Table Of ContentCOLONIC DISEASES
COLONIC
DISEASES
Edited by
R.
TIMOTHY KOCH, MD
Medical College ofWisconsin,
Milwaukee, WI
Foreword by
jOSEPH B. KIRSNER, MD, PhD, DSci (Hon)
The Louis Block Distinguished Service Professor o[M edicine, Department o[M edicine,
The University o[ Chicago Pritzker School o[M edicine, Chicago, IL
~
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Originally published by Humana Press Inc. in 2003
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respect to its contents.
Cover illustrations: Fig. IA from Chapter 16, "Colonoscopy," by Donald G. Seibert; Fig. 6 from Chapter 17, "Interpretation
of Colonic Biopsies in Patients with Diarrhea," by Sarah M. Dry, Galen R. Cortina, and Klaus J. Lewin; Figs. 2C and 3E from
Chapter 22, "Cross-Sectional Imaging ofthe Large Bowel," by Diego R. Martin, Ming Yang, and Paul Hamilton; Fig. 1 from
Chapter 24, "Acute Megacolon, Acquired Megacolon, and Volvulus," by Marc Stauffer and Timothy R. Koch; and Fig 4. from
Chapter 31, "Ischemic Colitis," by Peter Grtibel and David R. Cave.
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Library of Congress Cataloging-in-Publication Data
Main entry under title:
Colonic diseases / edited by Timothy R. Koch
p. ;cm.
IncIudes bibliographica! references and index.
ISBN 978-1-4684-9740-3 ISBN 978-1-59259-314-9 (eBook)
DOI 10.1007/978-1-59259-314-9
1. Colon (Anatomy)--Diseases. 2. Colon (Anatomy)--Pathophysiology. 1. Koch, Timothy R.
[DNLM: 1. Colonic Diseases. 2. Rectal Diseases. 3. Colon--physiology. 4. Rectum--physiology. WI 520 C7177 2003]
RC860 .C656 2003
616.3'4--dc21 2002032857
Foreword
The Scientification of Gastroenterology
During the 20th Century
*
Science contributes to medicine in three ways: It provides a body of relatively secure knowl
edge. Some of that knowledge has been applied to develop technologies which have had a
major impact upon the practice and effectiveness ofm edicine. Last, science offers to medicine
a way of thinking.
- 1. McCormick
[(1993) The Contribution of Science to Medicine. Perspect. Bioi. Med. 16,315.]
Awareness of the digestive system began with the dawn of civilization, when man,
observing the feeding habits of animals in the surrounding environment, experimented with
foods, edible and inedible. Identity came with discoveries of the digestive organs during the
16th and 17th centuries. Function was revealed by physiologic studies of digestion, absorp
tion and secretion, metabolism, and motility during the 18th and 19th centuries. Diagnostic
access improved with the technological advances of the 20th century. Understanding of gas
trointestinal (GI) disease followed the growth of the basic sciences and gastroenterology's
involvement in scientific research during the latter half of the 20th century.
Early in the 20th century, gastroenterology was yet an undefined activity without clinical
or scientific guidelines. Diagnostic approach to the digestive tract was minimal. Valid con
cepts of disease were lacking. Visceroptosis, sitophobia, and "colonic autointoxication"
were common "diagnoses." Therapeutic resources were scarce.
The scientification of medicine began during the latter part of the 19th century with the
discovery of bacterial causes of disease, and when the dogma of the past began to yield to
perceptive observation and investigation. Additional impetus came from A. Flexner's 1910
report on Medical Education, documenting the necessity for a scientific foundation in medi
cine. Funds for gastroenterologic investigation remained small, but research was in progress
in the physiology laboratories of academic medical centers.
During the 1920s, organized clinical gastroenterology programs, led by outstanding phy
sicians (1. Friedenwald, W. L. Palmer, H. L. Bockus, C. M. Jones, G. Eusterman), were
established at several institutions. The entry of scientifically oriented young physicians into
gastroenterology during the 1930s and 1940s energized laboratory and clinical research.
Specialization in medicine was underway in the United States, and in 1940 Gastroenterol
ogy was certified as a medical and academic specialty. Further progress was interrupted by
World War II (1941-1945).
Post-World War II was the most productive period in history for the basic and biomedi
cal sciences. Wartime discoveries had demonstrated the unlimited potential of research and
motivated the public, charitable foundations, and government to support "basic research."
