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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


First Edition
Marisa Halpern, M.D.
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

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.

Development of the Swallowable Video 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 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.

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.

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. 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.
A - External view

Wireless Capsule Endoscope


B - Schematic cross-section
3
11mm

2 4 3

6 7

26mm

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).

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.

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 4 - Field of illumination 5 - Field of view

a
1 - Endoscope inside intestine

6 - Intestinal wall

3 - Lens

7 - Air filling, due to insufflation

B - Capsule endoscope
b
3 - Lens 8 - Optical dome 4 - Field of illumination
1 - Wireless capsule endoscope inside intestine

7 - Liquid filling, intestinal liquids 5 - Field of view 2 - Illumination source

6 - Intestinal wall

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.

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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.
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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 mmHg2, 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.

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.

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.

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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).

Physiological Endoscopy

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 2

Litynski GS. The history of laparoscopy. Frankfurt/M: Bernert Ve Katzgraber F, Glenewinkel F, Fischler S. Mechanism of fatal air after gastrointestinal endoscopy. Int J Legal Med 1998; 111(3):

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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.

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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.

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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.

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.

References and Suggested Readings


1 2

Lewis B. Enteroscopy. Gastrointest Endosc Clin N Am; 2000;1:101-16. Meron G. The development of the swallowable video capsule (M2A). Gastrointest Endosc 2000;6:817-9. Appleyard Glukhovsky A, Jacob H, et al. Transit times for the capsule endoscope. Gastrointest Endosc 2001;53:AB122

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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. 2. 3. 4. First name:__________________ Middle name:________________ Last name:__________________ Social security number: _______-_______-________ 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.

5. Gender: Male Female 6. Birthdate:______/________/_______ 7. Weight (lbs):_________________ 8. Height (inches):______________ 9. Waist (inches):_______________

Thank You

For Office Use P (Time pill swallowed) L (Time of first eating) D (Time of disconnection) Recorder # Pt. # _

18

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.

The Performance of Capsule Endoscopy

Capsule Endoscopy Report Form 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

Chapter 2 Figure 5. Time Capsule Swallowed:____________ Recorder Disconnect Time:___________

The Performance of Capsule Endoscopy

Review Length of Review Start: Stop: Time: Start: Stop: Time: Start: Stop: Time: Start: Stop: Time: Start: Stop: 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:______________________

20

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.

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

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

23

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,

Normal M2A Anatomy 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
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.

24

Chapter 3

Normal M2A Anatomy

M2A
Figure 3.1 As M2A capsule is being ingested, a well papillated normal appearing tongue is seen.

M2A
Figure 3.2a Pharynx.

M2A
Figure 3.2b Optical dome of capsule exerting slight pressure on esophageal tissue as it is passing through.

M2A
Figure 3.2c EG junction.

25

Chapter 3

Normal M2A Anatomy

M2A
Figure 3.2d Detailed view of the Z line.

M2A
Figure 3.2e View of normal proximal gastric folds.

M2A
Figure 3.3a Details of gastric folds seen by physiological capsule endoscopy in the mid-gastric region.

M2A
Figure 3.3b View of gastric antrum.

26

Chapter 3

Normal M2A Anatomy

M2A
Figure 3.4a Typical stellate-like appearance of normal pyloric opening as seen by capsule.

M2A
Figure 3.4b Brunners gland hyperplasia with suspected ectopic gastric mucosa within duodenal bulb.

M2A
Figure 3.4c Normal proximal small bowel.

M2A
Figure 3.5a Normal jejunum.

27

Chapter 3

Normal M2A Anatomy

M2A
Figure 3.5b Normal jejunum with normal villi as seen in former figure. Figure 3.5c Histological appearance of normal villi.

M2A
Figure 3.6a The Ampulla of Vater. Not commonly visualized by the M2A capsule.

M2A
Figure 3.6b Detailed view of the normal vasculature of the small bowel.

28

Chapter 3

Normal M2A Anatomy

Figure 3.7a Small bowel follow through showing evidence of nodular lymphoid hyperplasia in the terminal Ileum.

Figure 3.7b Ileoscopy done on same patient revealing nodular lymphoid hyperplasia.

M2A
Figure 3.7c Capsule view of the same area showing lymphoid hyperplasia.

M2A
Figure 3.8 Normal Ampulla of Vater.

29

Chapter 3

Normal M2A Anatomy

M2A
Figure 3.9a Lymphangiectasia of the small bowel. These are frequently seen in normal patients.

M2A
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 3.10 M2A capsule approaching the ileocecal valve.

M2A
Figure 3.11a Normal vascular pattern of the cecal wall.

30

Chapter 3

Normal M2A Anatomy

M2A
Figure 3.11b M2A capsule imaging the right colon.

M2A
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

Chapter 4

Inflammatory Diseases of the Small Intestine 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.

