LaRochelle for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for the Official Patient’s Sourcebook series published by ICON Health Publications.
Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for the Official Patient’s Sourcebook series published by ICON Health Publications.
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About ICON Health Publications In addition to gallstones, Official Patient’s Sourcebooks are available for the following related topics: ·
The Official Patient's Sourcebook on Appendicitis
·
The Official Patient's Sourcebook on Autoimmune Hepatitis
·
The Official Patient's Sourcebook on Bacteria and Foorborne Illness
·
The Official Patient's Sourcebook on Barrett's Esophagus
·
The Official Patient's Sourcebook on Celiac Disease
·
The Official Patient's Sourcebook on Cirrhosis of the Liver
·
The Official Patient's Sourcebook on Constipation
·
The Official Patient's Sourcebook on Crohn Disease
·
The Official Patient's Sourcebook on Cyclic Vomiting Syndrome
·
The Official Patient's Sourcebook on Diarrhea
·
The Official Patient's Sourcebook on Diverticular Disease
·
The Official Patient's Sourcebook on Fecal Incontinence
·
The Official Patient's Sourcebook on Gas
·
The Official Patient's Sourcebook on Gastritis
·
The Official Patient's Sourcebook on Gastroparesis
·
The Official Patient's Sourcebook on Hemolytic Uremic Syndrome
·
The Official Patient's Sourcebook on Hemorrhoids
·
The Official Patient's Sourcebook on Hepatitis a
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The Official Patient's Sourcebook on Hepatitis B
·
The Official Patient's Sourcebook on Hepatitis C
·
The Official Patient's Sourcebook on Hiatal Hernia
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The Official Patient's Sourcebook on Hirschsprung
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The Official Patient's Sourcebook on Indigestion
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The Official Patient's Sourcebook on Inguinal Hernia
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The Official Patient's Sourcebook on Intestinal Pseudo-obstruction
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The Official Patient's Sourcebook on Irritable Bowel Syndrome
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The Official Patient's Sourcebook on Lactose Intolerance
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The Official Patient's Sourcebook on Ménétrier
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The Official Patient's Sourcebook on Pancreatitis
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The Official Patient's Sourcebook on Peptic Ulcer
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The Official Patient's Sourcebook on Porphyria
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The Official Patient's Sourcebook on Primary Biliary Cirrhosis
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The Official Patient's Sourcebook on Primary Sclerosing Cholangitis
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The Official Patient's Sourcebook on Proctitis
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The Official Patient's Sourcebook on Rapid Gastric Emptying
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·
The Official Patient's Sourcebook on Short Bowel Syndrome
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The Official Patient's Sourcebook on Ulcerative Colitis
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The Official Patient's Sourcebook on Whipple Disease
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The Official Patient's Sourcebook on Wilson's Disease
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The Official Patient's Sourcebook on Zollinger-ellison Syndrome
To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
Contents
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Table of Contents INTRODUCTION ................................................................................................................................. 1 Overview ....................................................................................................................................... 1 Organization ................................................................................................................................. 3 Scope.............................................................................................................................................. 3 Moving Forward............................................................................................................................ 4 PART I: THE ESSENTIALS ............................................................................................................. 7 CHAPTER 1. THE ESSENTIALS ON GALLSTONES: GUIDELINES......................................................... 9 Overview ....................................................................................................................................... 9 What Are Gallstones?.................................................................................................................. 11 What Causes Gallstones? ............................................................................................................ 12 Who Is at Risk for Gallstones? .................................................................................................... 13 What Are the Symptoms? ........................................................................................................... 14 How Are Gallstones Diagnosed?................................................................................................. 15 Surgical Treatment...................................................................................................................... 15 Nonsurgical Treatment ............................................................................................................... 17 Do People Need Their Gallbladders? ........................................................................................... 17 Points to Remember..................................................................................................................... 18 More Guideline Sources .............................................................................................................. 18 Vocabulary Builder...................................................................................................................... 30 CHAPTER 2. SEEKING GUIDANCE ................................................................................................... 37 Overview ..................................................................................................................................... 37 Associations and Gallstones ........................................................................................................ 37 Finding More Associations ......................................................................................................... 39 Finding Doctors........................................................................................................................... 41 Selecting Your Doctor ................................................................................................................. 42 Working with Your Doctor ......................................................................................................... 43 Broader Health-Related Resources .............................................................................................. 44 PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL ........................... 45 CHAPTER 3. STUDIES ON GALLSTONES .......................................................................................... 47 Overview ..................................................................................................................................... 47 The Combined Health Information Database .............................................................................. 47 Federally-Funded Research on Gallstones................................................................................... 53 E-Journals: PubMed Central ....................................................................................................... 65 The National Library of Medicine: PubMed................................................................................ 66 Vocabulary Builder...................................................................................................................... 66 CHAPTER 4. PATENTS ON GALLSTONES ......................................................................................... 73 Overview ..................................................................................................................................... 73 Patents on Gallstones .................................................................................................................. 74 Patent Applications on Gallstones .............................................................................................. 81 Keeping Current .......................................................................................................................... 81 Vocabulary Builder...................................................................................................................... 81 CHAPTER 5. BOOKS ON GALLSTONES............................................................................................. 83 Overview ..................................................................................................................................... 83 Book Summaries: Federal Agencies ............................................................................................. 83 Book Summaries: Online Booksellers .......................................................................................... 87 The National Library of Medicine Book Index............................................................................. 90 Chapters on Gallstones ................................................................................................................ 92 General Home References .......................................................................................................... 101 Vocabulary Builder.................................................................................................................... 102
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Contents CHAPTER 6. MULTIMEDIA ON GALLSTONES ................................................................................ 105 Overview ................................................................................................................................... 105 Video Recordings....................................................................................................................... 105 Audio Recordings ...................................................................................................................... 108 Bibliography: Multimedia on Gallstones................................................................................... 109 Vocabulary Builder.................................................................................................................... 112 CHAPTER 7. PERIODICALS AND NEWS ON GALLSTONES ............................................................. 113 Overview ................................................................................................................................... 113 News Services & Press Releases ................................................................................................ 113 Newsletter Articles .................................................................................................................... 118 Academic Periodicals covering Gallstones ................................................................................ 120 Vocabulary Builder.................................................................................................................... 121 CHAPTER 8. PHYSICIAN GUIDELINES AND DATABASES .............................................................. 123 Overview ................................................................................................................................... 123 NIH Guidelines ......................................................................................................................... 123 NIH Databases .......................................................................................................................... 124 Other Commercial Databases .................................................................................................... 133 The Genome Project and Gallstones .......................................................................................... 134 Specialized References ............................................................................................................... 138 Vocabulary Builder.................................................................................................................... 139 CHAPTER 9. DISSERTATIONS ON GALLSTONES ............................................................................ 141 Overview ................................................................................................................................... 141 Dissertations on Gallstones ....................................................................................................... 141 Keeping Current ........................................................................................................................ 142
PART III. APPENDICES .............................................................................................................. 143 APPENDIX A. RESEARCHING YOUR MEDICATIONS ..................................................................... 145 Overview ................................................................................................................................... 145 Your Medications: The Basics ................................................................................................... 146 Learning More about Your Medications ................................................................................... 147 Commercial Databases............................................................................................................... 149 Contraindications and Interactions (Hidden Dangers)............................................................. 150 A Final Warning ....................................................................................................................... 151 General References..................................................................................................................... 152 Vocabulary Builder.................................................................................................................... 152 APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ............................................................... 153 Overview ................................................................................................................................... 153 What Is CAM? .......................................................................................................................... 153 What Are the Domains of Alternative Medicine? ..................................................................... 154 Can Alternatives Affect My Treatment?................................................................................... 157 Finding CAM References on Gallstones ................................................................................... 158 Additional Web Resources......................................................................................................... 167 General References..................................................................................................................... 181 Vocabulary Builder.................................................................................................................... 182 APPENDIX C. RESEARCHING NUTRITION..................................................................................... 185 Overview ................................................................................................................................... 185 Food and Nutrition: General Principles .................................................................................... 186 Finding Studies on Gallstones................................................................................................... 190 Federal Resources on Nutrition................................................................................................. 193 Additional Web Resources......................................................................................................... 194 Vocabulary Builder.................................................................................................................... 201 APPENDIX D. FINDING MEDICAL LIBRARIES ............................................................................... 203 Overview ................................................................................................................................... 203 Preparation ................................................................................................................................ 203
Contents
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Finding a Local Medical Library ............................................................................................... 204 Medical Libraries Open to the Public ........................................................................................ 204 APPENDIX E. NIH CONSENSUS STATEMENT ON GALLSTONES AND LAPAROSCOPIC CHOLECYSTECTOMY ..................................................................................................................... 211 Overview ................................................................................................................................... 211 Abstract ..................................................................................................................................... 212 Epidemiology of Gallstones........................................................................................................ 212 What Is Laparoscopic Cholecystectomy?................................................................................... 213 Which Patients with Gallstones Should Be Treated? ................................................................ 214 Patients Who Should Be Treated with Laparoscopic Cholecystectomy ..................................... 216 Alternative Medical and Surgical Treatments of Gallstone Disease ......................................... 218 Laparoscopic Cholecystectomy Compared with Other Treatments ........................................... 221 How Should Bile Duct Stones Be Detected and Treated? ......................................................... 223 Directions for Future Research.................................................................................................. 225 Conclusions ............................................................................................................................... 227 Vocabulary Builder.................................................................................................................... 229 ONLINE GLOSSARIES ............................................................................................................... 231 Online Dictionary Directories................................................................................................... 232 GALLSTONES GLOSSARY........................................................................................................ 233 General Dictionaries and Glossaries ......................................................................................... 250 INDEX.............................................................................................................................................. 252
Introduction
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INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that every patient incorporate education into the treatment process. According to the AHRQ: Finding out more about your condition is a good place to start. By contacting groups that support your condition, visiting your local library, and searching on the Internet, you can find good information to help guide your treatment decisions. Some information may be hard to find—especially if you don’t know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist patients in obtaining reliable information, in March 2001 the National Institutes of Health issued the following warning: The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading.3
Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 From the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2
2
Gallstones
Since the late 1990s, physicians have seen a general increase in patient Internet usage rates. Patients frequently enter their doctor’s offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding patients through sound therapies. The 2002 Official Patient’s Sourcebook on Gallstones has been created for patients who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to gallstones, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on gallstones. Given patients’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on gallstones should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your best option. This sourcebook is no exception. Each patient is unique. Deciding on appropriate
Introduction
3
options is always up to the patient in consultation with their physician and healthcare providers.
Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching gallstones (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other patient networks dedicated to gallstones. It also gives you sources of information that can help you find a doctor in your local area specializing in treating gallstones. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with gallstones. Part II moves on to advanced research dedicated to gallstones. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on gallstones. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “free-to-use” options. Part III provides appendices of useful background reading for all patients with gallstones or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with gallstones. Accessing materials via medical libraries may be the only option for some readers, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing patients with gallstones.
Scope While this sourcebook covers gallstones, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that gallstones is often considered a synonym or a condition closely related to the following: ·
Gallstones
4
Gallstones
In addition to synonyms and related conditions, physicians may refer to gallstones using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world’s illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for gallstones:4 ·
560.31 gallstone ileus
·
574.0 calculus of the gallbladder with acute cholecystitis
·
574.2 calculus of gallbladder without mention of cholecystitis
·
574.2 calculus of the gallbladder without mention of cholecystitis
For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to gallstones. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.
Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides covering most illnesses. Some are written by patients or their family members. These generally take a layperson’s approach to understanding and coping with an illness or disorder. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful. As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for the purpose of educating you about basic and advanced knowledge as recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? All too often, patients diagnosed with gallstones will log on to the Internet, type words into a search engine, and receive several Web site listings which are mostly irrelevant or redundant. These patients 4 This list is based on the official version of the World Health Organization’s 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.”
