capsule experience - MG Lorenzatto

Atlas of Capsule Endoscopy
Editors: Marisa Halpern, M.D. and Harold Jacob, M.D.

Atlas of Capsule Endoscopy
Wireless capsule endoscopy allows painless endoscopic
imaging of the entire small bowel. In addition the
examination of the intestine takes place in the physiological
state. Artifact induction does not occur as in push
enteroscopy as there is no need to push the device. These
differences between wireless endoscopy and push
endoscopy are the major factors governing the physiological
and bio-optical principles of image acquisition, resulting
in clear and detailed visualization of intestinal structures.

Atlas of Capsule Endoscopy
Marisa Halpern, M.D.
First Edition
Senior Pathologist
Director of Gastrointestinal Pathology Unit
Rabin Medical Center, Golda Campus
Petach Tiqva, Israel
Harold Jacob, M.D. Director of Medical Affairs
Given Imaging Ltd.
Yoqneam, Israel

Preface
We are proud to present this first Atlas of Capsule Endoscopy. With the rapid adoption
of Capsule Endoscopy by practicing gastroenterologists, a new spectrum of
pathological images are being generated. New dimensions of the common diseases
we treat are coming to light. In response to the intense interest and growth in the
area of Capsule Endoscopy, we have produced the first Atlas of Capsule Endoscopy.
By placing these images in your hand, we know that it will enhance
your ability to diagnose and treat patients with gastrointestinal disorders.
In this book we present the spectrum of disease that has been seen to
date by Capsule Endoscopy. Where possible, we have correlated the
M2A ® Capsule images with other diagnostic modalities including endoscopy, radiology
and histopathology findings. This first edition of the Atlas of Capsule
Endoscopy also contains information on normal capsule endoscopic anatomy,
how to perform Capsule Endoscopy and principles of physiological image
acquisition. Some consideration is also given to Capsule Endoscopy findings in other
parts of the GI tract as well.
The companion CD to the Atlas will enable you to load the M2A ® Capsule images
onto your computer for easy reference in your practice.
With the increased use and expanding indications of Capsule Endoscopy,
we know that the Atlas of Capsule Endoscopy will continue to develop and grow.
We hope this Atlas will be a useful tool for physicians who care for patients
with gastrointestinal disease.
Harold Jacob, M.D.
Marisa Halpern, M.D.

Acknowledgments
We would like to thank all the worldwide contributors to the "Atlas of
Capsule Endoscopy" for their devoted efforts (see Contributors list).
We would like to thank Sharon Besser for her immense devotion to this
publication. Without her dedication, this project would not be completed.
Dr Halpern would like to acknowledge her colleagues at the Department of
Pathology and especially Professor Rivka Gal who understood the meaning
of this project.
Finally, we would like to thank our families for their understanding,
moral support and patience during this period of long hours and hard work.

Given Imaging Inc.
Oakbrook Technology Center
5555 Oakbrook Parkway #355
Norcross, GA, 30093, USA
Managing Editor and Production...............Sharon S. Besser
This first edition of the Atlas of Capsule Endoscopy does not integrate Capsule Endoscopy Standard Terminology.
For comments or suggestions, please contact terminology@givenimaging.com
Copyright © 2002 Given Imaging, Ltd. All rights reserved.
Given,M2A, RAPID and/or other products and/or services referenced herein are either registered trademarks,
trademarks or service marks of Given Imaging, Ltd. All other names are or may be registered trademarks or
trademarks of their respective owners.
This publication and its content are for your personal and non-commercial use. You may not modify, copy,
distribute, transmit, display, perform, reproduce, publish, license, create derivative works from, transfer or sell
any part of this publication and/or its content, without prior written permission from Given Imaging, Ltd.
Given Imaging Ltd. Is not and will not be responsible or liable for any damage or loss caused or alleged to be
caused due to inaccuracies or typographical errors in this publication, or for any action taken in reliance thereon.
Contents are subject to change without notification.
Please send all inquiries to sbesser@givenimaging.com
Graphic Design......... Studio Rosinger Ltd., Haifa, Israel
Printing ................... Rahash Offset Printing Ltd., Haifa, Israel
Expanding the scope of GI

Table of contents
Development of the Swallowable Video Capsule (G. Meron, Ph.D.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Notes from the Inventor (G. J. Iddan, D.Sc.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Chapter 1 - Physiological Endoscopy (A. Glukhovsky, D.Sc., H. Jacob, M.D., P. Halpern, B.Sc.) . . . . . . . . . . . . . . . . . . . . . . . . 9
Chapter 2 - Performance of the Capsule Endoscopy (B. Lewis, M.D., C. J. Gostout, M.D.) . . . . . . . . . . . . . . . . . . . . . . . . . 15
Chapter 3 - Normal M2A ® Anatomy (P. Swain, M.D., M. Appleyard, M.D.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Chapter 4 - Inflammatory Diseases of the Small Intestine (A. L. Buchman, M.D.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Chapter 5 - Neoplastic Diseases (F.P. Rossini, M.D., M. Pennazio, M.D.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Chapter 6 - Iatrogenic Diseases (D. Cave, M.D.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Chapter 7 - Vascular Abnormalities (M. Hahne, M.D., J. F. Riemann, M.D.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
Chapter 8 - Malabsorption (G. Gay, M.D., I. Fassler, M.D., Ch. Florent, M.D., M. Delvaux, M.D.) . . . . . . . . . . . . . . . . . . . . . . . 83
Chapter 9 - Pediatrics (E. Seidman, M.D., G. L. de Angelis, M.D., Ana Maria Sant Anna, M.D.) . . . . . . . . . . . . . . . . . . . . . . . . . 103
Chapter 10 - Transplantation (R. de Franchis, M.D., E. Rondonotti, M.D., C. Abbiati, M.D., G. Beccari, M.D., E. Villa, M.D., A. Merighi, M.D., A. Pinna, M.D.) . . 111
Chapter 11 - Non Small Bowel Pathology (S. Adler, M.D., S. Kadish, M.D.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Contributors List . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125

Development of the Swallowable Video Capsule
Gavriel Meron, Ph.D.
It was in 1981 while on a sabbatical leave from his regular
position as Senior Engineer at the Electro-Optical Design Section
of Rafael, the R&D group of the Israeli Ministry of Defense, that
Dr. Gavriel Iddan, a talented mechanical engineer, started his
long term interest in medical imaging. The idea started as a
seed of an invention in the midst of defense projects, particularly
the development of electro-optical imaging devices for missiles.
During the sabbatical, Dr. Iddan relocated to Boston to perform
research for another Israeli company, Elscint Inc., doing x-ray
and ultrasound medical imaging R&D. In Boston, Dr. Gavriel
Iddan befriended Professor Eitan Scapa, an Israeli
gastroenterologist, who was, at that time, at the local medical
center. They had many mutual interests and discussions, which
made Dr. Iddan wonder how he could "help" gastroenterologists.
It was then that he dreamed up the idea of a miniature "missile"
that could be easily swallowed and passed through the GI tract,
transmitting images along the way. Dr. Iddan was specifically
interested in "opening up a new frontier" by enabling direct
imaging of the small intestine, which was until then, terra
incognito, due to the inability of the other imaging methods to
reach the small intestine.
Dr. Iddan and a team of engineers and technicians in Rafael
worked on the development of an initial prototype in the
laboratories, and performed some feasibility trials of imaging
and transmission through animal tissue developing some of the
basic technologies. Based on the initial research performed in
the Rafael laboratories, the first of a number of patents were
written up and submitted by Rafael in January 1994.
At the same time and totally unbeknownst to Dr. Iddan, in the
United States, Dr. Paul Swain presented the possibility of wireless
endoscopy during the Los Angeles World Congress of
Gastroenterology, in an invited talk entitled Microwaves in
Gastroenterology in September 1994.
In London, Dr. Swain had made some progress in making several
(rather large) prototype wireless endoscopy devices from
commercially available components in 1995 and 1996. It was
in 1996 that his team achieved the first live transmissions from
the stomach of a pig.
The first two abstracts published by Swain's team on this topic
were:
Wireless transmission of a color television moving image from
the stomach using a miniature CCD camera, light source and
microwave transmitter. Swain CP, Gong F, Mills TN. Gut
1996;39:A26
3

4
Development of the Swallowable Video Capsule
The Evolution of the Capsule. (from top to bottom). Components of the prototype capsule in a container. In the
center, the prototype capsule is shown. Finally, the existing M2A Capsule.

Wireless transmission of a color television moving image from
the stomach using a miniature CCD camera, light source
and microwave transmitter. Swain CP, Gong F, Mills TN.
Gastrointest Endosc 1997;45:AB40.
Meanwhile, back in Israel, Dr. Iddan knew that if there was
to be a future for the capsule for small intestine imaging, it
would have to be championed by a commercial organization.
He began to arrange meetings with different organizations
in the hope that they would take the challenge and invest
in the business.
It was one of these meetings that brought Dr. Iddan to me.
We had first met in 1995 when I was CEO of Applitec Ltd., an
Israeli company that had developed and was selling video
cameras for endoscopy.
In 1997, the patent in the US was approved, and the available
technologies needed for the capsule's development had
moved in the right direction. It was at this time that I
approached the Rafael Development Corporation (RDC), who
has the right of first refusal to commercialize technologies
coming out of Rafael, in order to found together a start-up
that would develop the capsule and bring it to market.
I left my position at Applitec and set out to raise funds and
develop a business model and strategy for the new company,
which was named Given (GastroIntestinal Video Endoscopy)
Imaging Ltd., and established in January 1998.
At that time, I defined the fledgling company's mission as "to
develop, produce, and achieve worldwide leadership in the
marketing and sales of swallowable disposable electronic
capsules, for diagnostics and therapy of the gastrointestinal
(GI) tract". This was clearly a much wider mandate than the
Development of the Swallowable Video Capsule
initial small intestine capsule, and was based on the
development of a technological platform that would then be
further developed by listening to gastroenterologists,
understanding the barriers in small intestine imaging, and
implementing solutions to overcome them.
By the end of 1998, the initial team, that included Dr. Gavriel
Iddan, Dr. Paul Swain, and Dr. Arkady Glukhovsky, was in
place and serious research & development went underway
to transform the idea into reality. Successfully overcoming
the enormous obstacles of size, transmission strength, battery
power and image resolution, among many others, working
prototypes were produced in January 1999. In May 2000, at
the DDW 2000 meeting, Dr. Swain, together with Given
Imaging, presented the results of the animal trials performed
with the prototype system that was developed. [Wireless
Capsule Endoscopy, Nature, Vol. 405, 25 May 2000].
During 2001, Given achieved major milestones with the
completion of successful clinical trials, receipt of FDA
clearance, CE Mark certification, and launch of the Given ®
Diagnostic Imaging System worldwide. The initial clinical
results have been excellent, and the feedback from patients
and physicians has been remarkable.
The idea of publishing this Atlas of Capsule Endoscopy came
in recognition of the need that was expressed by many
physicians to see with their own eyes specific pathologies
and findings, and compare the images between the different
available modalities. We hope the content of this Atlas assists
in educating gastroenterologists and furthers the
understanding and acceptance of the M2A ® as a standard
tool of GI diagnostics in the clinical path.
5

Notes From the Inventor
Gavriel J. Iddan, D.Sc.
Approximately 20 years ago, I took a sabbatical from my
position as an electro-optical systems engineer at Rafael, the
Armaments Development division of the Israeli Ministry
of Defense, and went to work for a medical instrument
manufacturer in Boston, Mass. Coincidentally, I discovered
that my next-door neighbor was a gastroenterologist, Prof.
Eitan Scapa, who was also on sabbatical and working at a
local hospital. After getting to know each other, we would
spend time discussing our respective professions. Among
other things, I learned about the field of endoscopy and was
exposed to some of its challenges.
After returning to my work at Rafael, I became deeply
interested in medical devices and did some design work in
this area. During my next sabbatical, and after further
discussions with Professor Scapa, I decided to focus on the
specific problems of imaging of the small intestine. After
consulting with a number of gastroenterologists, I finally
decided to attempt the development of a wireless camera.
The major obstacles that I encountered and needed to
overcome included: attaining an adequate field of view,
achieving power requirements for the CCD, and the challenge
of performing a diagnostic study that required close contact
with the patient for many hours. A major breakthrough came
in 1993 when I realized that the system could be separated
into 3 major units: capsule/transmitter, receiver/recorder
and a workstation. The separation of these components would
allow the patient to be ambulatory without the need to be
connected to a monitor.
During this period, the scientific literature started to report
a breakthrough in video imaging. This was the introduction
of the CMOS imager which consumed only a fraction of the
energy required by a CCD, had all the required circuits on the
same chip, and was not expensive to manufacture. To complete
the idea, a special self-cleaning optical configuration was
added and detailed design and experiments commenced.
(One of the first experiments was done on a frozen chicken
purchased in the supermarket.)
By the second half of 1993, I began writing a patent
application, which was submitted in January 1994. While
searching urgently for financing to create this device, I
approached Dr Gavriel Meron, who at that time was the
manager of a company specializing in small endoscopic
cameras. Taking my invention and developing a viable
business plan, Dr. Gavriel Meron established Given Imaging
Ltd in 1998, thus launching the new field of capsule endoscopy
and making the dream a reality.
7

Chapter 1
Physiological Endoscopy
Arkady Glukhovsky, D.Sc.
Harold Jacob, M.D.
Pablo Halpern, B.Sc.
INTRODUCTION
Wireless capsule endoscopy allows painless endoscopic
imaging of the entire small bowel, but more significantly, the
examination of the intestine takes place in the physiological
state. Since there is no need to push the device, artifact
induction does not occur as in push enteroscopy. In addition,
capsule endoscopy is wireless, obviating the need for air
insufflation and the rate of the propulsion is determined by
peristalsis. These differences between wireless endoscopy
and push endoscopy are the major factors governing the
physiological and bio-optical principles of image acquisition,
resulting in clear and detailed visualization of intestinal
structures.
CAPSULE EXPERIENCE
PHYSIOLOGICAL ENDOSCOPY
The M2A ® wireless capsule endoscope is shown in Figure 1A.
A schematic cross-section appears in Figure 1B. The wireless
capsule endoscope has a cylindrical shape, with a diameter
of 11mm, and a length of 26mm. It has two convex domes,
one of them being the optical dome (1). The intestine is
illuminated through the optical dome by white Light Emitting
Diodes (LEDs) (3).
The acquired image is focused by a short focal aspherical lens
(2), on the Complementary Metal-Oxide Silicone (CMOS)
imager (4). The optical dome has a shape that prevents light
reflected by the dome to reach the imager, thus enhancing
the image quality. The capsule is powered by two silver-oxide
batteries (5). An Application Specific Integrated Circuit (ASIC)
transmitter (6) is located in the rear dome. The Radio Frequency
(RF) signal is transmitted by the antenna (7).
Figure 1. Wireless Capsule Endoscope
A - External view B - Schematic cross-section
11mm
1 2 4
Legend:
1 - Optical dome
2 - Short focal aspheric lens
3 - White LEDs
4 - CMOS imager
5 - Watch batteries
6 - ASIC transmitter
7 - Antenna
There are two major factors that are thought to govern image
acquisition by of the M2A ® capsule. These factors are: the
proprietary optical dome and the fact that image acquisition
occurs in the physiological state.
3
3
5 5 6 7
26mm
9