'Based in part on 100 Years of American Gastroenterology (1900-2000). Medscape Gastroen
terology January 4, 2000. Available at Website: hup:llwww.medscape.com/medscape/gastrol
journa1/2000/v02.nO 1I mgeO 10 3.kirs/mgeO 10 3 .kirs-Ol.html
v
VI Foreword
This trend was accelerated at the end of World War II (August 1945), when the office of
Scientific Research and Development (US War Department) transferred 44 military-ori
ented research contracts with universities to the National Institutes of Health (NIH). The
General Medicine Study Section of the National Institute of Arthritis and Metabolic Dis
eases (NIH), established in 1955, became a major support of research and training in medi
cine and in gastroenterology. During the 1960s, 1970s, and 1980s, university medical center
faculties enlarged, training programs proliferated, and research activities increased, creat
ing new technologies and new disciplines. Because science represented knowledge and
prestige, Gastroenterology sought to become more "scientific," incorporating basic science
into its research.
By 1980, gastrointestinal etiopathogenetic concepts had advanced significantly. Because
Colonic Diseases deals with the colon, the following selected observations relate to this
area of GI. Innovative research on CNS-neurohumoral and neuroimmune interactions of
the GI tract, mediating colonic motility, and visceral sensitivity replaced psychogenic
hypotheses of the irritable bowel. Physiologic studies modified the process of colon diver
ticular formation from pulsion by intraluminal gases to sustained colonic musculature con
traction, compartmentalizing the colon into high-pressure segments and forcing mucosa
through weaknesses in the bowel wall. Studies of gastrointestinal immunology, including
the gut mucosal immune system and the molecular mechanisms of inflammation, generated
new etiologic concepts and therapeutic resources in IBD. Advancing fiberoptic methodol
ogy expanded access to the GI tract, including the colon. Laser-scanning confocal micros
copy enabled study of epithelial cells and intracellular protein processing. Microbiological
and chromatographic studies of the enteric flora facilitated the diagnosis of bacterial over
growth responsive to antibacterial therapy. Gas chromatographic techniques, breath H2
excretion, and measurement of colonic CH and CO production elevated the study of intes
4 2
tinal gas to a scientific discipline.
Quantitative measurements of GI blood flow including laser Doppler velocimetry and
the Stromuhr blood-flow technique facilitated recognition of colonic vascular impairment.
Neurogastroenterology introduced methods of electrophysiology and cellular neurophysi
ology, identified the enteric nervous system as a "minibrain with intelligent circuits," and
provided new understanding of "physiologic" GI disorders. Transgenic methodology cre
ated innovative animal models, enabling multidisciplinary studies of intestinal inflamma
tion. Molecular genetics established the genetic basis of colorectal cancer, identified a
colorectal cancer marker among Ashkenazi Jews, and demonstrated the possible preven
tion of colorectal cancer via the modulation of APC gene function.
Many favoring circumstances converged to bring gastroenterology into the mainstream
of advancing scientific thought:
l. An enlarging body of basic scientific know ledge and its translation to clinical problems.
2. Technological advances permitting safer and more precise human studies.
3. Public, pharmaceutical, and governmental support of research.
4. The adoption of controlled studies.
5. The contribution of philanthropic organizations (e.g., Rockefeller).
6. The growth and influence of academic medical centers.
7. NIH-supported research and training.
8. The impact of research-oriented societies (e.g., AGA, Gastroenterology Research Group).
9. The enlarging global scientific communication network (journals, databases, and electronic and com
puter systems).
lO. Increasing awareness of the significant health problems represented in digestive diseases.
Foreword vii
Karl Popper said "The more we learn ... and the deeper is our learning, the more conscious,
specific and articulate will be our knowledge of what we do not know." Gastroenterology's
scientific progress notwithstanding, the etiology and pathogenesis of colonic diseases remain
incompletely understood and stand as challenges for the 21st century. The expanding fron
tiers of gastroenterologic research now include the immunogenetic biology of the intestinal
epithelium and the molecular disciplines (microbiology, cell biology, immunology, genetics)
mediating colonic physiology and the expression of disease, as reflected in Timothy Koch's
well-designed and authoritative book. These remarkable resources form the basis of our opti
mism for the future.
Joseph B. Kirsner, MD, PhD, DSci (Hon)
The Louis Block Distinguished Service Professor of Medicine
Department of Medicine
The University of Chicago Pritzker School of Medicine, Chicago, IL
Preface
Colorectal disorders are common diseases that are often chronic in nature. Weare now
working with an increasingly older population. This population trend increases the number
of individuals with colorectal neoplasia, inflammatory bowel disease, diverticular disease,
and constipation. We therefore thought that the beginning of the new millennium was an
extremely relevant and timely period to prepare a new book about colorectal disorders.
The purpose of Colonic Diseases is to provide a bridge between basic and clinical
research and the present clinical care of individuals with colonic disorders. Colonic Dis
eases examines the origins and treatment of common colorectal disorders, and it blends
new outcomes and epidemiological research with molecular mechanisms of disease to
improve our present and future understanding of colonic diseases and their management.