Introduction
5
are left to wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with gallstones is even indexed in search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. While we focus on the more scientific aspects of gallstones, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find peer groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give you the most options available in moving forward. In this way, we wish you the best in your efforts to incorporate this educational approach into your treatment plan. The Editors
7
PART I: THE ESSENTIALS
ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on gallstones. The essentials of a disease typically include the definition or description of the disease, a discussion of who it affects, the signs or symptoms associated with the disease, tests or diagnostic procedures that might be specific to the disease, and treatments for the disease. Your doctor or healthcare provider may have already explained the essentials of gallstones to you or even given you a pamphlet or brochure describing gallstones. Now you are searching for more in-depth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what your doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.
Guidelines
CHAPTER 1. GUIDELINES
THE
ESSENTIALS
ON
9
GALLSTONES:
Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on gallstones. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. The great advantage of guidelines over other sources is that they are often written with the patient in mind. Since new guidelines on gallstones can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
The National Institutes of Health (NIH)5 The National Institutes of Health (NIH) is the first place to search for relatively current patient guidelines and fact sheets on gallstones. Originally founded in 1887, the NIH is one of the world’s foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world’s most illustrious scientists and physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine.
5
Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.
10 Gallstones
There is no guarantee that any one Institute will have a guideline on a specific disease, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare diseases. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with gallstones and associated conditions: ·
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
·
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines available at http://www.nlm.nih.gov/medlineplus/healthtopics.html
·
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
Among these, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is particularly noteworthy. The NIDDK’s mission is to conduct and support research on many of the most serious diseases affecting public health.6 The Institute supports much of the clinical research on the diseases of internal medicine and related subspecialty fields as well as many basic science disciplines. The NIDDK’s Division of Intramural Research encompasses the broad spectrum of metabolic diseases such as diabetes, inborn errors of metabolism, endocrine disorders, mineral metabolism, digestive diseases, nutrition, urology and renal disease, and hematology. Basic research studies include biochemistry, nutrition, pathology, histochemistry, chemistry, physical, chemical, and molecular biology, pharmacology, and toxicology. NIDDK extramural research is organized into divisions of program areas: ·
Division of Diabetes, Endocrinology, and Metabolic Diseases
·
Division of Digestive Diseases and Nutrition
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Division of Kidney, Urologic, and Hematologic Diseases
The Division of Extramural Activities provides administrative support and overall coordination. A fifth division, the Division of Nutrition Research Coordination, coordinates government nutrition research efforts. The Institute supports basic and clinical research through investigator-initiated This paragraph has been adapted from the NIDDK: http://www.niddk.nih.gov/welcome/mission.htm. “Adapted” signifies that a passage is reproduced exactly or slightly edited for this book. 6
Guidelines 11
grants, program project and center grants, and career development and training awards. The Institute also supports research and development projects and large-scale clinical trials through contracts. The following patient guideline was recently published by the NIDDK on gallstones.
What Are Gallstones?7 Gallstones form when liquid stored in the gallbladder hardens into pieces of stone-like material. The liquid, called bile, is used to help the body digest fats. Bile is made in the liver, then stored in the gallbladder until the body needs to digest fat. At that time, the gallbladder contracts and pushes the bile into a tube—called a duct—that carries it to the small intestine, where it helps with digestion. Bile contains water, cholesterol, fats, bile salts, and bilirubin. Bile salts break up fat, and bilirubin gives bile and stool a brownish color. If the liquid bile contains too much cholesterol, bile salts, or bilirubin, it can harden into stones. The two types of gallstones are cholesterol stones and pigment stones. Cholesterol stones are usually yellow-green and are made primarily of hardened cholesterol. They account for about 80 percent of gallstones. Pigment stones are small, dark stones made of bilirubin. Gallstones can be as small as a grain of sand or as large as a golf ball. The gallbladder can develop just one large stone, hundreds of tiny stones, or almost any combination.
Adapted from The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): http://www.niddk.nih.gov/health/digest/pubs/gallstns/gallstns.htm. 7
12 Gallstones
The gallbladder and the ducts that carry bile and other digestive enzymes from the liver, gallbladder, and pancreas to the small intestine are called the biliary system. Gallstones can block the normal flow of bile if they lodge in any of the ducts that carry bile from the liver to the small intestine. That includes the hepatic ducts, which carry bile out of the liver; the cystic duct, which takes bile to and from the gallbladder; and the common bile duct, which takes bile from the cystic and hepatic ducts to the small intestine. Bile trapped in these ducts can cause inflammation in the gallbladder, the ducts, or, rarely, the liver. Other ducts open into the common bile duct, including the pancreatic duct, which carries digestive enzymes out of the pancreas. If a gallstone blocks the opening to that duct, digestive enzymes can become trapped in the pancreas and cause an extremely painful inflammation called pancreatitis. If any of these ducts remain blocked for a significant period of time, severe— possibly fatal—damage can occur, affecting the gallbladder, liver, or pancreas. Warning signs of a serious problem are fever, jaundice, and persistent pain.
What Causes Gallstones? Cholesterol Stones Scientists believe cholesterol stones form when bile contains too much cholesterol, too much bilirubin, or not enough bile salts, or when the gallbladder does not empty as it should for some other reason. Pigment Stones The cause of pigment stones is uncertain. They tend to develop in people who have cirrhosis, biliary tract infections, and hereditary blood disorders such as sickle cell anemia.
Other Factors It is believed that the mere presence of gallstones may cause more gallstones to develop. However, other factors that contribute to gallstones have been identified, especially for cholesterol stones.
Guidelines 13
·
Obesity. Obesity is a major risk factor for gallstones, especially in women. A large clinical study showed that being even moderately overweight increases one’s risk for developing gallstones. The most likely reason is that obesity tends to reduce the amount of bile salts in bile, resulting in more cholesterol. Obesity also decreases gallbladder emptying.
·
Estrogen. Excess estrogen from pregnancy, hormone replacement therapy, or birth control pills appears to increase cholesterol levels in bile and decrease gallbladder movement, both of which can lead to gallstones.
·
Ethnicity. Native Americans have a genetic predisposition to secrete high levels of cholesterol in bile. In fact, they have the highest rates of gallstones in the United States. A majority of Native American men have gallstones by age 60. Among the Pima Indians of Arizona, 70 percent of women have gallstones by age 30. Mexican-American men and women of all ages also have high rates of gallstones.
·
Gender. Women between 20 and 60 years of age are twice as likely to develop gallstones as men.
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Age. People over age 60 are more likely to develop gallstones than younger people.
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Cholesterol-lowering drugs. Drugs that lower cholesterol levels in blood actually increase the amount of cholesterol secreted in bile. This in turn can increase the risk of gallstones.
·
Diabetes. People with diabetes generally have high levels of fatty acids called triglycerides. These fatty acids increase the risk of gallstones.
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Rapid weight loss. As the body metabolizes fat during rapid weight loss, it causes the liver to secrete extra cholesterol into bile, which can cause gallstones.
·
Fasting. Fasting decreases gallbladder movement, causing the bile to become overconcentrated with cholesterol, which can lead to gallstones.
Who Is at Risk for Gallstones? ·
Women
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People over age 60
·
Native Americans
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Mexican-Americans
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Overweight men and women
14 Gallstones
·
People who fast or lose a lot of weight quickly
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Pregnant women, women on hormone therapy, and women who use birth control pills
What Are the Symptoms? Symptoms of gallstones are often called a gallstone “attack” because they occur suddenly. A typical attack can cause ·
Steady, severe pain in the upper abdomen that increases rapidly and lasts from 30 minutes to several hours.
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Pain in the back between the shoulder blades.
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Pain under the right shoulder.
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Nausea or vomiting.
Gallstone attacks often follow fatty meals, and they may occur during the night. Other gallstone symptoms include ·
Abdominal bloating.
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Recurring intolerance of fatty foods.
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Colic.
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Belching.
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Gas.
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Indigestion.
People who also have the following symptoms should see a doctor right away: ·
Sweating.
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Chills.
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Low-grade fever.
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Yellowish color of the skin or whites of the eyes.
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Clay-colored stools.
Many people with gallstones have no symptoms. These patients are said to be asymptomatic, and these stones are called “silent stones.” They do not
Guidelines 15
interfere in gallbladder, liver, or pancreas function and do not need treatment.
How Are Gallstones Diagnosed? Many gallstones, especially silent stones, are discovered by accident during tests for other problems. But when gallstones are suspected to be the cause of symptoms, the doctor is likely to do an ultrasound exam. Ultrasound uses sound waves to create images of organs. Sound waves are sent toward the gallbladder through a handheld device that a technician glides over the abdomen. The sound waves bounce off the gallbladder, liver, and other organs, and their echoes make electrical impulses that create a picture of the organ on a video monitor. If stones are present, the sound waves will bounce off them, too, showing their location. Other tests used in diagnosis include: ·
Cholecystogram or cholescintigraphy. The patient is injected with a special iodine dye, and x-rays are taken of the gallbladder over a period of time. (Some people swallow iodine pills the night before the x-ray.) The test shows the movement of the gallbladder and any obstruction of the cystic duct.
·
Endoscopic retrograde cholangiopancreatography (ERCP). The patient swallows an endoscope—a long, flexible, lighted tube connected to a computer and TV monitor. The doctor guides the endoscope through the stomach and into the small intestine. The doctor then injects a special dye that temporarily stains the ducts in the biliary system. ERCP is used to locate stones in the ducts.
·
Blood tests. Blood tests may be used to look for signs of infection, obstruction, pancreatitis, or jaundice.
Gallstone symptoms are similar to those of heart attack, appendicitis, ulcers, irritable bowel syndrome, hiatal hernia, pancreatitis, and hepatitis. So accurate diagnosis is important.
Surgical Treatment Surgery to remove the gallbladder is the most common way to treat symptomatic gallstones. (Asymptomatic gallstones usually do not need
16 Gallstones
treatment.) Each year more than 500,000 Americans have gallbladder surgery. The surgery is called cholecystectomy. The standard surgery is called laparoscopic cholecystectomy. For this operation, the surgeon makes several tiny incisions in the abdomen and inserts surgical instruments and a miniature video camera into the abdomen. The camera sends a magnified image from inside the body to a video monitor, giving the surgeon a closeup view of the organs and tissues. While watching the monitor, the surgeon uses the instruments to carefully separate the gallbladder from the liver, ducts, and other structures. Then the cystic duct is cut and the gallbladder removed through one of the small incisions. Because the abdominal muscles are not cut during laparoscopic surgery, patients have less pain and fewer complications than they would have had after surgery using a large incision across the abdomen. Recovery usually involves only one night in the hospital, followed by several days of restricted activity at home. If the surgeon discovers any obstacles to the laparoscopic procedure, such as infection or scarring from other operations, the operating team may have to switch to open surgery. In some cases the obstacles are known before surgery, and an open surgery is planned. It is called “open” surgery because the surgeon has to make a 5- to 8-inch incision in the abdomen to remove the gallbladder. This is a major surgery and may require about a 2- to 7-day stay in the hospital and several more weeks at home to recover. Open surgery is required in about 5 percent of gallbladder operations. The most common complication in gallbladder surgery is injury to the bile ducts. An injured common bile duct can leak bile and cause a painful and potentially dangerous infection. Mild injuries can sometimes be treated nonsurgically. Major injury, however, is more serious and requires additional surgery. If gallstones are in the bile ducts, the surgeon may use ERCP in removing them before or during the gallbladder surgery. Once the endoscope is in the small intestine, the surgeon locates the affected bile duct. An instrument on the endoscope is used to cut the duct, and the stone is captured in a tiny basket and removed with the endoscope. This two-step procedure is called ERCP with endoscopic sphincterotomy. Occasionally, a person who has had a cholecystectomy is diagnosed with a gallstone in the bile ducts weeks, months, or even years after the surgery. The two-step ERCP procedure is usually successful in removing the stone.
