Download pdf - Atlante Immagini Pillcam

Transcript
Page 1: Atlante Immagini Pillcam

Atlas of Capsule Endoscopy

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

Page 2: Atlante Immagini Pillcam

Atlas of Capsule Endoscopy

Wireless capsule endoscopy allows painless endoscopicimaging of the entire small bowel. In addition theexamination of the intestine takes place in the physiologicalstate. Artifact induction does not occur as in pushenteroscopy as there is no need to push the device. Thesedifferences between wireless endoscopy and pushendoscopy are the major factors governing the physiologicaland bio-optical principles of image acquisition, resultingin clear and detailed visualization of intestinal structures.

Page 3: Atlante Immagini Pillcam

Atlas of Capsule EndoscopyFirst Edition

Harold Jacob, M.D. Director of Medical Affairs

Given Imaging Ltd.

Yoqneam, Israel

Senior Pathologist

Director of Gastrointestinal Pathology Unit

Rabin Medical Center, Golda Campus

Petach Tiqva, Israel

Marisa Halpern, M.D.

Page 4: Atlante Immagini Pillcam

We are proud to present this first Atlas of Capsule Endoscopy. With the rapid adoptionof Capsule Endoscopy by practicing gastroenterologists, a new spectrum ofpathological images are being generated. New dimensions of the common diseaseswe treat are coming to light. In response to the intense interest and growth in thearea of Capsule Endoscopy, we have produced the first Atlas of Capsule Endoscopy.By placing these images in your hand, we know that it will enhanceyour ability to diagnose and treat patients with gastrointestinal disorders.

In this book we present the spectrum of disease that has been seen todate by Capsule Endoscopy. Where possible, we have correlated theM2A® Capsule images with other diagnostic modalities including endoscopy, radiologyand histopathology findings. This first edition of the Atlas of CapsuleEndoscopy also contains information on normal capsule endoscopic anatomy,how to perform Capsule Endoscopy and principles of physiological imageacquisition. Some consideration is also given to Capsule Endoscopy findings in otherparts of the GI tract as well.

The companion CD to the Atlas will enable you to load the M2A® Capsule imagesonto 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 patientswith gastrointestinal disease.

Harold Jacob, M.D.Marisa Halpern, M.D.

Preface

Page 5: Atlante Immagini Pillcam

We would like to thank all the worldwide contributors to the "Atlas ofCapsule Endoscopy" for their devoted efforts (see Contributors list).

We would like to thank Sharon Besser for her immense devotion to thispublication. Without her dedication, this project would not be completed.

Dr Halpern would like to acknowledge her colleagues at the Department ofPathology and especially Professor Rivka Gal who understood the meaningof 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.

Acknowledgments

Page 6: Atlante Immagini Pillcam

Given Imaging Inc.Oakbrook Technology Center5555 Oakbrook Parkway #355Norcross, 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 [email protected]

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 ortrademarks 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 sellany 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 becaused 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 [email protected]

Graphic Design......... Studio Rosinger Ltd., Haifa, IsraelPrinting ................... Rahash Offset Printing Ltd., Haifa, Israel

Expanding the scope of GI

Page 7: Atlante Immagini Pillcam

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

Page 8: Atlante Immagini Pillcam

3

It was in 1981 while on a sabbatical leave from his regularposition as Senior Engineer at the Electro-Optical Design Sectionof Rafael, the R&D group of the Israeli Ministry of Defense, thatDr. Gavriel Iddan, a talented mechanical engineer, started hislong term interest in medical imaging. The idea started as aseed of an invention in the midst of defense projects, particularlythe development of electro-optical imaging devices for missiles.

During the sabbatical, Dr. Iddan relocated to Boston to performresearch for another Israeli company, Elscint Inc., doing x-rayand ultrasound medical imaging R&D. In Boston, Dr. GavrielIddan befriended Professor Eitan Scapa, an Israeligastroenterologist, who was, at that time, at the local medicalcenter. They had many mutual interests and discussions, whichmade 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 specificallyinterested in "opening up a new frontier" by enabling directimaging of the small intestine, which was until then, terraincognito, due to the inability of the other imaging methods toreach the small intestine.

