DISEASES OF THE GASTROESOPHAGEAL MUCOSA CLINICAL GASTROENTEROLOGY George Y. Wu, MD, PhD SERIES EDITOR Diseases of the Gastroesophageal Mucosa: The Acid-Related Disorders, edited by James W. Freston, 2001. DISEASES OF THE GAsTROESOPHAGFAL MUCOSA THE ACID-RELATED DISORDERS Edited by W. JAMES FRESTON, MD, PhD Division ofG astroenterology and Hepatology, University ofC onnecticut Health Center, Farmington, CT © 2001 Humana Press Inc. Softcover reprint of the hardcover 1s t edition 2001 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 AII rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permis sion from the Publisher. AII artic1es, comments, opinions, conc1usions, or recommendations are those of the author( s), and do not neces sarily reflect the views of the publisher. Production Editor: Jason S. 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The fee code for users of the Transactional Reporting Service is: [O-89603-965-XlOI $10.00 + $00.25]. Library of Congress Cataloging-in-Publication Data Diseases of the gastroesophageal mucosa: the acid-related disorders / edited by James W. Freston. p. ;cm. Inc1udes bibliographical references and index. ISBN 978-1-4684-9642-0 ISBN 978-1-59259-103-9 (eBook) DOI 10.1007/978-1-59259-103-9 1. Indigestion. 2. Peptic ulcer. 3. Gastroesophageal reflux. 4. Gastrointestinal mucosa. 5. Gastric acid--Pathophysiology. 1. Freston, James W. [DNLM: 1. Peptic Ulcer. 2. Dyspepsia. 3. Gastric Mucosa--pathology. 4. Gastroesophageal Reflux. 5. Helicobacter Infections--physiopathology. WI 350 D611 2001] RC827 .D575 2001 616.3'3--dc21 2001016575 PREFACE Acid-related diseases are among the most commonly encountered disorders in clinical practice. The last decade has witnessed profound changes in the clini cal approach to this family of conditions, which includes gastroesophageal reflux disease (GERD) in its protean manifestations, peptic ulcers of all etiologies, and dyspepsia of the uninvestigated and investigated (nonulcer dyspepsia) varieties. The changes have arisen largely from the discovery of H. pylori's important role in various acid-related diseases and in response to the rising tide of patients with GERO. Major alterations in health care delivery, spawned by efforts to control health care costs, have also had an impact on the way clinicians deal with these diseases. One result has been the introduction of various practice guidelines that are intended to assist clinicians in managing their patients in a fashion that reflects recent advances in medical science as well as economics. In this field, however, the pace of advances quickly renders most guidelines obsolete. Dis eases oft he Gastroesophageal Mucosa: The Acid-Related Disorders is intended to help primary care physicians and clinical gastroenterologists stay abreast of the important developments in this field. The emphasis is on diagnosis and treatment, but epidemiology and patho physiology are not neglected in instances where their understanding sets the stage for management recommendations. The first section addresses the clinical evaluation of patients suspected of harboring peptic ulcers, and it provides spe cific information about drugs used in treating acid-related diseases. Subsequent chapters address ulcers of various causes, with particular emphasis on new as pects of H. pylori infection. A chapter is devoted to dyspepsia because this condition is ubiquitous in practice and new information is available to assist clinicians in efficiently managing patients with this condition. The section on GERD contains important developments in epidemiology, mechanisms of dis ease, and practical aspects of diagnosis and treatment. The extraesophageal manifestations of GERD, recognized increasingly in primary care, are addressed in a separate chapter in recognition of the new approaches to their management that have been described recently. Finally, upper gastrointestinal bleeding is addressed because an understanding of new management modalities can assist clinicians in triaging bleeding patients more effectively. No attempt has been made to include nonacid-related diseases of the upper gastrointestinal tract, such as esophageal opportunistic infections, malignancies, except those related to v vi Preface GERD or H. pylori infection, and motor disturbances of the esophagus and stomach. The focus is on conditions in which gastric acid is fundamentally important in the pathophysiology and in which modulation of gastric acidity influences the clinical response. The editor is grateful for the secretarial and administrative assistance of Dana A. Finello. James W. Freston, MD, PhD CONTENTS Preface ......................................................................................... v List of Contributors .................................................................... ix Part I. Peptic Ulcer Diseases 1 Peptic Ulcer Disease: Overview and Management. ............. 