Guidelines 17
Nonsurgical Treatment Nonsurgical approaches are used only in special situations—such as when a patient’s condition prevents using an anesthetic—and only for cholesterol stones. Stones recur after nonsurgical treatment about half the time.
Oral Dissolution Therapy Drugs made from bile acid are used to dissolve the stones. The drugs, ursodiol (Actigall) and chenodiol (Chenix), work best for small cholesterol stones. Months or years of treatment may be necessary before all the stones dissolve. Both drugs cause mild diarrhea, and chenodiol may temporarily raise levels of blood cholesterol and the liver enzyme transaminase.
Contact Dissolution Therapy This experimental procedure involves injecting a drug directly into the gallbladder to dissolve stones. The drug—methyl tert butyl—can dissolve some stones in 1 to 3 days, but it must be used very carefully because it is a flammable anesthetic that can be toxic. The procedure is being tested in patients with symptomatic, noncalcified cholesterol stones. Extracorporeal shockwave lithotripsy (ESWL). This treatment uses shock waves to break up stones into tiny pieces that can pass through the bile ducts without causing blockages. Attacks of biliary colic (intense pain) are common after treatment, and ESWL’s success rate is not very high. Remaining stones can sometimes be dissolved with medication.
Do People Need Their Gallbladders? Fortunately, the gallbladder is an organ that people can live without. Losing it won’t even require a change in diet. Once the gallbladder is removed, bile flows out of the liver through the hepatic ducts into the common bile duct and goes directly into the small intestine, instead of being stored in the gallbladder. However, because the bile isn’t stored in the gallbladder, it flows into the small intestine more frequently, causing diarrhea in some people. Also, some studies suggest that removing the gallbladder may cause higher blood cholesterol levels, so occasional cholesterol tests may be necessary.
18 Gallstones
Points to Remember ·
Gallstones form when substances in the bile harden.
·
Gallstones are common among women, Native Americans, MexicanAmericans, and people who are overweight.
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Gallstone attacks often occur after eating a fatty meal.
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Symptoms can mimic those of other problems, including heart attack, so accurate diagnosis is important.
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Gallstones can cause serious problems if they become trapped in the bile ducts.
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Laparoscopic surgery to remove the gallbladder is the most common treatment.
More Guideline Sources The guideline above on gallstones is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to gallstones. Many of the guidelines listed below address topics that may be of particular relevance to your specific situation or of special interest to only some patients with gallstones. Due to space limitations these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly.
Topic Pages: MEDLINEplus For patients wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and patientoriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas.
Guidelines 19
If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is similar to the NIH Search Utility, with the exception that it only includes material linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search.
The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on gallstones and related conditions. One of the advantages of CHID over other sources is that it offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: ·
Gallstones: Finding Relief for an Uncomfortable Problem Source: San Bruno, CA: StayWell Company. 1999. [2 p.]. Contact: Available from StayWell Company. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 2444512. E-mail:
[email protected]. Website: www.staywell.com. Price: $17.95 for pack of 50; plus shipping and handling. Summary: This patient education brochure describes gallstones and their treatment. Written in nontechnical language, the brochure first lists the populations in which gallstones are more likely: women (especially those who have been pregnant), people of American Indian or Hispanic descent, people who are overweight, people who have lost weight quickly, women who have taken estrogen birth control pills or hormone replacement therapy, and people who eat a high fat diet. Common symptoms of gallstones range from no symptoms to disabling pain and can include mild to severe pain in the upper abdomen; frequent stomach upset, burping, or bloating; fever, nausea, or vomiting; or jaundice (a liver problem that makes the skin yellowish). Gallstones may be found on x rays done for other reasons, or symptoms may lead the physician to suspect gallstones. Diagnosis will include the patient's medical history and some diagnostic tests such as ultrasound, x rays, and endoscopic
20 Gallstones
retrograde cholangiopancreatography (ERCP). Treatments for gallstones include monitoring (watchful waiting), medications to dissolve the stones, ERCP, or surgery (laparoscopic cholecystectomy or open cholecystectomy, both of which remove the gallbladder). One section of the brochure illustrates the gallbladder and surrounding organs and describes how gallstones form. The last page of the brochure summarizes the recommendations for preventing future gallstones, notably by eating a low fat diet. The brochure is illustrated with full color line drawings. 7 figures. ·
Gastro-Esophageal Reflux Disease: A Common and Uncomfortable Problem. [Enfermedad de Reflujo Gastroesofagico: Un Problema Molesto y Comun] Source: San Bruno, CA: StayWell Company. 1999. [2 p.]. Contact: Available from StayWell Company. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 2444512. E-mail:
[email protected]. Website: www.staywell.com. Price: $17.95 for pack of 50; plus shipping and handling. Summary: This patient education brochure describes gastroesophageal reflux disease (GERD) and its treatment. Written in nontechnical language, the brochure first defines GERD as reflux (return) of the stomach's gastric acid back up into the esophagus. Common symptoms of GERD include frequent heartburn or heartburn at night; sour tasting fluid in the mouth; frequent need for antacids; frequent burping or belching; symptoms that get worse after eating, bending over, or lying down; and difficult or painful swallowing. Diagnosis will include the patient's medical history and some diagnostic tests such endoscopy and blood tests. Treatments for gallstones include watching one's eating habits (avoiding certain foods), ceasing to use tobacco and alcohol, raising the head of the bed, and working closely with a physician to determine which medications may be used to reduce stomach acid and improve the working of the digestive system. In very rare cases, GERD may not respond to lifestyle changes or medications. Surgery may then be necessary. One section of the brochure illustrates the upper digestive system, including the lower esophageal sphincter (LES) and its role in GERD. The last page of the brochure summarizes additional strategies that may help relieve GERD symptoms. The brochure is illustrated with full color line drawings and is available in English or Spanish. 8 figures.
·
Pancreatitis: Understanding This Painful Condition Source: San Bruno, CA: StayWell Company. 1998. [2 p.].
Guidelines 21
Contact: Available from StayWell Company. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 2444512. Price: $ 17.95 for 50 copies; plus shipping and handling; bulk copies available. Order number 9779. Summary: This brochure describes acute pancreatitis (irritated or inflamed pancreas), a condition most often caused by gallstones. Acute pancreatitis is very painful and emergency medical treatment is usually needed. Symptoms include severe pain in the upper abdomen (that goes through to the back), nausea and vomiting, abdominal swelling and tenderness, fever, rapid pulse, and shallow, fast breathing. Blood tests are used to determine whether the symptoms are due to acute pancreatitis; health history and physical exam can help confirm the diagnosis. Other tests used include ultrasound (to confirm gallstones), CT scan (computed tomography, used to show how much the pancreas is inflamed), and ERCP (endoscopic retrograde cholangiopancreatography, which examines the common bile duct for gallstones). The brochure briefly describes the treatment for acute pancreatitis, which can include resting the pancreas (nutrition and fluids are given through an intravenous line), medications for the pain, and dietary modifications (after leaving the hospital). The brochure emphasizes the importance of avoiding alcohol. One sidebar describes chronic pancreatitis, which is most often due to continued drinking of alcohol. Another section describes the anatomy and function of the pancreas. The brochure is illustrated with full color drawings. 6 figures. ·
Gallstones. [Calculos Biliares] Source: Camp Hill, PA: Chek-Med Systems, Inc. 1996. 2 p. Contact: Available from Chek-Med Systems, Inc. 200 Grandview Avenue, Camp Hill, PA 17011. (800) 451-5797. Fax (717) 761-0216. Price: $22 per pack of 50 pamphlets for order of 3-10 packs; 3 packet minimum. Discounts available for larger quantities and complete kits of gastroenterology pamphlets. Summary: This patient brochure, available in English and Spanish, provides information about the causes, symptoms, diagnosis, and treatment of gallstones. As many as half of all gallstone patients experience one of three principal symptoms: colic pain; gallbladder inflammation; or yellow jaundice. The nature of each of these symptoms is described. Diagnosis is typically made by gallbladder X-ray. It is recommended that patients with colic pain avoid large meals (especially fatty foods, either animal or vegetable), and reduce excess body weight. Effective treatments for gallstones are described. These include watchful
22 Gallstones
waiting, elective surgery, gallstone dissolving, or shockwave therapy (lithotripsy). ·
Gallstones at Time of Diagnosis Source: New York, NY: Patient Education Media, Inc. Time Life Medical. 1996. (videocassette). Contact: Available from Milner-Fenwick, Inc. 2125 Greenspring Drive, Timonium, MD 21093. (800) 432-8433. Fax (410) 252-6316. Website: www.milner-fenwick.com. Summary: This videocassette program provides information for patients newly diagnosed with gallstones. The half-hour, newsmagazine style educational program features four sections or 'reports.' The first report examines what is going on inside the body and how the diagnosis was made; computer animation is used to aid viewer understanding. The second report discusses what happens after the diagnosis and introduces the viewer to practical issues, including the types of health professionals they may encounter and what lifestyle changes may need to occur. The third report explores options for treatment and management of the condition. The final report addresses issues and answers common questions through the use of an in-studio question and answer session. The videotape comes with a personal workbook that includes the program highlights, a glossary, a resource guide, and blank space for readers to record their personal medical journal. (AA-M).
·
Common Gastrointestinal Problems: A Consumer Health Guide. Volume II Source: Arlington, VA: American College of Gastroenterology. 1996. 23 p. Contact: Available from American College of Gastroenterology. 4900B South 31st Street, Arlington, VA 22206. (703) 820-7400. Price: Single copy free. Summary: This brochure provides an overview of common gastrointestinal problems, including constipation, gallstones, hemochromatosis, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), viral liver disease, and alcoholic liver disease. Each topic is addressed by a specialist in the field and the information is provided in a question and answer format. The section on constipation covers normal digestive function, normal bowel habits, a definition of constipation, how to know when to consult a health care provider, diagnostic tests that may be performed, treatment options, and dietary fiber. The section on gallstones describes the gallbladder and its functions, how gallstones are formed, risk factors for developing gallstones, the symptoms of
Guidelines 23
gallstones, diagnostic tests used to confirm gallstones, treatment options, and prevention. The section on hemochromatosis describes the condition and its symptoms, diagnostic tests, treatment options, how hemochromatosis can be confused with other liver diseases, and the indications for screening of family members. The chapter on IBD covers the difference between ulcerative colitis and Crohn's disease, how IBD differs from IBS, the causes of IBD, how stress affects IBD, diagnostic tests, complications of IBD, medication treatments available, complications from medical treatment, diet therapy for patients with IBD, and surgical options for IBD. The section on IBS focuses on recommended treatment strategies, including consulting a health care provider, reducing stress, watching dietary intake, and using medications. The section on viral liver disease describes the liver and its function, a definition of hepatitis and its symptoms, the different viruses and how they are transmitted, prevention issues, treatment options, and the longterm consequences of hepatitis. The final section, on alcoholic liver disease, covers the impact of alcohol consumption on the liver, gender differences in alcoholic liver disease, fatty liver, alcoholic hepatitis, alcohol-induced cirrhosis, differentially diagnosis, complications of alcoholic liver disease, and treatment options. 3 figures. 1 table. (AA-M). ·
Gallstones and Their Treatment: A Guide for Patients Source: San Ramon, CA: HIN, Inc., The Health Information Network. 1995. 25 p. Contact: Available from HIN, Inc. 231 Market Place, Number 331, San Ramon, CA 94583. (800) HIN-1121. Fax (925) 358-4377. Website: www.hinbooks.com. Price: $36.25 plus shipping per set of 25 booklets; quantity discounts available. Order Number 0201. ISBN: 188527421x. Summary: This patient education brochure familiarizes readers with gallstones and their treatment. It is written in non-technical language and includes information about what gallstones are; how they develop; risk factors; complications; symptoms; diagnostic tests; treatment options; preparing for laparoscopic surgery; the operation itself; recovery after surgery; and nonsurgical treatment options. The brochure is illustrated with simple line drawings and figures and includes a glossary.