Dr. Iddan and a team of engineers and technicians in Rafaelworked on the development of an initial prototype in the

laboratories, and performed some feasibility trials of imagingand transmission through animal tissue developing some of thebasic technologies. Based on the initial research performed inthe Rafael laboratories, the first of a number of patents werewritten up and submitted by Rafael in January 1994.

At the same time and totally unbeknownst to Dr. Iddan, in theUnited States, Dr. Paul Swain presented the possibility of wirelessendoscopy during the Los Angeles World Congress ofGastroenterology, in an invited talk entitled Microwaves inGastroenterology in September 1994.

In London, Dr. Swain had made some progress in making several(rather large) prototype wireless endoscopy devices fromcommercially available components in 1995 and 1996. It wasin 1996 that his team achieved the first live transmissions fromthe stomach of a pig.

The first two abstracts published by Swain's team on this topicwere:

Wireless transmission of a color television moving image fromthe stomach using a miniature CCD camera, light source andmicrowave transmitter. Swain CP, Gong F, Mills TN. Gut1996;39:A26

Development of the Swallowable Video CapsuleGavriel Meron, Ph.D.

Page 9: Atlante Immagini Pillcam

Development of the Swallowable Video Capsule

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

4

Page 10: Atlante Immagini Pillcam

5

Wireless transmission of a color television moving image fromthe stomach using a miniature CCD camera, light sourceand microwave transmitter. Swain CP, Gong F, Mills TN.Gastrointest Endosc 1997;45:AB40.

Meanwhile, back in Israel, Dr. Iddan knew that if there wasto be a future for the capsule for small intestine imaging, itwould have to be championed by a commercial organization.He began to arrange meetings with different organizationsin the hope that they would take the challenge and investin 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., anIsraeli company that had developed and was selling videocameras for endoscopy.

In 1997, the patent in the US was approved, and the availabletechnologies needed for the capsule's development hadmoved in the right direction. It was at this time that Iapproached the Rafael Development Corporation (RDC), whohas the right of first refusal to commercialize technologiescoming out of Rafael, in order to found together a start-upthat would develop the capsule and bring it to market.

I left my position at Applitec and set out to raise funds anddevelop 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 "todevelop, produce, and achieve worldwide leadership in themarketing and sales of swallowable disposable electroniccapsules, for diagnostics and therapy of the gastrointestinal(GI) tract". This was clearly a much wider mandate than the

Development of the Swallowable Video Capsule

initial small intestine capsule, and was based on thedevelopment of a technological platform that would then befurther developed by listening to gastroenterologists,understanding the barriers in small intestine imaging, andimplementing solutions to overcome them.

By the end of 1998, the initial team, that included Dr. GavrielIddan, Dr. Paul Swain, and Dr. Arkady Glukhovsky, was inplace and serious research & development went underwayto transform the idea into reality. Successfully overcomingthe enormous obstacles of size, transmission strength, batterypower and image resolution, among many others, workingprototypes were produced in January 1999. In May 2000, atthe DDW 2000 meeting, Dr. Swain, together with GivenImaging, presented the results of the animal trials performedwith the prototype system that was developed. [WirelessCapsule Endoscopy, Nature, Vol. 405, 25 May 2000].

During 2001, Given achieved major milestones with thecompletion of successful clinical trials, receipt of FDAclearance, CE Mark certification, and launch of the Given®

Diagnostic Imaging System worldwide. The initial clinicalresults have been excellent, and the feedback from patientsand physicians has been remarkable.

The idea of publishing this Atlas of Capsule Endoscopy camein recognition of the need that was expressed by manyphysicians to see with their own eyes specific pathologiesand findings, and compare the images between the differentavailable modalities. We hope the content of this Atlas assistsin educating gastroenterologists and furthers theunderstanding and acceptance of the M2A® as a standardtool of GI diagnostics in the clinical path.

Page 11: Atlante Immagini Pillcam

Approximately 20 years ago, I took a sabbatical from myposition as an electro-optical systems engineer at Rafael, theArmaments Development division of the Israeli Ministryof Defense, and went to work for a medical instrumentmanufacturer in Boston, Mass. Coincidentally, I discoveredthat my next-door neighbor was a gastroenterologist, Prof.Eitan Scapa, who was also on sabbatical and working at alocal hospital. After getting to know each other, we wouldspend time discussing our respective professions. Amongother things, I learned about the field of endoscopy and wasexposed to some of its challenges.