10
Chapter 1
THE OPTICAL DOME
The optical dome and its relationship to the other optical
components create two important advantages in capsule
endoscopy:
a. Improved illumination efficiency.
b. Favorable imaging geometry within the field of view.
Another minor factor which may be contributing to image
quality is the presence of a fluid interface between the optical
dome and tissue at the time of examination improving the
resolution of different anatomical structures such as villi.
Finally, another advantage of the optical dome is that it lends
itself to cleaning by the GI tract mucosa.
Geometric and optical differences between image acquisition
in wired and wireless endoscopy are compared in Figure 2A
and Figure 2B. Figure 2A depicts the geometrical relationship
for a push enteroscope inserted into the intestine. Geometrical
relationship for the M2A ® capsule endoscope is depicted in
Figure 2B. The standard endoscope (Figure 2A) includes an
illumination source (2), and a lens (3), producing the field of
illumination (4), and the field of view (5) shown in Figure 2A.
Collapse of the intestinal wall (6) may obscure either the field
of view or field of illumination. This technical problem is
resolved in standard endoscopy by insufflating the intestine
with air (7), resulting in the distancing of the intestinal muco
from the tip of the endoscope, clearing both the field of view
and the field of illumination. Air insufflation also enables the
operator to orient the tip of the endoscope in the proper
luminal direction, and to advance the endoscope tip accordingly.
Figure 2B shows the wireless capsule endoscope (1) in the
intestine. The capsule includes its illumination sources (2),
and the lens (3), comprising a field of illumination (4), and a
field of view (5) respectively. In order to prevent collapse of
Physiological Endoscopy
the intestinal wall (6), and resultant obscuring of either the
field of illumination or the field of view, a specially designed
optical dome (8) covers both the source of illumination and
the lens. The space remaining between the dome and the
intestinal wall may at times be occupied by fluid.
Figure 2. Geometrical and optical interrelationships for
the enteroscope and capsule endoscope in the
intestine.
A - Push enteroscope
2 - Illumination source
1 - Endoscope inside
intestine
6 - Intestinal wall
B - Capsule endoscope
6 - Intestinal wall
3 - Lens
4 - Field of illumination 5 - Field of view
3 - Lens
1 - Wireless capsule
endoscope inside
intestine
7 - Air filling, due to insufflation
8 - Optical dome
The field of view of most commercially available endoscopes
is within the range of 120˚-140˚, similar to the M2A ® capsule
endoscope. Depth of field of the standard endoscope starts
from 3-5mm from the endoscope tip and extends to a distance
of 100 mm. Unlike in the push endoscope, depth of view of
the capsule endoscope starts on the optical dome itself.
b
2 - Illumination source
4 - Field of illumination
5 - Field of view
a
7 - Liquid filling,
intestinal
liquids

Chapter 1
The illumination efficiency in capsule endoscopy is higher
due to the fact that the illumination angles are not sharp,
thereby allowing the illumination to be returned back to the
imager. Fig 3a shows that some of the illumination is not
being returned to the imager in standard endoscopy as a
result of air insufflation. Fig 3b demonstrates the effectivenes
of the illumination provided by airless endoscopy.
Figure 3. Efficiency of illumination in air insufflating
and airless endoscopy.
A - In air insufflating case the illumination is less efficient
due to the fact that some of the rays are reaching the
intestine at flat edges, and are not returned back to the
lens and to the camera.
B - In airless endoscopy, most of the illumination is
returned back to the lens due to sharp edges of
illumination, close to perpendicular.
2
PHYSIOLOGICAL ENDOSCOPY
Performing endoscopy in the physiological state is a paradigm
shift in the approach to endoscopic diagnosis. The elements
that are present in physiological capsule endoscopy include
the use of peristalsis to propel, orient and steer the M2A ®
capsule in the intestine.
1
Physiological Endoscopy
The elements that are absent in physiological capsule
endoscopy, thereby creating an advantageous environment
include:
a. Sedation and its resultant change in the
physiological state.
b. Air insufflation resulting in increased pressure on
the intestinal wall.
An additional factor that is integral to push endoscopy and
does not play a role in capsule endoscopy is forceful insertion
of the endoscope which impacts on the intestinal wall.
Physiological changes may develop due to insufflation and
increasing air pressure in the intestine:
a. Under normal physiological conditions blood pressure
in the blood vessels of the GI tract may be within the
following range: arterioles 40-80 mmHg, capillaries
20-40 mmHg, and venules 15-30 mmHg. During push
enteroscopy, the intraluminal pressure within the
intestine may reach values above 300 mmHg 2 ,
significantly higher than the blood pressure. We may
speculate that this increase in pressure may decrease
the blood flow to small vessels, and in some cases
even temporarily arrest the flow. Although we have
not found reference of the tamponade effect in
endoscopy, this phenomena in well-known in
laparoscopy for more than a century. In rare cases,
air insufflation may even cause a fatal air embolism
during gastrointestinal endoscopy.
b. Insufflation of the small intestine, and insertion
of a long flexible tube (the endoscope), affects the
pressure receptors embedded in the small intestinal
wall. In the case of wireless endoscopy, the intestine's
physiological or ‘natural’ conditions remain undisturbed.
11

12
Chapter 1
c. Conscious sedation is usually administered during
push enteroscopy. The adminisration of sedation to
patients alters systemic physiology. This may have
an effect on the ability of the endoscope to detect
vascular or inflammatory lesions.
d. Examination of the intestine under physiological
conditions may enable measurement of additional
physiological parameters, some of them unrelated
to the image, e.g. gastric emptying, small and large
bowel passage times, and peristaltic contraction
cycles (rhythms).
CONCLUSION
Wireless capsule endoscopy acquires detailed images of the
GI tract, which allows identification of the spectrum of
pathologies present within the small bowel. Specific design
elements of the capsule, coupled with the fact that the M2A ®
device acquires images in the physiological state are the
major contributing factors to this breakthrough in GI
endoscopy.
References and Suggested Readings
1 Litynski GS. The history of laparoscopy. Frankfurt/M: Bernert Ve
2 Katzgraber F, Glenewinkel F, Fischler S. Mechanism of fatal air
after gastrointestinal endoscopy. Int J Legal Med 1998; 111(3):
Physiological Endoscopy

Chapter 2
The Performance of Capsule Endoscopy
Blair S. Lewis, M.D.
Christopher J. Gostout, M.D.
Since the inception of gastrointestinal endoscopy, physicians
have wanted to obtain direct visualization of the entire GI
tract. Standard endoscopic and colonoscopic exams view
only small amounts of the proximal and distal ends of the
small bowel. Endoscopic examination of the entire small
bowel has remained elusive. Push enteroscopy was the first
step in the endoscopic evaluation of the intestine. Initially,
colonoscopes, both adult and pediatric, were used to evaluate
the entire duodenum and proximal jejunum. On average, a
160 cm long instrument can be advanced 40 cm beyond the
ligament of Treitz. Present 2.1-2.5 meter long push
enteroscopes have greatly improved the depth of insertion
and visualization of the small bowel and it is now possible to
inspect the jejunum in its entirety. Examination of the distal
small bowel has previously been achieved using Sonde and
Rope-way techniques. Both exams are lengthy and quite
uncomfortable, even painful. The medical community has
largely abandoned these exams.
An endoscopic capsule (Given
Imaging Limited, Yoqneam, Israel)
has been developed to obtain
images from the entire small
bowel. Developed by Dr. Gavriel
Iddan in 1981, the capsule, which
measures 11 x 26 mm, contains 4
LEDs (light emitting diodes), a lens, a color camera chip, two
batteries, a radio frequency transmitter and an antenna. The
camera is a CMOS (complementary metal oxide sensor) chip.
This chip requires less power than present CCD (charged
coupled device) chips found on video endoscopes and digital
cameras, and it can operate at very low levels of illumination.
The capsule obtains two images per second and transmits
the data via radio frequency to a recording device worn about
a patient's waist. Once the acquisition time is reached, the
data from the recording device is downloaded to a computer
workstation whose software processes the images to be
viewed on the computer screen.
The capsule is disposable and does not need to be retrieved
by the patient. It is passed naturally. An average of 50,000
images are obtained during an eight-hour exam. Thus capsule
endoscopy appears to be the answer to the long-standing
desire for the complete endoscopic examination of the entire
small bowel and it accomplishes this goal in a non-invasive way.
The capsule is indicated as an adjunctive tool for evaluation
of suspected diseases of the small intestine. It is
contraindicated in patients with known or suspected small
bowel obstruction since the capsule may become lodged
within the intestinal tract. The capsule has not been approved
for use in patients with pacemakers or implanted defibrillators.
15

16
Chapter 2
Typical timing of a capsule exam is to have a patient swallow
the capsule at 8 am and disconnect them from the recorder
at 4 pm. This allows 8 hours of acquisition of images during
the day. Capsule endoscopy is performed after the patient
follows a 12 hour fast. Patients are told to have nothing to
eat or drink after dinner on the evening before the examination.
Patients should not smoke cigarettes, since this may cause
a change in the color of the stomach lining. They are also
told not to take medications or antacids. Medications such
as iron and sucralfate can coat the intestinal lining limiting
visualization. Narcotics and antispasmodics can delay both
gastric and intestinal emptying making it difficult to visualize
the entire small bowel during the 8-hour acquisition time.
Patients are told to bring their medications with them to take
accordingly during the day if necessary. If a patient is diabetic,
insulin doses need to be adjusted. Patients are also told to
wear loose clothing on the day of the exam. Dresses should
be avoided. A buttoned shirt and loose fitting pants work
best. During the evening prior to the exam, the recorder's
battery pack is trickle charged through a standard outlet.
Initially on the day of the exam, the patient's personal data
is entered into the computer workstation (Figure 1). The
recording device is then initialized to the patient. This ensures
that once completed the recording device and the data
contained within cannot be confused with any other patient.
At this point, patients may be asked to drink a small glass of
water containing simethicone. This surfactant eliminates any
bubbles inside the
stomach.
The patient's abdomen is
marked with a surgical
marker using a template
for accurate placement
of sensors.
The Performance of Capsule Endoscopy
The markings are best removed at the end of the exam using
rubbing alcohol. The sensor array leads are attached by
adhesive to the patient's abdomen. Some patients may need
to shave their abdomen prior to sensor attachment.
The empty belt is placed around the patient's waist.
The recording device and battery pack are then placed into
the belt pouches. The sensor leads are attached to the
recording device which is then attached to the battery pack.
The powered recorder will illuminate its light for a short period
of time. This light will go out once the hard drive has
successfully booted. The capsule is then removed from its
blister pack. Removing the capsule from the magnet in the
pack turns the capsule on and it begins to flash twice per
second and transmit images. It is important to look at the
recorder and ascertain that its light flashes in synchrony with
the capsule verifying successful transmission.
The patient then
swallows the capsule
followed by a full glass of
water. We ask patients
to drink two additional
glasses of water to assure
that the capsule
impasses through the esophagus into the stomach. The
patient is then told that she/he can leave the facility and carry
about a normal day. Patients are told to refrain from exercising
and heavy lifting during the exam. They should avoid large
transmitters and MRI machines. They may walk, sit and lay
down. They can drive a car. They can return to work. They
may use a computer, radio, stereo or cell phone. They should
not stand directly next to another patient undergoing capsule
endoscopy. They should not touch the recorder or the antenna
array leads, nor should they remove the leads.

Chapter 2
Patients may loosen the Velcro on the belt to allow them to
go to the bathroom. They are told not to take the belt off and
that the shoulder straps should never come off. Patients are
also told to be very careful when bringing up underwear over
the sensors to avoid disconnection. Patients can eat beginning
4 hours after swallowing the capsule. They can take their
medications at this time as well.
Capsule transit times have been reported in several studies.
The average gastric time is approximately 60 minutes, the
average time in the small bowel is 240 minutes, and the
average passage time to the colon is 300 minutes. An 8-hour
acquisition time assures that most capsules will reach the
colon allowing for complete inspection of the small bowel.
Patients return to the facility after this amount of time to have
the recorder, belt and sensor array removed. They are
instructed to avoid MRI machines for at least 3 days or until
the capsule is seen to pass. An x-ray can be obtained should
there be a question if the capsule has remained within the
patient and not excreted.
Downloading begins with clearing the download memory
in the workstation. Once accomplished, the recorder is
attached to the workstation. Generally, download of a
complete patient study lasts 2 and one-half hours. Once
downloaded, the recorder can be disconnected from the
workstation or it can be initialized for a new patient.
The images of the capsule exam are then reviewed on the
workstation. A sample working endoscopy report form can
be seen in Figure 5.
Review of the images should be
performed by individuals who are
experienced in viewing and
interpreting endoscopic images.
References and Suggested Readings
The Performance of Capsule Endoscopy
There is a brief learning curve to achieve competency in
reviewing, as the images are somewhat different than
conventional endoscopic images. The ideal environment for
review is a darkened quiet room. The computer controls are
similar to using a videotape machine and images may be
viewed singly or as a video stream. In the following chapters
the images and diagnoses that can be made using capsule
endoscopy will be described.
1 Lewis B. Enteroscopy. Gastrointest Endosc Clin N Am; 2000;1:101-16.
2 ® Meron G. The development of the swallowable video capsule (M2A ).
Gastrointest Endosc 2000;6:817-9.
3 Appleyard Glukhovsky A, Jacob H, et al. Transit times for the capsule
endoscope. Gastrointest Endosc 2001;53:AB122
17

18
Chapter 2
Figure 1.
Intializing Information Form
Prior to swallowing a capsule endoscope, we need certain
information to initialize the computer for your study.
Please complete the following:
All information is confidential.
Please print.
1. First name:__________________
2. Middle name:________________
3. Last name:__________________
4. Social security number: _______-_______-________
5. Gender: Male Female
6. Birthdate:______/________/_______
7. Weight (lbs):_________________
8. Height (inches):______________
9. Waist (inches):_______________
For Office Use
P (Time pill swallowed) -
L (Time of first eating) -
D (Time of disconnection) -
Recorder # -
Pt. # _
Thank You
Figure 2.
The Performance of Capsule Endoscopy
During the Examination Instructions Form
You have just swallowed a capsule endoscope. This sheet
contains information about what to expect over the next 8
hours.
Please call our office if you have severe or persistent
abdominal or chest pain, fever, difficulty swallowing, or if
you just have a question.
Our phone number is __________.
Ask to speak with ____________ .
1. Do not eat for 4 hours after swallowing the capsule.
After _____ PM, you may eat or drink normally. You may
take your medications at this time as well.
2. Do not exercise. Avoid heavy lifting. You may walk, sit
and lay down. You can drive a car. You can return to
work.
3. Avoid going near MRI machines and radio transmitters.
You may use a computer, radio, stereo, or cell phone.
4. Do not stand directly next to another patient undergoing
capsule endoscopy.
5. Do not touch the recorder or the antenna array leads.
Do not remove the leads.
6. You may loosen the belt to allow yourself to go to the
bathroom. Do not take the belt off.
7. Return to the office at _____ PM for disconnection and
removal of the equipment.