·
Gallstones: A National Health Problem Source: Cedar Grove, NJ: American Liver Foundation. 4 p. Contact: Available from American Liver Foundation. 1425 Pompton Avenue, Cedar Grove, NJ 07009. (800) 223-0179 or (201) 256-2550. Price:
24 Gallstones
$0.50 each; $6 for 25 copies; $12 for 50 copies (as of 1995); discounts available for larger quantities. Summary: An estimated 20 million Americans, more than 10 percent of the population, have gallstones. Another million develop gallstones each year. Recognition and understanding of the problem is needed to support research to find solutions to the problem. Information is provided on the gallbladder and its function and on gallstones: their causes, symptoms, diagnosis, and treatment. ·
Your Gallstones: Diagnosis and Treatment Source: Washington, DC: Digestive Disease National Coalition. 1991. 4 p. Contact: Available from Digestive Disease National Coalition. 711 Second Street, NE, Suite 2. Washington, DC 20002. (202) 544-7497. Price: Single copy free. Summary: Written in a question and answer format, this brochure reviews the diagnosis and treatment of common gallstones. Topics include the role of the gallbladder, the occurrence of gallstones, how rapid weight loss affects the formation of gallstones, the symptoms of gallstones, how gallstones are diagnosed, how gallstones typically progress, traditional surgical treatment of gallstones, laparoscopic removal of the gallbladder, oral medication used for dissolving cholesterol gallstones, and shock wave lithotripsy used to fragment the stones. The brochure stresses the importance of learning about all the options available to treat gallstones, in order to make an informed decision about treatment. 4 figures.
·
Erythropoietic Protoporphyria (EPP): A Description for Patients and Their Relatives Source: Houston, TX: American Porphyria Foundation. 199x. 2 p. Contact: Available from American Porphyria Foundation. P.O. Box 22712, Houston, TX 77227. (713) 266-9617. Price: Single copy free; $2.50 for 5 pamphlets. Summary: Erythropoietic protoporphyria (EPP) is a disease of porphyrin metabolism characterized by abnormally elevated levels of protoporphyrin IX in erythrocytes, feces and plasma, and by sensitivity to visible light. This brochure, from the American Porphyria Foundation, describes the disease, its diagnosis, clinical features, and treatment. The disease of EPP is often coexistent with cholelithiasis (gallstones) and sometimes can lead to serious liver disease. The brochure discusses the drug therapy used to treat EPP, as well as some suggestions for
Guidelines 25
environmental changes that can be made to improve the quality of life for those with this disease. ·
Cirrhosis of the Liver Source: Bethesda, MD: American Gastroenterological Association. 199x. [4 p.]. Contact: American Gastroenterological Association (AGA). 7910 Woodmont Avenue, Seventh Floor, Bethesda, MD 20814. (800) 668-5237 or (301) 654-2055. Fax (301) 652-3890. Website: www.gastro.org. Price: Single copy free; bulk copies available. Summary: When chronic diseases cause the liver to become permanently injured and scarred, the condition is called cirrhosis. This brochure, from the American Gastroenterological Association (AGA), reviews the problem of cirrhosis. Topics include the major causes of cirrhosis, the symptoms of the condition, diagnostic methods used to confirm cirrhosis, treatment strategies, and treatment options for the complications of cirrhosis. Cirrhosis can result from direct injury to the liver cells (i.e., hepatitis), or from indirect injury via inflammation or obstruction to bile ducts (e.g., primary biliary cirrhosis, primary sclerosing cholangitis), which drain the liver cells of bile. Chronic alcoholism is the most common cause of cirrhosis in the United States. People with cirrhosis often have few symptoms at first. The two major problems that eventually cause symptoms are loss of functioning liver cells and distortion of the liver caused by scarring. Associated problems include fluid accumulation (ascites), jaundice (yellow skin), gallstones, intense itching, loss of appetite, fatigue and weakness, buildup of toxins, slowed drug processing, portal hypertension (high blood pressure in the main veins of the liver), and varices (thin walled, enlarged blood vessels). Diagnosis is confirmed from the patient's symptoms and from diagnostic tests such as CT scan, ultrasound, and biopsy. Treatment of cirrhosis is aimed to stop the development of scar tissue in the liver and prevent complications. Regardless of the cause of cirrhosis, every patient must avoid all substances, habits, and drugs that may further damage the liver, cause complications, or speed the progression to liver failure. Liver failure refers to the end stage of liver disease and cirrhosis when the liver stops working and cannot support life. The brochure includes a list of references and a diagram of the digestive tract, with organs labeled. 3 figures. 6 references.
·
Gallstones Source: Bethesda, MD: American Gastroenterological Association. 199x. [4 p.].
26 Gallstones
Contact: American Gastroenterological Association (AGA). 7910 Woodmont Avenue, Seventh Floor, Bethesda, MD 20814. (800) 668-5237 or (301) 654-2055. Fax (301) 652-3890. Website: www.gastro.org. Price: Single copy free; bulk copies available. Summary: Gallstone disease is a common medical problem in the United States. This brochure from the American Gastroenterological Association (AGA) reviews the problem of gallstones and advances in the diagnosis and treatment of this condition. Topics include a definition of gallstones and how they form, diagnostic tests used to confirm the presence of gallstones, and treatment options. Gallstones form when the components of bile (a digestive juice) precipitate out of solution and form crystals. Pigment (bilirubin) gallstones and cholesterol gallstones are the most common types. The most typical symptom of gallstone disease is severe steady pain in the upper abdomen or right side. If the blockage caused by a gallstone is prolonged, the gallbladder may become inflamed (acute cholecystitis), which usually requires hospitalization for treatment. Abdominal ultrasound and oral cholecystograms are used to diagnose gallstones. Surgical removal of the gallbladder (cholecystectomy) remains the most widely used therapy for gallstones; surgical options include the standard open procedure and a less invasive procedure using laparoscopy ('belly button surgery'). Alternatives to surgery include endoscopic removal of the stone, chemical dissolution, and lithotripsy (in which sound waves are used to disintegrate the stones). Unfortunately, in all nonsurgical approaches, the gallstones tend to recur in about half of patients treated. The brochure includes a diagram of the digestive tract, with organs labeled. 2 figures. ·
Dieting and Gallstones Source: Bethesda, MD: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 4 p., 1993. Contact: Weight-Control Information Network, 1 Win Way, Bethesda, MD 20892-3665. (301) 570-2178 OR (800) 946-8098. Summary: This patient education brochure provides an overview of the problems associated with low-calorie diets and the development of gallstones. The difference between silent and symptomatic gallstones is explained. Overweight people are at greater risk of developing gallstones than people of average weight. People who are considering embarking on a diet program requiring very low intake of calories each day should be aware that during rapid or substantial weight loss, a person's risk of developing gallstones is increased. The risks and benefits of weight loss
Guidelines 27
are considered, along with a discussion of possible treatment for gallstones and a suggested reading list.
The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search their site located at http://www.guideline.gov by using the keyword “gallstones” or synonyms. The following was recently posted: ·
AACE/ACE position statement on the prevention, diagnosis and treatment of obesity. Source: American Association of Clinical Endocrinologists/American College of Endocrinology.; 1997 (revised 1998); 35 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 0976&sSearch_string=gallstones
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ACR Appropriateness Criteria™ for evaluation of patients with acute right upper quadrant pain. Source: American College of Radiology.; 1996 (revised 1999); 5 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1628&sSearch_string=gallstones
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Cholecystectomy. Source: Optimed Medical Systems Clinical Development Group.; 1989 (revised 2000); The software includes over 19 menus and requires user to spend 2-5 minutes depending on the clinical information. http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1489&sSearch_string=gallstones
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Drug treatment for hyperlipidaemias. Source: Finnish Medical Society Duodecim.; 2001 April 4; Various pagings http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1837&sSearch_string=gallstones
28 Gallstones
·
Early discharge of the term newborn. Source: National Association of Neonatal Nurses.; 1999; 33 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1374&sSearch_string=gallstones
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Effects of menopause and estrogen replacement therapy or hormone replacement therapy in women with diabetes mellitus: consensus opinion of The North American Menopause Society. Source: The North American Menopause Society.; 2000 March; 9 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1792&sSearch_string=gallstones
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Guidelines for the clinical application of laparoscopic biliary tract surgery. Source: Society of American Gastrointestinal Endoscopic Surgeons.; 1990 (updated 1999); 3 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1091&sSearch_string=gallstones
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Hormone replacement therapy: collaborative decision making and management. Source: Institute for Clinical Systems Improvement.; 1999 August (revised 2001 Jul); 64 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2210&sSearch_string=gallstones
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Lipids. Source: National Committee on Cardiac Care (Singapore)/National Medical Research Council (Singapore Ministry of Health)/Singapore Cardiac Society/Singapore Ministry of Health.; 2001 July; 52 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2301&sSearch_string=gallstones
Healthfinder™ Healthfinder™ is an additional source sponsored by the U.S. Department of Health and Human Services which offers links to hundreds of other sites that
Guidelines 29
contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: ·
Dieting and Gallstones Summary: This online document gives consumers basic information on gallstones and the effect of weight loss on this condition. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=1448
·
Gallstones Summary: Gallstones are pieces of solid material that form in the gallbladder. This consumer health information fact sheet contains basic information about this digestive disorder. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=2745
·
Gallstones: A National Health Problem Summary: This online document was written for consumers and answers questions about the causes, diagnosis, prognosis and treatment of this disorder. Source: American Liver Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=2211 The NIH Search Utility
After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to gallstones. The drawbacks of this approach are that the information is not organized by theme and that the references are often a
30 Gallstones
mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.