After returning to my work at Rafael, I became deeplyinterested in medical devices and did some design work inthis area. During my next sabbatical, and after furtherdiscussions with Professor Scapa, I decided to focus on thespecific problems of imaging of the small intestine. Afterconsulting with a number of gastroenterologists, I finallydecided to attempt the development of a wireless camera.

The major obstacles that I encountered and needed toovercome included: attaining an adequate field of view,achieving power requirements for the CCD, and the challengeof performing a diagnostic study that required close contactwith the patient for many hours. A major breakthrough camein 1993 when I realized that the system could be separated

7

Notes From the InventorGavriel J. Iddan, D.Sc.

into 3 major units: capsule/transmitter, receiver/recorderand a workstation. The separation of these components wouldallow the patient to be ambulatory without the need to beconnected to a monitor.

During this period, the scientific literature started to reporta breakthrough in video imaging. This was the introductionof the CMOS imager which consumed only a fraction of theenergy required by a CCD, had all the required circuits on thesame chip, and was not expensive to manufacture. To completethe idea, a special self-cleaning optical configuration wasadded and detailed design and experiments commenced.(One of the first experiments was done on a frozen chickenpurchased in the supermarket.)

By the second half of 1993, I began writing a patentapplication, which was submitted in January 1994. Whilesearching urgently for financing to create this device, Iapproached Dr Gavriel Meron, who at that time was themanager of a company specializing in small endoscopiccameras. Taking my invention and developing a viablebusiness plan, Dr. Gavriel Meron established Given ImagingLtd in 1998, thus launching the new field of capsule endoscopyand making the dream a reality.

Page 12: Atlante Immagini Pillcam

9

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 lightreflected by the dome to reach the imager, thus enhancingthe image quality. The capsule is powered by two silver-oxidebatteries (5). An Application Specific Integrated Circuit (ASIC)transmitter (6) is located in the rear dome. The Radio Frequency(RF) signal is transmitted by the antenna (7).

Figure 1. Wireless Capsule Endoscope

There are two major factors that are thought to govern imageacquisition by of the M2A® capsule. These factors are: theproprietary optical dome and the fact that image acquisitionoccurs in the physiological state.

Physiological EndoscopyArkady Glukhovsky, D.Sc.Harold Jacob, M.D.Pablo Halpern, B.Sc.

INTRODUCTION

Wireless capsule endoscopy allows painless endoscopicimaging of the entire small bowel, but more significantly, theexamination of the intestine takes place in the physiologicalstate. Since there is no need to push the device, artifactinduction does not occur as in push enteroscopy. In addition,capsule endoscopy is wireless, obviating the need for airinsufflation and the rate of the propulsion is determined byperistalsis. These differences between wireless endoscopyand push endoscopy are the major factors governing thephysiological and bio-optical principles of image acquisition,resulting in clear and detailed visualization of intestinalstructures.

CAPSULE EXPERIENCE

PHYSIOLOGICAL ENDOSCOPYThe M2A® wireless capsule endoscope is shown in Figure 1A.A schematic cross-section appears in Figure 1B. The wirelesscapsule endoscope has a cylindrical shape, with a diameterof 11mm, and a length of 26mm. It has two convex domes,one of them being the optical dome (1). The intestine isilluminated through the optical dome by white Light EmittingDiodes (LEDs) (3).

Legend:1 - Optical dome2 - Short focal aspheric lens3 - White LEDs4 - CMOS imager5 - Watch batteries6 - ASIC transmitter7 - Antenna

1 2

3

4

3

5 5 6 7

26mm

11mm

Chapter 1

A - External view B - Schematic cross-section

Page 13: Atlante Immagini Pillcam

10

Physiological Endoscopy

THE OPTICAL DOMEThe optical dome and its relationship to the other opticalcomponents create two important advantages in capsuleendoscopy:

a. Improved illumination efficiency.b. Favorable imaging geometry within the field of view.

Another minor factor which may be contributing to imagequality is the presence of a fluid interface between the opticaldome and tissue at the time of examination improving theresolution of different anatomical structures such as villi.Finally, another advantage of the optical dome is that it lendsitself to cleaning by the GI tract mucosa.