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

CONCLUSION
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 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 Cameron D. Upper and lower gastrointestinal endoscopy in children and adolescents with Crohn's disease. J Gastroenterol Hepatol 6:355-358, 1991 Jeffires GH, Steinberg H, Sleisenger MH. Chronic ulcerative (nongranulomatous) jejunitis. Am J Med 44:47-59, 1968 Baer AN, Bayless TM, Yardley JH. Intestinal ulceration and malabsorption syndromes. Gastroenterology 79:754-765, 1980

34

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6

Inflammatory Diseases of the Small Intestine

Sayek I, Aran O, Uzunaliamoglu B, et al. Intestinal Behcet's disease: surgical experience in seven cases. Hepatogastroenterology 38:81-83, 1991 Tawil S, Brandt LJ, Bernstein LH. Scalloping of the valvulae conniventes and mosaic mucosa in tropical sprue. Gastrointestinal Endosc 37:365-366, 1991 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 Lescut D, Vanco D, Bonniere P, et al. Perioperative endoscopy of the whole small bowel in Crohn's disease. Gut 34:647-649, 1993

35

Chapter 4

Inflammatory Diseases of the Small Intestine

M2A
Figure 4.1a Villous erosion with fibrosis in the jejunal area. Presence of prominent whitish villi suggests submucosal fibrosis.

M2A
Figure 4.1b Area of edema, erythema and villous erosion in a patient with small bowel inflammatory disease.

M2A

M2A
Figure 4.3 Superficial jejunal ulcer in a patient with patchy areas of moderate to severe enteritis.

Figure 4.2 Ulceration in the terminal ileum in a patient with IBD.

36

Chapter 4

Inflammatory Diseases of the Small Intestine

M2A
Figure 4.4a Focal area of inflammation characterized by erythema, edema, dilated lymphatics and mucosal breakdown.

M2A
Figure 4.4b Jejunum with nodular area of inflammation and superficial ulceration.

M2A
Figure 4.4c The biopsy shows mild to moderate inflammation with partial villous atrophy and blunting. (H&E X 20). Figure 4.5a Jejunum of patient with Crohns disease showing thickened infiltrated folds.

37

Chapter 4

Inflammatory Diseases of the Small Intestine

M2A
Figure 4.5b Ongoing infiltration, ulceration and nodularity in Crohns disease.

M2A
Figure 4.5c Inflammatory process infiltrating and thickening this small bowel fold.

M2A
Figure 4.5d Small bowel stricture in this patient with Crohns disease. Note the slit-like opening of the stricture. Capsule passed easily.

M2A
Figure 4.5e Small bowel inflammation with edema, erythema and prominent folds.

38

Chapter 4

Inflammatory Diseases of the Small Intestine

M2A
Figure 4.5f Pseudopolyp with surrounding cobblestoning in Crohns disease.

M2A
Figure 4.5g Near total obliteration of lumen secondary to inflammatory process.

M2A
Figure 4.5h Irregular ulcer in IBD.

M2A
Figure 4.6a M2A Capsule entering a narrowed area with surrounding geographic ulceration.

39

Chapter 4

Inflammatory Diseases of the Small Intestine

M2A
Figure 4.6b M2A Capsule passing through the narrowed area as depicted in 4.6a.

M2A
Figure 4.6c Narrowed lumen with surrounding ulceration in Crohns disease.

M2A
Figure 4.6d Isolated ulcer in a normal surrounding area in a patient with known IBD.

M2A
Figure 4.6e Inflammation, ulceration and narrowing in a patient with IBD.

40

Chapter 4

Inflammatory Diseases of the Small Intestine

M2A
Figure 4.6f Extensive linear ulceration in IBD.

M2A
Figure 4.7 Apthous ulcer of distal ileum.

M2A
Figure 4.8a Early lesion of inflammatory bowel disease revealing submucosal edema and ulceration.

M2A
Figure 4.8b Early inflammatory lesions with spectrum of abnormalities showing edema, villous erosion and ulceration.

41

Chapter 4

Inflammatory Diseases of the Small Intestine

M2A
Figure 4.9a 18 year old male. CE revealed ulcer in the distal part of the small bowel.

M2A
Figure 4.9b Same patient. View of additional ulcer with narrowing of lumen.

Figure 4.9c At surgery Crohns disease was diagnosed. A deep fissure can be seen in the histological examination. (H&E).

Figure 4.9d Typical granulotoma can be seen in the wall of the small intestine. (H&E).

42

Chapter 4

Inflammatory Diseases of the Small Intestine

M2A
Figure 4.10a Lymphoid hyperplasia. This is a normal variant and should not be interpreted as pathological nodularity.

M2A
Figure 4.10b Lymphoid hyperplasia.

M2A
Figure 4.11 Early duodenal fissuring in a patient with early Crohns lesion.

M2A
Figure 4.12 Ileal linear ulceration.

43

Chapter 4

Inflammatory Diseases of the Small Intestine

M2A
Figure 4.13a Segment of proximal small bowel with edema and erythema.

M2A
Figure 4.13b Early proximal small bowel inflammation.

M2A
Figure 4.13c Area of proximal jejunum with erythema, edema. Note the ulcer between 6 and 7 oclock.

M2A
Figure 4.14 Ileal lesion in Crohns disease.

44

Chapter 4

Inflammatory Diseases of the Small Intestine

M2A
Figure 4.15a Jejunal linear ulcerations.

M2A
Figure 4.15b Jejunal linear ulcerations.

M2A
Figure 4.15c Linear ulceration in Crohns disease.