Additional Web Sources A number of Web sites that often link to government sites are available to the public. These can also point you in the direction of essential information. The following is a representative sample: ·
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDÒHealth: http://my.webmd.com/health_topics
Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter: Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Appendicitis: Acute inflammation of the vermiform appendix. [NIH] Ascites: Effusion and accumulation of serous fluid in the abdominal cavity; called also abdominal or peritoneal dropsy, hydroperitonia, and hydrops abdominis. [EU]
Guidelines 31
Asymptomatic: No symptoms; no clear sign of disease present. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Biliary: Pertaining to the bile, to the bile ducts, or to the gallbladder. [EU] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Cardiac: Pertaining to the heart. [EU] Cholangitis: Inflammation of a bile duct. [EU] Cholecystectomy: Surgical removal of the gallbladder. [NIH] Cholecystitis: Inflammation of the gallbladder. [EU] Cholelithiasis: The presence or formation of gallstones. [EU] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chronic: Persisting over a long period of time. [EU] Cirrhosis: Liver disease characterized pathologically by loss of the normal microscopic lobular architecture, with fibrosis and nodular regeneration. The term is sometimes used to refer to chronic interstitial inflammation of any organ. [EU] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Colitis: Inflammation of the colon. [EU] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endoscopy: Visual inspection of any cavity of the body by means of an endoscope. [EU] Enzyme: A protein molecule that catalyses chemical reactions of other substances without itself being destroyed or altered upon completion of the reactions. Enzymes are classified according to the recommendations of the
32 Gallstones
Nomenclature Committee of the International Union of Biochemistry. Each enzyme is assigned a recommended name and an Enzyme Commission (EC) number. They are divided into six main groups; oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. [EU] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH] Fats: One of the three main classes of foods and a source of energy in the body. Fats help the body use some vitamins and keep the skin healthy. They also serve as energy stores for the body. In food, there are two types of fats: saturated and unsaturated. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hepatic: Pertaining to the liver. [EU] Hepatitis: Inflammation of the liver. [EU] Hernia: (he protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [EU] Hyperlipidaemia: A general term for elevated concentrations of any or all of the lipids in the plasma, including hyperlipoproteinaemia, hypercholesterolaemia, etc. [EU] Hypertension: Persistently high arterial blood pressure. Various criteria for its threshold have been suggested, ranging from 140 mm. Hg systolic and 90 mm. Hg diastolic to as high as 200 mm. Hg systolic and 110 mm. Hg diastolic. Hypertension may have no known cause (essential or idiopathic h.) or be associated with other primary diseases (secondary h.). [EU] Incision: 1. cleft, cut, gash. 2. an act or action of incising. [EU] Inflammation: A pathological process characterized by injury or destruction
Guidelines 33
of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Intravenous: Within a vein or veins. [EU] Invasive: 1. having the quality of invasiveness. 2. involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]
Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [NIH] Lithotripsy: The destruction of a calculus of the kidney, ureter, bladder, or gallbladder by physical forces, including crushing with a lithotriptor through a catheter. Focused percutaneous ultrasound and focused hydraulic shock waves may be used without surgery. Lithotripsy does not include the dissolving of stones by acids or litholysis. Lithotripsy by laser is lithotripsy, laser. [NIH] Menopause: Cessation of menstruation in the human female, occurring usually around the age of 50. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU] Neonatal: Pertaining to the first four weeks after birth. [EU] Oral: Pertaining to the mouth, taken through or applied in the mouth, as an oral medication or an oral thermometer. [EU] Pancreas: An organ behind the lower part of the stomach that is about the size of a hand. It makes insulin so that the body can use glucose (sugar) for energy. It also makes enzymes that help the body digest food. Spread all over the pancreas are areas called the islets of Langerhans. The cells in these areas each have a special purpose. The alpha cells make glucagon, which raises the level of glucose in the blood; the beta cells make insulin; the delta cells make somatostatin. There are also the PP cells and the D1 cells, about which little is known. [NIH]
34 Gallstones
Pancreatitis: Inflammation (pain, tenderness) of the pancreas; it can make the pancreas stop working. It is caused by drinking too much alcohol, by disease in the gallbladder, or by a virus. [NIH] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Reflux: A backward or return flow. [EU] Retrograde: 1. moving backward or against the usual direction of flow. 2. degenerating, deteriorating, or catabolic. [EU] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Tomography: The recording of internal body images at a predetermined plane by means of the tomograph; called also body section roentgenography. [EU]
Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Transaminase: Aminotransferase (= a subclass of enzymes of the transferase class that catalyse the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally 2-keto acid). Most of these enzymes are pyridoxal-phosphate-proteins. [EU] Ulcer: A break in the skin; a deep sore. People with diabetes may get ulcers from minor scrapes on the feet or legs, from cuts that heal slowly, or from the rubbing of shoes that do not fit well. Ulcers can become infected. [NIH] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [NIH] Veins: The vessels carrying blood toward the heart. [NIH]
Guidelines 35
Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viruses: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. [NIH]
Seeking Guidance 37
CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with gallstones. These associations can become invaluable sources of information and advice. Many associations offer aftercare support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.8 In addition to support groups, your physician can be a valuable source of guidance and support. Therefore, finding a physician that can work with your unique situation is a very important aspect of your care. In this chapter, we direct you to resources that can help you find patient organizations and medical specialists. We begin by describing how to find associations and peer groups that can help you better understand and cope with gallstones. The chapter ends with a discussion on how to find a doctor that is right for you.
Associations and Gallstones As mentioned by the Agency for Healthcare Research and Quality, sometimes the emotional side of an illness can be as taxing as the physical side.9 You may have fears or feel overwhelmed by your situation. Everyone has different ways of dealing with disease or physical injury. Your attitude, your expectations, and how well you cope with your condition can all Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 9 This section has been adapted from http://www.ahcpr.gov/consumer/diaginf5.htm. 8
38 Gallstones
influence your well-being. This is true for both minor conditions and serious illnesses. For example, a study on female breast cancer survivors revealed that women who participated in support groups lived longer and experienced better quality of life when compared with women who did not participate. In the support group, women learned coping skills and had the opportunity to share their feelings with other women in the same situation. In addition to associations or groups that your doctor might recommend, we suggest that you consider the following list (if there is a fee for an association, you may want to check with your insurance provider to find out if the cost will be covered): ·
American Liver Foundation Address: American Liver Foundation 75 Maiden Lane, Suite 603, New York, NY 10038 Telephone: (212) 668-1000 Toll-free: (800) 465-4837 Fax: (973) 256-3214 Email:
[email protected] Web Site: http://www.liverfoundation.or Background: The American Liver Foundation is a national voluntary notfor-profit organization dedicated to the prevention, treatment, and cure of diseases of the liver through programs of research and education. Established in 1976, the Foundation's activities include support groups, patient advocacy, support of medical research, and patient and professional education. Educational materials include brochures on Hepatitis, Cirrhosis, Biliary Atresia, liver transplantation, gallstones, and Hereditary Hemochromatosis. Fact sheets are also available on a variety of liver diseases including Alagille Syndrome, Alpha-1-Antitrypsin Deficiency, Cancer of the Liver, Fatty Liver, Gilbert Syndrome, Primary Biliary Cirrhosis, Porphyria, and others. Videotapes produced by the Foundation include 'A Healthy Liver: A Happier Life,' 'Foundations for Decision Making,' 'Hepatitis B: Patient Information,' 'Hepatitis C: A Guide for Primary Care Physicians,' and 'The Visionaries.' The Foundation also offers liver wellness and substance abuse prevention programs to elementary schools and corporations. Relevant area(s) of interest: Gallstones, Hepatitis C, Porphyria, Wilson's Disease
·
Canadian Liver Foundation Address: Canadian Liver Foundation 365 Bloor Street, Suite 200, Toronto, Ontario, M4W 3L4, Canada
Seeking Guidance 39
Telephone: (416) 964-4935 Toll-free: (800) 563-5483 Fax: (416) 964-0024 Email:
[email protected] Web Site: http://www.liver.c Background: The Canadian Liver Foundation (CLF) is a not-for-profit health organization committed to reducing the incidence and impact of liver disease by providing support for research and education into the causes, diagnosis, prevention and treatment of more than 100 diseases of the liver. Established in 1969, the CLF has established 30 chapters across Canada and provides information in both English and French. Some of the liver diseases discussed in brochures and medical information sheets available from CLF include gallstones, hemochromatosis, primary biliary cirrhosis, several forms of hepatitis, porphyria, fatty liver, and liver cancer. Further information is provided on liver transplantation, the effects of sodium, and management of variceal bleeding. The Foundation also produces a newsletter and maintains World Wide Web site at http://www.liver.ca. Relevant area(s) of interest: Cirrhosis of the Liver, Gallstones, Hepatitis A, Hepatitis B, Hepatitis C, Porphyria
Finding More Associations There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information than what is listed above, by consulting all of them, you will have nearly exhausted all sources for patient associations.
The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about gallstones. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.
40 Gallstones
DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov/. Simply type in “gallstones” (or a synonym) or the name of a topic, and the site will list information contained in the database on all relevant organizations.
The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “gallstones”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” By making these selections and typing in “gallstones” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with gallstones. You should check back periodically with this database since it is updated every 3 months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by specific diseases. You can access this database at the following Web site: http://www.rarediseases.org/cgi-bin/nord/searchpage. Select the option called “Organizational Database (ODB)” and type “gallstones” (or a synonym) in the search box. Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms for people with different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site:
Seeking Guidance 41
http://boards.webmd.com/roundtable. These online self-help communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your doctor or other healthcare providers, as the treatments or discoveries you hear about may not be scientifically proven to be safe and effective.
Finding Doctors One of the most important aspects of your treatment will be the relationship between you and your doctor or specialist. All patients with gallstones must go through the process of selecting a physician. While this process will vary from person to person, the Agency for Healthcare Research and Quality makes a number of suggestions, including the following:10 ·
If you are in a managed care plan, check the plan’s list of doctors first.
·
Ask doctors or other health professionals who work with doctors, such as hospital nurses, for referrals.
·
Call a hospital’s doctor referral service, but keep in mind that these services usually refer you to doctors on staff at that particular hospital. The services do not have information on the quality of care that these doctors provide.
·
Some local medical societies offer lists of member doctors. Again, these lists do not have information on the quality of care that these doctors provide.
Additional steps you can take to locate doctors include the following: ·
Check with the associations listed earlier in this chapter.
·
Information on doctors in some states is available on the Internet at http://www.docboard.org. This Web site is run by “Administrators in Medicine,” a group of state medical board directors.
·
The American Board of Medical Specialties can tell you if your doctor is board certified. “Certified” means that the doctor has completed a training program in a specialty and has passed an exam, or “board,” to assess his or her knowledge, skills, and experience to provide quality patient care in that specialty. Primary care doctors may also be certified as specialists. The AMBS Web site is located at
10
This section is adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.
42 Gallstones
http://www.abms.org/newsearch.asp.11 You can also contact the ABMS by phone at 1-866-ASK-ABMS. ·
You can call the American Medical Association (AMA) at 800-665-2882 for information on training, specialties, and board certification for many licensed doctors in the United States. This information also can be found in “Physician Select” at the AMA’s Web site: http://www.amaassn.org/aps/amahg.htm.
If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with expertise in various rare diseases. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.
Selecting Your Doctor12 When you have compiled a list of prospective doctors, call each of their offices. First, ask if the doctor accepts your health insurance plan and if he or she is taking new patients. If the doctor is not covered by your plan, ask yourself if you are prepared to pay the extra costs. The next step is to schedule a visit with your chosen physician. During the first visit you will have the opportunity to evaluate your doctor and to find out if you feel comfortable with him or her. Ask yourself, did the doctor: ·
Give me a chance to ask questions about gallstones?
·
Really listen to my questions?
·
Answer in terms I understood?
·
Show respect for me?
·
Ask me questions?
·
Make me feel comfortable?
·
Address the health problem(s) I came with?
·
Ask me my preferences about different kinds of treatments for gallstones?
While board certification is a good measure of a doctor’s knowledge, it is possible to receive quality care from doctors who are not board certified. 12 This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. 11
Seeking Guidance 43
·
Spend enough time with me?
Trust your instincts when deciding if the doctor is right for you. But remember, it might take time for the relationship to develop. It takes more than one visit for you and your doctor to get to know each other.
Working with Your Doctor13 Research has shown that patients who have good relationships with their doctors tend to be more satisfied with their care and have better results. Here are some tips to help you and your doctor become partners: ·
You know important things about your symptoms and your health history. Tell your doctor what you think he or she needs to know.
·
It is important to tell your doctor personal information, even if it makes you feel embarrassed or uncomfortable.
·
Bring a “health history” list with you (and keep it up to date).
·
Always bring any medications you are currently taking with you to the appointment, or you can bring a list of your medications including dosage and frequency information. Talk about any allergies or reactions you have had to your medications.
·
Tell your doctor about any natural or alternative medicines you are taking.
·
Bring other medical information, such as x-ray films, test results, and medical records.
·
Ask questions. If you don’t, your doctor will assume that you understood everything that was said.
·
Write down your questions before your visit. List the most important ones first to make sure that they are addressed.
·
Consider bringing a friend with you to the appointment to help you ask questions. This person can also help you understand and/or remember the answers.