Geometric and optical differences between image acquisitionin wired and wireless endoscopy are compared in Figure 2Aand Figure 2B. Figure 2A depicts the geometrical relationshipfor a push enteroscope inserted into the intestine. Geometricalrelationship for the M2A® capsule endoscope is depicted inFigure 2B. The standard endoscope (Figure 2A) includes anillumination source (2), and a lens (3), producing the field ofillumination (4), and the field of view (5) shown in Figure 2A.Collapse of the intestinal wall (6) may obscure either the fieldof view or field of illumination. This technical problem isresolved in standard endoscopy by insufflating the intestinewith air (7), resulting in the distancing of the intestinal mucofrom the tip of the endoscope, clearing both the field of viewand the field of illumination. Air insufflation also enables theoperator to orient the tip of the endoscope in the properluminal direction, and to advance the endoscope tip accordingly.

Figure 2B shows the wireless capsule endoscope (1) in theintestine. The capsule includes its illumination sources (2),and the lens (3), comprising a field of illumination (4), and afield of view (5) respectively. In order to prevent collapse of

the intestinal wall (6), and resultant obscuring of either thefield of illumination or the field of view, a specially designedoptical dome (8) covers both the source of illumination andthe lens. The space remaining between the dome and theintestinal wall may at times be occupied by fluid.

Figure 2. Geometrical and optical interrelationships forthe enteroscope and capsule endoscope in theintestine.

The field of view of most commercially available endoscopesis within the range of 120˚-140˚, similar to the M2A® capsuleendoscope. Depth of field of the standard endoscope startsfrom 3-5mm from the endoscope tip and extends to a distanceof 100 mm. Unlike in the push endoscope, depth of view ofthe capsule endoscope starts on the optical dome itself.

a

b

7 - Air filling, due to insufflation

1 - Endoscope insideintestine

2 - Illumination source

3 - Lens

4 - Field of illumination 5 - Field of view

6 - Intestinal wall

Chapter 1

A - Push enteroscope

8 - Optical dome

1 - Wireless capsuleendoscope insideintestine

2 - Illumination source

3 - Lens

4 - Field of illumination

5 - Field of view6 - Intestinal wall

7 - Liquid filling,intestinalliquids

B - Capsule endoscope

Page 14: Atlante Immagini Pillcam

11

The illumination efficiency in capsule endoscopy is higherdue to the fact that the illumination angles are not sharp,thereby allowing the illumination to be returned back to theimager. Fig 3a shows that some of the illumination is notbeing returned to the imager in standard endoscopy as aresult of air insufflation. Fig 3b demonstrates the effectivenesof the illumination provided by airless endoscopy.

Figure 3. Efficiency of illumination in air insufflatingand airless endoscopy.

PHYSIOLOGICAL ENDOSCOPYPerforming endoscopy in the physiological state is a paradigmshift in the approach to endoscopic diagnosis. The elementsthat are present in physiological capsule endoscopy includethe use of peristalsis to propel, orient and steer the M2A®

capsule in the intestine.

Physiological Endoscopy

The elements that are absent in physiological capsuleendoscopy, thereby creating an advantageous environmentinclude:

a. Sedation and its resultant change in thephysiological state.

b. Air insufflation resulting in increased pressure onthe intestinal wall.

An additional factor that is integral to push endoscopy anddoes not play a role in capsule endoscopy is forceful insertionof the endoscope which impacts on the intestinal wall.

Physiological changes may develop due to insufflation andincreasing air pressure in the intestine:

a. Under normal physiological conditions blood pressurein the blood vessels of the GI tract may be within thefollowing range: arterioles 40-80 mmHg, capillaries20-40 mmHg, and venules 15-30 mmHg. During pushenteroscopy, the intraluminal pressure within theintestine may reach values above 300 mmHg2,significantly higher than the blood pressure. We mayspeculate that this increase in pressure may decreasethe blood flow to small vessels, and in some caseseven temporarily arrest the flow. Although we havenot found reference of the tamponade effect inendoscopy, this phenomena in well-known inlaparoscopy for more than a century. In rare cases,air insufflation may even cause a fatal air embolismduring gastrointestinal endoscopy.

b. Insufflation of the small intestine, and insertionof a long flexible tube (the endoscope), affects thepressure receptors embedded in the small intestinalwall. In the case of wireless endoscopy, the intestine'sphysiological 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 theintestine at flat edges, and are not returned back to thelens and to the camera.