3 Shyam Varadarajulu and James W. Freston 2 Hylicobacter pylori-Related Diseases:Demographics, Epidemiology, Pathophysiology of Gastritis, Ulcers, and Cancer. ................................................................... 29 James S. Hoffman and David R. Cave 3 H. pylori-Related Diseases: Diagnosis and Treatment... ... .43 Colin W. Howden 4 NSAID Ulcers: Overview and Management... ..................... 59 David J. Bjorkman and Kathryn Tessnow 5 Nonvariceal Upper Gastrointestinal Bleeding .................... 75 Gustavo A. Machicado and Dennis M. Jensen 6 Zollinger-Ellison Syndrome and Other Acid- Hypersecretory States ..................................................... 89 Paul N. Maton Part II. Dyspepsia: Classification and Management 7 Dyspepsia and Nonulcer Dyspepsia ................................ 10 5 Nimish Vakil Part III. Gastroesophageal Reflux Disease 8 Gastroesophageal Reflux Disease: Epidemiology and Pathophysiology. ................................................... 121 Philip O. Katz and Amine Hila 9 Gastroesophageal Reflux Disease: Diagnosis and Treatment ............................................................ 137 Jaroslaw H. Cymorek and James W. Freston 10 Barrett's Esophagus and Adenocarcinoma ..................... 167 John Yalam and Richard E. Sampliner 11 Extraesophageal Manifestations of Gastroesophageal Reflux Disease ............................................................. 177 John E. Pandolfino and Peter J. Kahrilas Index ...................................................................................... 193 vii CONTRIBUTORS DAVID J. BJORKMAN, MD, MSPH, SM· Division of Gastroenterology, University of Utah, Salt Lake City, UT DAVID R. CAVE, MD, PhD· Section of Gastroenterology, St. Elizabeth's Medical Center, Brighton, MA JAROSLAW H. CYMOREK, MD· Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT JAMES W. FRESTON, MD, PhD • Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT AMINE HILA, MD • Department ofM edicine, Graduate Hospital, Philadephia, PA JAMES S. HOFFMAN, MD, • Section of Gastroenterology, St. Elizabeth's Medical Center, Brighton, MA COLIN W. HOWDEN, MD • Division of Gastroenterology and Hepatology, Northwestern, University Medical School, Northwestern Center for Clinical Research, Chicago, IL DENNIS M. JENSEN, MD· CURE Digestive Disease Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA PETER J. KAHRILAS, MD • Northwestern University Medical School, Division of Gastroenterology and Hepatology, Department of Medicine, Chicago, IL PHILIP O. KATZ, MD • Graduate Hospital, Department of Medicine, Philadelphia, PA GUSTAVO A. MACHICADO, MD· UCLA Center for the Health Sciences, CURE Digestive Disease Research Center and VA Greater Los Angeles Healthcare System, Los Angeles; and Northbridge Hospital Medical Center, Van Nuys, CA PAUL N. MATON, MD • Digestive Disease Research Institute, Oklahoma City, OK JOHN E. PANDOLFINO, MD· Department of Medicine, Northwestern University Medical School, Chicago, IL RICHARD E. SAMPLINER, MD • University of Arizona Health Sciences Center, Southern Arizona VA Health Care System, Tucson, AZ KATHRYN TESSNOW, MD • Division of Gastroenterology, University of Utah, Salt Lake City, UT NIMISH VAKIL, MD· University of Wisconsin Medical School, Sinai Samaritan Medical Center, Milwaukee, WI SHYAM VARADARAJULU, MD· Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT JOHN YA LAM, MD • University of Arizona Health Science Center, Southern Arizona VA Health Care System, Tucson, AZ ix I PEPTIC ULCER DISEASES 1 Peptic Ulcer Disease Overview and Management Shyam Varadarajulu, MD and James W Freston, MD, PhD CONTENTS INTRODUCTION CHANGING EPIDEMIOLOGY OF PEPTIC ULCER DISEASE PATHOGENESIS AND ETIOLOGY OF PEPTIC ULCER NSTEROIDAL ANTI-INFLAMMATORY DRUGS DIAGNOSIS OF PEPTIC ULCER DISEASE PHARMACOLOGY OF ANTIULCER MEDICATIONS MEDICAL TREATMENT OF PEPTIC ULCER DISEASE REFERENCES INTRODUCTION In the past decade, the causes of peptic ulcer disease (PUD) have been clarified. Infection with Helicobacter pylori has emerged as the most frequent cause, and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) has become an increasingly important cause. PUD, a term encompassing both gastric and duodenal ulcers continues to be a serious medical problem, primarily because of its ubiquity: approximately 500,000 new cases develop each year in the United States and 4 million recur. The high prevalence of PUD results in significant morbidity, mortality, and economic costs. Over 80% of patients experience pain or gastrointestinal bleeding; more than 5000 patients die each year of ulcer complications, and the economic costs of this are staggering. The estimated annual direct costs, such as physician visits, diagnostic From: Clinical Gastroenterology: Diseases of the Gastroesophageal Mucosa: The Acid-Related Disorders Edited by: J. W. Freston © Humana Press Inc., Totowa, NJ 3