·
Ask your doctor to draw pictures if you think that this would help you understand.
·
Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.
This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.
13
44 Gallstones
·
Let your doctor know if you need more time. If there is not time that day, perhaps you can speak to a nurse or physician assistant on staff or schedule a telephone appointment.
·
Take information home. Ask for written instructions. Your doctor may also have brochures and audio and videotapes that can help you.
·
After leaving the doctor’s office, take responsibility for your care. If you have questions, call. If your symptoms get worse or if you have problems with your medication, call. If you had tests and do not hear from your doctor, call for your test results. If your doctor recommended that you have certain tests, schedule an appointment to get them done. If your doctor said you should see an additional specialist, make an appointment.
By following these steps, you will enhance the relationship you will have with your physician.
Broader Health-Related Resources In addition to the references above, the NIH has set up guidance Web sites that can help patients find healthcare professionals. These include:14 ·
Caregivers: http://www.nlm.nih.gov/medlineplus/caregivers.html
·
Choosing a Doctor or Healthcare Service: http://www.nlm.nih.gov/medlineplus/choosingadoctororhealthcareserv ice.html
·
Hospitals and Health Facilities: http://www.nlm.nih.gov/medlineplus/healthfacilities.html
You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.
14
45
PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL
ABOUT PART II In Part II, we introduce you to additional resources and advanced research on gallstones. All too often, patients who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on gallstones. In Part II, as in Part I, our objective is not to interpret the latest advances on gallstones or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with gallstones is suggested.
Studies 47
CHAPTER 3. STUDIES ON GALLSTONES Overview Every year, academic studies are published on gallstones or related conditions. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on gallstones. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on gallstones and teach you how to keep current on new studies as they are published or undertaken by the scientific community.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and gallstones, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the
48 Gallstones
format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type in “gallstones” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is a sample of what you can expect from this type of search: ·
Acupuncture for Gastrointestinal and Hepatobiliary Disorders Source: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice and Policy. 5(1): 27-45. 1999. Summary: This journal article provides an overview of the basic scientific data regarding the effects of acupuncture on gastrointestinal (GI) function, areas of clinical application, and promising directions for future research. Extensive research in both animal models and human subjects supports the effect of acupuncture on the physiology of the GI tract, including acid secretion, motility, neurohormonal changes, and changes in sensory thresholds. Much of the neuroanatomic pathway of these effects has been identified in animal models. A large body of clinical evidence supports the effectiveness of acupuncture for suppressing nausea associated with chemotherapy, postoperative state, and pregnancy. Prospective randomized controlled trials have shown the efficacy of acupuncture for analgesia for endoscopic procedures, including colonoscopy and upper endoscopy. Acupuncture also has been used for a variety of other conditions, including postoperative ileus, achalasia, peptic ulcer disease, functional bowel disease, diarrhea, constipation, inflammatory bowel disease, expulsion of gallstones and biliary ascariasis, and pain associated with pancreatitis. Although there are few randomized clinical trials, the author concludes that the welldocumented effects of acupuncture on the physiology of the GI tract and its extensive history of successful clinical use makes this a promising modality that warrants further study. The article has 3 figures and 117 references. (AA-M).
·
Shock-Wave Lithotripsy in Gallstones and Bile Duct Stones: LongTerm Evaluation of Extracorporeal Shock-Wave Lithotripsy for Cholesterol Gallstones Source: Journal of Gastroenterology and Hepatology. 16(1): 93-99. January 2001.
Studies 49
Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail:
[email protected]. Website: www.blackwell-science.com. Summary: Extracorporeal (outside the body) shock wave lithotripsy (ESWL) is a treatment for gallstones that preserves the gallbladder. Problems after ESWL treatment can include stone recurrence and the development of biliary symptoms. This article reports on a study of 262 patients with cholesterol type gallstones (the best indication for ESWL treatment) who underwent ESWL and 42 control patients with cholesterol type gallstones who received no treatment. The authors evaluated the factors associated with recurrence of gallstones after stone clearance and the development of biliary symptoms after ESWL treatment. The 3, 5, and 7 year cumulative probabilities of gallstone recurrent were 20.6, 27.1, and 33.1 percent, respectively, with the recurrence probability significantly lower in patients with good gallbladder contractility. In patients with recurrence, treatment with ursodeoxycholic acid (UDCA, given orally) was effective. In 69 patients with residual gallstones, the 3, 5, and 7 year cumulative risks of biliary symptoms were 17.3, 24.9, and 30.5 percent, respectively. With residual gallstones, the risk of biliary symptoms developing was significantly lower in patients with a smaller than 3 mm fragment size at the end of ESWL treatment and in those treated consistently with UDCA for 6 months or more after treatment with ESWL. The risk of biliary symptoms was significantly lower in ESWL treated patients with residual stones who had a less than 3 mm fragment size after treatment, compared with control patients. The authors conclude that UDCA was effective in clearing stones in patients with gallstone recurrence. In patients with residual stones, the fragmentation of stones to less than 3 mm and UDCA administration effectively reduced the risk of subsequent biliary symptoms. 3 figures. 4 tables. 18 references. ·
Epidemiology of Gallstones: Prevalence of Gallstone Disease in Iran Source: Journal of Gastroenterology and Hepatology. 16(5): 564-567. May 2001. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail:
[email protected]. Website: www.blackwell-science.com. Summary: The prevalence of gallstone disease varies depending on the geographic region involved. Few studies, in Asia but not from Iran, about the frequency of gallstone disease have been published. This article reports on a study of the prevalence of gallstone disease in Iran. The study included 477 nomads from southern Iran, 513 industrial laborers
50 Gallstones
older than 34 years, and 421 laborers from a pharmaceutical company above 30 years of age, and 471 elderly persons from three nursing homes near Tehran underwent abdominal sonography. There was a total of 1,373 men and 509 women. Gallstone disease was present in 89 subjects; 10.1 percent of them had undergone cholecystectomy (removal of the gallbladder). While the prevalence in the men and women in the age group 31 to 40 years was very low (0.3 percent in men and 1.8 percent in women), it increases sharply in men older than 60 years and women older than 50 years to more than 10 fold (12.5 and 24.6 percent in males and females aged 71 to 80 years, respectively). The author concludes that, in Iran, gallstone disease is very uncommon in middle aged people, but increases sharply in older people. However, this does not reach the high prevalence seen in Western countries. The intake of a high fiber containing diet, and low numbers of overweight people, smoking habits, and hyperlipidemia (elevated concentrations of fats in the blood) are probably the cause for this low prevalence. 2 tables. 44 references. ·
Management of Gallstones and Their Complications Source: American Family Physician. 61(6): 1673-1680. March 15, 2000. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: This article reviews the management of gallstones (cholelithiasis) and their complications. The accurate differentiation of gallstone induced biliary colic (pain) from other abdominal disease processes is the most crucial step in the successful management of gallstone disease. Despite the availability of many imaging techniques to demonstrate the presence of gallstones, clinical judgement ultimately determines the association of symptoms with cholelithiasis and its complications. The authors contend that adult patients with silent or incidental gallstones should be observed and managed expectantly, with few exceptions. In symptomatic patients, the intervention varies with the type of gallstone induced complication. Diagnostic tests reviewed include laboratory tests, ultrasonography, endoscopic retrograde cholangiopancreatography, bile microscopy, computed tomography (CT) and magnetic resonance imaging (MRI), and hepatobiliary scintigraphy. Ultrasound provides more than 95 percent sensitivity and specificity for the diagnosis of gallstones greater than 2 mm in diameter. Ultrasonography of the gallbladder should follow a fast of at least 8 hours because gallstones are visualized better in a distended, bile filled gallbladder. Nonoperative therapies for symptomatic gallstones include oral bile acid dissolution, contact solvents, and extracorporeal shock
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wave lithotripsy. A patient care algorithm offers management strategy for gallstones. 1 figure. 5 tables. 26 references. ·
Gallstones, from Gallbladder to Gut: Management Options for Diverse Complications Source: Postgraduate Medicine. 108(3): 143-146, 149-153. September 1, 2000. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: Gallstones may be incidental and asymptomatic or painful and accompanied by life threatening obstruction or infection. A thorough knowledge of potential complications is therefore critical, especially because some asymptomatic stones require prompt treatment. In this article, the authors offer guidelines for recognizing and treating the various manifestations of gallstone disease (cholelithiasis). Once the gallstones become symptomatic, surgical removal of the gallbladder (cholecystectomy) is usually recommended. Endoscopic retrograde cholangiopancreatography (ERCO) with sphincterotomy and stone extraction is performed if bile duct stones are evident on imaging studies or suspected on the basis of the clinical picture or liver enzyme abnormalities. In patients with cholangitis (a consequence of bacterial infection superimposed on an obstructed biliary system), the mainstay of therapy is biliary drainage, which should be performed as early as possible, even before determining and treating the cause of obstruction. In selected patients with gallstone pancreatitis, use of early ERCP, sphincterotomy, and stone extraction results in lower morbidity (illness) and mortality (death). Nonsurgical treatment is appropriate for patients with recurrent biliary colic or chronic cholecystitis (gallbladder infection), but not for those with acute cholecystitis. Recurrence rates are high with nonsurgical treatment. 3 figures. 29 references.
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Gallstones in Elderly Patients: Impact of Laparoscopic Cholecystectomy Source: Canadian Journal of Gastroenterology. 14(11): 929-932. December 2000. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail:
[email protected]. Summary: The use of laparoscopic cholecystectomy (LC, removal of the gallbladder) in elderly patients may pose problems because of their poor general condition, especially of cardiopulmonary (heart and lung)
52 Gallstones
function. Moreover, these patients present with acute cholecystitis (inflammation of the gallbladder) and associated common bile duct stones more often than their younger counterparts. In this article, the authors report on their experience from 1990 to 1999 when they performed 943 LCs; 31 (3.2 percent) were attempted on elderly patients, 11 (35 percent) of which were on an emergency basis because of acute cholecystitis, cholangitis (bile duct inflammation) or acute biliary pancreatitis. Ten percent of LCs needed to be converted to an open cholecystectomy, most often because of an increase in the partial pressure of carbon dioxide in the blood produced by excessive operative time. A gasless procedure (LC usually uses gas to increase the abdominal cavity for access and visualization purposes) was used in the last three years of the study on eight cases; the overall rate of conversion from LC to open cholecystectomy in this group was 0 percent. Associated gallbladder and common bile duct stones were found in five (16 percent) patients. The success rate was 100 percent, overall morbidity was 29 percent and there was no mortality. The authors conclude that their results show that LC is a feasible and safe procedure for use in elderly patients. Gasless LC should be preferred in patients classified as American Society of Anesthesiologists' class III. 4 figures. 21 references. ·
Obesity: Effects on the Liver and Gastrointestinal System Source: Current Opinion in Gastroenterology. 15(2): 154-158. March 1999. Contact: Available from Lippincott Williams and Wilkins Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Summary: Obesity, determined by a body mass index (BMI) greater than 30, has assumed epidemic proportions in the U.S. More than a cosmetic issue, obesity is associated with many comorbidities that contribute to multiple organ dysfunction, illness, and shortened life span. This review article covers new and emerging information on the relationship between obesity and common and debilitating hepatic and gastrointestinal disorders, including nonalcoholic steatohepatitis, gastroesophageal reflux, gallstones, and colon and esophageal cancer. Because these complications can be prevented or treated by optimizing body weight, it is important that the practicing gastroenterologist include the evaluation and treatment of obesity as part of the general approach to the patient. Calculation of BMI is the most reliable and predictive tool for assessing obesity and effective weight reduction. Multiple, often unsatisfactory, medical strategies exist for weight reduction, each optimally requiring the ancillary services of a professional dietitian. Compelling evidence points to the surgical approach to the severely obese. The author
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concludes that understanding the role of obesity in these disorders should lead to new insights into the pathogenesis of common liver and gastrointestinal diseases and to new treatment strategies for the practicing gastroenterologist. 41 references (21 annotated). ·
Gallstones and Diabetes: A Case-Control Study in a Free-Living Population Sample Source: Hepatology. 25(4): 787-790. April 1997. Summary: This article reports on a case-control study to determine the prevalence of diabetes mellitus in a group of subjects with gallstones or who have undergone cholecystectomy (cases). The authors compared these subjects with a control group of subjects without gallstones, selected during an epidemiological study. The subjects were matched for sex, age, and body mass index; there were 336 cases and 336 controls, aged 30 to 69 years. All subjects with fasting glycemic levels of less than 140 mg per dL and without a documented history of diabetes were submitted to a simplified oral glucose tolerance test (OGTT) and then classified according to the National Diabetes Data Group criteria. The prevalence of diabetes in the subjects affected by gallstone disease was significantly higher than that in controls (11.6 percent versus 4.8 percent). Diabetes was more frequent in subjects with gallstone disease than in the control group, even according to sex (18.3 percent versus 9.9 percent for men; 9.3 percent versus 2.6 percent for women). The authors conclude that an altered glucose metabolism may increase the risk of developing cholelithiasis in certain subjects. 3 tables. 36 references. (AA-M).