B - In airless endoscopy, most of the illumination isreturned back to the lens due to sharp edges ofillumination, close to perpendicular.

1

2

Chapter 1

Page 15: Atlante Immagini Pillcam

12

c. Conscious sedation is usually administered duringpush enteroscopy. The adminisration of sedation topatients alters systemic physiology. This may havean effect on the ability of the endoscope to detectvascular or inflammatory lesions.

d. Examination of the intestine under physiologicalconditions may enable measurement of additionalphysiological parameters, some of them unrelatedto the image, e.g. gastric emptying, small and largebowel passage times, and peristaltic contractioncycles (rhythms).

CONCLUSION

Wireless capsule endoscopy acquires detailed images of theGI tract, which allows identification of the spectrum ofpathologies present within the small bowel. Specific designelements of the capsule, coupled with the fact that the M2A®

device acquires images in the physiological state are themajor contributing factors to this breakthrough in GIendoscopy.

Physiological EndoscopyChapter 1

References and Suggested Readings

1 Litynski GS. The history of laparoscopy. Frankfurt/M: Bernert Ve2 Katzgraber F, Glenewinkel F, Fischler S. Mechanism of fatal air

after gastrointestinal endoscopy. Int J Legal Med 1998; 111(3):

Page 16: Atlante Immagini Pillcam

15

The Performance of Capsule EndoscopyBlair S. Lewis, M.D.Christopher J. Gostout, M.D.

Since the inception of gastrointestinal endoscopy, physicianshave wanted to obtain direct visualization of the entire GItract. Standard endoscopic and colonoscopic exams viewonly small amounts of the proximal and distal ends of thesmall bowel. Endoscopic examination of the entire smallbowel has remained elusive. Push enteroscopy was the firststep in the endoscopic evaluation of the intestine. Initially,colonoscopes, both adult and pediatric, were used to evaluatethe entire duodenum and proximal jejunum. On average, a160 cm long instrument can be advanced 40 cm beyond theligament of Treitz. Present 2.1-2.5 meter long pushenteroscopes have greatly improved the depth of insertionand visualization of the small bowel and it is now possible toinspect the jejunum in its entirety. Examination of the distalsmall bowel has previously been achieved using Sonde andRope-way techniques. Both exams are lengthy and quiteuncomfortable, even painful. The medical community haslargely abandoned these exams.

An endoscopic capsule (GivenImaging Limited, Yoqneam, Israel)has been developed to obtainimages from the entire smallbowel. Developed by Dr. GavrielIddan in 1981, the capsule, whichmeasures 11 x 26 mm, contains 4

LEDs (light emitting diodes), a lens, a color camera chip, twobatteries, a radio frequency transmitter and an antenna. Thecamera is a CMOS (complementary metal oxide sensor) chip.This chip requires less power than present CCD (chargedcoupled device) chips found on video endoscopes and digitalcameras, and it can operate at very low levels of illumination.The capsule obtains two images per second and transmitsthe data via radio frequency to a recording device worn abouta patient's waist. Once the acquisition time is reached, thedata from the recording device is downloaded to a computerworkstation whose software processes the images to beviewed on the computer screen.

The capsule is disposable and does not need to be retrievedby the patient. It is passed naturally. An average of 50,000images are obtained during an eight-hour exam. Thus capsuleendoscopy appears to be the answer to the long-standingdesire for the complete endoscopic examination of the entiresmall bowel and it accomplishes this goal in a non-invasive way.

The capsule is indicated as an adjunctive tool for evaluationof suspected diseases of the small intestine. It iscontraindicated in patients with known or suspected smallbowel obstruction since the capsule may become lodgedwithin the intestinal tract. The capsule has not been approvedfor use in patients with pacemakers or implanted defibrillators.

Chapter 2

Page 17: Atlante Immagini Pillcam

The markings are best removed at the end of the exam usingrubbing alcohol. The sensor array leads are attached byadhesive to the patient's abdomen. Some patients may needto 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 intothe belt pouches. The sensor leads are attached to therecording device which is then attached to the battery pack.The powered recorder will illuminate its light for a short periodof time. This light will go out once the hard drive hassuccessfully booted. The capsule is then removed from itsblister pack. Removing the capsule from the magnet in thepack turns the capsule on and it begins to flash twice persecond and transmit images. It is important to look at therecorder and ascertain that its light flashes in synchrony withthe capsule verifying successful transmission.