Chapter 2
Figure 3.
Post Examination Instructions Form
You have just had a capsule endoscopy. This sheet contains
information about what to expect over the next two days.
Please call our office if you have severe or persistent
abdominal or chest pain, fever, difficulty swallowing,
or if you just have a question.
1. Pain: Pain is uncommon following capsule endoscopy.
Should you feel sharp or persistent pain, please call
our office.
2. Nausea: This is also very uncommon and should it occur,
please notify the office.
3. Diet: You may eat. There are no dietary restrictions.
4. Activities: You may resume normal activities including
exercise tomorrow.
5. Medications: You may resume all medications
immediately. Do not make up for doses you have
missed, but rather just begin your normal dosage.
6. Further Testing: Until the capsule passes, further testing
that includes any type of MRI should be avoided. If you
have a MRI scheduled for the next 3 days, this should
be postponed.
7. The Capsule: The capsule passes naturally in a bowel
movement, typically in 24 hours. Most likely you will
be unaware of its passage. It does not need to be
retrieved and can safely be flushed down the toilet.
Occasionally, the capsule lights will still be flashing
when it passes.
This is of no importance. Should you be concerned that
the capsule did not pass, in the absence of symptoms,
an abdominal x-ray can be obtained after 3 days to
confirm its passage.
Figure 4.
Capsule Endoscopy Report Form
The Performance of Capsule Endoscopy
Patient Name:_______________________________
Recorder ID#:________________
Date:_______________________
Capsule ID#_________________
Pre-Exam Checklist:
1. Overnight fast confirmed
2. Consent obtained
3. Battery pack fully charged
4. Recorder powered and connected to workstation
5. Recorder initialized
6. Simethicone administered (4 drops in cup of water)
7. Skin marked with stencil
8. Sensor array applied to skin
9. Belt applied
10. Recorder and battery pack installed in belt pack
11. Sensor array attached to Recorder
12. Recorder connected to battery pack
13. Continuous light appears and then stops
14. Capsule blinking on removal from holder
15. Recorder flashes
16. Patient told no drinking for 4 hrs, no eating for 5 hrs
Post-Exam Checklist:
8. Recorder disconnected from battery
9. Recorder disconnected from sensor array
10. Belt removed
11. Sensor array removed
12. Recorder powered and connected to workstation
13. Download begun
14. Battery pack powered for charging
19

20
Chapter 2
Figure 5.
Time Capsule Swallowed:____________
Recorder Disconnect Time:___________
Review
Length of Review
Start: Start: Start: Start: Start:
Stop: Stop: Stop: Stop: Stop:
Time: Time: Time: Time: Time: Total Time:
Colon Reached: Yes No
Time in Stomach:_____ Time to Colon:_____ Time in SB:_____
Findings: (Give time codes for all findings/Use additional pages if necessary)
Signature:______________________
The Performance of Capsule Endoscopy

Chapter 3
Normal M2A ® Anatomy
Paul Swain, M.D.
Mark Appleyard, M.D.
INTRODUCTION
It is important to be familiar with normal M2A ® anatomy. This
knowledge will serve as a basis while evaluating images with
potential abnormalities. After placing the M2A ® capsule in
the oral cavity there may be some transient condensation
that rapidly clears as the capsule reaches body temperature.
As the capsule is manipulated with the tongue, excellent
views of the tongue and oral anatomy are obtained.
CAPSULE EXPERIENCE
ESOPHAGUS
The M2A ® esophageal transit time is usually rapid, thereby
limiting the number of images transmitted from the esophagus.
Typically one or two frames of the esophagus are acquired.
There is a tendency for slight hold up at the lower esophageal
sphincter so good images of the Z line at the gastroesophageal
junction can be acquired. Subjects are more likely to swallow
the capsule with the optical dome pointing down, which may
help with acquisition of images of the lower esophageal sphincter.
STOMACH
Average M2A ® capsule gastric emptying time is approximately
one hour, the range being very wide. The closed pylorus has
a more pleated clover leaf like appearance than at conventional
endoscopy because the antrum is not distended with air. The
most common characteristic appearance in the stomach is of
the large folds and intermittent movement often with repetitive
viewing of various areas of the stomach. Detailed physiological
images of the gastric mucosa can be seen.
Gastric movements can be divided into propulsive and nonpropulsive.
Propulsive movements force the capsule into the
antrum and the pylorus may be seen if the optical dome is
pointing in that direction. Non-propulsive contractions are
much commoner and may be due to the contraction of the
abdominal wall. The RAPID ® (the software used to review the
M2A ® images) viewer should keep in mind that the stomach
as well as the other images displayed are being viewed at
a much faster speed than in real time.
DUODENUM
As the capsule is propelled forward into the duodenal bulb,
the pylorus may be well seen. There is usually a color change
since the 11 mm capsule fits the small intestine more snugly
so the images are brighter. Bile can at times be seen streaming
proximally from the third portion of the duodenum. In the
bulb a nodular appearance due to the presence of Brunner's
glands may be seen. The capsule usually passes quickly into
the second part of the duodenum where the villous pattern
23

24
Chapter 3
becomes very obvious. Because the wireless images are
acquired without distension with air, and because there is
usually some liquid present, the villi often appear to be sticking
up and are more easily seen than at conventional endoscopy.
The ampulla is rarely seen because it is concealed by folds
and lies below a linear fold. The transit in the second part of
the duodenum is usually rapid. Sometimes serpiginous linear
white lines can be seen which are an artifact caused by the
capsule pressing on and parting the villi. Another unusual
artifact, which can be seen in the normal small intestine, is
an appearance reminiscent of the convolutions of the brain.
This is probably due to folds of small intestine being flattened
by pressure, either due to gravity with the optical dome
pressing downwards, or due to a small intestinal wave of
contraction pressing the capsule against the folds.
The vascular pattern of the small bowel becomes easier to
identify once the capsule has entered the distal jejunum.
Sometimes quite large veins with their accompanying arteries
can be seen in normal subjects. White spots are sometimes
apparent especially in the proximal jejunum, which are
probably dilated lymphatic vessels. Lymphangiectatic cysts
are very commonly seen in normal subjects. Bile becomes
concentrated, darkening the images further down the small
intestine. Villi may become less obvious as the capsule
progresses into the ileum. Backwards and forwards movement
is not uncommon.
TERMINAL ILEUM
The transition from the terminal ileum to cecum is usually
apparent. The ileum usually includes lymphoid follicles that
appear as small white nodules in its villous pattern. There
may be a delay if the valve fails to relax and retains the capsule
for a while. The capsule then drops into a large lumen as it
enters the cecum. The pattern of movement changes,
becoming much slower. The different and more marked
vascular pattern of the colonic mucosa will become apparent.
COLON
Even without preparation, some views of colonic mucosa and
its vascular pattern are seen. Usually the capsule remains in
the cecal pole for an extended period of time without moving.
Because the lumen of the colon is larger than that of the small
bowel, the views may be slightly darker, but if the colon is
clean, usually good views are obtained. The appendiceal
orifice can sometimes be seen. The classic triangulated
appearance of the transverse colon may be seen. It is often
possible to see a bluish color, which may feature a meniscuslike
edge through the wall of the colon. This may be due to
transillumination of the liver or spleen. At times blood can be
seen pulsing through the colonic arteries.
The more vascular appearance of rectal mucosa can be
distinguished from that of the more proximal colonic mucosa.
The normal hemorrhoidal vasculature is sometimes seen
clearly if the capsule is still transmitting images. When the
capsule passes through the anus, images change and turn
whiter and brighter.
CONCLUSION
Normal M2A ß Anatomy
M2A ® capsule endoscopy gives detailed physiological images
of the normal GI tract. To achieve competence in interpreting
M2A ® capsule abnormalities, it is important to become first
familiar with normal M2A ® anatomy.

Chapter 3
M2A ® M2A ®
Figure 3.1 As M2A ® capsule is being ingested, a well
papillated normal appearing tongue is seen.
M2A ® M2A ®
Figure 3.2b Optical dome of capsule exerting slight
pressure on esophageal tissue as it is passing through.
Figure 3.2a Pharynx.
Figure 3.2c EG junction.
Normal M2A ß Anatomy
25

26
Chapter 3
M2A ® M2A ®
Figure 3.2d Detailed view of the Z line.
M2A ® M2A ®
Figure 3.3a Details of gastric folds seen by physiological
capsule endoscopy in the mid-gastric region.
Figure 3.2e View of normal proximal gastric folds.
Figure 3.3b View of gastric antrum.
Normal M2A ß Anatomy

Chapter 3
M2A ®
Figure 3.4a Typical stellate-like appearance of normal
pyloric opening as seen by capsule.
M2A ®
Figure 3.4c Normal proximal small bowel.
M2A ®
M2A ®
Figure 3.5a Normal jejunum.
Normal M2A ß Anatomy
Figure 3.4b Brunner’s gland hyperplasia with suspected
ectopic gastric mucosa within duodenal bulb.
27

28
Chapter 3
M2A ®
Figure 3.5b Normal jejunum with normal villi as seen
in former figure.
M2A ® M2A ®
Figure 3.6a The Ampulla of Vater. Not commonly
visualized by the M2A ® capsule.
Normal M2A ß Anatomy
Figure 3.5c Histological appearance of normal villi.
Figure 3.6b Detailed view of the normal vasculature
of the small bowel.

Chapter 3
Figure 3.7a Small bowel follow through showing
evidence of nodular lymphoid hyperplasia in the
terminal Ileum.
M2A ®
Figure 3.7c Capsule view of the same area showing
lymphoid hyperplasia.
Normal M2A ß Anatomy
Figure 3.7b Ileoscopy done on same patient revealing
nodular lymphoid hyperplasia.
M2A ®
Figure 3.8 Normal Ampulla of Vater.
29

30
Chapter 3
M2A ® M2A ®
Figure 3.9a Lymphangiectasia of the small bowel.
These are frequently seen in normal patients.
M2A ®
Figure 3.10 M2A ® capsule approaching the ileocecal
valve.
M2A ®
Normal M2A ß Anatomy
Figure 3.9b Lymphangiectasia of the small bowel.
Sometimes referred to as Xanthomas of the small
bowel and are rarely associated with GI bleeding.
M2A ®
Figure 3.11a Normal vascular pattern of the cecal wall.

Chapter 3
M2A ®
Figure 3.11b M2A ® capsule imaging the right colon.
M2A ®
Normal M2A ß Anatomy
Figure 3.11c View of the anus by the M2A ® capsule.
31

Chapter 4
Inflammatory Diseases of the Small Intestine
Alan L. Buchman, M.D.
INTRODUCTION
Development of the flexible enteroscope in the 1960's allowed
the practitioner direct visualization of the intestinal tract for
the first time. Insertion of these forward-viewing fiber-optic
endoscopes (now supplanted by video endoscopes) permitted
visualization of the complete duodenum. Subsequently,
longer endoscopes were used and continue to be used today
in order to visualize distally to the proximal or mid-jejunum.
Enteroscopes have been developed over the last 10-15 years
that permit visualization of the proximal and mid-jejunum.
Such endoscopes utilize an overtube through which the
endoscope is inserted through the stomach. This limits gastric
looping of the endoscope, permitting more distal intubation.
However, even the push enteroscope does not allow
visualization of the majority of small intestine, although it
does permit steering, re-visualization of lesions, and targeted
biopsy and therapeutic maneuvers. In addition, conventional
enteroscopes have a field of vision that approaches 110-120
degrees, versus approximately 140 degrees with the M2A ®
Capsule Endoscope.
The Sonde enteroscope is a very thin endoscope that is passed
transnasally into the gastrointestinal tract. This endoscope
has a balloon at its tip which is propelled via peristalsis, to
the distal extent of the small intestine. The endoscope
position is monitored using fluoroscopy, and may often require
4-6 hours until the terminal ileum is reached. The clinician
then observes the intestinal mucosa as the endoscope is
slowly withdrawn. Unfortunately, this instrument is expensive,
cumbersome, and usually more than half of the intestine
cannot be viewed as the tip of the instrument often becomes
lodged in the intestinal folds and the image is obscured.
The primary use for the enteroscope in inflammatory bowel
disease is to diagnose celiac sprue, Crohn's disease as well
as other, more uncommon forms of inflammatory bowel
disease, including systemic lupus erythematosus (SLE),
radiation enteritis, ischemic enteritis, eosinophilic
gastroenteritis as well as infectious enteritis, including
giardiasis, Whipple's disease, mycobacteria, and tropical
sprue. Celiac sprue, giardiasis, and Whipple's disease typically
involve the proximal intestine. Crohn's disease typically
involves the terminal ileum and is rarely isolated to the
duodenum or jejunum in the absence of involvement of other
areas of the gastrointestinal tract. Rare cases of chronic, nongranulomatous
jejunoileitis have been described. Tropical
sprue typically involves both the proximal jejunum as well as
the ileum. Mycobacterium Avium may involve any portion of
the small intestine, although M. tuberculosis, histoplasmosis,
Yersinia enterocolitis, and Behcet 's syndrome usually involve
the ileocecal region.
33

34
Chapter 4
CAPSULE EXPERIENCE
Endoscopic appearance of celiac sprue, eosinophilic
gastroenteritis, and infectious enteritis may be normal,
although non-specific findings may be evident. These include
mucosal thickening, erythema, nodularity, or even ulceration.
The endoscopic appearance of celiac or topical sprue may
include scalloping of the valvulae conniventes as well as a
mosaic pattern of the mucosa.
The endoscopic appearance of Crohn's disease may include
erythema, apthoid and linear ulceration, thickening of mucosal
folds, nodules, stenosis, and even fistula formation. The latter
may be exceedingly difficult to visualize endoscopically.
Ulcers may be linear, longitudinal or transverse, and may
coalesce, forming a grid over non-ulcerated mucosa.
Characteristically, there are areas of normal intervening
mucosa in between areas of mucosal involved with Crohn's
disease ("skip lesions"). Capsule Endoscopy has revealed an
entirely new spectrum of inflammatory lesions allowing
endoscopic diagnosis of small bowel inflammation before it
is apparent by other diagnostic modalities.
Barium contrast radiographic studies, complemented by
computerized tomography (CT) have been the primary tool
for the diagnosis of inflammatory lesions of the small intestine.
The findings from these studies are often non-specific, and
include dilated intestinal loops, separation of the intestinal
loops, or mucosal spiculation which suggests the outline of
mucosal ulceration. Although CT does not detect mucosal
inflammation, marked transmural thickening and signs of
extraintestinal inflammation such as peri-intestinal fat
stranding and mesenteric lymphadenopathy may be evident;
fistula formation may also be identified. Since barium fills
the lumen, strictures are often readily identified, although
may not always be evident. Whether the stricture is
inflammatory, fibrotic, or carcinogenic, cannot be
differentiated.
In this chapter, a spectrum of new images reflecting
inflammatory pathology is described. As more experience
is gained with capsule endoscopy, these abnormalities
will redefine our approach to suspected inflammatory
bowel disease.
CONCLUSION
Inflammatory Diseases of the Small Intestine
Video capsule endoscopy permits the direct viewing of mucosa
throughout the entire small intestine. Strictures and other
mucosal abnormalities not evident on radiographic studies
or beyond the reach of convention endoscopy can be
visualized. This noninvasive technique avoids many of the
pitfalls inherent in the use of standard push or Sonde
enteroscopy, although mucosal biopsy sampling is not
possible at the present time.
References and Suggested Readings
1 Sasamura H, Nakamoto H, Ryuzaki M, et al. Repeated intestinal ulcerations
in a patient with systemic lupus erythematosus and high serum
antiphospholipid antibody levels. South Med J 84:515- 517, 1991
2 Mashako MN, Cezard JP, Navarro J, et al. Crohn's disease lesions in the
upper gastrointestinal tract: Correlation between clinical, radiological,
endoscopic, and histologic features in adolescents and children.
J Pediatr Gastroenterol Nutr 8:442-446 1989
3 Cameron D. Upper and lower gastrointestinal endoscopy in children and
adolescents with Crohn's disease. J Gastroenterol Hepatol 6:355-358, 1991
4 Jeffires GH, Steinberg H, Sleisenger MH. Chronic ulcerative
(nongranulomatous) jejunitis. Am J Med 44:47-59, 1968
5 Baer AN, Bayless TM, Yardley JH. Intestinal ulceration and malabsorption
syndromes. Gastroenterology 79:754-765, 1980

Chapter 4
6 Sayek I, Aran O, Uzunaliamoglu B, et al. Intestinal Behcet's disease: surgical
experience in seven cases. Hepatogastroenterology 38:81-83, 1991
7 Tawil S, Brandt LJ, Bernstein LH. Scalloping of the valvulae conniventes and
mosaic mucosa in tropical sprue. Gastrointestinal Endosc 37:365-366, 1991
8 Alcantara M, Rodriguez R, Potenciano JL, et al. Endoscopic and bioptic
findings in the upper gastrointestinal tract in patients with Crohn's disease.
Endoscopy 25:282-286, 1993
9 Lescut D, Vanco D, Bonniere P, et al. Perioperative endoscopy of the whole
small bowel in Crohn's disease. Gut 34:647-649, 1993
Inflammatory Diseases of the Small Intestine
35

36
Chapter 4
M2A ® M2A ®
Figure 4.1a Villous erosion with fibrosis in the jejunal
area. Presence of prominent whitish villi suggests
submucosal fibrosis.
M2A ®
M2A ® M2A ®
Figure 4.2 Ulceration in the terminal ileum in a patient
with IBD.
Inflammatory Diseases of the Small Intestine
Figure 4.1b Area of edema, erythema and villous
erosion in a patient with small bowel inflammatory
disease.
Figure 4.3 Superficial jejunal ulcer in a patient with
patchy areas of moderate to severe enteritis.