M2A
Figure 4.16 Crohns 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

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 2

Rossini FP, Risio M, Pennazio M. Small bowel tumors and polyposis syndromes. Gastrointest Endosc Clin N Am 1999; 9: 93-114 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 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 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 Rossini FP, Pennazio M. Small bowel endoscopy. Endoscopy 2002; 34:13-20

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Chapter 5

Neoplastic Diseases

M2A
Figure 5.1 Benign appearing polyp of small bowel.

M2A
Figure 5.2 80 year old patient with chronic GI blood loss requiring transfusion. CE revealed a large polypoid mass of small intestine

M2A
Figure 5.3a Duodenal polyp in patient with familial polyposis. Figure 5.3b Histology of polyp in figure 5.3a reveals a villous adenoma with high grade dysplasia. (H & E).

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Chapter 5

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M2A
Figure 5.4a Large hamartomatous polyp in PeutzJeghers Syndrome. Figure 5.4b Small bowel series of same patient revealing the polyp.

M2A
Figure 5.5a Large jejunal polyp causing recurrent bleeding in a 70 year old patient. Figure 5.5b Surgical specimen of case 5.5a. Notice polyp at 6 oclock.

50

Chapter 5

Neoplastic Diseases

M2A
Figure 5.6a Diffuse lymphoid hyperplasia present throughout the entire GI tract in a patient with Common Variable Immunodeficiency.

M2A
Figure 5.6b Detailed view of the lymphoid nodular hyperplasia in same case.

M2A
Figure 5.6c Small intestine. Lymphoid hyperplasia. There are hyperplastic B-cell follicles as well as a prominent interfollicular infiltrate. Figure 5.7a Patient with PJS. CE revealed hamartomatous polyp in duodenum.

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Chapter 5

Neoplastic Diseases

M2A
Figure 5.7b Same patient with polyps in distal jejunum.

M2A
Figure 5.7c Same patient with hamartomatous polyp.

M2A
Figure 5.8a Carcinoid tumor of small bowel. 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).

52

Chapter 5

Neoplastic Diseases

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 5.10a Gastrointestinal Stromal Tumor. The white mass at 5 oclock 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.

M2A
Figure 5.10b Same GIST as in former figure. Figure 5.10c High magnification of GIST shows a dense cellular area with pleomorphic spindle-shaped cells. (H&E).

53

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Neoplastic Diseases

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.

M2A
Figure 5.11b Same patient with lymphomatous polypoid mass in jejunum.

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.

Figure 5.11d Close up of tumor in distal duodenum showing filling defect and wall infiltration.

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M2A
Figure 5.11e Histology reveals Non-Hodgkin Follicular Lymphoma (grade 1). Immunohistochemical staining showed: CD20, bcl-2 and CD10: (+). CD3, CD5, Cyclin D: (-). Figure 5.11f Same patient with a small polyp in ileum.

M2A
Figure 5.12a 52 year old male with advanced cirrhosis (HCV), portal hypertension and esophageal varices. Capsule endoscopy reveals duodenal lymphoma.

M2A
Figure 5.12b Duodenal lesion in the same patient.

55

Chapter 5

Neoplastic Diseases

Figure 5.12c Biopsy of the duodenal mucosa showed lymphomatous polyposis. The lymphocytes infiltrating the lamina propria were B, CD5 positive. (H&E).

Figure 5.12d Higher magnification of the monotonous infiltrate of B lymphocytes. (H&E).

Figure 5.12e Endoscopy reveals lymphoma of the duodenum.

Figure 5.12f Endoscopy reveals the same area in the duodenum.

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Chapter 5

Neoplastic Diseases

M2A
Figure 5.13a Images of proximal small bowel showing thickened folds with onset of ulceration.

M2A
Figure 5.13b A narrowed lumen with a key hole configuration is seen in this infiltrating Non-Hodgkins T-Cell Lymphoma, same patient.

M2A
Figure 5.14a Infiltrating adenocarcinoma of the jejunum with active bleeding.

M2A
Figure 5.14b Infiltrating adenocarcinoma of the jejunum with ulceration in the center.

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Chapter 5

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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 5.15b Additional view of same case.

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. Figure 5.16b Push enteroscopy of the same case.

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M2A
Figure 5.16c Same case revealing an elongated polypoid lesion. 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 5.17a Submucosal jejunal mass in a patient with GI bleeding.

M2A
Figure 5.17b As capsule endocope passes the mass, an ulcer is seen in the center of it.

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Neoplastic Diseases

M2A
Figure 5.18a Nodular lesion of small bowel in AIDS patient with biopsy proven Kaposis.

M2A
Figure 5.18b Submucosal nodular lesion of small bowel in Kaposis sarcoma.

M2A
Figure 5.19a Nodular bluish lesion in a patient with suspected Kaposis sarcoma.

M2A
Figure 5.19b Nodular bluish lesion in a patient with suspected Kaposis sarcoma, same case.

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M2A
Figure 5.19c Nodular bluish lesion in a patient with suspected Kaposis sarcoma, same case.

M2A
Figure 5.20 AIDS patient with recurrent unexplained GI bleeding. Note bluish nodular lesion suspected to be Kaposis 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

Chapter 6 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

Iatrogenic Diseases 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.

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Iatrogenic Diseases

M2A
Figure 6.1a Ulcer secondary to NSAID use. Patient was on COX-1 inhibitors.

M2A
Figure 6.1b Membranous stricture caused by NSAID use, same case.

