Atlas of Capsule Endoscopy

Editors: Marisa Halpern, M.D. and Harold Jacob, M.D.

Atlas of Capsule EndoscopyWireless 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 EndoscopyFirst EditionMarisa 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

PrefaceWe 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.

AcknowledgmentsWe 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 CapsuleGavriel 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

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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.

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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.

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Notes From the InventorGavriel 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.

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Chapter 1

Physiological EndoscopyArkady Glukhovsky, D.Sc. Harold Jacob, M.D. Pablo Halpern, B.Sc.INTRODUCTIONWireless 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 EndoscopeB - Schematic cross-section311mm

1

2 4 3

5

5

6 7

26mm

CAPSULE EXPERIENCEPHYSIOLOGICAL 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.

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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 enteroscope2 - Illumination source 4 - Field of illumination 5 - Field of view

a1 - Endoscope inside intestine

6 - Intestinal wall

3 - Lens

7 - Air filling, due to insufflation

B - Capsule endoscopeb3 - Lens 8 - Optical dome 4 - Field of illumination1 - 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.1

Physiological Endoscopy The elements that are absent in physiological capsule endoscopy, thereby creating an advantageous environment include: a. Sedation and its resultant change in the physiological state. b. Air insufflation resulting in increased pressure on the intestinal wall. An additional factor that is integral to push endoscopy and does not play a role in capsule endoscopy is forceful insertion of the endoscope which impacts on the intestinal wall. Physiological changes may develop due to insufflation and increasing air pressure in the intestine: a. Under normal physiological conditions blood pressure in the blood vessels of the GI tract may be within the following range: arterioles 40-80 mmHg, capillaries 20-40 mmHg, and venules 15-30 mmHg. During push enteroscopy, the intraluminal pressure within the intestine may reach values above 300 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 efficientdue 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.

2

B - In airless endoscopy, most of the illumination isreturned 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

CONCLUSIONWireless 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 Readings1 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 EndoscopyBlair 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 Readings1 2

3

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. # _

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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:______________________

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Chapter 3

Normal M2A AnatomyPaul Swain, M.D. Mark Appleyard, M.D.

INTRODUCTIONIt 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 EXPERIENCEESOPHAGUS 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.

CONCLUSIONM2A 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

M2AFigure 3.1 As M2A capsule is being ingested, a well papillated normal appearing tongue is seen.

M2AFigure 3.2a Pharynx.

M2AFigure 3.2b Optical dome of capsule exerting slight pressure on esophageal tissue as it is passing through.

M2AFigure 3.2c EG junction.

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Normal M2A Anatomy

M2AFigure 3.2d Detailed view of the Z line.

M2AFigure 3.2e View of normal proximal gastric folds.

M2AFigure 3.3a Details of gastric folds seen by physiological capsule endoscopy in the mid-gastric region.

M2AFigure 3.3b View of gastric antrum.

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Normal M2A Anatomy

M2AFigure 3.4a Typical stellate-like appearance of normal pyloric opening as seen by capsule.

M2AFigure 3.4b Brunners gland hyperplasia with suspected ectopic gastric mucosa within duodenal bulb.

M2AFigure 3.4c Normal proximal small bowel.

M2AFigure 3.5a Normal jejunum.

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Normal M2A Anatomy

M2AFigure 3.5b Normal jejunum with normal villi as seen in former figure. Figure 3.5c Histological appearance of normal villi.

M2AFigure 3.6a The Ampulla of Vater. Not commonly visualized by the M2A capsule.

M2AFigure 3.6b Detailed view of the normal vasculature of the small bowel.

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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.

M2AFigure 3.7c Capsule view of the same area showing lymphoid hyperplasia.

M2AFigure 3.8 Normal Ampulla of Vater.

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M2AFigure 3.9a Lymphangiectasia of the small bowel. These are frequently seen in normal patients.

M2AFigure 3.9b Lymphangiectasia of the small bowel. Sometimes referred to as Xanthomas of the small bowel and are rarely associated with GI bleeding.

M2AFigure 3.10 M2A capsule approaching the ileocecal valve.

M2AFigure 3.11a Normal vascular pattern of the cecal wall.

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M2AFigure 3.11b M2A capsule imaging the right colon.

M2AFigure 3.11c View of the anus by the M2A capsule.

31

Chapter 4

Inflammatory Diseases of the Small IntestineAlan L. Buchman, M.D.

INTRODUCTIONDevelopment 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 EXPERIENCEEndoscopic 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

CONCLUSIONVideo 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 Readings1

2

3

4

5

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

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7

8

9

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

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Inflammatory Diseases of the Small Intestine

M2AFigure 4.1a Villous erosion with fibrosis in the jejunal area. Presence of prominent whitish villi suggests submucosal fibrosis.

M2AFigure 4.1b Area of edema, erythema and villous erosion in a patient with small bowel inflammatory disease.

M2A

M2AFigure 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.