Chapter 4
M2A ® M2A ®
Figure 4.4a Focal area of inflammation characterized
by erythema, edema, dilated lymphatics and mucosal
breakdown.
Figure 4.4c The biopsy shows mild to moderate
inflammation with partial villous atrophy and blunting.
(H&E X 20).
Inflammatory Diseases of the Small Intestine
Figure 4.4b Jejunum with nodular area of inflammation
and superficial ulceration.
M2A ®
Figure 4.5a Jejunum of patient with Crohn’s disease
showing thickened infiltrated folds.
37

38
Chapter 4
M2A ®
Figure 4.5b Ongoing infiltration, ulceration and
nodularity in Crohn’s disease.
M2A ®
Figure 4.5d Small bowel stricture in this patient with
Crohn’s disease. Note the slit-like opening of the
stricture. Capsule passed easily.
M2A ®
Inflammatory Diseases of the Small Intestine
Figure 4.5c Inflammatory process infiltrating and
thickening this small bowel fold.
M2A ®
Figure 4.5e Small bowel inflammation with edema,
erythema and prominent folds.

Chapter 4
M2A ®
Figure 4.5f Pseudopolyp with surrounding
cobblestoning in Crohn’s disease.
M2A ®
Figure 4.5h Irregular ulcer in IBD.
M2A ®
Inflammatory Diseases of the Small Intestine
Figure 4.5g Near total obliteration of lumen secondary
to inflammatory process.
M2A ®
Figure 4.6a M2A ® Capsule entering a narrowed area
with surrounding geographic ulceration.
39

40
Chapter 4
M2A ®
Figure 4.6b M2A ® Capsule passing through the
narrowed area as depicted in 4.6a.
M2A ®
Figure 4.6d Isolated ulcer in a normal surrounding
area in a patient with known IBD.
M2A ®
Inflammatory Diseases of the Small Intestine
Figure 4.6c Narrowed lumen with surrounding
ulceration in Crohn’s disease.
M2A ®
Figure 4.6e Inflammation, ulceration and narrowing
in a patient with IBD.

Chapter 4
M2A ®
Figure 4.6f Extensive linear ulceration in IBD.
M2A ®
Figure 4.8a Early lesion of inflammatory bowel disease
revealing submucosal edema and ulceration.
M2A ®
Inflammatory Diseases of the Small Intestine
Figure 4.7 Apthous ulcer of distal ileum.
M2A ®
Figure 4.8b Early inflammatory lesions with spectrum
of abnormalities showing edema, villous erosion and
ulceration.
41

42
Chapter 4
M2A ®
Figure 4.9a 18 year old male. CE revealed ulcer in the
distal part of the small bowel.
Figure 4.9c At surgery Crohn’s disease was diagnosed.
A deep fissure can be seen in the histological
examination. (H&E).
M2A ®
Inflammatory Diseases of the Small Intestine
Figure 4.9b Same patient. View of additional ulcer
with narrowing of lumen.
Figure 4.9d Typical granulotoma can be seen in the
wall of the small intestine. (H&E).

Chapter 4
M2A ® M2A ®
Figure 4.10a Lymphoid hyperplasia. This is a normal
variant and should not be interpreted as pathological
nodularity.
M2A ®
Figure 4.11 Early duodenal fissuring in a patient with
early Crohn’s lesion.
M2A ®
Inflammatory Diseases of the Small Intestine
Figure 4.10b Lymphoid hyperplasia.
Figure 4.12 Ileal linear ulceration.
43

44
Chapter 4
M2A ®
Figure 4.13a Segment of proximal small bowel with
edema and erythema.
M2A ®
Figure 4.13c Area of proximal jejunum with erythema,
edema. Note the ulcer between 6 and 7 o’clock.
M2A ®
M2A ®
Inflammatory Diseases of the Small Intestine
Figure 4.13b Early proximal small bowel inflammation.
Figure 4.14 Ileal lesion in Crohn’s disease.

Chapter 4
M2A ®
Figure 4.15a Jejunal linear ulcerations.
M2A ®
Figure 4.15c Linear ulceration in Crohn’s disease.
M2A ®
M2A ®
Inflammatory Diseases of the Small Intestine
Figure 4.15b Jejunal linear ulcerations.
Figure 4.16 Crohn’s disease with mucosal fissure in
proximal jejunum.
45

Chapter 5
Neoplastic Diseases
Francesco P. Rossini, M.D.
Marco Pennazio, M.D.
INTRODUCTION
Tumors of the small bowel comprise 5% to 7% of all
gastrointestinal tumors. With the use of more accurate
diagnostic methods, diagnosis of small bowel tumors has
become more frequent and it is probable that the actual
incidence is underestimated. The most important symptom
in cases of small bowel neoplasia is undoubtedly obscure
bleeding with secondary iron deficiency anemia. Indeed, small
bowel tumors are the second most common cause of obscure
gastrointestinal bleeding, accounting for 5% to 10% of all
cases of chronic blood loss. Among patients with obscure
gastrointestinal bleeding, small bowel tumors are the single
most common lesion in patients below 50 years of age.
Having excluded the upper and lower portions of the
gastrointestinal tract, attention should be concentrated on
the small bowel as being responsible for bleeding. This
strategy probably affords the rapid identification of a tumor
as a cause of the bleeding. The most frequent location both
for epithelial tumors and for non-epithelial small bowel tumors
is the jejunum rather than the ileum. Adenomas,
adenocarcinomas, and gastrointestinal stromal tumors (GISTs)
are much more frequent in the duodenum and jejunum.
Metastatic tumors may occur in different parts of the small
bowel and carcinoids are more common in the ileum.
Adenomas are the most common benign small bowel tumors
with malignant potential and adenocarcinoma is the most
common malignant small bowel tumor. Carcinoid tumors are
the second most frequent neoplasm encountered in the small
bowel. Primary intestinal lymphoma accounts for about 20
to 30% of malignant neoplasms of the small bowel and is the
third most common small bowel neoplasm. Among vascular
tumors, hemangiomas and lymphangiomas account for 3%
to 8% of all benign small bowel neoplasms; Kaposi's sarcoma
is the most frequent neoplasm in AIDS patients. GISTs are
non-epithelial neoplasms that originate from cells located in
the wall of the stomach and small bowel and are characterized
by extreme variability of differentiaton potential. GISTs with
smooth muscle differentiation (leiomyomas) are the secondcommonest
benign tumors of the small bowel. GISTs with
neural differentiation (schwannomas, gastrointestinal
autonomic nerve tumors) are rare neoplasms that may be the
cause of obscure gastrointestinal bleeding.
CAPSULE EXPERIENCE
Diagnostic methods for small bowel tumors include
enteroclysis, CT, MR imaging, arteriography, enteroscopy and
capsule endoscopy. Barium studies of the small bowel have
low diagnostic yield. In our personal experience of 24 patients
47

48
Chapter 5
with small bowel tumors identified enteroscopically, only 25%
had enteroclysis compatible with the presence of a small
bowel tumor. Although tumors may escape diagnosis even
with enteroscopy, in any case it appears to be superior to
barium studies of the small bowel in patients with obscure
bleeding in whom tumor is suspected. The two methods are
usually considered to be complementary, but it is hoped that
recently introduced diagnostic methods such as helical CT
enteroclysis, MR enteroclysis and, above all, capsule
endoscopy may modify the non invasive diagnostic approach
to this important pathology.
In the two clinical trials performed in the United States and
in Italy to evaluate the use of capsule endoscopy in patients
with obscure bleeding reported so far, 2 out of 36 patients
(5%) were ultimately diagnosed to have a small bowel tumor
and had curative surgery. This further stresses that capsule
endoscopy is an extremely promising tool for the diagnosis
of small bowel tumors.
Capsule endoscopy and push enteroscopy are also extremely
important in the surveillance of groups of patients with
increased risk of small bowel tumors, such as the following
precancerous conditions: celiac disease, ulcerative jejunoileitis,
familial adenomatous polyposis (FAP), Peutz-Jeghers
syndrome (PJS), juvenile polyposis, immunodeficiency
syndromes, alpha-chain disease, small bowel adenomas,
hereditary non-polyposis colorectal cancer syndrome (HNPCC).
In particular, in patients with FAP or PJS, whereas surveillance
of the upper and lower gastrointestinal tract is easily achieved
through esophagogastroduodenoscopy and total colonoscopy
with terminal ileoscopy, the small bowel is still an important
and challenging problem. Capsule endoscopy offers the great
opportunity to identify polyps and map their distribution.
It is to be hoped that this new technique will be able to replace
Neoplastic Diseases
the more invasive enteroclysis in the surveillance strategy for
the small bowel. A follow-up program might be based on
periodic capsule endoscopies, and the use of other techniques
such as push enteroscopy and/or intraoperative enteroscopy
could be targeted on the basis of the data acquired by
the capsule.
CONCLUSION
Capsule endoscopy is highly innovative both from the
technological and the clinical standpoint, since it provides
non invasive visualization of areas of the small bowel that
are not easily accessible using wired endoscopy. There is
also the undoubted advantage of a simple, complication-free
procedure that does not require hospitalization. Capsule
endoscopy opens up new horizons for the diagnosis of small
bowel tumors. It will very probably bring about the progressive
abandonment of some currently used invasive and costly
diagnostic methodologies (which also have a low diagnostic
yield), which greatly increase the cost of managing
gastroenterological patients.
References and Suggested Readings
1 Rossini FP, Risio M, Pennazio M. Small bowel tumors and polyposis
syndromes. Gastrointest Endosc Clin N Am 1999; 9: 93-114
2 Lewis BS, Swain P. Capsule endoscopy in the evaluation of patients with
suspected small intestinal bleeding: the results of the first clinical trial.
Gastrointest Endosc 2001; 53: 70
3 Pennazio M, Santucci R, Rondonotti E, et al. Wireless capsule endoscopy
in patients with obscure gastrointestinal bleeding: preliminary results of
the Italian multicentre experience. Digest Liver Dis 2001; 33: 2
4 Pennazio M, Rossini FP. Small bowel polyps in Peutz-Jeghers syndrome:
management by combined push enteroscopy and intraoperative enteroscopy.
Gastrointest Endosc 2000; 51: 304-8
5 Rossini FP, Pennazio M. Small bowel endoscopy. Endoscopy 2002; 34:13-20

Chapter 5
M2A ®
Figure 5.1 Benign appearing polyp of small bowel.
M2A ®
Figure 5.3a Duodenal polyp in patient with familial
polyposis.
M2A ®
Neoplastic Diseases
Figure 5.2 80 year old patient with chronic GI blood
loss requiring transfusion. CE revealed a large polypoid
mass of small intestine
Figure 5.3b Histology of polyp in figure 5.3a reveals
a villous adenoma with high grade dysplasia. (H & E).
49

50
Chapter 5
M2A ®
Figure 5.4a Large hamartomatous polyp in Peutz-
Jegher’s Syndrome.
M2A ®
Figure 5.5a Large jejunal polyp causing recurrent
bleeding in a 70 year old patient.
Neoplastic Diseases
Figure 5.4b Small bowel series of same patient
revealing the polyp.
Figure 5.5b Surgical specimen of case 5.5a. Notice
polyp at 6 o’clock.

Chapter 5
M2A ®
Figure 5.6a Diffuse lymphoid hyperplasia present
throughout the entire GI tract in a patient with Common
Variable Immunodeficiency.
Figure 5.6c Small intestine. Lymphoid hyperplasia.
There are hyperplastic B-cell follicles as well as a
prominent interfollicular infiltrate.
M2A ®
M2A ®
Neoplastic Diseases
Figure 5.6b Detailed view of the lymphoid nodular
hyperplasia in same case.
Figure 5.7a Patient with PJS. CE revealed hamartomatous
polyp in duodenum.
51

52
Chapter 5
M2A ®
Figure 5.7b Same patient with polyps in distal jejunum.
M2A ®
Figure 5.8a Carcinoid tumor of small bowel.
M2A ®
Neoplastic Diseases
Figure 5.7c Same patient with hamartomatous polyp.
Figure 5.8b Histology of carcinoid tumor of small bowel
shows solid nests of tumor cells in the submucosa
which were positive for neuroendocrine markers. (H&E).

Chapter 5
M2A ®
Figure 5.9 Ileal Carcinoid. A 45 year old patient with
three episodes of GI hemmorrhage. Multiple evaluations
did not reveal a bleeding source. M2A ® Capsule
endoscopy revealed an ileal submucosal mass.
M2A ®
Figure 5.10b Same GIST as in former figure.
M2A ®
Neoplastic Diseases
Figure 5.10a Gastrointestinal Stromal Tumor. The
white mass at 5 o’clock is the submucosal portion of
a 3 cm exophytic malignant GIST causing repeated GI
bleeding. The vessel coursing at its apex is being
eroded by the tumor.
Figure 5.10c High magnification of GIST shows a dense
cellular area with pleomorphic spindle-shaped cells. (H&E).
53

54
Chapter 5
M2A ®
Figure 5.11a A 49 year old male, suffering from weight
loss, recurrent abdominal pain and diarrhea. Polypoid
lesions in duodenum, with thickened mucosa and linear
erosions. This lesion was proven to be a lymphoma of
the small bowel.
Figure 5.11c Upper GI series showing an irregularity in
the 3rd and 4th portion of the duodenum corresponding
to an infiltration of the wall by the lymphoma.
M2A ®
Neoplastic Diseases
Figure 5.11b Same patient with lymphomatous
polypoid mass in jejunum.
Figure 5.11d Close up of tumor in distal duodenum
showing filling defect and wall infiltration.

Chapter 5
Figure 5.11e Histology reveals Non-Hodgkin Follicular
Lymphoma (grade 1). Immunohistochemical staining
showed: CD20, bcl-2 and CD10: (+). CD3, CD5, Cyclin D: (-).
M2A ®
Figure 5.12a 52 year old male with advanced cirrhosis
(HCV), portal hypertension and esophageal varices.
Capsule endoscopy reveals duodenal lymphoma.
M2A ®
Neoplastic Diseases
Figure 5.11f Same patient with a small polyp in ileum.
M2A ®
Figure 5.12b Duodenal lesion in the same patient.
55

56
Chapter 5
Figure 5.12c Biopsy of the duodenal mucosa showed
lymphomatous polyposis. The lymphocytes infiltrating
the lamina propria were B, CD5 positive. (H&E).
Figure 5.12e Endoscopy reveals lymphoma of the
duodenum.
Neoplastic Diseases
Figure 5.12d Higher magnification of the monotonous
infiltrate of B lymphocytes. (H&E).
Figure 5.12f Endoscopy reveals the same area in the
duodenum.

Chapter 5
M2A ®
Figure 5.13a Images of proximal small bowel showing
thickened folds with onset of ulceration.
M2A ®
Figure 5.14a Infiltrating adenocarcinoma of the
jejunum with active bleeding.
M2A ®
Neoplastic Diseases
Figure 5.13b A narrowed lumen with a key hole
configuration is seen in this infiltrating Non-Hodgkin’s
T-Cell Lymphoma, same patient.
M2A ®
Figure 5.14b Infiltrating adenocarcinoma of the
jejunum with ulceration in the center.
57

58
Chapter 5
M2A ®
Figure 5.15a Adenocarcinoma of small bowel in a 57
year old male with a pancreatic mass. The pancreatic
mass proved to be a metastatic lesion from this primary.
M2A ®
Figure 5.16a CE reveals small bowel polyps in a patient
who underwent resection for a small bowel
adenocarcinoma two years prior to CE.
M2A ®
Figure 5.15b Additional view of same case.
Neoplastic Diseases
Figure 5.16b Push enteroscopy of the same case.

Chapter 5
M2A ®
Figure 5.16c Same case revealing an elongated
polypoid lesion.
M2A ®
Figure 5.17a Submucosal jejunal mass in a patient
with GI bleeding.
Neoplastic Diseases
Figure 5.16d Histological examination of one of the
polyps showing normal mucosa with no signs of
malignancy. These polyps proved to be normal tissue
in a polypoid configuration.
M2A ®
Figure 5.17b As capsule endocope passes the mass,
an ulcer is seen in the center of it.
59

60
Chapter 5
M2A ®
Figure 5.18a Nodular lesion of small bowel in AIDS
patient with biopsy proven Kaposi’s.
M2A ®
Figure 5.19a Nodular bluish lesion in a patient with
suspected Kaposi’s sarcoma.
M2A ®
Neoplastic Diseases
Figure 5.18b Submucosal nodular lesion of small
bowel in Kaposi’s sarcoma.
M2A ®
Figure 5.19b Nodular bluish lesion in a patient with
suspected Kaposi’s sarcoma, same case.