Colonic Diseases has been divided into three parts: Colorectal Physiology, Investigation
of Disease Processes, and Colorectal Disease. Part I provides an extensive overview of
normal colonic physiology. Part II utilizes the expertise of active investigators who are
studying the pathophysiology of colonic disorders, and includes a survey of techniques that
are used in clinical research of colonic diseases. Understanding the mechanisms of disease
development may provide important clues for future therapy. In Part III potential symp
toms, pathological and radiological findings, the differential diagnosis, presently recom
mended evaluation and therapy, and potential future alternative therapies for common
colorectal diseases are reviewed.
Colonic Diseases is intended for gastroenterologists, gastrointestinal fellows, and scien
tists in gastrointestinal research who are interested in bridging basic and clinical research
and diseases processes. This book will be a useful reference resource for primary care phy
sicians who care for patients with chronic colonic disorders, and may also prove of interest
to colorectal surgeons, although it is not designed to be a textbook for the performance of
colorectal surgery.
I wish to dedicate this book to Dr. Joseph B. Kirsner, who inspired our great interest in
colonic diseases at the University of Chicago, and to Dr. Joseph Szurszewski, who pro
moted a strong quantitative approach to basic colonic physiology at the Mayo Clinic in
Rochester.
I would like to acknowledge the great patience of my wife, Nancy, and my daughter,
Kristina, during the preparation of this book. I wish to thank Ms. Debbie Williams for her
excellent secretarial and managerial assistance.
Timothy R. Koch,
MD
IX
Contents
Foreword ............................................................................................................................................... v
Preface .................................................................................................................................................. ix
Contributors ....................................................................................................................................... xiii
Color Plates ....................................................................................................................................... xvii
I.
PART COLORECTAL PHYSIOLOGY
1 Absorption-Secretion and Epithelial Cell Function.................................................... 3
Pradeep K. Dudeja, Ravinder Gill, and K. Ramaswamy
2 Normal Motility and Smooth Muscle Function .......................................................... 25
Mary Francis Otterson
3 Neural Regulation of Colonic Motor Function .......................................................... 35
Kenton M. Sanders and Terence K. Smith
4 Mucin and Goblet Cell Function ................................................................................ 53
Samuel B. Ho and Laurie L. Shekels
5 Endocrine Cells of the Colon ............................................................................... ' ...... 73
Sebastian G. de la Fuente, Christopher R. Mantyh,
and Theodore N. Pappas
6 Micronutrients ................................................ ' ............................................................ 85
Emmanuel C. Opara
7 Aging ........................................................................................................................... 95
Emmanuel C. Opara and Timothy R. Koch
8 Immunology of the Gastrointestinal Tract................................................................ 105
Jonathan R. Fulton, Cynthia A. Cunningham,
and Christopher F. Cuff
9 Colonic Lymphatics .................................................................................................. 123
Stacey A. Weiland and Yang K. Chen
10 Probiotics and the Colon: Therapeutic and Prophylactic Uses ............................... 141
Thomas J. Borody and Patricia L Conway
11 Physiology and Pathophysiology of Colorectal Sensory Processes ........................ 163
Michael D. Crowell and Brian E. Lacy
II.
PART INVESTIGATION OF DISEASE PROCESSES
12 Oxidative Stress ......................................................................................................... 179
Emmanuel C. Opara
13 Genetic Testing for Colon Cancer.................... ................................... ..................... 191
Russell F. Jacoby and Carolyn E. Cole
14 Inflammation ............................................................................................................. 211
Cynthia A. Cunningham, Jonathan R. Fulton,
and Christopher F. Cuff
Xl
xu Contents
15 Epidemiologic Studies and Outcomes Research in Colonic Diseases ..................... 227
John F. Johanson
16 Colonoscopy .............................................................................................................. 243
Donald G. Seibert
17 Interpretation of Colonic Biopsies in Patients with Diarrhea .................................. 275
Sarah M. Dry, Galen R. Cortina, and Klaus J. Lewin
18 Anorectal Manometry ............................................................................................... 297
Devang N. Prajapati and Walter J. Hogan
19 Endoanal and Endorectal Ultrasound ....................................................................... 321
Lisa M. Gangarosa
20 Colonic Transit and Motility ..................................................................................... 335
William J. Snape, Jr.
21 Defecography and Related Radiologic Techniques ................................................. 345
Vincent H. S. Low
22 Cross-Sectional Imaging of the Large Bowel .......................................................... 357
Diego R. Martin, Ming Yang, and Paul Hamilton
III.