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M2AFigure 4.4a Focal area of inflammation characterized by erythema, edema, dilated lymphatics and mucosal breakdown.

M2AFigure 4.4b Jejunum with nodular area of inflammation and superficial ulceration.

M2AFigure 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.

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M2AFigure 4.5b Ongoing infiltration, ulceration and nodularity in Crohns disease.

M2AFigure 4.5c Inflammatory process infiltrating and thickening this small bowel fold.

M2AFigure 4.5d Small bowel stricture in this patient with Crohns disease. Note the slit-like opening of the stricture. Capsule passed easily.

M2AFigure 4.5e Small bowel inflammation with edema, erythema and prominent folds.

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M2AFigure 4.5f Pseudopolyp with surrounding cobblestoning in Crohns disease.

M2AFigure 4.5g Near total obliteration of lumen secondary to inflammatory process.

M2AFigure 4.5h Irregular ulcer in IBD.

M2AFigure 4.6a M2A Capsule entering a narrowed area with surrounding geographic ulceration.

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M2AFigure 4.6b M2A Capsule passing through the narrowed area as depicted in 4.6a.

M2AFigure 4.6c Narrowed lumen with surrounding ulceration in Crohns disease.

M2AFigure 4.6d Isolated ulcer in a normal surrounding area in a patient with known IBD.

M2AFigure 4.6e Inflammation, ulceration and narrowing in a patient with IBD.

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M2AFigure 4.6f Extensive linear ulceration in IBD.

M2AFigure 4.7 Apthous ulcer of distal ileum.

M2AFigure 4.8a Early lesion of inflammatory bowel disease revealing submucosal edema and ulceration.

M2AFigure 4.8b Early inflammatory lesions with spectrum of abnormalities showing edema, villous erosion and ulceration.

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M2AFigure 4.9a 18 year old male. CE revealed ulcer in the distal part of the small bowel.

M2AFigure 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).

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M2AFigure 4.10a Lymphoid hyperplasia. This is a normal variant and should not be interpreted as pathological nodularity.

M2AFigure 4.10b Lymphoid hyperplasia.

M2AFigure 4.11 Early duodenal fissuring in a patient with early Crohns lesion.

M2AFigure 4.12 Ileal linear ulceration.

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M2AFigure 4.13a Segment of proximal small bowel with edema and erythema.

M2AFigure 4.13b Early proximal small bowel inflammation.

M2AFigure 4.13c Area of proximal jejunum with erythema, edema. Note the ulcer between 6 and 7 oclock.

M2AFigure 4.14 Ileal lesion in Crohns disease.

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M2AFigure 4.15a Jejunal linear ulcerations.

M2AFigure 4.15b Jejunal linear ulcerations.

M2AFigure 4.15c Linear ulceration in Crohns disease.

M2AFigure 4.16 Crohns disease with mucosal fissure in proximal jejunum.

45

Chapter 5

Neoplastic DiseasesFrancesco P. Rossini, M.D. Marco Pennazio, M.D.

INTRODUCTIONTumors 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 EXPERIENCEDiagnostic 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.

CONCLUSIONCapsule 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 Readings1 2

3

4

5

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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M2AFigure 5.1 Benign appearing polyp of small bowel.

M2AFigure 5.2 80 year old patient with chronic GI blood loss requiring transfusion. CE revealed a large polypoid mass of small intestine

M2AFigure 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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M2AFigure 5.4a Large hamartomatous polyp in PeutzJeghers Syndrome. Figure 5.4b Small bowel series of same patient revealing the polyp.

M2AFigure 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.

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M2AFigure 5.6a Diffuse lymphoid hyperplasia present throughout the entire GI tract in a patient with Common Variable Immunodeficiency.

M2AFigure 5.6b Detailed view of the lymphoid nodular hyperplasia in same case.

M2AFigure 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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M2AFigure 5.7b Same patient with polyps in distal jejunum.

M2AFigure 5.7c Same patient with hamartomatous polyp.

M2AFigure 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).

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M2AFigure 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.

M2AFigure 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.

M2AFigure 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).

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M2AFigure 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.

M2AFigure 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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M2AFigure 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.

M2AFigure 5.12a 52 year old male with advanced cirrhosis (HCV), portal hypertension and esophageal varices. Capsule endoscopy reveals duodenal lymphoma.

M2AFigure 5.12b Duodenal lesion in the same patient.

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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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M2AFigure 5.13a Images of proximal small bowel showing thickened folds with onset of ulceration.

M2AFigure 5.13b A narrowed lumen with a key hole configuration is seen in this infiltrating Non-Hodgkins T-Cell Lymphoma, same patient.

M2AFigure 5.14a Infiltrating adenocarcinoma of the jejunum with active bleeding.

M2AFigure 5.14b Infiltrating adenocarcinoma of the jejunum with ulceration in the center.

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M2AFigure 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.

M2AFigure 5.15b Additional view of same case.