Chapter 5
M2A ®
Figure 5.19c Nodular bluish lesion in a patient with
suspected Kaposi’s sarcoma, same case.
M2A ®
Neoplastic Diseases
Figure 5.20 AIDS patient with recurrent unexplained
GI bleeding. Note bluish nodular lesion suspected to
be Kaposi’s sarcoma of the small bowel.
61

Chapter 6
Iatrogenic Diseases
David R. Cave, M.D.
INTRODUCTION
Capsule endoscopy [CE] has provided a revolutionary and
sensitive method for the visualization of the small intestinal
mucosa at an 8:1 magnification with excellent resolution. This
technology allows us for the first time to view non-invasively
the majority of the intestinal mucosa. Any technology is
subject to the Heisenberg uncertainty principle. In brief, this
states that, in the process of making an observation, the
measurement alters the behavior of the object of study. In
the case of CE, the capsule behaves as a large particle of food.
Because of this, the mucosal folds are in their near natural
state unlike during conventional push enteroscopy where the
insufflation of air opens the lumen and flattens the mucosa.
Furthermore, the process of mucosal flattening may obscure
subtle villous changes. Similarly diverticula are generally not
seen with CE, because the lumen is collapsed and are therefore
unlikely to trap a capsule.
It is important to understand that succus entericus and partially
digested food are liquid and rarely contain large food particles.
Therefore quite tight strictures may only be revealed by
passage or retention of the video capsule that has a diameter
of 11mm. The implications of this are, that the pros and cons
of the procedure should be carefully considered, by both
patient and physician, prior to capsule ingestion. This is
particularly true in patients who use NSAIDs and who have
had radiation, because these strictures may not be
demonstratable by conventional technology including
enteroclysis. Therefore, CE should not be performed on
patients who are an unacceptable operative risk, since
retention of a capsule in such a patient could put all concerned
in a serious predicament. Retained capsules have remained
in patients for up to 14 weeks without causing symptoms,
but more long-term data regarding retained capsules is
needed. The small bowel may be injured by a variety of
medications, ionizing radiation and surgery with short and/or
long-term consequences. This chapter will review these
conditions and provide images that demonstrate each of
these situations.
CAPSULE EXPERIENCE
NSAIDS AND OTHER MEDICATIONS
NSAIDs are well known to cause gastro-duodenal injury. Less
commonly, injury to the more distal small bowel and colon
has been reported. Well described, but rare, are NSAID
associated webs or strictures. How common these latter
lesions are is unknown, as they will only draw attention to
themselves if they cause bleeding or iron deficiency anemia.
Generally small bowel series or enteroclysis will not show
them, as they are often only more rigid versions of the normal
63

64
Chapter 6 Iatrogenic Diseases
plicae circulares. A history of NSAIDs or aspirin use should
be a caveat to users of CE that a normal small bowel series
or enteroclysis does not preclude the presence of a stricture
tight enough to cause retention of the capsule. Usually the
capsule will tumble around proximal to the stricture,
asymptomatically, and eventually pass spontaneously.
However it may produce pain and transient obstruction and
even require surgical retrieval. The stricture may or may not
be ulcerated. Ulcers may occur without strictures. It is
not clear as to whether the process of stricturing and
ulceration continues after the cessation of NSAID use. Other
medications have been implicated in small intestinal
strictures such as slow release potassium tablets. This
is very rare. Chemotherapy induced mucositis is quite
common, but usually easily detected with an endoscope
in the duodenum.
RADIATION INJURY
Radiation therapy for a variety of neoplastic conditions,
especially cervical and endometrial lesions, may unavoidably
radiate the small intestine, despite the radio therapist having
taken measures to avoid this problem. The small intestine
is moderately resistant to long-term injury but may
nevertheless develop chronic radiation injury including
mucosal changes, strictures and ulcerations leading to
obscure gastrointestinal bleeding and bacterial overgrowth.
Careful choice of patient for CE is mandatory in patients who
have received radiation. Only those who are operative
candidates should be considered for study, since capsule
retention and subsequent retrieval may entail a difficult
dissection of matted loops of small bowel and a resection
of a long length of irradiated bowel. Anastomoses may heal
poorly in this setting. Small bowel series may reveal strictures
but may miss them. Limited experience using intra-operative
enteroscopy has demonstrated tight strictures not seen
on small bowel series.
SURGICAL INTERVENTION
Small bowel resective surgery, unless for Crohn's disease, is
uncommon. The blood supply to the small bowel is usually
excellent and hence small intestinal anastomoses rarely heal
with stricturing. Ileo-colonic anastomoses also usually heal
well. Anastomoses as well as staples and sutures can be
visualized by CE. Development of small bowel adhesions is
quite common after any abdominal surgery. The role of CE in
this setting remains to be determined. In any patient who
presents with presumed adhesions and intermittent or partial
small bowel obstruction, a small bowel series should be a
necessary prelude to CE. The patient and physician should
clearly understand the potential for retention of the capsule
and possible need for surgical retrieval of the capsule, prior
to embarking on the study.
CONCLUSION
Iatrogenic small intestinal mucosal abnormalities, ulcers and
strictures may be found with much higher frequency than was
possible with conventional endoscopy and radiology. These
often-unanticipated small intestinal strictures may lead to
capsule retention. The capsule passes the majority of
strictures uneventfully within a few hours or days. A small
proportion of these patients may need surgical removal of
the capsule and the related lesions.

Chapter 6 Iatrogenic Diseases
M2A ®
Figure 6.1a Ulcer secondary to NSAID use. Patient
was on COX-1 inhibitors.
M2A ®
Figure 6.1c NSAID induced membranous stricture,
same case.
M2A ®
Figure 6.1b Membranous stricture caused by NSAID
use, same case.
M2A ®
Figure 6.1d NSAID induced small intestinal ulcer, same
case.
65

66
Chapter 6 Iatrogenic Diseases
M2A ®
Figure 6.1e Membranous stricture with ulceration
secondary to NSAID use.
M2A ®
Figure 6.3 Surgical staples at an anastomosis.
M2A ®
Figure 6.2 NSAID induced small bowel stricture.
M2A ®
Figure 6.4 NSAID induced small bowel stricture.

Chapter 6 Iatrogenic Diseases
M2A ®
Figure 6.5 NSAID associated ileal ulcer.
M2A ®
Figure 6.7 Small erosion in a patient on COX-2 inhibitors.
Patient was not symptomatic from this lesion.
M2A ®
Figure 6.6 Ulcerated stricture secondary to NSAIDs.
M2A ®
Figure 6.8 Small sub-clinical erosions and mild
erythema were found in a patient on COX-2 inhibitors.
67

68
Chapter 6 Iatrogenic Diseases
M2A ®
Figure 6.9a NSAID stricture with active bleeding.
Figure 6.9c Microscopic examination showing
ulceration of stricture depicted in Fig. 6.9a (H&E).
Figure 6.9b Histology showing fibromuscular
hyperplasia of stricture depicted in Fig. 6.9a (H&E).
M2A ®
Figure 6.10a Minor erosion secondary to NSAID use.

Chapter 6 Iatrogenic Diseases
M2A ®
Figure 6.10b NSAID induced erosions. Patient was on
COX-2 inhibitors.
M2A ®
Figure 6.11a Radiotherapy induced stricture. Note
coffee grounds.
M2A ®
Figure 6.10c Mucosal erythema and edema secondary
to NSAIDs.
M2A ®
Figure 6.11b Radiotherapy induced stricture. Note
abnormal villous pattern.
69

70
Chapter 6 Iatrogenic Diseases
M2A ®
Figure 6.12a CE reveals edematous erythematous
mucosa with early neo-vascularization. This patient
underwent abdominal radiotherapy within the last 12
months.
M2A ®
Figure 6.12c Above patient showing active bleeding.
M2A ®
Figure 6.12b Same case as previous image.

Chapter 7
Vascular Abnormalities
Margit Hahne, M.D.
Jürgen F. Riemann, M.D.
INTRODUCTION
Vascular abnormalities in the small bowel have been
increasingly recognized as important causes of bleeding.
They may affect any section of the small bowel and in some
patients with hereditary conditions are associated with
vascular anomalies elsewhere, particularly in the skin. Terms
used to describe these lesions include telangiectasias,
phlebectasias, angioectasias and angiodysplasias or
arteriovenous malformations (AVMs).
Obscure bleeding typically refers to recurrent or persistent
iron deficiency anemia, positive FOBT, or visible bleeding
with no bleeding source found at original endoscopy (EGD
and colonoscopy). These cases pose difficult diagnostic
and management problems. They require numerous
transfusions, repeated hospital admissions and multiple
endoscopic procedures. Up to 25% of lower intestinal
bleeding causes remain undiagnosed after initial and
sometimes exhaustive investigation. The main problem is,
that not all parts of the small bowel can be reached by
conventional endoscopy and flat lesions like AVMs
angioectasia cannot be detected by radiological
examinations. Invasive intraoperative enteroscopy with its
risk for complications was the only possibility for total
visualization of the small bowel. Today, the M2A ® capsule
allows diagnostic exploration of the whole small intestine
with very low risk and high comfort for the patient.
CAPSULE EXPERIENCE
AVMs of the small bowel are lesions that occur with increasing
frequency secondary to aging. These lesions are presumed
to be degenerative in nature, secondary to either intermittent
obstruction of the submucosal veins or hypoxemia of the
microcirculation resulting from cardiac or pulmonary disease.
They can appear as small red spots, sometimes slightly
elevated. They may be large and flat or even spider like. In
contrast to congenital or neoplastic vascular lesions such as
hemangioma and arteriovenous malformations they are not
associated with dermal angiomas. The differential diagnoses
of AVMs of the GI tract should include post-radiation
telangiectasia and lesions of Hereditary Hemorrhagic
Telangiectasia and Osler-Weber-Rendu.
Small bowel AVMs are a source of significant morbidity from
bleeding and are the most common cause of obscure GI
bleeding, regardless of presentation (obscure-occult or
obscure-overt) or mode of investigation. They were identified
as the source of bleeding by push-enteroscopy in 8%-45%
by sonde enteroscopy in 7%-27% and by combination of both
73

74
Chapter 7
diagnostic tools in 31% of obscure bleeding cases. In large
studies involving intraoperative enteroscopy angiodysplasias
were identified in 34%-40% of patients.
We performed capsule endoscopy in 28 patients with obscureoccult
or obscure-overt bleeding and we found bleeding
sources in 72% of these patients. In 11 cases the capsule
found AVMs: one or multiple flat telangiectasias in 10 patients
and jejunal varices in one case. 7 patients showed sites of a
bleeding source, in these cases AVMs are also a probable
origin of bleeding. Many authors have reported on the
increased incidence of AVMs in patients with aortic stenosis
(Heyde-syndrome), renal failure, von Willebrand’s disease,
cirrhosis and pulmonary disease. Association with aortic
stenosis and decrease of bleeding after aortic valve
replacement is widely described, but because of
methodological flaws of these mostly retrospective studies
a clear relationship has not yet be confirmed. Three of our 10
patients with small bowel telangiectasias suffered from
additional aortic stenosis. Not all of the other associations
have been subjected to critical analysis, but available evidence
does not support a strong relationship in most instances.
Therapeutic options for vascular abnormalities of the GI tract
include interventional-endoscopic procedures like electro- or
lasercoagulation, argon plasma coagulation, sclerotherapy
and ligation. According to a recent multicenter, randomized
clinical trial hormonal replacement therapy does not seem to
be useful in the prevention of rebleeding from gastrointestinal
angiodysplasia.
Vascular abnormalities of the small bowel other than acquired
AVMs are rare. Some case reports describe phlebectasia or
varices of the small bowel, solitary jejunal or ileal vascular
abnormalities or jejunal Dieulafoy’s lesions as gastrointestinal
bleeding sources. In one of our younger patients (36 years
old) with recurrent obscure-overt bleeding capsule
examination could reveal a short part of the jejunum with
extensive varices. After successful surgery the patient did not
bleed any more.
Syndromes like Hereditary Hemorrhagic Telangiectasia (HHT),
von Willebrand’s disease, the Blue Rubber Bleb Nevus
Syndrome or Klippel-Trenaunay syndrome can be associated
with gastrointestinal vascular malformations. Hereditary
hemorrhagic telangiectasia is transmitted in an autosomal
dominant way and is characterized by multiple telangiectasias
of the skin, mucous membranes, extremities, lung and brain.
The prevalence of typical telangiectases throughout the
gastrointestinal tract is estimated to be about 15 to 44% of
persons affected with HHT. Intestinal bleeding occurs in 10
- 40% of these patients, mostly in the older patients with this
disorder. Epistaxis is found more frequently in the young.
CONCLUSION
Vascular Abnormalities
Vascular abnormalities are important causes of gastrointestinal
bleeding, especially obscure bleeding. The lesions can occur
throughout the whole intestine and can often not be reached
by conventional endoscopic examinations. In these cases
visualization of the total intestine as provided by the M2A ®
Capsule is a crucial addition to our diagnostic approach to
these cases.

Chapter 7
References and Suggested Readings
1 Zuckerman GR, Prakash C, Askin MP, Lewis BS. AGA technical review on the
evaluation and management of occult and obscure gastrointestinal bleeding.
Gastroenterology 2000;118:201-221.
2 Zuckerman GR, Prakash C. Acute lower intestinal bleeding. Part II; etiology,
therapy and outcomes. Gastrointest Endosc 1999;49:228-238
3 Boley SJ, Sprayregen S, Sammartano RJ, Adams A, Kleinhaus S.
The pathophysiologic basis for the angiographic signs of vascular ectasis
of the colon. Radiology 1977;125:615-621
4 Rogers BHG. Endoscopic diagnosis and therapy of mucosal vascular
abnormalities of the gastrointestinal tract occuring in elderly patients
and associated with cardiac, vascular and pulmonary disease.
Gastrointest Endosc 1980;26:134-138
5 Foutch PG, Sawyer R, Sanowski RA. Push-enteroscopy for diagnosis
of patients with gastrointestinal bleeding of obscure origin.
Gastrointest Endosc 1990;36:337-341
6 Landi B, Tkoub M, Gaudric M, Guimbaud R, Cervoni JP, Chaussade S, Couturier
D, Barbier JP, Cellier C. Diagnostic yield of push-type enteroscopy in relation
to indication. Gut 1998;42:421-425
7 Schmit A, Gay F, Adler M, Cremer M, van Gossum A. Diagnostic efficacy of
push-enteroscopy and long-term follow-up of patients with small bowel
angiodysplasias. Dig Dis Sci 1996;41:2348-2352
8 Lewis BS, Waye JD. Chronic gastrointestinal bleeding of obscure origin:
role of small bowel enteroscopy. Gastroenterology 1998;94:1117-1120
9 Berner JS, Mauer K, Lewis BS. Push and Sonde enteroscopy for the diagnosis
of obscure gastrointestinal bleeding. Am J Gastroenterol 1994;89:2139-
2142
10 Szold A, Katz LB, Lewis BS. Surgical approach to occult gastrointestinal
bleeding. Am J Surg 1992;163:90-92
11 Ress AM, Benacci JC, Sarr MG. Efficacy of intraoperative enteroscopy in
diagnosis and prevention of recurrent, occult gastrointestinal bleeding.
Am J Surg 1992;163:94-98
12 Imperiale TF, Ransohoff DF. Aortic stenosis, idiopathic gastrointestinal
bleeding and angiodysplasia: is there an association, Gastroenterology
1988;95:1670-1676
13 Sharma R, Gorbien MJ. Angiodysplasia and lower gastrointestinal tract
bleeding in elderly patients. Arch Intern Med 1995;155:807-812
14 Krevsky B. Detection and treatment of angiodysplasias. Gastrointest Endosc
Clin N Am 1997;7:509-524
Vascular Abnormalities
15 Junquera F, Feu F, Papo M, Videla S, Armengol JR, Bordas JM, Saperas E,
Piqué JM, Malagelada J-R. A multicenter, randomized, clinical trial of hormonal
therapy in the prevention of rebleeding from gastrointestinal angiodysplasia.
Gastroenterology 2001;121:1073-1079
16 Kumar P, Salcedo J, al-Kawas FH. Enteroscopic diagnosis of bleeding jejunal
phlebectasia: a case report and review of literature. Gastrointest Endosc
1997;46:185-7
17 Chen JJ, Changchien CS, Lin CC. Dieulafoy’s lesion of the jejunum.
Hepatogastroenterology 1999;46:1699-701
18 Saunders MP. A solitary jejunal vascular abnormality: a source of massive
rectal bleeding. Postgrad Med J 1991;67:683-6
19 Baba R, Hashimoto E, Yashiro K. Multiple abdominal telangiectases and
lymphangiectases. A limited form of Osler-Weber-Rendu disease, J Clin
Gastroenterol 1995;21:154-157
75