M2A
Figure 6.1c NSAID induced membranous stricture, same case.

M2A
Figure 6.1d NSAID induced small intestinal ulcer, same case.

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M2A
Figure 6.1e Membranous stricture with ulceration secondary to NSAID use.

M2A
Figure 6.2 NSAID induced small bowel stricture.

M2A
Figure 6.3 Surgical staples at an anastomosis.

M2A
Figure 6.4 NSAID induced small bowel stricture.

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M2A
Figure 6.5 NSAID associated ileal ulcer.

M2A
Figure 6.6 Ulcerated stricture secondary to NSAIDs.

M2A
Figure 6.7 Small erosion in a patient on COX-2 inhibitors. Patient was not symptomatic from this lesion.

M2A
Figure 6.8 Small sub-clinical erosions and mild erythema were found in a patient on COX-2 inhibitors.

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M2A
Figure 6.9a NSAID stricture with active bleeding. Figure 6.9b Histology showing fibromuscular hyperplasia of stricture depicted in Fig. 6.9a (H&E).

M2A
Figure 6.9c Microscopic examination showing ulceration of stricture depicted in Fig. 6.9a (H&E). Figure 6.10a Minor erosion secondary to NSAID use.

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M2A
Figure 6.10b NSAID induced erosions. Patient was on COX-2 inhibitors.

M2A
Figure 6.10c Mucosal erythema and edema secondary to NSAIDs.

M2A
Figure 6.11a Radiotherapy induced stricture. Note coffee grounds.

M2A
Figure 6.11b Radiotherapy induced stricture. Note abnormal villous pattern.

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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 6.12b Same case as previous image.

M2A
Figure 6.12c Above patient showing active bleeding.

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Chapter 7

Vascular Abnormalities
Margit Hahne, M.D. Jrgen 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

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 Willebrands 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 Dieulafoys lesions as gastrointestinal

Vascular Abnormalities 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 Willebrands 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 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.

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References and Suggested Readings
1

Vascular Abnormalities

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;89:21392142 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

15 Junquera F, Feu F, Papo M, Videla S, Armengol JR, Bordas JM, Saperas E,

Piqu 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 16Kumar 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. Dieulafoys lesion of the jejunum. Hepatogastroenterology 1999;46:1699-701 18Saunders 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

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M2A
Figure 7.1a Patient with phlebactasia. Work-up for varices, including angiogram was negative.

M2A
Figure 7.1b Phlebactasia of small intestine.

M2A
Figure 7.1c Same case as above.

M2A
Figure 7.1d Additional view of same case.

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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 7.3 36 year old male with lower gastrointestinal bleeding and asplenia. Capsule endoscopy revealed short jejunal segment with varices. Section was successfully resected.

M2A
Figure 7.4a Arteriovenous malformation of jejunum as a source of recurrent bleeding. Figure 7.4b Histology of AVM (same case as 7.4a) showing mucosal and submucosal dilated vessels with fresh superficial bleeding (H&E).

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M2A
Figure 7.5a Duodenal angiodysplasia in 73 year old male with recurrent massive bleeding.

M2A
Figure 7.5b Same case as Fig. 7.5a showing ileocecal angiodysplasia at 6 oclock.

M2A
Figure 7.6 Angiodysplasia of small intestine.

M2A
Figure 7.7 Angiodysplasia of small bowel.

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M2A
Figure 7.8a Small angiodysplasia of jejunum. Figure 7.8b Histology of Fig. 7.8a revealing prominent and congested vessels (PAS stain, 50 X).

M2A
Figure 7.9 Venous malformation in a patient with Blue Rubber Bleb Nevus Syndrome.

M2A
Figure 7.10 Giant ileal angiodysplasias.

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M2A
Figure 7.11a Venous malformation in Blue Rubber Bleb Nevus Syndrome.

M2A
Figure 7.11b Venous malformation in Blue Rubber Bleb Nevus Syndrome, same case.

M2A
Figure 7.12 Jejunal Dieulafoys lesion with active bleeding.

M2A
Figure 7.13 Dilated and tortouous vein in a patient with portal hypertension. This lesion may represent an early stage of small bowel varices.

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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.

PARTIAL (HYPOBETALIPOPROTEINEMIA) OR COMPLETE (ABETALIPOPROTEINEMIA) DEFICIENCY IN -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

CAPSULE EXPERIENCE
Available reports are mainly isolated clinical cases of patients with intestinal diseases that are responsible for marked malabsorption of nutrients.

83

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,

Malabsorption 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
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.

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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 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 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 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 GAY G, DELMOTTE JS. Abeta and hypobetalipoproteinemias in Atlas of Enteroscopy. Eds FP ROSSINI, G. GAY. Springer Verlag Eds 1998 : 119-120 CORAZZA GR, DI STEPHANO M, PISTOIA MA. Celiac disease in Atlas of enteroscopy, Eds FP Rossini, G Gay. Springer Verlag Milan 1998 : 93-96 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

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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

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Endoscopic management of patients with intestinal malabsorption


Suspected intestinal disease e.g. celiac disease

EGD + Duodenal Biopsies

Abnormal

Inconclusive

Specific treatment

Abnormal

Inconclusive

Push video enteroscopy + duodenal and jejunal biopsies if jejunal lesions

Repeat examinations ?