Federally-Funded Research on Gallstones The U.S. Government supports a variety of research studies relating to gallstones and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.15 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally-funded biomedical research projects conducted at universities, hospitals, and other institutions. Visit the CRISP Web site at http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket. You can 15 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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perform targeted searches by various criteria including geography, date, as well as topics related to gallstones and related conditions. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally-funded studies use animals or simulated models to explore gallstones and related conditions. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for gallstones: ·
Project Title: Second Messengers, Gallbladder Absorption and Gallstones Principal Investigator & Institution: Abedin, Mohammad Z.; Surgery; Mcp Hahnemann University Broad & Vine Sts Philadelphia, Pa 19102 Timing: Fiscal Year 2000; Project Start 1-AUG-1997; Project End 1-JUL2002 Summary: (Adapted from investigator's abstract) The development of cholesterol gallstones involves alterations in the relationship of the amount of cholesterol, phospholipid and bile salts present in bile resulting in bile becoming supersaturated with cholesterol. Cholesterol crystal formation then occurs and aggregation of crystals results in macro stone formation. During the crystalline and early stages of gallstone formation increased absorption of sodium and water occurs which is believed to contribute to the formation of stones by potentially increasing the concentration of crystals and nucleating factors. The proposed research is directed at determining the mechanisms by which supersaturated bile increase gallbladder absorption. The absorption of water is dependent on the transport of sodium which is dependent on the function of various Na+/H+ exchangers. The activity of the Na/HE is regulated by a number of factors which possibly include cyclic nucleotides and calcium. The proposed research intends to determine if lithogenic bile increases gallbladder absorption and the activity of the second messenger system and if these alterations are necessary for gallstone formation. The research will determine the mechanisms of sodium absorption, if it is regulated by the cyclic AMP/ Ca++ second messenger system and if these alterations accompany cholesterol gallstone formation in the cholesterol fed prairie dog. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
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Project Title: Alimentary Tract Lipids in Health and Disease Principal Investigator & Institution: Carey, Martin C.; Brigham and Women's Hospital 75 Francis St Boston, Ma 02115 Timing: Fiscal Year 2000; Project Start 1-JUL-1985; Project End 1-MAR2004 Summary: Bile formation and secretion control homeostatic mechanisms for eliminating cholesterol and tetrapyrrole molecules form the organism as well as absorption of dietary fat. Bile dysfunction causes several common diseases, including gallstones and cholestasis. This proposal employs biophysical rationale and physical-chemical methodology to further molecular understanding of the physical biochemistry of bile, its formation, secretion and functions. The PI and colleagues will design and study appropriate model systems and correlate the results with pathophysiological phenomena pertaining to the function and dysfunction of native systems. They will use I)novel flurocholesterol methodology, cryoelectron microscopy and electron energy-loss spectroscopy to elucidate physical-chemical pathways whereby cholesterol molecules are transferred from blood to liver cell and bile, ii) characterize interactions of bile salt molecules with sphingomyelin in micellar solutions and at interfaces related to cholesterol secretion, absorption and apoptosis, iii) determine the physical-chemical origin and pathophysiology of lipoprotein X in bile secretory failure, iv) define how phosphatidylcholine, cholesterol and calcium influence the physicalchemical state of natural conjugated bilrubins in model (bilrubin ditaurate) and native biles employing analytical ultracentrifugation and spectrophotometric techniques, v) measure the metastable and equilibrium solubilities of unconjugated bilirubin in modelbiles utilizing potentiometric titration and dissolution and correlate the information pathophysiologically with pigment-stone biles, vi) discover whether humans with ~black~ pigment gallstones have dysfunctional mutations of the ileal bile acid transporter gene. These objectives are designed to advance our understanding of physical chemistry of bile as ell as normal and abnormal movements of cholesterol and billirubin to and from the liver and alimentary tract. The systematic project should lead to new targets and strategies for prevention of pigment and cholesterol gallstone diseases as well as lipid transport abnormalities sin cholestasis. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
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Project Title: Bile Salts, Membranes, and Cytotoxicity Principal Investigator & Institution: Heuman, Douglas; Virginia Commonwealth University 901 W Franklin St Richmond, Va 23284
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Timing: Fiscal Year 2000 Summary: Bile salts adsorb to membranes, at high concentrations causing membrane disruption. Adsorption of bile salts to intracellular membranes may determine many of their physiological effects, and bile salt induced membrane injury may be important in pathogenesis of cholestatic liver disease and gallstones. We have studied the adsorption of bile salts to lecithin-cholesterol vesicles and have developed and validated a quantitative model which predicts the distribution of bile salt taurine conjugates in mixed bile salt solutions between lecithincholesterol bilayers and the aqueous phase. In the studies proposed, this model will be generalized to a broad array of bile acids and other organic anions, membrane lipids, and solution conditions. Using large unilamellar vesicles of varying lipid composition, we will examine the relationship between membrane binding of bile salts, mixed micellar dissolution of membrane lipids (observed with quasielastic light scattering) and altered membrane permeability (release of trapped soluble markers assessed by ultrafiltration) to determine if the mixed micellar threshold concentration and the permeation threshold at which membrane leakage begins are predictable consequences of the membrane-bound ionized bile salt/lecithin ratio. Pure protein kinase C isoenzymes (alpha, betaII, delta, epsilon) prepared in a baculovirus system will be employed to test the hypothesis that bile salts activate protein kinase C isoenzymes by binding to membranes and serving as a "bridge" between the enzymes and membrane lipids. The model of bile salt-lecithin interactions will be extended beyond the limits of the two phase (monomer-membrane) region into micellar regions of the phase diagram by combining techniques of gel filtration and ultrafiltration, in order to permit modelling of detergent effects of mixed bile salt solutions. Using synthetic vesicles, isolated canalicular plasma membranes, and living cells (erythrocytes, cultured neoplastic gallbladder epithelia) we will test the hypothesis that lecithin in bile normally protects high cholesterol plasma membranes from bile salt injury by depressing the non-lecithin- associated bile salt concentration to non-toxic levels, and that this protective effect declines predictably as the cholesterol content of biliary vesicles increases. Finally the hepatoprotective role of biliary lipids and biliary bile salt-lipid interactions will be studied in two in vivo models of bile salt-induced liver injury: acute infusion of bile salts in the choline deficient bile fistula rat and chronic feeding of bile salts in hamsters fed lithogenic diets. The ultimate goal of these studies is to provide a conceptual framework for understanding the toxic and protective properties of bile salts and the role of bile salt toxicity in human disease.
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Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Genetics of Gallbladder Disease in Mexican Americans Principal Investigator & Institution: Duggirala, Ravindranath; Medicine; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2000; Project Start 0-SEP-1998; Project End 9-SEP-2003 Summary: (Adapted from investigator's abstract) Gallbladder disease (GBD) is one of the major causes of morbidity and mortality in the United States. In populations such as the Mexican Americans, the prevalence of GBD is high, and it often clusters with diseases such as non-insulin dependent diabetes mellitus (NIDDM) and obesity. The etiology of GBD is unclear, but it is believed to be multifactorial in origin involving abnormalities of the hepatobiliary system such as supersaturation of bile with cholesterol, changes in cholesterol nucleation, and hypomotility of the gallbladder. Despite the epidemiological evidence for its association with risk factors such as age, sex (higher in women), obesity, native American ancestry, NIDDM, and cardiovascular disease risk factors, evidence for genetic determination of GBD is very limited. The purpose of this project is to conduct a genetic epidemiologic investigation involving molecular genetic data, GBD phenotypes, and statistical genetic techniques to examine the genetic basis for variation in GBD phenotypes in a set of 32 low-income Mexican American families that is currently under investigation in relation to the genetic determination of NIDDM (San Antonio Family Diabetes Study: SAFADS). The overall objectives of this study are to measure genetic effects on GBD phenotypes, and to identify and localized GBD susceptibility genes. The specific aims are 1) to define GBD phenotypes such as gallstone disease (presence of gallstones), gallstone number (solitary versus multiple), gallstone diameter, and gallbladder wall thickness using ultrasonography; 2) to perform genetic analysis in order to estimate heritabilities for GBD phenotypes, to detect initial evidence of linkage to GBD susceptibility loci, to refine the initial screening using multipoint linkage analysis, and to detect linkage or association using non-parametric methods. Ultrasound GBD phenotypic data will be collected from 720 individuals distributes across 32 families. The initial genome screening will be based on a subset of SAFADS families involving 444 subjects for whom the 1015 centiMorgan (cM) genome map based on more than 360 markers is already available. After detecting potential signals for linkage, a high resolution 5 cM gene map to be obtained from a full set of SAFADS families(720 individuals) will be used to precisely localize susceptibility loci influencing GBD phenotypes.