M2AFigure 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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M2AFigure 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.

M2AFigure 5.17a Submucosal jejunal mass in a patient with GI bleeding.

M2AFigure 5.17b As capsule endocope passes the mass, an ulcer is seen in the center of it.

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M2AFigure 5.18a Nodular lesion of small bowel in AIDS patient with biopsy proven Kaposis.

M2AFigure 5.18b Submucosal nodular lesion of small bowel in Kaposis sarcoma.

M2AFigure 5.19a Nodular bluish lesion in a patient with suspected Kaposis sarcoma.

M2AFigure 5.19b Nodular bluish lesion in a patient with suspected Kaposis sarcoma, same case.

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M2AFigure 5.19c Nodular bluish lesion in a patient with suspected Kaposis sarcoma, same case.

M2AFigure 5.20 AIDS patient with recurrent unexplained GI bleeding. Note bluish nodular lesion suspected to be Kaposis sarcoma of the small bowel.

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Iatrogenic DiseasesDavid R. Cave, M.D.

INTRODUCTIONCapsule 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 EXPERIENCENSAIDS 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

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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.

CONCLUSIONIatrogenic 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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M2AFigure 6.1a Ulcer secondary to NSAID use. Patient was on COX-1 inhibitors.

M2AFigure 6.1b Membranous stricture caused by NSAID use, same case.

M2AFigure 6.1c NSAID induced membranous stricture, same case.

M2AFigure 6.1d NSAID induced small intestinal ulcer, same case.

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M2AFigure 6.1e Membranous stricture with ulceration secondary to NSAID use.

M2AFigure 6.2 NSAID induced small bowel stricture.

M2AFigure 6.3 Surgical staples at an anastomosis.

M2AFigure 6.4 NSAID induced small bowel stricture.

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M2AFigure 6.5 NSAID associated ileal ulcer.

M2AFigure 6.6 Ulcerated stricture secondary to NSAIDs.

M2AFigure 6.7 Small erosion in a patient on COX-2 inhibitors. Patient was not symptomatic from this lesion.

M2AFigure 6.8 Small sub-clinical erosions and mild erythema were found in a patient on COX-2 inhibitors.

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M2AFigure 6.9a NSAID stricture with active bleeding. Figure 6.9b Histology showing fibromuscular hyperplasia of stricture depicted in Fig. 6.9a (H&E).

M2AFigure 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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M2AFigure 6.10b NSAID induced erosions. Patient was on COX-2 inhibitors.

M2AFigure 6.10c Mucosal erythema and edema secondary to NSAIDs.

M2AFigure 6.11a Radiotherapy induced stricture. Note coffee grounds.

M2AFigure 6.11b Radiotherapy induced stricture. Note abnormal villous pattern.

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M2AFigure 6.12a CE reveals edematous erythematous mucosa with early neo-vascularization. This patient underwent abdominal radiotherapy within the last 12 months.

M2AFigure 6.12b Same case as previous image.

M2AFigure 6.12c Above patient showing active bleeding.

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Chapter 7

Vascular AbnormalitiesMargit Hahne, M.D. Jrgen F. Riemann, M.D.

INTRODUCTIONVascular 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 EXPERIENCEAVMs 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

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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.

CONCLUSIONVascular 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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Chapter 7References and Suggested Readings1

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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M2AFigure 7.1a Patient with phlebactasia. Work-up for varices, including angiogram was negative.

M2AFigure 7.1b Phlebactasia of small intestine.

M2AFigure 7.1c Same case as above.

M2AFigure 7.1d Additional view of same case.

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M2AFigure 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.

M2AFigure 7.3 36 year old male with lower gastrointestinal bleeding and asplenia. Capsule endoscopy revealed short jejunal segment with varices. Section was successfully resected.

M2AFigure 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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M2AFigure 7.5a Duodenal angiodysplasia in 73 year old male with recurrent massive bleeding.

M2AFigure 7.5b Same case as Fig. 7.5a showing ileocecal angiodysplasia at 6 oclock.

M2AFigure 7.6 Angiodysplasia of small intestine.

M2AFigure 7.7 Angiodysplasia of small bowel.

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M2AFigure 7.8a Small angiodysplasia of jejunum. Figure 7.8b Histology of Fig. 7.8a revealing prominent and congested vessels (PAS stain, 50 X).

M2AFigure 7.9 Venous malformation in a patient with Blue Rubber Bleb Nevus Syndrome.

M2AFigure 7.10 Giant ileal angiodysplasias.

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M2AFigure 7.11a Venous malformation in Blue Rubber Bleb Nevus Syndrome.

M2AFigure 7.11b Venous malformation in Blue Rubber Bleb Nevus Syndrome, same case.

M2AFigure 7.12 Jejunal Dieulafoys lesion with active bleeding.

M2AFigure 7.13 Dilated and tortouous vein in a patient with portal hypertension. This lesion may rep