PART COLO RECTAL DISEASE
23 Hirschsprung's Disease and Neonatal Disorders ..................................................... 383
Carol Lynn Berseth
24 Acute Megacolon, Acquired Megacolon, and Volvulus .......................................... 395
Marc Stauffer and Timothy R. Koch
25 Diverticular Disease .................................................................................................. 409
Gordon L. Telford, Susan W. Telford, and Mary F. Otterson
26 Current Understanding of Colorectal Neoplasia ...................................................... 423
Melanie B. Thomas and Robert A. Wolff
27 Constipation ............................................................................................................... 441
Anne Lutz-Vorderbruegge and Arnd Schulte-Bockholt
28 Crohn's Disease ......................................................................................................... 459
Amit G. Shah and Stephen B. Hanauer
29 Ulcerative Colitis ....................................................................................................... 479
Bret A. Lashner
30 Irritable Bowel Syndrome ......................................................................................... 491
Michael Camilleri
31 Ischemic Colitis ......................................................................................................... 505
Peter Griibel and David R. Cave
32 Surgical Treatments for Colonic Diseases ................................................................ 523
Joseph P. Muldoon and Steven J. Stryker
33 Anorectal Disorders ................................................................................................... 535
Mohammed M. H. Kalan and Bruce A. Orkin
Index .................................................................................................................................................. 545
Contributors
CAROL LYNN BERSETH, MD, Director, Medical Affairs, North America, Mead Johnson
Nutritionals, Evansville, IN
THOMAS J. BORODY, MD, Centre for Digestive Diseases, Sydney, Australia
MICHAEL CAMILLERI, MD, Professor of Medicine and Physiology, Division of Gastroenterology,
Mayo Clinic and Foundation, Rochester, MN
DAVID R. CAVE, MD, Chief of Gastroenterology, St. Elizabeth Medical Center, Brighton, MA
YANG K. CHEN, MD, Professor of Medicine, Division of Gastroenterology and Hepatology,
University of Colorado Health Sciences Center, Denver, CO
CAROLYN E. COLE, MSN, MM, Associate Director, Colon Cancer Prevention Program,
University of Wisconsin, Madison, WI
PATRICIA L. CONWAY, MSC, PhD, School of Microbiology and Immunology, University of New
South Wales, Sydney, Australia
GALEN R. CORTINA, MD, PhD, Department of Pathology and Laboratory Medicine, UCLA
Center for the Health Sciences, Los Angeles, CA
MICHAEL D. CROWELL, PhD, Senior Director of Scientific Affairs, Novartis Pharmaceuticals
Corporation, East Hanover, NJ; and Marvin M. Schuster Center for Digestive and
Motility Disorders, The Johns Hopkins University School of Medicine, Baltimore, MD
CHRISTOPHER F. CUFF, PhD, Department of Microbiology, Immunology, and Cell Biology,
Robert C. Byrd Health Science Center, West Virginia University, Morgantown, WV
CYNTHIA A. CUNNINGHAM, PhD, Department of Microbiology, Immunology, and Cell Biology,
Robert C. Byrd Health Science Center, West Virginia University, Morgantown, WV
SEBASTIAN G. DE LA FUENTE, MD, Fellow, Gastrointestinal Surgery Research,
Duke University Medical Center, Durham NC
SARAH M. DRY, MD, Department of Pathology and Laboratory Medicine, UCLA Center
for the Health Sciences, Los Angeles, CA
PRADEEP K. DUDEJA, PhD, Associate Professor of Physiology in Medicine,
Department of Medicine, Chicago Westside Veterans Affairs System,
University of Illinois at Chicago, Chicago, IL
JONATHAN R. FULTON, PhD, Department of Microbiology and Immunobiology, Robert C. Byrd
Health Science Center, West Virginia University, Morgantown, WV
LISA M. GANGAROSA, MD, Division of Digestive Diseases, University of North Carolina
at Chapel Hill, Chapel Hill, NC
RAVINDER GILL, PhD, Research Associate, Department of Medicine, Chicago Westside
Veterans Affairs System, University of Illinois at Chicago, Chicago, IL
PETER GRUBEL, MD, Division of Gastroenterology, New England Medical Center, Boston, MA
PAUL HAMILTON, MD, Sunnybrook and Women's College of Health Sciences Center, University
of Toronto, Toronto, Canada
STEPHEN B. HANAUER, MD, Chief, Division of Gastroenterology, University of Chicago,
Chicago,IL
SAMUEL B. Ho, MD, Gastroenterology Division, Department of Medicine, Veterans Affairs
Medical Center and University of Minnesota, Minneapolis, MN
Xlll