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Figure 8.1a Yellow and snowy jejunal mucosa and blood acanthocytosis in a patient with Hypobetalipoproteinemia.

Figure 8.1b Yellow and snowy jejunal mucosa without atrophic area in same patient.

M2A
Figure 8.1c Yellow and snowy ileal mucosa in same patient. 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.

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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 8.1f CE reveals yellow and snowy mucosa with lymphatic stasis without atrophic area of the ileal mucosa in same patient.

M2A
Figure 8.1g Additional view of same case. Figure 8.2a Enteroscopy reveals scalloped folds, atrophic area, mosaic pattern in the duodenum and jejunum in patient with celiac disease.

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Figure 8.2b Enteroscopy reveals scalloped folds, atrophic area, mosaic pattern in the duodenum and jejunum in same patient.

Figure 8.2c Close-up of same diagnosis as in Fig. 8.2b.

M2A
Figure 8.2d CE reveals scalloped folds, atrophic area, mosaic pattern in the duodenum in this patient.

M2A
Figure 8.2e Same diagnosis as Fig. 8.2d.

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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.

Figure 8.3b Enteroscopy in same patient as in previous figure.

M2A
Figure 8.3c CE reveals same aspect as PE before treatment along the jejunum but also along the length of the ileum.

M2A
Figure 8.3d CE reveals same diagnosis as in previous image.

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M2A
Figure 8.3e CE reveals same aspect as PE before treatment along the jejunum but also along the length of the ileum.

M2A
Figure 8.3f Chronic Non Granulomatous Ulcerative Jejuno-ileitis, same case.

M2A
Figure 8.3g Note presence of small bowel diverticula and telangiectasia, same case.

M2A
Figure 8.3h Additional view of same case.

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M2A
Figure 8.3i CE reveals same aspect as PE before treatment.

M2A
Figure 8.3j Different view of same case.

Figure 8.3k Enteroscopy performed shows normal aspect of the jejunum after treatment.

Figure 8.3l Additional view of enteroscopy performed in same patient.

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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 8.3n Additional view of same case.

M2A
Figure 8.3o Additional view of same case.

M2A
Figure 8.3p Additional view of same case.

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M2A
Figure 8.4a Celiac sprue with active jejunal bleeding. Note AVM at 4 oclock.

M2A
Figure 8.4b Note AVM at 5 oclock, same case as previous Fig. 8.4a.

M2A
Figure 8.4c Villous atrophy, same case as Fig. 8.4a. Note AVM at 6 oclock.

M2A
Figure 8.5 Primary lymphangiectasia of GI tract with poor villous formation and disarray.

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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 8.6b Eosinophilic enteritis. Note thickened infiltrated folds, same case as in Fig. 8.6a.

M2A
Figure 8.6c 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.

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Figure 8.6e Histological overview of jejunal mucosa with prominent lymphofollicular hyperplasia. (x10, H&E), same case.

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 8.6g Tip of the villi of jejunum showing discrete eosinophilic infiltration in lamina propria consistent with eosinophilic enteritis (x500, H&E), same case.
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.

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M2A
Figure 8.7b Diffuse bleeding was observed during capsule endoscopy procedure, same case.

M2A
Figure 8.7c Distally in ileum villi reappear slowly, same case.

M2A
Figure 8.7d Note lymphangiectasia, 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).

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Figure 8.7f Higher magnification. Hyperplastic crypts and dense lymphoid infiltrate (Reticulin, x500), same case.

Figure 8.7g Microscopic overview showing villous atrophy, hypertrophic crypts and lymphoid infiltrate (PAS stain, x100), same case.

Figure 8.7h Sprue-like picture with hyperplastic crypts, lymphoid cellular infiltrate (PAS stain, x500), same case.

Figure 8.7i Sprue-like picture with hyperplastic crypts, lymphoid cellular infiltrate in lamina propria (PAS stain, x500), same case.

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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 8.8b Infiltration of the GI tract with ulceration, same case.

M2A
Figure 8.8c Thickened infiltrated folds with erythema and early mucosal breakdown, same case.

M2A
Figure 8.8d Small erosion seen in same case.

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

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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

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.

Pediatrics

CONCLUSION
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.

References and Suggested Readings


1

3 4

Seidman EG. Role of endoscopy in inflammatory bowel disease. Gastrointest Endosc N Am 2001; 11: 641-57. 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. Lewis BS. Enteroscopy. Gastrointest Endosc Clin N Am 2000; 10: 101-16. Mackenzie JF. Push enteroscopy. Gastrointest Endosc Clin N Am 1999; 9: 29-36. Seidman E. Wireless Capsule Video-endoscopy: An Odyssey Beyond the End of The Scope. J Pediatr Gastroenterol Nutr 2002; 34: 333-4.

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Pediatrics

M2A
Figure 9.1a Celiac disease in the descending duodenum of a 10 year old girl.

M2A
Figure 9.1b Jejunum in this patient begins to show recovery of villi.

M2A
Figure 9.1c Ileum in this 10 year old girl. The villi are present but blunted, same case.

M2A
Figure 9.1d Suspected intestinal duplication in the jejunum of a 10 year old girl, same case.

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Pediatrics

M2A
Figure 9.2a Capsule endoscopy reveals gastric fundic polyps in a 9 year old child with Peutz-Jeghers.