T h e p a t i e n t t h e nswallows the capsulefollowed by a full glass ofwater. We ask patientsto drink two additionalglasses of water to assuret h a t t h e c a p s u l eimpasses through the esophagus into the stomach. Thepatient is then told that she/he can leave the facility and carryabout a normal day. Patients are told to refrain from exercisingand heavy lifting during the exam. They should avoid largetransmitters and MRI machines. They may walk, sit and laydown. They can drive a car. They can return to work. Theymay use a computer, radio, stereo or cell phone. They shouldnot stand directly next to another patient undergoing capsuleendoscopy. They should not touch the recorder or the antennaarray leads, nor should they remove the leads.

Typical timing of a capsule exam is to have a patient swallowthe capsule at 8 am and disconnect them from the recorderat 4 pm. This allows 8 hours of acquisition of images duringthe day. Capsule endoscopy is performed after the patientfollows a 12 hour fast. Patients are told to have nothing toeat or drink after dinner on the evening before the examination.Patients should not smoke cigarettes, since this may causea change in the color of the stomach lining. They are alsotold not to take medications or antacids. Medications suchas iron and sucralfate can coat the intestinal lining limitingvisualization. Narcotics and antispasmodics can delay bothgastric and intestinal emptying making it difficult to visualizethe entire small bowel during the 8-hour acquisition time.Patients are told to bring their medications with them to takeaccordingly during the day if necessary. If a patient is diabetic,insulin doses need to be adjusted. Patients are also told towear loose clothing on the day of the exam. Dresses shouldbe avoided. A buttoned shirt and loose fitting pants workbest. During the evening prior to the exam, the recorder'sbattery pack is trickle charged through a standard outlet.

Initially on the day of the exam, the patient's personal datais entered into the computer workstation (Figure 1). Therecording device is then initialized to the patient. This ensuresthat once completed the recording device and the datacontained within cannot be confused with any other patient.At this point, patients may be asked to drink a small glass ofwater containing simethicone. This surfactant eliminates any

bubbles inside thestomach.The patient's abdomen ismarked with a surgicalmarker using a templatefor accurate placementof sensors.

The Performance of Capsule EndoscopyChapter 2

16

Page 18: Atlante Immagini Pillcam

17

Patients may loosen the Velcro on the belt to allow them togo to the bathroom. They are told not to take the belt off andthat the shoulder straps should never come off. Patients arealso told to be very careful when bringing up underwear overthe sensors to avoid disconnection. Patients can eat beginning4 hours after swallowing the capsule. They can take theirmedications at this time as well.

Capsule transit times have been reported in several studies.The average gastric time is approximately 60 minutes, theaverage time in the small bowel is 240 minutes, and theaverage passage time to the colon is 300 minutes. An 8-houracquisition time assures that most capsules will reach thecolon allowing for complete inspection of the small bowel.Patients return to the facility after this amount of time to havethe recorder, belt and sensor array removed. They areinstructed to avoid MRI machines for at least 3 days or untilthe capsule is seen to pass. An x-ray can be obtained shouldthere be a question if the capsule has remained within thepatient and not excreted.

Downloading begins with clearing the download memoryin the workstation. Once accomplished, the recorder isattached to the workstation. Generally, download of acomplete patient study lasts 2 and one-half hours. Oncedownloaded, the recorder can be disconnected from theworkstation or it can be initialized for a new patient.The images of the capsule exam are then reviewed on theworkstation. A sample working endoscopy report form canbe seen in Figure 5.

Review of the images should beperformed by individuals who areexperienced in viewing andinterpreting endoscopic images.

References and Suggested Readings

1 Lewis B. Enteroscopy. Gastrointest Endosc Clin N Am; 2000;1:101-16.2 Meron G. The development of the swallowable video capsule (M2A®).

Gastrointest Endosc 2000;6:817-9.3 Appleyard Glukhovsky A, Jacob H, et al. Transit times for the capsule

endoscope. Gastrointest Endosc 2001;53:AB122

The Performance of Capsule EndoscopyChapter 2

There is a brief learning curve to achieve competency inreviewing, as the images are somewhat different thanconventional endoscopic images. The ideal environment forreview is a darkened quiet room. The computer controls aresimilar to using a videotape machine and images may beviewed singly or as a video stream. In the following chaptersthe images and diagnoses that can be made using capsuleendoscopy will be described.