76
Chapter 7
M2A ®
Figure 7.1a Patient with phlebactasia. Work-up for
varices, including angiogram was negative.
M2A ®
Figure 7.1c Same case as above.
M2A ®
Figure 7.1b Phlebactasia of small intestine.
M2A ®
Figure 7.1d Additional view of same case.
Vascular Abnormalities

Chapter 7
M2A ®
Figure 7.2 74 year old female with severe
gastrointestinal bleeding. A repeat deep ileocolonoscopy
revealed the vascular malformation. It
was treated by argon plasma coagulation. No bleeding
episodes occurred in follow-up.
M2A ®
Figure 7.4a Arteriovenous malformation of jejunum
as a source of recurrent bleeding.
M2A ®
Vascular Abnormalities
Figure 7.3 36 year old male with lower gastrointestinal
bleeding and asplenia. Capsule endoscopy revealed
short jejunal segment with varices. Section was
successfully resected.
Figure 7.4b Histology of AVM (same case as 7.4a)
showing mucosal and submucosal dilated vessels with
fresh superficial bleeding (H&E).
77

78
Chapter 7
M2A ®
Figure 7.5a Duodenal angiodysplasia in 73 year old
male with recurrent massive bleeding.
M2A ®
Figure 7.6 Angiodysplasia of small intestine.
M2A ®
Vascular Abnormalities
Figure 7.5b Same case as Fig. 7.5a showing ileocecal
angiodysplasia at 6 o’clock.
M2A ®
Figure 7.7 Angiodysplasia of small bowel.

Chapter 7
M2A ®
Figure 7.8a Small angiodysplasia of jejunum.
M2A ®
Figure 7.9 Venous malformation in a patient with Blue
Rubber Bleb Nevus Syndrome.
Vascular Abnormalities
Figure 7.8b Histology of Fig. 7.8a revealing prominent
and congested vessels (PAS stain, 50 X).
M2A ®
Figure 7.10 Giant ileal angiodysplasias.
79

80
Chapter 7
M2A ®
Figure 7.11a Venous malformation in Blue Rubber
Bleb Nevus Syndrome.
M2A ®
Figure 7.12 Jejunal Dieulafoy’s lesion with active
bleeding.
M2A ®
M2A ®
Vascular Abnormalities
Figure 7.11b Venous malformation in Blue Rubber
Bleb Nevus Syndrome, same case.
Figure 7.13 Dilated and tortouous vein in a patient
with portal hypertension. This lesion may represent
an early stage of small bowel varices.

Chapter 8
Malabsorption
Gerard Gay, M.D.
Isaac Fassler, M.D.
Christian Florent, M.D.
Michel Delvaux, M.D.
INTRODUCTION
The clinical work-up of patients with intestinal malabsorption
needs a precise medical history and detailed physical
examination. In addition, laboratory tests for biochemistry,
hematology and immunology will provide the physician
with an initial diagnostic orientation. In most cases, this
initial set of tests will allow the choice of morphological
investigations that will firmly establish the diagnosis.
Gastroduodenoscopy with duodenal biopsies and now,
Capsule Endoscopy (CE) help in determining the cause of
malabsorption. The wireless endoscopic video capsule (Given
Imaging M2A ® , Yoqneam, Israel) allows a safe and complete
examination of the small bowel, not requiring
patient sedation.
CAPSULE EXPERIENCE
Available reports are mainly isolated clinical cases of patients
with intestinal diseases that are responsible for marked
malabsorption of nutrients.
PARTIAL (HYPOBETALIPOPROTEINEMIA) OR COMPLETE
(ABETALIPOPROTEINEMIA) DEFICIENCY IN ß-LIPOPROTEIN.
Hypobetalipoproteinemia (HBL) and abetalipoproteinemia
(ABL) are the consequence of various genetic disorders and
are characterized by low, almost undetectable plasma level
of Apo-B or Apo-B containing lipoproteins: chylomicrons, very
low density lipoproteins (VLDL) and light density lipoproteins
(LDL) and consequently, of triglycerides and cholesterol.
In ABL, the genetic defect affects the synthesis and secretion
of VLDL in the liver and of the chylomicrons in the intestine
due to the absence of microsomal triglyceride transfer protein
(MTP). In HBL, the disorder is caused by a mutation or deletion
of the apo-B gene, which produces a truncated Apo-B protein.
The biological and clinical pictures are similar to those in
abetalipoproteinemia. The diagnosis can be evoked in patients
with hypocholesterolemia. Endoscopic examination of the
small intestine shows a whitish or yellow discoloration of the
intestinal mucosa (Figures 8.1a, 8.1b, 8.1c). This aspect is
similar when observed with the wireless endoscopic capsule
and is characterized by a marked mucosal swelling that
involves the whole intestine (Figures 8.1d, 8.1e, 8.1f). The
advantage of the wireless capsule is that it investigates
83

84
Chapter 8
the ileum and does not need to be followed by retrograde
ileoscopy (Figures 8.1f, 8.1g).
CELIAC DISEASE
The diagnosis of celiac disease is usually based upon the
presence of villous atrophy on endoscopic duodenal biopsies.
The endoscopic pattern is characterized by a decrease in
height or a disappearance of Kerckring folds, the presence
of swollen mucosal folds, a mosaic pattern and a marked
vascular pattern (Figures 8.2a, 8.2b, 8.2c). Again, the wireless
endoscopic capsule will observe the same aspect (Figure
8.2d) and the precise extent of the lesions in the jejunum
(Figure 8.2e).
CHRONIC NON GRANULOMATOUS ULCERATIVE
JEJUNO-ILEITIS
Chronic non granulomatous ulcerative jejuno-ileitis was first
described by Jeffries as an idiopathic ulcerative sprue of
unknown origin. The condition might be a pre-lymphomatous
state like refractory sprue. The clinical picture is one of a
malabsorption syndrome, possibly associated with a proteinlosing
enteropathy. Its evolution is characterized by a high
mortality rate, more than 70 %, due to chronic bleeding,
intestinal perforation or obstruction. Gluten-free diet,
corticosteroids and other immunosuppressive medications
are usually ineffective. VPE shows a swollen inflammatory
pattern of the mucosa, ulcerations, and plaques of atrophic
mucosa (Figures 8.3a, 8.3b). Pathological examination of
intestinal biopsies is not specific and shows a thickened wall,
inflammatory infiltrate and variable mucosal atrophy but no
specific granuloma. The wireless endoscopic capsule shows
patterns similar as those described during PE (Figures 8.3c,
8.3d, 8.3e, 8.3f, 8.3g, 8.3h, 8.3i, 8.3j). As these conditions
may become pre-lymphomatous, as shown by
immunohistochemical and molecular biology studies,
patients will require repeated examinations for surveillance.
The capsule could make these repeated procedures less
invasive and thus, more acceptable to the patient.
Repeated investigations with the capsule could then allow
monitoring of the response to treatment in patients on
immunosuppressive therapy or specific diet, without repeating
PE (Figures 8.3k, 8.3l, 8.3m, 8.3n, 8.3o, 8.3p).
CONCLUSION
Malabsorption
Although it does not allow the collection of mucosal biopsies,
the wireless endoscopic M2A ® Capsule will play an important
role in the diagnostic strategy and follow-up of patients with
intestinal malabsorption. Advantages that need to be
evaluated in clinical trials include its ease of use, excellent
tolerance, and the possibility of investigation of the whole
small intestine. Presently one may outline two clinical
situations where Capsule Endoscopy is indicated: 1) in
malabsorptive disease patients with complex clinical
conditions like gastrointestinal manifestations of systemic
diseases involving the whole small bowel, 2) follow-up of
patients with celiac disease to exclude ulcerative jejunitis
and potential lymphoma. In any case, one should carefully
exclude an intestinal obstruction that might impede
progression of the capsule before it is used.

Chapter 8
References and Suggested Readings
1 RICEY SA, MARSH MN. Maldigestion and malabsorption in : Sleisenger MH,
Fordtran JS Eds. Gastrointestinal disease. Pathophysiology, diagnosis,
management, Philadelphia, WB Saunders 1998 : 1501-1522
2 GAY G, PENNAZIO M, DELMOTTE JS, ROSSINI FP. Push enteroscopy in Atlas
of enteroscopy, Eds FP Rossini, G Gay. Springer Verlag Milan 1998 : 51-55
3 SCOAZEC JG, BOUMA ME, ROCHE JF, BLACHE D, VERTHIER N, FELDMANN G,
GAY G. Liver fibrosis in a patient with familial homozygous
hypobetalipoproteinemia : possible role of vitamin supplementation.
Gut 1992 ; 32 : 414-417
4 WETTEREAU JR, AGGERBECK LP, BOUMA ME, EISENBERG C, MUNCK A,
HERMIER, SCHMITZ J, GAY G, RADER DJ, GREGG RE. Absence of microsomal
triglyceride transfer proteins in individuals with abetalipoproteinemia.
Science 1992 ; 258 : 99-101
5 GAY G, DELMOTTE JS. Abeta and hypobetalipoproteinemias in Atlas of
Enteroscopy. Eds FP ROSSINI, G. GAY. Springer Verlag Eds 1998 : 119-120
6 CORAZZA GR, DI STEPHANO M, PISTOIA MA. Celiac disease in Atlas of
enteroscopy, Eds FP Rossini, G Gay. Springer Verlag Milan 1998 : 93-96
7 DAUMS S, WEISS D, HUMMEL M, ULRICH R, HEISE W, STEIN H, RIECKEN E
O, FOSS HD and the intestinal lymphoma group. Frequency of clonal
intraepithelial T lymphocyte proliferations in enteropathy-type intestinal T
cell lymphoma, coeliac disease, and refractory sprue. Gut 2001 ; 49 : 804-812
Malabsorption
85

86
Chapter 8
Intestinal diseases and pathological conditions responsible for malabsorption
Lactose and other disaccharide intolerance
Specific intestinal infections
Giardiasis
HIV
Other immuno-deficiency syndromes
Lymphomas and IPSID
Abeta- and hypobetalipoproteinemias
Mastocytosis
Whipple's disease
Eosinophilic enteropathy
Crohn's disease
Waldenstrom's disease
Amyloidosis
Malabsorption

Chapter 8
Endoscopic management of patients with intestinal malabsorption
Abnormal
Specific treatment
Suspected intestinal disease
e.g. celiac disease
EGD + Duodenal Biopsies
Abnormal
Push video enteroscopy +
duodenal and jejunal biopsies
if jejunal lesions
Inconclusive
Malabsorption
Inconclusive
Repeat examinations ?
87

88
Chapter 8
Figure 8.1a Yellow and snowy jejunal mucosa
and blood acanthocytosis in a patient with
Hypobetalipoproteinemia.
Figure 8.1c Yellow and snowy ileal mucosa in same
patient.
Figure 8.1b Yellow and snowy jejunal mucosa without
atrophic area in same patient.
M2A ®
Malabsorption
Figure 8.1d CE shows yellow and snowy mucosa with
lymphatic stasis without atrophic area of the duodenal
and jejunal mucosa in this same patient.

Chapter 8
M2A ® M2A ®
Figure 8.1e CE reveals yellow and snowy mucosa with
lymphatic stasis without atrophic area of the duodenal
and jejunal mucosa in same patient.
M2A ®
Figure 8.1g Additional view of same case.
Malabsorption
Figure 8.1f CE reveals yellow and snowy mucosa with
lymphatic stasis without atrophic area of the ileal
mucosa in same patient.
Figure 8.2a Enteroscopy reveals scalloped folds,
atrophic area, mosaic pattern in the duodenum and
jejunum in patient with celiac disease.
89

90
Chapter 8
Figure 8.2b Enteroscopy reveals scalloped folds,
atrophic area, mosaic pattern in the duodenum and
jejunum in same patient.
M2A ® M2A ®
Figure 8.2d CE reveals scalloped folds, atrophic area,
mosaic pattern in the duodenum in this patient.
Figure 8.2c Close-up of same diagnosis as in Fig. 8.2b.
Figure 8.2e Same diagnosis as Fig. 8.2d.
Malabsorption

Chapter 8
Figure 8.3a Enteroscopy performed reveals
pathological aspect before treatment: ulcers, lymphatic
stasis, and atrophic area in a patient with Chronic Non
Granulomatous Ulcerative Jejuno-ileitis.
M2A ® M2A ®
Figure 8.3c CE reveals same aspect as PE before
treatment along the jejunum but also along the length
of the ileum.
Figure 8.3b Enteroscopy in same patient as in previous
figure.
Figure 8.3d CE reveals same diagnosis as in previous
image.
Malabsorption
91

92
Chapter 8
M2A ® M2A ®
Figure 8.3e CE reveals same aspect as PE before
treatment along the jejunum but also along the length
of the ileum.
M2A ® M2A ®
Figure 8.3g Note presence of small bowel diverticula
and telangiectasia, same case.
Figure 8.3f Chronic Non Granulomatous Ulcerative
Jejuno-ileitis, same case.
Figure 8.3h Additional view of same case.
Malabsorption

Chapter 8
M2A ® M2A ®
Figure 8.3i CE reveals same aspect as PE before
treatment.
Figure 8.3k Enteroscopy performed shows normal
aspect of the jejunum after treatment.
Figure 8.3j Different view of same case.
Malabsorption
Figure 8.3l Additional view of enteroscopy performed
in same patient.
93

94
Chapter 8
M2A ®
Figure 8.3m CE post-therapy reveals persistance of
lesions as ulcers, atrophic area with no bleeding.
No lymphatic stasis along the jejunum and the ileum
is seen.
M2A ®
Figure 8.3o Additional view of same case.
M2A ®
Figure 8.3n Additional view of same case.
M2A ®
Figure 8.3p Additional view of same case.
Malabsorption

Chapter 8
M2A ®
Figure 8.4a Celiac sprue with active jejunal bleeding.
Note AVM at 4 o’clock.
M2A ®
Figure 8.4c Villous atrophy, same case as Fig. 8.4a.
Note AVM at 6 o’clock.
M2A ®
Figure 8.4b Note AVM at 5 o’clock, same case as
previous Fig. 8.4a.
M2A ®
Figure 8.5 Primary lymphangiectasia of GI tract with
poor villous formation and disarray.
Malabsorption
95

96
Chapter 8
M2A ®
Figure 8.6a Eosinophilic enteritis in a 32 year old
female with asthma, iron deficiency, anaemia and
hypoproteinaemia. Patient has eosinophilia in peripheral
blood and positive anti nuclear antibodies. No diarrhea.
M2A ®
Figure 8.6c Eosinophilic enteritis. Note thickened
infiltrated folds, same case as in Fig. 8.6a.
M2A ®
Malabsorption
Figure 8.6b Eosinophilic enteritis. Note thickened
infiltrated folds, same case as in Fig. 8.6a.
M2A ®
Figure 8.6d Eosinophilic enteritis. Note thickened
infiltrated folds, same case as in Fig. 8.6a.