M2A
Figure 9.2b Same patient with PJ. Note gastric fundic polyps.

M2A
Figure 9.2c Small hamartomatous polyp in ileum in patient with Peutz-Jeghers.

M2A
Figure 9.2d Multiple small hamartomatous polyps in proximal ileum in same patient with Peutz-Jeghers.

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M2A
Figure 9.2e Hamartomatous polyps in Peutz-Jeghers.

M2A
Figure 9.2f Large hamartomatous polyp in mid-ileum in patient with Peutz-Jeghers.

M2A
Figure 9.3a 15 year old male with FAP post colectomy. Underwent CE for surveillance. Images show nodularity of bulbar mucosa.

M2A
Figure 9.3b Same case as 9.3a. Adenomatous polyps are seen in the mid ileum.

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Pediatrics

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 9.4b Note abnormal venous pattern in the terminal ileum of this same 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 Crohns disease.

M2A
Figure 9.5b Same patient as in Figure 9.5a. A collar button ulcer in mid small bowel is present at 4 oclock.

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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

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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).

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

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

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 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 Meron G The development of the swallowable video-capsule (M2A). Gastrointestinal Endoscopy 2000;52:817-819 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 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

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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.

M2A
Figure 10.1b 20 days post-transplant. Same patient as Figure 10.1a.

M2A
Figure 10.1c Histology 20 days post-transplant. Normal ileal mucosa (H&E). Figure 10.2a 46 days post-transplant. Blunted villi in a patient examined at 6 weeks after transplantation.

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M2A
Figure 10.2b 46 days post-transplant. Same patient as figure 10.2a.

M2A
Figure 10.2c 46 days post-transplant. Same patient as previous figure.

M2A
Figure 10.2d 46 days post-transplant. Villous architecture more preserved here, same patient as before.

M2A
Figure 10.2e 2 months post-transplant. Normal distal ileum.

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M2A
Figure 10.3a 64 days post-transplant. Slight villous blunting with ulcer at 8 oclock.

M2A
Figure 10.3b 64 days post-transplant. This segment shows erythema and edematous club shaped blunted villi. The patient was asymptomatic.

M2A
Figure 10.4a 183 days post-transplant. Normal villi in a patient examined 6 months after small bowel transplantation.

M2A
Figure 10.4b 183 days post-transplant. Normal small bowel with two small areas of lymphangiectasia.

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M2A
Figure 10.4c 183 days post-transplant. Normal appearing small bowel.

M2A
Figure 10.4d 183 days post-transplant. Normal appearing small bowel.

M2A
Figure 10.5a 192 days post-transplant. Normal appearing small bowel.

M2A
Figure 10.5b 192 days post-transplant. Normal appearing small bowel.

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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.

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 .

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.

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Non Small Bowel Pathology

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.

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Non Small Bowel Pathology

M2A
Figure 11.1 Distal esophagitis seen as capsule passes through.

M2A
Figure 11.2 CE revealed Watermelon stomach in a patient with chronic bleeding.

M2A
Figure 11.3a Low-grade-malt lymphoma, confined to stomach. Figure 11.3b Gastroscopy in a patient with low-grademalt lymphoma, confined to stomach, same case.

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Chapter 11

Non Small Bowel Pathology

M2A
Figure 11.4a Kaposis sarcoma of the stomach in an HIV positive patient.

M2A
Figure 11.4b Same case as before.

M2A
Figure 11.5 Capsule endoscopy in a patient with GI bleeding of unknown etiology, Camerons lesion seen in a hiatal hernia.

M2A
Figure 11.6 Mild atrophic changes of gastric folds.

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Non Small Bowel Pathology

M2A
Figure 11.7a Colon polyp seen as capsule passes through cecum. Figure 11.7b Colon polyp. After the patient underwent prep and colonoscopy, the polyp was confirmed.

M2A
Figure 11.8 Appearance of stomach mucosa after biopsy was taken.

123

Contributors
Carla Abbiati, M.D.
University of Milan and IRCCS Ospedale Maggiore Policlinico Milan, Italy

Brett Bernstein, M.D.


Beth Israel Medical Center New York, NY USA

Alan L. Buchman, M.D.


Northwestern University Chicago, IL, USA

Rhonda Cole, M.D.


Veterans Affairs Medical Center Houston, Texas, USA

Samuel Adler, M.D.


Bikur Cholim Hospital Jerusalem, Israel

Luigi Berreta, M.D.


Ospedaliera S.Gerardo Monza , Italy

Carol A. Burke, M.D.


The Cleveland Clinic Foundation Cleveland, OH, USA

Felice Consentino, M.D.


S. Paolo Hospital Milan, Italy

Mark Appleyard, M.D.


Royal Brisbane Hopital Herston, Queensland, Australia

Faisal Bhinder, M.D.


St Elizabeth s Medical Center Boston, MA , USA

Marcus J. Burnstein, M.D.


St. Michael's Hospital Toronto, ON, Canada

Guido Costamagna, M.D.


Catholic University of Rome Rome, Italy

Jeffrey P. Baker, M.D.


St. Michael's Hospital Toronto, ON, Canada

Edmund Bini, M.D.


NYU Medical Center New York, NY, USA

Lucio Capurso, M.D.