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Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Identification of Genes Activated by Bile Acids Principal Investigator & Institution: Edwards, Peter A.; Professor; Medicine; University of California Los Angeles Box 951361, 405 Hilgard Ave Los Angeles, Ca 90095 Timing: Fiscal Year 2001; Project Start 1-SEP-2001; Project End 1-JUL-2005 Summary: (provided by applicant): Chenodeoxycholic acid (CDCA), a primary bile acid, has recently been shown to activate the farnesoid X receptor (FXR), a member of the nuclear hormone receptor superfamily. Recent data suggest that activated FXR controls both bile acid biosynthesis and plasma lipid levels. As such, FXR may affect the development of gallstones and/or atherosclerosis. However at the current time, very little is known about the target genes and metabolic pathways that are affected by activated FXR. In the first specific aim, we propose to use Suppression Subtractive Hybridization and DNA microarrays to identify genes that are regulated by CDCA-activated FXR. These studies will utilize HepG2 and Caco2 cells that stably overexpress high levels of FXR in order to more easily identify FXR-target genes. We will use normal, FXR-/- or VP16-FXR transgenic mice, treated with FXR ligands, to demonstrate (i) that these same genes are induced in vivo and (ii) that activation of FXR results in a decrease in plasma lipids. In the second specific aim, we will identify FXREs and other critical cis elements in the promoters of a few selected genes that have been identified in aim 1, so as to confirm that these genes are direct targets of FXR/CDCA. In the third aim, we will generate mice that overexpress rat VP16-FXR in their livers (see aim 1). Finally, in specific aim 4, we will isolate cell lines derived from HepG2 and Caco2 cells that express either FXR1, FXR2, or FXR3. The induction of target genes, identified in aim 1, by each FXR isoform will be determined in order to test the hypothesis that specific genes/metabolic pathways are activated by each FXR isoforms. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
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Project Title: Pathogenesis
Mucin
and
Non-Mucin
Proteins
in
Gallstone
Principal Investigator & Institution: Offner, Gwynneth D.; Medicine; Boston University 121 Bay State Rd Boston, Ma 02215 Timing: Fiscal Year 2000; Project Start 1-FEB-1992; Project End 1-MAR2002 Summary: The overall goal of this project is to understand the role of gallbladder mucin in the pathogenesis of cholesterol gallstones. Medical
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or surgical treatment for symptomatic gallstones is a frequent cause for hospitalization in the United States and consumes more than 8 billion dollars in health care costs per year. Gallbladder mucin has been shown to have a central role in gallstone pathogenesis. Mucin hypersecretion occurs prior to stone formation in both experimental animals and man. Mucin also promotes cholesterol crystal nucleation, a critical early step in stone formation, and the mucin gel lining. The gallbladder provides an ideal environment for growth of cholesterol crystals into mature stones. Human gallbladder expresses genes for five different mucins and two of these, MUC5B and MUC3 have been identified as the major human gallbladder mucins. Nothing is known about the structural features of these proteins which interact with biliary lipids and lead to the lithogenic state. In this project, a novel recombinant approach will be used to identify the structural domains of MUC5B and MUC3 which bind biliary lipids. The specific aims of this proposal are to: (l) characterize the major human gallbladder mucins MUC5B and MUC3 by determining the nucleotide and deduced amino acid sequences of the poorly glycosylated amino- and carboxyl-terminal regions, (2) determine the genomic organization of these mucins and (3) to identify functional domains in MUC5B and MUC3. Information obtained in specific aims 1 and 2 will be used to design constructs containing individual mucin domains. Recombinant mucin polypeptides will be expressed in bacteria and examined in lipid binding, cholesterol crystal nucleation and vesicle fusion assays. The results of these studies will provide new information about the relationship between the structure of the major human gallbladder mucins and their function in normal and pathologic gallbladder. This information is necessary for the rational design of therapies for the prevention and treatment of gallstone disease. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Myogenic Disorders of the Gallbladder Principal Investigator & Institution: Behar, Jose; Professor of Medicine; Rhode Island Hospital (Providence, Ri) 593 Eddy St Providence, Ri 02902 Timing: Fiscal Year 2000; Project Start 1-SEP-1980; Project End 0-JUN2005 Summary: Acute cholecystitis (AC) affects 88% of patients with symptomatic gallbladder (GB) stones over a 18 year period and has a significant morbidity and mortality in elderly patients. in spite of its high prevalence, its pathogenesis has yet to be elucidated. Our preliminary studies suggest the hypothesis that human AC develops in a permissive GB environment characterized by GB stasis and impaired muscle cytoprotection that allows biliary aggressive factors to initiate the
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inflammatory process. This proposal therefore will study the myogenic abnormalities responsible for creating this GB environment and examine hydrophobic bile salts and reactive oxygen species (ROS) as possible aggressive factors. Specifically, it will investigate: 1) the role of bile stasis induced by lithogenic bile and excessive cholesterol (Ch) incorporation by muscle cells that seems to worsen during the inflammatory process; 2) the mechanisms of cytoprotection utilized by GB muscle cells. It will focus on the role of PGE2 in the upregulation of scavengers of free radicals and whether its receptors and pathways remain functional after exposure to soluble mediators of inflammation. It will examine the mechanisms of receptor protection and resistance to agonist induced desensitization a well as the detrimental influence of excessive membrane Ch on cytoprotective functions mediated by PGE2 receptors. Defective PGE2 receptors could make these cells more susceptible to damage by lower concentrations o aggressive factors; 3) whether hydrophobic bile salts and ROS initiate the inflammatory process and cause the muscle defects demonstrated in human and experimental AC. It will examine whether bile stasis enhances the diffusion of bile salts through the GB wall. It will also investigate the mechanisms whereby they affect muscle cells by examining whether they are mediated by ROS and whether they induce cytoprotective responses in normal and defective muscle cells; and, 4) whether hydrophobic bile salts prevent the deleterious effects of hydrophobic bile salts in vitro and whether they are effective in the prophylactic treatment of experimental AC in GB's with normal and lithogenic bile. These studies will be conducted in dissociated muscle cells from human GB's with gallstones with or without AC and from experimental AC induced by ligation of the common bile duct in animals with normal and lithogenic bile. The results of these studies may provide evidence and a rationale in support for using hydrophobic bile acids in the prophylactic treatment of this complication. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Novel Erythromycin Analogs for GI Motility Disorders Principal Investigator & Institution: Carreras, Christopher W.; Kosan Biosciences 3832 Bay Center Pl Hayward, Ca 94545 Timing: Fiscal Year 2000; Project Start 1-MAR-2000; Project End 1-AUG2000 Summary: The long-term objective of this proposal is to discover novel prokinetic agents with superior pharmacological and pharmacokinetic properties for the treatment of gastrointestinal motility disorders such as gastroesophogeal reflux disease (GERD), gastroparesis, postoperative ileus, scleroderma, gallstones, and as a quick and effective drug to
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stimulate stomach emptying in patients requiring emergency surgery. We propose to prepare the first member of a new class of acid-stable erythromycin analogs from a novel erythromycin scaffold obtained through genetic engineering of the erythromycin gene cluster. The analog will be tested for acid stability and its ability to serve as an effective prokinetic agent ("motilide"). A lead compound made in this fashion will serve as a scaffold for future preparations of novel acid-stable semisynthetic motilides during Phase II of this program. PROPOSED COMMERCIAL APPLICATIONS: The ideal motilide will be a safe and effective treatment for common heartburn. Motilides are anticipated to have applications for the treatment of diabetic gastroparesis, postoperative ileus and scleroderma. The stimulatory effects of motilides on gallbladder contraction suggest that they may' find application in patients at risk of gallstone formation. Finally, intravenous administration of motilides has been recommended as a quick and safe procedure to empty the stomach before emergency surgery, and in pregnant women undergoing caesarian delivery. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Protein Lipid Interactions in Gallstone Pathogenesis Principal Investigator & Institution: Afdhal, Nezam H.; Chief of Hepatology; Beth Israel Deaconess Medical Center 330 Brookline Ave Boston, Ma 02215 Timing: Fiscal Year 2000; Project Start 5-JUL-1993; Project End 1-MAY2003 Summary: Cholesterol gallstone disease is one of the commonest digestive diseases in the United States and results in 700,000 cholecystectomies annually with a direct health care cost in excess of $3 billion. Gallbladder mucin plays a central role in gallstone formation and this proposal will examine the mechanism by which mucin interacts with biliary lipids to promote gallstones. The specific Aims are to 1) Characterize the interaction of specific sites of the mucin molecule with lipid vesicles to improve our understanding of how mucin promotes crystallization of cholesterol monohydrate; 2) Characterize how mucin effects the morphology and rate of crystal growth in solution and in gels so that growth inhibitors can eventually be developed; 3) Examine the central role of mucin as the matrix protein in the biomineralization of both calcium and cholesterol. These Aim's will be achieved by utilizing multiple biophysical techniques to examine model systems where mucin and its modified structural forms will interact with biliary lipids similar to those seen in gallstone bile. Fluorescent assays, dynamic light scattering and magic angle spinning magnetic resonance will examine
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how mucin promotes vesicle fusion and sub- microscopic nucleation. Light and electron microscopy will examine the way in which mucin can promote both the pattern and rate of crystal growth. These studies may lead to strategies for the prevention and non-surgical therapy of this very common disease. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Role of Gallbladder Ion Transport in Gallstone Formation Principal Investigator & Institution: Moser, a J.; Surgery; University of Pittsburgh at Pittsburgh 4200 5Th Ave Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 5-FEB-2002; Project End 1-JAN2007 Summary: (provided by applicant) The candidate is an academic gastrointestinal surgeon whose career objective is to become an independently funded clinician scientist. After graduating at the top of his class from college and medical school, the candidate trained in surgery at UCLA. He undertook a Research Fellowship during residency that provided preliminary experience in membrane biology and instilled a strong desire to become a clinician scientist and an innovator in the treatment of gallstones. To develop his research career, the candidate needs significantly more time for scientific pursuits as well as the mentorship of an experienced membrane biologist. His career development plan includes both didactic and practical studies of gallbladder ion transport with the supervision of two highly successful and innovative scientists at the University of Pittsburgh. The environment provided by the Laboratory of Epithelial Cell Biology is outstanding and has already trained numerous accomplished clinician scientists. The sponsors have dedicated their laboratory resources, equipment, and time to insure the candidate's success. The research plan focuses on one therapeutically promising aspect of gallstone pathogenesis: increased salt and water absorption by the gallbladder prior to gallstone formation. Increased electrolyte absorption excessively concentrates gallbladder bile and promotes the crystallization of cholesterol. The potential clinical relevance of increased gallbladder salt and water transport is dramatized by data showing that amiloride prevents the formation of gallstones in cholesterol-fed prairie dogs. Contrary to the paradigm for gallbladder transport described in stoneresistant animals, we now demonstrate electrogenic ion transport in human and prairie dog gallbladder. Alterations in electrogenic ion transport precede the formation of gallstones and cause absorption to increase, and the mechanism is unknown. We propose studies with three Specific Aims to test our hypothesis that electrogenic ion transport
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confers susceptibility to the formation of gallstones; Aim 1: Determine the mechanism for electrogenic ion transport in prairie dog gallbladder. Although prairie dogs are used extensively as a model of human disease, the basic mechanism for gallbladder ion transport in normal prairie dogs has not been established. Aim 2: Characterize alterations in gallbladder ion transport prior to the formation of gallstones. Using cholesterol-fed animals, we will test our hypothesis that alterations in channel-mediated ion transport stimulate electrolyte absorption and promote gallstones. Aim 3: Determine the mechanism for human gallbladder ion transport in health and disease. Given the high incidence of gallstones in patients with abnormal gallbladder ion transport, these studies will test our hypothesis that increased gallbladder electrolyte absorption is also a cause of gallstones in man. These studies are ideal for teaching the Principal Investigator critical new skills required for a successful research career as a clinician scientist in an era of increasingly sophisticated membrane biology. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: The Unsuspected Small Stone Study (USSS) Principal Investigator & Institution: Disario, James A.; Associate Professor; Internal Medicine; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2000; Project Start 5-AUG-2000; Project End 1-JUL2001 Summary: (adapted from the application) Gallstones are the most common and the most costly digestive disease, with an annual estimated expenditure of 5 billion dollars. Fifteen percent of persons with symptomatic gallstones will have concomitant bile duct stones (BDS). Expert opinion varies, but there are several reports of leaving BDS in situ without adverse outcomes. The aim of this proposal is to determine if conservative or expectant management is a safe and effective therapy for patients with unsuspected small BDS found at intraoperative cholangiography (10C) during laparoscopic cholecystectomy (LC), compared to conventional therapy with endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy (ES). This is a randomized, prospective, multicenter study of patient outcomes and treatment costs. The primary endpoint is overall morbidity I year after randomization. Secondary endpoints include rates of severe morbidity, mortality, abdominal pain, jaundice, abnormal serum liver tests, abnormal transcutaneous abdominal ultrasound examinations, quality of life indices, and overall treatment costs. A database will be established for long-term follow up. The duration of the study is aimed to be 2 years
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from the onset of funding. One hundred and eighty two (91 per group) patients will be randomized to have expectant management or to have ERCP with sphincterotomy and stone extraction. Eligibility requirements include no history of jaundice, pancreatitis, or cholangitis, and