Page 19: Atlante Immagini Pillcam

18

The Performance of Capsule EndoscopyChapter 2

Figure 2.

During the Examination Instructions Form

You have just swallowed a capsule endoscope. This sheetcontains information about what to expect over the next 8hours.Please call our office if you have severe or persistentabdominal or chest pain, fever, difficulty swallowing, or ifyou 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 maytake your medications at this time as well.

2. Do not exercise. Avoid heavy lifting. You may walk, sitand lay down. You can drive a car. You can return towork.

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 undergoingcapsule 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 thebathroom. Do not take the belt off.

7. Return to the office at _____ PM for disconnection andremoval of the equipment.

Figure 1.

Intializing Information Form

Prior to swallowing a capsule endoscope, we need certaininformation to initialize the computer for your study.

Please complete the following:All information is confidential.Please print.

1. First name:__________________

2. Middle name:________________

3. Last name:__________________

4. Social security number: _______-_______-________

5. Gender: Male Female

6. Birthdate:______/________/_______

7. Weight (lbs):_________________

8. Height (inches):______________

9. Waist (inches):_______________

Thank You

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

Page 20: Atlante Immagini Pillcam

19

The Performance of Capsule EndoscopyChapter 2

Figure 3.

Post Examination Instructions Form

You have just had a capsule endoscopy. This sheet containsinformation about what to expect over the next two days.Please call our office if you have severe or persistentabdominal 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 havemissed, but rather just begin your normal dosage.

6. Further Testing: Until the capsule passes, further testingthat includes any type of MRI should be avoided. If youhave a MRI scheduled for the next 3 days, this shouldbe postponed.

7. The Capsule: The capsule passes naturally in a bowelmovement, typically in 24 hours. Most likely you willbe unaware of its passage. It does not need to beretrieved and can safely be flushed down the toilet.Occasionally, the capsule lights will still be flashingwhen it passes.This is of no importance. Should you be concerned thatthe capsule did not pass, in the absence of symptoms,an abdominal x-ray can be obtained after 3 days toconfirm its passage.

Figure 4.

Capsule Endoscopy Report Form

Patient Name:_______________________________Recorder ID#:________________Date:_______________________Capsule ID#_________________

Pre-Exam Checklist:

1. Overnight fast confirmed2. Consent obtained3. Battery pack fully charged4. Recorder powered and connected to workstation5. Recorder initialized6. Simethicone administered (4 drops in cup of water)7. Skin marked with stencil8. Sensor array applied to skin9. Belt applied10. Recorder and battery pack installed in belt pack11. Sensor array attached to Recorder12. Recorder connected to battery pack13. Continuous light appears and then stops14. Capsule blinking on removal from holder15. Recorder flashes16. Patient told no drinking for 4 hrs, no eating for 5 hrs

Post-Exam Checklist:

8. Recorder disconnected from battery9. Recorder disconnected from sensor array10. Belt removed11. Sensor array removed12. Recorder powered and connected to workstation13. Download begun14. Battery pack powered for charging

Page 21: Atlante Immagini Pillcam

Figure 5.

Time Capsule Swallowed:____________

Recorder Disconnect Time:___________

Review

Length of Review

Start: Start: Start: Start: Start:

Stop: Stop: Stop: Stop: Stop:

Time: Time: Time: Time: Time: Total Time:

Colon Reached: Yes No

Time in Stomach:_____ Time to Colon:_____ Time in SB:_____

Findings: (Give time codes for all findings/Use additional pages if necessary)

Signature:______________________

20

The Performance of Capsule EndoscopyChapter 2

Page 22: Atlante Immagini Pillcam

23

a more pleated clover leaf like appearance than at conventionalendoscopy because the antrum is not distended with air. Themost common characteristic appearance in the stomach is ofthe large folds and intermittent movement often with repetitiveviewing of various areas of the stomach. Detailed physiologicalimages of the gastric mucosa can be seen.