Chapter 8
Figure 8.6e Histological overview of jejunal mucosa
with prominent lymphofollicular hyperplasia. (x10,
H&E), same case.
Figure 8.6g Tip of the villi of jejunum showing discrete
eosinophilic infiltration in lamina propria consistent
with eosinophilic enteritis (x500, H&E), same case.
Malabsorption
Figure 8.6f Higher magnification of the base of the
crypts of the jejunum with Paneth cells, lymphoid cells
and eosinophils (x500, H&E), same case.
M2A ®
Figure 8.7a 70 year old male, transfusion dependent GI bleeding.
Was given oral steroids, bleeding ceased. Histology from biopsy
was compatible with celiac disease. Villous atrophy of jejunum.
97

98
Chapter 8
M2A ®
Figure 8.7b Diffuse bleeding was observed during
capsule endoscopy procedure, same case.
M2A ®
Figure 8.7d Note lymphangiectasia, same case.
M2A ®
Malabsorption
Figure 8.7c Distally in ileum villi reappear slowly,
same case.
Figure 8.7e Histologic view of atrophic villi. Note the
hypertrophic crypts, the “normal¢ basal membrane and
the dense lymphoid cell infiltrate. (Reticulin stain, x50).

Chapter 8
Figure 8.7f Higher magnification. Hyperplastic crypts
and dense lymphoid infiltrate (Reticulin, x500),
same case.
Figure 8.7h Sprue-like picture with hyperplastic crypts,
lymphoid cellular infiltrate (PAS stain, x500),
same case.
Malabsorption
Figure 8.7g Microscopic overview showing villous
atrophy, hypertrophic crypts and lymphoid infiltrate
(PAS stain, x100), same case.
Figure 8.7i Sprue-like picture with hyperplastic crypts,
lymphoid cellular infiltrate in lamina propria (PAS stain,
x500), same case.
99

100
Chapter 8
M2A ®
Figure 8.8a 42 year old male with primary amyloidosis
(Light chain Type) of GI tract. Note thickened infiltrated
folds with poor villous formation.
M2A ®
Figure 8.8c Thickened infiltrated folds with erythema
and early mucosal breakdown, same case.
M2A ®
Malabsorption
Figure 8.8b Infiltration of the GI tract with ulceration,
same case.
M2A ®
Figure 8.8d Small erosion seen in same case.

Chapter 8
M2A ®
Figure 8.9a 38 year old female with AIDS and chronic
diarrhea. M2A ® Capsule examination reveals significantly
thickened infiltrated folds with villous blunting.
Malabsorption
Figure 8.9b UGI series of small bowel follow through
of same case showing thickened small bowel folds and
erosions.
101

Chapter 9
Pediatrics
Ernest Seidman, M.D.
Gian L. de’ Angelis, M.D.
Ana Maria Sant Anna, M.D.
INTRODUCTION
Since its introduction over four decades ago, flexible fiberoptic
endoscopy has become an indispensable tool for the diagnosis
of a wide variety of gastrointestinal disorders in children, as
in adults. In addition to enabling direct visualization of much
of the gastrointestinal tract, endoscopic procedures afford
biopsy sampling of lesions. As well, endoscopy can be used
therapeutically to localize and treat bleeding, dilate strictures,
and to remove polyps. Despite advances in other imaging
techniques, endoscopy remains the most cost-effective
strategy to determine the type, extent and severity of
inflammatory bowel disease, particularly for colitis. A major
limitation of current endoscopic procedures is the inability to
evaluate small bowel disorders beyond the range of currently
available endoscopes. Experience with enteroscopy or small
bowel endoscopy has been limited in children. This technique
requires a large overtube (15mm), limiting its applicability in
the pediatric age group. Intraoperative enteroscopy is an
alternative technique, albeit much more invasive. Although
the entire small bowel can be visualized, this approach
necessitates abdominal laparotomy or laparoscopy.
The recent development of wireless video endoscopy using
a capsule provides the opportunity to evaluate the entire
small bowel in a completely non-invasive manner.
CAPSULE EXPERIENCE
The first study to examine the diagnostic value of the video
capsule in comparison with other imaging techniques in
children with obscure small bowel disease is currently
underway in our Montreal center.
Pediatric patients (more than 10 years of age) suspected of
having small bowel disorders were included in the study
in one of the following study groups: a) occult GI
bleeding/vascular malformations, b) polyposis, c) obscure
Crohn's disease. The first group was evaluated using
abdominal arteriography as the "gold standard" examination.
The second group was evaluated either with a barium
small bowel follow through and colonoscopy/gastroscopy.
The third group consisted of patients clinically suspected,
but not confirmed to have Crohn's disease. They had all been
investigated with barium small bowel follow through
and colonoscopy/gastroscopy before the capsule procedure,
without a confirmed diagnosis. Strictures of the bowel
were first excluded in view of their potential to preclude
passage of the capsule. The investigators reviewing the video
capsule results were blinded to the patients' case records or
imaging results.
103

104
Chapter 9
Our preliminary data includes evaluations on 14 patients
between 10 and 16 years. Among the group with occult
bleeding, the capsule exam confirmed a diagnosis of
arteriovenous malformations in two cases. The one remaining
case stopped bleeding spontaneously, and no diagnosis was
made with any modality of investigation. Among the three
with polyposis disorders, the video capsule confirmed the
presence of small bowel polyps in all cases. Among the eight
patients suspected to have Crohn's disease, the diagnosis
was confirmed with the video capsule in five. The exam was
negative in one other case with a functional bowel disorder.
Among the two others, one was ultimately diagnosed with an
eosinophilic gastroenteropathy. The capsule revealed edema
and erythema of the small bowel mucosa, with pit-like lesions.
In the one remaining case with a history of perianal abscess
two years ago, no evidence of small bowel Crohn's disease
was found.
All the video capsule studies (M2A ® ) were well tolerated,
without any adverse events. All patients were able to resume
their usual activities during the examination.
The results of this preliminary study confirm the high diagnostic
accuracy of this extraordinary, novel diagnostic technique.
Moreover this non-invasive exam was well tolerated in all
cases. The children were able to return to school during the
exam. This imaging procedure is likely to become one of the
initial diagnostic procedures to be carried out where small
bowel pathologies are suspected, but not otherwise
documented.
CONCLUSION
References and Suggested Readings
Pediatrics
Wireless capsule endoscopy appears to permit a more accurate
and non-invasive approach for diagnosing occult lesions in
the small bowel distal to duodenum in children.
1 Seidman EG. Role of endoscopy in inflammatory bowel disease.
Gastrointest Endosc N Am 2001; 11: 641-57.
2 Deutsch DE, Olson AD. Colonoscopy or sigmoidoscopy as the initial evaluation
of pediatric patients with colitis: a survey of physician behavior and a cost
analysis. J Pediatr Gastroenterol Nutr 1997; 25: 26-31.
3 Lewis BS. Enteroscopy. Gastrointest Endosc Clin N Am 2000; 10: 101-16.
4 Mackenzie JF. Push enteroscopy. Gastrointest Endosc Clin N Am 1999; 9:
29-36.
5 Seidman E. Wireless Capsule Video-endoscopy: An Odyssey Beyond the
End of The Scope. J Pediatr Gastroenterol Nutr 2002; 34: 333-4.

Chapter 9
M2A ® M2A ®
Figure 9.1a Celiac disease in the descending duodenum
of a 10 year old girl.
M2A ® M2A ®
Figure 9.1c Ileum in this 10 year old girl. The villi are
present but blunted, same case.
Figure 9.1b Jejunum in this patient begins to show
recovery of villi.
Figure 9.1d Suspected intestinal duplication in the
jejunum of a 10 year old girl, same case.
Pediatrics
105

106
Chapter 9
M2A ® M2A ®
Figure 9.2a Capsule endoscopy reveals gastric fundic
polyps in a 9 year old child with Peutz-Jegher’s.
M2A ® M2A ®
Figure 9.2c Small hamartomatous polyp in ileum in
patient with Peutz-Jegher’s.
Figure 9.2b Same patient with PJ. Note gastric fundic
polyps.
Figure 9.2d Multiple small hamartomatous polyps in
proximal ileum in same patient with Peutz-Jegher’s.
Pediatrics

Chapter 9
M2A ® M2A ®
Figure 9.2e Hamartomatous polyps in Peutz-Jegher’s. Figure 9.2f Large hamartomatous polyp in mid-ileum
in patient with Peutz-Jegher’s.
M2A ® M2A ®
Figure 9.3a 15 year old male with FAP post colectomy.
Underwent CE for surveillance. Images show nodularity
of bulbar mucosa.
Figure 9.3b Same case as 9.3a. Adenomatous polyps
are seen in the mid ileum.
Pediatrics
107

108
Chapter 9
M2A ®
Figure 9.4a 11 year old girl, frequent episodes of melena.
Required repeated transfusions and previous surgery. Capsule
endoscopy diagnosed vascular malformation observed in
the terminal ileum. This is a normal area in this patient.
M2A ®
Figure 9.5a 14 year old male with 8 months of chronic abdominal
pain and negative evaluation. Capsule endoscopy reveals triangular
ulcer in mid jejunum consistent with Crohn’s disease.
M2A ®
Figure 9.4b Note abnormal venous pattern in the
terminal ileum of this same patient.
M2A ®
Figure 9.5b Same patient as in Figure 9.5a. A collar
button ulcer in mid small bowel is present at 4 o’clock.
Pediatrics

Chapter 10
Transplantation
Roberto de Franchis, M.D.
Emanuele Rondonotti, M.D.
Carla Abbiati, M.D.
Gizela Beccari, M.D.
Erica Villa, M.D.
Alberto Merighi, M.D.
Antonio Pinna, M.D.
INTRODUCTION
Small bowel transplantation (SBTx) has recently become a
clinical reality, owing to major progress in harvesting and
preservation procedures, surgical techniques and
immunosuppression. However, major immunological or
infectious complications still continue to pose threatening
problems in SBTx recipients. As a consequence, post-operative
monitoring and management of these patients require a very
aggressive and multidisciplinary approach. In particular, postoperative
monitoring is crucial for the early detection of posttransplant
complications and for the assessment of the graft's
anatomical and functional integrity. In this setting, intestinal
graft enteroscopy plays a key role. The indications for
enteroscopy in SBTx recipients are routine surveillance, and
the onset of clinical symptoms or physical signs suggestive
of the occurrence of major complications. Routine surveillance
enteroscopies are done twice a week for the first month after
SBTx, once a week for the next 2 months, monthly for the
next 3 months and every 3-6 months thereafter.
Standard trans-stomal terminal ileoscopy or jejunoscopy
performed in SBTx recipients are invasive, and may be unsafe
in frail patients. In addition, they allow only incomplete
exploration of the transplanted graft, which may be
unsatisfactory, since the distribution of the immunological or
infectious lesions is often patchy or segmental. The
swallowable M2A ® endoscopic capsule developed by Given ® ,
allows noninvasive examination of the entire small bowel.
The technique has been proven to be safe and extremely well
tolerated by the patients. In this chapter, we present the first
images obtained by preliminary experience with the use of
the Given ® capsule endoscope in SBTx recipients.
CAPSULE EXPERIENCE
Five patients who underwent isolated small bowel transplant
or multivisceral transplant between December, 2000 and
September, 2001 were studied at various intervals post
111

112
Chapter 10
transplant. Indications for SB transplantation were: intestinal
pseudo-obstruction, post-surgical short bowel syndrome and
radiation enteritis. All patients had both ileostomy and natural
canalization and were on immunosuppressive, antibiotic and
antimycotic drugs.
Ileoscopy is poorly tolerated in these patients, as they
complain of bloating and discomfort. The capsule is swallowed
easily and passed naturally in all patients without adverse
events. Standard ileoscopy revealed that the ileal mucosa
was normal in all patients. Ileal histology showed mild
inflammatory infiltrate and edema in the lamina propria in all
cases. Using capsule endoscopy, it was demonstrated that
the mucosa in the ileal segments reached by ileoscopy was
normal. However, mucosal changes were observed in more
proximal segments in 3 of the 4 patients in whom capsule
enteroscopy yielded small bowel images. These changes
were: diffuse blunted or ridge-shaped villi and isolated
hyperemic spots in a patient examined 20 days after
transplantation (Figure 10.1a); small areas with blunted and
ridge-shaped villi and isolated petechiae (Figure 10.2a, 10.2b)
in a patient examined at 6 weeks; diffuse blunted edematous
villi and isolated small erosions in a patient examined at 2
months. In the fourth patient, studied 6 months after small
bowel transplantation, normal well-shaped long villi were
observed (Figure 10.5a).
CONCLUSION
Capsule enteroscopy is better tolerated than retrograde
ileoscopy, and allows a complete examination of the
transplanted small bowel. Proximal mucosal changes missed
by retrograde ileoscopy were identified in 3/4 patients.
Whether these findings seen at different time intervals after
Transplantation
transplantation represent the normal evolution of the graft
over time, or were early signs of immunological or infectious
complications, or represent the normal evolution of the graft
is unknown. Owing to its excellent tolerability, capsule
enteroscopy could become the first step in the endoscopic
monitoring of patients after SBTx. Standard ileoscopy
with biopsy could be reserved for further assessment
in the patients in whom mucosal lesions are identified by
capsule enteroscopy.
References and Suggested Readings
1 Hassainen T, Schade RR, Soldevilla-Pico C, Tabasco-Minguillan J, Abu-Elmagd
K, Furukawa K, Kadry Z, Demetris A, Tzakis A, Todo S. Endoscopy Is Essential
for Early Detection of Rejection in Small Bowel Transplant Recipients.
Transplantation Proceedings 1994;26:1414-15
2 Scotti-Foglieni T, Tinozzi SD, Abu-Elmagd K, Starzl TE. Enteroscopy of the
transplanted small bowel. In Rossini FP, Gay G (editors) Atlas of Enteroscopy.
Springer, Milan, 1998:151-169
3 Meron G The development of the swallowable video-capsule (M2A ® ).
Gastrointestinal Endoscopy 2000;52:817-819
4 Lewis BS, Swain P Capsule endoscopy in the evaluation of patients with
suspected small intestinal bleeding: the results of the first clinical trial.
Gastrointestinal Endoscopy 2001;53:AB70
5 Pennazio M, Santucci R, Rondonotti E, Abbiati C, Beccari G, Luchetti R, Dezi
A, Capurso L, de Franchis R, Rossini FP. Wireless capsule endoscopy in
patients with obscure gastrointestinal bleeding: preliminary results of the
Italian multicentre experience. Digest Liver Dis. 2001;33 (Suppl. 1): A2

Chapter 10
M2A ®
Figure 10.1a 20 days post-transplant.
Blunted and ridge-shaped whitish villi and hyperemic
spot in a patient examined 20 days after transplantation.
Figure 10.1c Histology 20 days post-transplant.
Normal ileal mucosa (H&E).
M2A ®
Figure 10.1b 20 days post-transplant.
Same patient as Figure 10.1a.
M2A ®
Transplantation
Figure 10.2a 46 days post-transplant.
Blunted villi in a patient examined at 6 weeks after
transplantation.
113

114
Chapter 10
M2A ®
Figure 10.2b 46 days post-transplant.
Same patient as figure 10.2a.
M2A ®
Figure 10.2d 46 days post-transplant.
Villous architecture more preserved here, same patient
as before.
M2A ®
Figure 10.2c 46 days post-transplant.
Same patient as previous figure.
M2A ®
Figure 10.2e 2 months post-transplant.
Normal distal ileum.
Transplantation

Chapter 10
M2A ®
Figure 10.3a 64 days post-transplant.
Slight villous blunting with ulcer at 8 o’clock.
M2A ®
Figure 10.4a 183 days post-transplant.
Normal villi in a patient examined 6 months after small
bowel transplantation.
M2A ®
M2A ®
Figure 10.4b 183 days post-transplant.
Normal small bowel with two small areas of
lymphangiectasia.
Transplantation
Figure 10.3b 64 days post-transplant.
This segment shows erythema and edematous club
shaped blunted villi. The patient was asymptomatic.
115

116
Chapter 10
M2A ®
Figure 10.4c 183 days post-transplant.
Normal appearing small bowel.
M2A ®
Figure 10.5a 192 days post-transplant.
Normal appearing small bowel.
M2A ®
Figure 10.4d 183 days post-transplant.
Normal appearing small bowel.
M2A ®
Figure 10.5b 192 days post-transplant.
Normal appearing small bowel.
Transplantation