S. Filippo Neri Hospital Rome, Italy

Ingrid Davies, R.N.


South Shore Gastroenterology PC & South Nassau Communities Hospital Oceanside, NY , USA

Jamie Barkin, M.D.


University of Miami Mount Sinai Medical Center Miami, Florida, USA

Alain Bitoun, M.D.


CHU Paris Paris, France

Angel Caunedo, M.D.


Virgen Macarena University Hospital Seville, Spain

Gian L. deAngelis, M.D.


Instituto Di Clinica Pediatrica Parma, Italy

Gizela Beccari, M.D.


University of Milan and IRCCS Ospedale Maggiore Policlinico Milan, Italy

Peter D. Bloom, M.D.


University School of Medicine & Atlanta Veterans Admin. Med. Ctr. Atlanta, GA, USA

David R. Cave, M.D.


St. Elizabeths Medical Center Boston, MA , USA

Roberto De Franchis, M.D.


University of Milan and IRCCS Ospedale Maggiore Policlinico Milan, Italy

125

Contributors (continued)
Michel Delvaux, M.D.
CHU Nancy Nancy, France

Gareth Dulai, M.D.


CURE VA Greater L.A. Health Care System Los Angeles, CA, USA

Isaac Fassler, M.D.


CHU Nancy Nancy, France

David Fleischer, M.D.


Mayo Clinic Scottsdale Scottsdale, Arizona, USA

Ingrid Demedts, M.D.


University Hospital of Gasthuisberg Leuven, Belgium

Frank Duperier, M.D.


The Cleveland Clinic Foundation Cleveland, OH, USA

Jay Fenster, M.D.


South Shore Gastroenterology Center Cedarhurst Cedarhurst, NY,USA

Christian Florent, M.D.


CHU Paris Paris, France

Jacques Deviere, M.D.


Hopital Erasme Brussels, Belgium

Rami Eliakim, M.D.


Rambam Medical Center Haifa, Israel

Pedro Figueiredo, M.D.


University Hospital of Coimbra Coimbra, Portugal

Frans T. Fork, M.D.


Malm University Hospital Malm, Sweden

Angelo Dezi, M.D.


S. Filippo Neri Hospital Rome, Italy

Christian Ell, M.D.


HSK Wiesbaden, Germany

Zvi Fireman, M.D.


Hillel-Yaffe Medical Center Hadera, Israel

Francesca Foschia, M.D.


Catholic University of Rome Rome, Italy

Elena Dubcenco, M.D.


St. Michael's Hospital Toronto, ON, Canada

Douglas Faigel, M.D.


Portland VA Medical Center Portland, WA, USA

Babak Firoozi, M.D.


NYU Medical Center New York, NY, USA

Erik Francois, M.D.


Hopital Erasme Brussels, Belgium

Jose Dubois, M.D.


Ste Justine Hospital University of Montreal Montreal, Canada

Kent Farris, M.D.


Gastrointestinal Assoc. Knoxville, TN, USA

Doron Fischer, M.D.


Rambam Medical Center Haifa, Israel

Diniz Freitas, M.D.


University Hospital of Coimbra Coimbra, Portugal

126

Contributors (continued)
Sandor Joffe, M.D.
Beth Israel Medical Center New York, NY, USA

Devon Klein, M.D.


Beth Israel Medical Center New York, NY, USA

David Lieberman, M.D.


Portland VA Medical Center Portland, Oregon, USA

Gavriel Meron, Ph.D.


Given Imaging Ltd. Yoqneam, Israel

Enrico Jovine, M.D.


University of Modena and Regio Emilia Modena, Italy

Yehudith Kraizer, Ph.D.


Given Imaging Ltd. Yoqneam, Israel

Ramona Lim, M.D.


University of Miami Mount Sinai Medical Center Miami, Florida, USA

Marie Claude Miron, M.D.


Ste Justine Hospital University of Montreal Montreal, Canada

Renee Jovine, M.D.


St. Elizabeths Medical Center Boston, MA , USA

Jonathan A. Leighton, M.D.


Mayo Clinic Scottsdale Scottsdale, Arizona, USA

Roberto Luchetti, M.D.


S. Filippo Neri Hospital Rome, Italy

Roger Mitty, M.D.


St. Elizabeths Medical Center Boston, MA , USA

Steven Kadish, M.D.


South Shore Gastroenterology PC & South Nassau Communities Hospital Oceanside, NY, USA

Gavin Levinthal, M.D.


The Cleveland Clinic Foundation Cleveland, OH, USA

Pasquale Marano, M.D.


Catholic University of Rome Rome, Italy

Danette Musil, M.D.


Mayo Clinic Scottsdale Scottsdale, Arizona, USA

Dalia Katz, M.D.


Rambam Medical Center Haifa, Israel

Blair S. Lewis, M.D.


Mt. Sinai Hospital New York, NY, USA

Andrea May, M.D.


HSK Wiesbaden, Germany

Massimiliano Mutignani, M.D.


Catholic University of Rome Rome, Italy

Martin Keuchel, M.D.


Medizinische Abteilung Allgemeines Krankenhaus Altona Hamburg, Germany

Shlomo Lewkowicz, D.Sc.


Given Imaging Ltd. Yoqneam, Israel

Alberto Merighi, M.D.


University of Modena and Reggio Emilia Modena, Italy

Colm O Loughlin, M.D.


University of Miami Mount Sinai Medical Center Miami, Florida, USA

128

Contributors (continued)
Antone R. Opekun, M.D.
Baylor College of Medicine Houston, Texas, USA

Antonio Pinna, M.D.


University of Modena and Regio Emilia Modena, Italy

Maria Elena Riccioni, M.D.


Catholic University of Rome Rome, Italy

Marc Rosenberg, M.D.


University School of Medicine & Atlanta Veterans Admin. Med. Ctr. Atlanta, GA, USA

Guillermo Payeras, M.D.


Hospital del Aire Madrid, Spain

Javier P. Piqueras, M.D.


Hospital del Aire Madrid, Spain

Jrgen F. Riemann, M.D.


Klinikum Ludwigshasen Ludwigshasen, Germany

Steven Rosenblatt, M.D.


The Cleveland Clinic Foundation Cleveland, OH, USA

Francisco J. Pellicer, M.D.


Virgen Macarena University Hospital Seville, Spain

Thierry Ponchon, M.D.


CHU Lyon Lyon, France

Jean-Francois Roche, M.D.


CHG Verdun Verdun, France

Francesco P. Rossini, M.D.


S.Giovanni AS Hospital Turin, Italy

Marco Pennazio, M.D.


S.Giovanni A.S. Hospital Turin, Italy

Massimo Primignani, M.D.


University of Milan and IRCCS Ospedale Maggiore Policlinico Milan, Italy

Manuel Rodriguez-Tellez, M.D.


Virgen Macarena University Hospital Seville, Spain

Paul Rutgeerts, M.D.


KU. Leuven Leuven, Belgium

Vincenzo Perri, M.D.


Catholic University of Rome Rome, Italy

Marlene Rackson , M.D.


Beth Israel Medical Center New York, NY, USA

Rafael Romero, M.D.


Virgen Macarena University Hospital Seville, Spain

Manuel Jimenez-Saenz, M.D.


Virgen Macarena University Hospital Seville, Spain

Rima Petroniene, M.D.


St. Michael's Hospital Toronto, ON, Canada

Stefanie Remke, M.D.


HSK Wiesbaden, Germany

Emanuele Rondonotti, M.D.


University of Milan and IRCCS Ospedale Maggiore Policlinico Milan, Italy

Miguel A. Saez, M.D.


Hospital del Aire Madrid, Spain

129

Contributors (continued)
Ana Sant Anna, M.D.
Ste Justine Hospital University of Montreal Montreal, Canada

Wolff Schmiegel, M.D.


Knappschaftskrankenhaus Bochum Ruhr-University Bochum, Germany

Nicholas Shackell, M.D.


Royal Prince Alfred Hospital & University of Sydney Sydney, Australia

David Stolpman, M.D.


Oregon Health & Science University Portland, Oregon, USA

Janice M. Santisi, R.N.


The Cleveland Clinic Foundation Cleveland, OH, USA

Alain Schmit, M.D.


Hopital Erasme ULB Brussels, Belgium

Saumil Shah, M.D.


Catholic University Rome, Italy

Alain Suissa, M.D.


Rambam Medical Center Haifa, Israel

Renato Santucci, M.D.


S.Giovanni A.S. Hospital Turin, Italy

Douglas Schneider, M.D.


St. Elizabeths Medical Center Boston, MA, USA

Virender K. Sharma, M.D.


Mayo Clinic Scottsdale Scottsdale, Arizona, USA

Paul Swain, M.D.


Royal London Hospital London, England

Shigeru Sato, M.D.


Fukuoka University Fukuoka, Japan

Karsten Schulmann, M.D.


Knappschaftskrankenhaus Bochum Ruhr-University Bochum, Germany

Nidhir Sheth, M.D.


Beth Israel Medical Center New York, NY, USA

Jan Tack, M.D.


KU. Leuven Leuven, Belgium

Jean-Christophe Saurin, M.D.


CHU Lyon Lyon, France

Ernest Seidman, M.D.


Ste Justine Hospital University of Montreal Montreal, Canada

Sandra Smith-Ziv
Given Imaging Ltd. Yoqneam, Israel

Ervin Toth, M.D.


Malm University Hospital Malm, Sweden

Eitan Scapa, M.D.


Assaf-Harofe Medical Center Zrifin, Israel

Warwick Selby, M.D.


Royal Prince Alfred Hospital & University of Sydney Sydney, Australia

Jean-Christophe Souquet, M.D.


CHU Lyon Lyon, France

Laura Toth, M.D.


St. Elizabeths Medical Center Boston, MA, USA

130

Contributors
Gert Van Assche, M.D.
KU. Leuven Leuven, Belgium

Mahmoud Yousfi, M.D.


Mayo Clinic Scottsdale Scottsdale, Arizona, USA

Andre Van Gossum, M.D.


Hopital Erasme ULB Brussels, Belgium

Arthur H. Zalev, M.D.


St. Michael's Hospital Toronto, ON, Canada

Maurizio Vecchi, M.D.


University of Milan & IRCCS Ospedale Maggiore Policlinico Milan, Italy

Johnathan Zinberg, M.D.


South Shore Gastroenterology PC & South Nassau Communities Hosp. Oceanside, NY, USA

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

131