Chapter 11
Non Small Bowel Pathology
Samuel Adler, M.D.
Steven Kadish, M.D.
INTRODUCTION
Capsule Endoscopy has revolutionized the gastroenterologist's
ability to diagnose and treat small bowel disease. However,
it has become apparent that in the process of performing
small bowel capsule endoscopy, high quality, clinically
meaningful images can be recorded from the esophagus,
stomach and colon as well. It is important for
gastroenterologists to recognize these abnormalities as they
may have implications in the treatment of their patients. In
this chapter, we highlight some of the findings outside the
limits of the small bowel that may be encountered in the
course of Capsule Endoscopy.
CAPSULE EXPERIENCE
As the capsule is swallowed, it rapidly enters the esophagus.
The striated muscle of the proximal esophagus contracts and
rapidly propels the capsule to the mid and distal part of the
esophagus. For this reason with the present design of the
video capsule, one can expect to see just a few images of the
distal esophagus. However the capsule may at times be
significantly delayed in the distal esophagus allowing a number
of clear images of the distal esophagus and of the z-line. In
these cases, findings of esophagitis are readily identified.
Just prior to swallowing the capsule, the patient should be
asked to drink a glass of water slowly with repeated swallows
to clear the distal esophagus from accumulated saliva.
The capsule transmits images from the stomach before it
traverses the pylorus into the small bowel. Presently it is
difficult to visualize the fundus with adequate reliability.
Nevertheless, the gastroenterologist should remain alert
to the possibility of pathology in the fundus and body of
the stomach as that area of the RAPID video is scanned.
The capsule is far more trustworthy in reference to pathology
in the distal body, antrum and pylorus. It is noteworthy that
the acquisition of images with the stomach in its normal
physiologic state (i.e., not altered by the insufflation of air
that occurs during endoscopy) may allow for resolution
and reproduction of mucosal detail that is superior to the
images obtained by standard commercial endoscopes.
It is therefore not surprising that cases of occult GI bleeding
were identified as actively bleeding lesions on capsule
endoscopy whereas they were missed on conventional
endoscopy. One frequently observes gastric mucosal detail
such as the areae gastricae. The ability to observe the area
gastricae likely corresponds to a six to eight fold magnification.
Minute focal erythema, mini erosions and even early atrophic
gastritis have been identified on capsule endoscopy and
missed on video endoscopy .
119

120
Chapter 11
CONCLUSION
During the course of small bowel capsule endoscopy,
gastroenterologists may be provided with important diagnostic
information in areas outside the small bowel. The RAPID
viewer should scan the area of the GI tract outside the small
bowel and report any abnormal findings.
Non Small Bowel Pathology

Chapter 11
M2A ®
Figure 11.1 Distal esophagitis seen as capsule passes
through.
M2A ®
Figure 11.3a Low-grade-malt lymphoma, confined to
stomach.
M2A ®
Non Small Bowel Pathology
Figure 11.2 CE revealed Watermelon stomach in a
patient with chronic bleeding.
Figure 11.3b Gastroscopy in a patient with low-grademalt
lymphoma, confined to stomach, same case.
121

122
Chapter 11
M2A ®
Figure 11.4a Kaposi’s sarcoma of the stomach in an
HIV positive patient.
M2A ®
Figure 11.5 Capsule endoscopy in a patient with GI
bleeding of unknown etiology, Cameron’s lesion seen
in a hiatal hernia.
M2A ®
Figure 11.4b Same case as before.
M2A ®
Non Small Bowel Pathology
Figure 11.6 Mild atrophic changes of gastric folds.

Chapter 11
M2A ®
Figure 11.7a Colon polyp seen as capsule passes
through cecum.
M2A ®
Figure 11.8 Appearance of stomach mucosa after
biopsy was taken.
Non Small Bowel Pathology
Figure 11.7b Colon polyp. After the patient underwent
prep and colonoscopy, the polyp was confirmed.
123

Contributors
Carla Abbiati, M.D.
University of Milan and IRCCS
Ospedale Maggiore Policlinico
Milan, Italy
Samuel Adler, M.D.
Bikur Cholim Hospital
Jerusalem, Israel
Mark Appleyard, M.D.
Royal Brisbane Hopital
Herston, Queensland, Australia
Jeffrey P. Baker, M.D.
St. Michael's Hospital
Toronto, ON, Canada
Jamie Barkin, M.D.
University of Miami
Mount Sinai Medical Center
Miami, Florida, USA
Gizela Beccari, M.D.
University of Milan and IRCCS
Ospedale Maggiore Policlinico
Milan, Italy
Brett Bernstein, M.D.
Beth Israel Medical Center
New York, NY USA
Luigi Berreta, M.D.
Ospedaliera S.Gerardo
Monza , Italy
Faisal Bhinder, M.D.
St Elizabeth s Medical Center
Boston, MA , USA
Edmund Bini, M.D.
NYU Medical Center
New York, NY, USA
Alain Bitoun, M.D.
CHU Paris
Paris, France
Peter D. Bloom, M.D.
University School of Medicine &
Atlanta Veterans Admin. Med. Ctr.
Atlanta, GA, USA
Alan L. Buchman, M.D.
Northwestern University
Chicago, IL, USA
Carol A. Burke, M.D.
The Cleveland Clinic Foundation
Cleveland, OH, USA
Marcus J. Burnstein, M.D.
St. Michael's Hospital
Toronto, ON, Canada
Lucio Capurso, M.D.
S. Filippo Neri Hospital
Rome, Italy
Angel Caunedo, M.D.
Virgen Macarena University Hospital
Seville, Spain
David R. Cave, M.D.
St. Elizabeth’s Medical Center
Boston, MA , USA
Rhonda Cole, M.D.
Veterans Affairs Medical Center
Houston, Texas, USA
Felice Consentino, M.D.
S. Paolo Hospital
Milan, Italy
Guido Costamagna, M.D.
Catholic University of Rome
Rome, Italy
Ingrid Davies, R.N.
South Shore Gastroenterology PC &
South Nassau Communities Hospital
Oceanside, NY , USA
Gian L. de’Angelis, M.D.
Instituto Di Clinica Pediatrica
Parma, Italy
Roberto De Franchis, M.D.
University of Milan and IRCCS
Ospedale Maggiore Policlinico
Milan, Italy
125

126
Contributors (continued)
Michel Delvaux, M.D.
CHU Nancy
Nancy, France
Ingrid Demedts, M.D.
University Hospital of Gasthuisberg
Leuven, Belgium
Jacques Deviere, M.D.
Hopital Erasme
Brussels, Belgium
Angelo Dezi, M.D.
S. Filippo Neri Hospital
Rome, Italy
Elena Dubcenco, M.D.
St. Michael's Hospital
Toronto, ON, Canada
Jose Dubois, M.D.
Ste Justine Hospital
University of Montreal
Montreal, Canada
Gareth Dulai, M.D.
CURE VA
Greater L.A. Health Care System
Los Angeles, CA, USA
Frank Duperier, M.D.
The Cleveland Clinic Foundation
Cleveland, OH, USA
Rami Eliakim, M.D.
Rambam Medical Center
Haifa, Israel
Christian Ell, M.D.
HSK
Wiesbaden, Germany
Douglas Faigel, M.D.
Portland VA Medical Center
Portland, WA, USA
Kent Farris, M.D.
Gastrointestinal Assoc.
Knoxville, TN, USA
Isaac Fassler, M.D.
CHU Nancy
Nancy, France
Jay Fenster, M.D.
South Shore Gastroenterology
Center Cedarhurst
Cedarhurst, NY,USA
Pedro Figueiredo, M.D.
University Hospital of Coimbra
Coimbra, Portugal
Zvi Fireman, M.D.
Hillel-Yaffe Medical Center
Hadera, Israel
Babak Firoozi, M.D.
NYU Medical Center
New York, NY, USA
Doron Fischer, M.D.
Rambam Medical Center
Haifa, Israel
David Fleischer, M.D.
Mayo Clinic Scottsdale
Scottsdale, Arizona, USA
Christian Florent, M.D.
CHU Paris
Paris, France
Frans T. Fork, M.D.
Malmô University Hospital
Malmô, Sweden
Francesca Foschia, M.D.
Catholic University of Rome
Rome, Italy
Erik Francois, M.D.
Hopital Erasme
Brussels, Belgium
Diniz Freitas, M.D.
University Hospital of Coimbra
Coimbra, Portugal

128
Contributors (continued)
Sandor Joffe, M.D.
Beth Israel Medical Center
New York, NY, USA
Enrico Jovine, M.D.
University of Modena
and Regio Emilia
Modena, Italy
Renee Jovine, M.D.
St. Elizabeth’s Medical Center
Boston, MA , USA
Steven Kadish, M.D.
South Shore Gastroenterology PC &
South Nassau Communities Hospital
Oceanside, NY, USA
Dalia Katz, M.D.
Rambam Medical Center
Haifa, Israel
Martin Keuchel, M.D.
Medizinische Abteilung
Allgemeines Krankenhaus Altona
Hamburg, Germany
Devon Klein, M.D.
Beth Israel Medical Center
New York, NY, USA
Yehudith Kraizer, Ph.D.
Given Imaging Ltd.
Yoqneam, Israel
Jonathan A. Leighton, M.D.
Mayo Clinic Scottsdale
Scottsdale, Arizona, USA
Gavin Levinthal, M.D.
The Cleveland Clinic Foundation
Cleveland, OH, USA
Blair S. Lewis, M.D.
Mt. Sinai Hospital
New York, NY, USA
Shlomo Lewkowicz, D.Sc.
Given Imaging Ltd.
Yoqneam, Israel
David Lieberman, M.D.
Portland VA Medical Center
Portland, Oregon, USA
Ramona Lim, M.D.
University of Miami
Mount Sinai Medical Center
Miami, Florida, USA
Roberto Luchetti, M.D.
S. Filippo Neri Hospital
Rome, Italy
Pasquale Marano, M.D.
Catholic University of Rome
Rome, Italy
Andrea May, M.D.
HSK
Wiesbaden, Germany
Alberto Merighi, M.D.
University of Modena
and Reggio Emilia
Modena, Italy
Gavriel Meron, Ph.D.
Given Imaging Ltd.
Yoqneam, Israel
Marie Claude Miron, M.D.
Ste Justine Hospital
University of Montreal
Montreal, Canada
Roger Mitty, M.D.
St. Elizabeth’s Medical Center
Boston, MA , USA
Danette Musil, M.D.
Mayo Clinic Scottsdale
Scottsdale, Arizona, USA
Massimiliano Mutignani, M.D.
Catholic University of Rome
Rome, Italy
Colm O’ Loughlin, M.D.
University of Miami
Mount Sinai Medical Center
Miami, Florida, USA

Contributors (continued)
Antone R. Opekun, M.D.
Baylor College of Medicine
Houston, Texas, USA
Guillermo Payeras, M.D.
Hospital del Aire
Madrid, Spain
Francisco J. Pellicer, M.D.
Virgen Macarena University Hospital
Seville, Spain
Marco Pennazio, M.D.
S.Giovanni A.S. Hospital
Turin, Italy
Vincenzo Perri, M.D.
Catholic University of Rome
Rome, Italy
Rima Petroniene, M.D.
St. Michael's Hospital
Toronto, ON, Canada
Antonio Pinna, M.D.
University of Modena
and Regio Emilia
Modena, Italy
Javier P. Piqueras, M.D.
Hospital del Aire
Madrid, Spain
Thierry Ponchon, M.D.
CHU Lyon
Lyon, France
Massimo Primignani, M.D.
University of Milan and IRCCS
Ospedale Maggiore Policlinico
Milan, Italy
Marlene Rackson , M.D.
Beth Israel Medical Center
New York, NY, USA
Stefanie Remke, M.D.
HSK
Wiesbaden, Germany
Maria Elena Riccioni, M.D.
Catholic University of Rome
Rome, Italy
Jürgen F. Riemann, M.D.
Klinikum Ludwigshasen
Ludwigshasen, Germany
Jean-Francois Roche, M.D.
CHG Verdun
Verdun, France
Manuel Rodriguez-Tellez, M.D.
Virgen Macarena University Hospital
Seville, Spain
Rafael Romero, M.D.
Virgen Macarena University Hospital
Seville, Spain
Emanuele Rondonotti, M.D.
University of Milan and IRCCS
Ospedale Maggiore Policlinico
Milan, Italy
Marc Rosenberg, M.D.
University School of Medicine &
Atlanta Veterans Admin. Med. Ctr.
Atlanta, GA, USA
Steven Rosenblatt, M.D.
The Cleveland Clinic Foundation
Cleveland, OH, USA
Francesco P. Rossini, M.D.
S.Giovanni AS Hospital
Turin, Italy
Paul Rutgeerts, M.D.
KU. Leuven
Leuven, Belgium
Manuel Jimenez-Saenz, M.D.
Virgen Macarena University Hospital
Seville, Spain
Miguel A. Saez, M.D.
Hospital del Aire
Madrid, Spain
129

130
Contributors (continued)
Ana Sant Anna, M.D.
Ste Justine Hospital
University of Montreal
Montreal, Canada
Janice M. Santisi, R.N.
The Cleveland Clinic Foundation
Cleveland, OH, USA
Renato Santucci, M.D.
S.Giovanni A.S. Hospital
Turin, Italy
Shigeru Sato, M.D.
Fukuoka University
Fukuoka, Japan
Jean-Christophe Saurin, M.D.
CHU Lyon
Lyon, France
Eitan Scapa, M.D.
Assaf-Harofe Medical Center
Zrifin, Israel
Wolff Schmiegel, M.D.
Knappschaftskrankenhaus Bochum
Ruhr-University
Bochum, Germany
Alain Schmit, M.D.
Hopital Erasme ULB
Brussels, Belgium
Douglas Schneider, M.D.
St. Elizabeth’s Medical Center
Boston, MA, USA
Karsten Schulmann, M.D.
Knappschaftskrankenhaus Bochum
Ruhr-University
Bochum, Germany
Ernest Seidman, M.D.
Ste Justine Hospital
University of Montreal
Montreal, Canada
Warwick Selby, M.D.
Royal Prince Alfred Hospital &
University of Sydney
Sydney, Australia
Nicholas Shackell, M.D.
Royal Prince Alfred Hospital &
University of Sydney
Sydney, Australia
Saumil Shah, M.D.
Catholic University
Rome, Italy
Virender K. Sharma, M.D.
Mayo Clinic Scottsdale
Scottsdale, Arizona, USA
Nidhir Sheth, M.D.
Beth Israel Medical Center
New York, NY, USA
Sandra Smith-Ziv
Given Imaging Ltd.
Yoqneam, Israel
Jean-Christophe Souquet, M.D.
CHU Lyon
Lyon, France
David Stolpman, M.D.
Oregon Health & Science University
Portland, Oregon, USA
Alain Suissa, M.D.
Rambam Medical Center
Haifa, Israel
Paul Swain, M.D.
Royal London Hospital
London, England
Jan Tack, M.D.
KU. Leuven
Leuven, Belgium
Ervin Toth, M.D.
Malmô University Hospital
Malmô, Sweden
Laura Toth, M.D.
St. Elizabeth’s Medical Center
Boston, MA, USA

Contributors
Gert Van Assche, M.D.
KU. Leuven
Leuven, Belgium
Andre Van Gossum, M.D.
Hopital Erasme ULB
Brussels, Belgium
Maurizio Vecchi, M.D.
University of Milan & IRCCS
Ospedale Maggiore Policlinico
Milan, Italy
Amorino Vecchioli, M.D.
Catholic University
Rome, Italy
Erica Villa, M.D.
University of Modena &
Regio Emilia
Modena, Italy
Kamal Yassin, M.D.
Rambam Medical Center
Haifa, Israel
Mahmoud Yousfi, M.D.
Mayo Clinic Scottsdale
Scottsdale, Arizona, USA
Arthur H. Zalev, M.D.
St. Michael's Hospital
Toronto, ON, Canada
Johnathan Zinberg, M.D.
South Shore Gastroenterology PC
& South Nassau Communities Hosp.
Oceanside, NY, USA
131