Gastric movements can be divided into propulsive and non-propulsive. Propulsive movements force the capsule into theantrum and the pylorus may be seen if the optical dome ispointing in that direction. Non-propulsive contractions aremuch commoner and may be due to the contraction of theabdominal wall. The RAPID® (the software used to review theM2A® images) viewer should keep in mind that the stomachas well as the other images displayed are being viewed ata 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 changesince the 11 mm capsule fits the small intestine more snuglyso the images are brighter. Bile can at times be seen streamingproximally from the third portion of the duodenum. In thebulb a nodular appearance due to the presence of Brunner'sglands may be seen. The capsule usually passes quickly intothe second part of the duodenum where the villous pattern

INTRODUCTION

It is important to be familiar with normal M2A® anatomy. Thisknowledge will serve as a basis while evaluating images withpotential abnormalities. After placing the M2A® capsule inthe oral cavity there may be some transient condensationthat rapidly clears as the capsule reaches body temperature.As the capsule is manipulated with the tongue, excellentviews of the tongue and oral anatomy are obtained.

CAPSULE EXPERIENCE

ESOPHAGUS

The M2A® esophageal transit time is usually rapid, therebylimiting 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 esophagealsphincter so good images of the Z line at the gastroesophagealjunction can be acquired. Subjects are more likely to swallowthe capsule with the optical dome pointing down, which mayhelp with acquisition of images of the lower esophageal sphincter.

STOMACH

Average M2A® capsule gastric emptying time is approximatelyone hour, the range being very wide. The closed pylorus has

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

Chapter 3

Page 23: Atlante Immagini Pillcam

24

becomes very obvious. Because the wireless images areacquired without distension with air, and because there isusually some liquid present, the villi often appear to be stickingup and are more easily seen than at conventional endoscopy.The ampulla is rarely seen because it is concealed by foldsand lies below a linear fold. The transit in the second part ofthe duodenum is usually rapid. Sometimes serpiginous linearwhite lines can be seen which are an artifact caused by thecapsule pressing on and parting the villi. Another unusualartifact, which can be seen in the normal small intestine, isan appearance reminiscent of the convolutions of the brain.This is probably due to folds of small intestine being flattenedby pressure, either due to gravity with the optical domepressing downwards, or due to a small intestinal wave ofcontraction pressing the capsule against the folds.

The vascular pattern of the small bowel becomes easier toidentify once the capsule has entered the distal jejunum.Sometimes quite large veins with their accompanying arteriescan be seen in normal subjects. White spots are sometimesapparent especially in the proximal jejunum, which areprobably dilated lymphatic vessels. Lymphangiectatic cystsare very commonly seen in normal subjects. Bile becomesconcentrated, darkening the images further down the smallintestine. Villi may become less obvious as the capsuleprogresses into the ileum. Backwards and forwards movementis not uncommon.

TERMINAL ILEUM

The transition from the terminal ileum to cecum is usuallyapparent. The ileum usually includes lymphoid follicles thatappear as small white nodules in its villous pattern. Theremay be a delay if the valve fails to relax and retains the capsulefor a while. The capsule then drops into a large lumen as itenters the cecum. The pattern of movement changes,

becoming much slower. The different and more markedvascular pattern of the colonic mucosa will become apparent.

COLON

Even without preparation, some views of colonic mucosa andits vascular pattern are seen. Usually the capsule remains inthe cecal pole for an extended period of time without moving.Because the lumen of the colon is larger than that of the smallbowel, the views may be slightly darker, but if the colon isclean, usually good views are obtained. The appendicealorifice can sometimes be seen. The classic triangulatedappearance of the transverse colon may be seen. It is oftenpossible to see a bluish color, which may feature a meniscus-like edge through the wall of the colon. This may be due totransillumination of the liver or spleen. At times blood can beseen pulsing through the colonic arteries.

The more vascular appearance of rectal mucosa can bedistinguished from that of the more proximal colonic mucosa.The normal hemorrhoidal vasculature is sometimes seenclearly if the capsule is still transmitting images. When thecapsule passes through the anus, images change and turnwhiter and brighter.

CONCLUSION

M2A® capsule endoscopy gives detailed physiological imagesof the normal GI tract. To achieve competence in interpretingM2A® capsule abnormalities, it is important to become firstfamiliar with normal M2A® anatomy.

Normal M2Aß AnatomyChapter 3

Page 24: Atlante Immagini Pillcam

25

Figure 3.1 As M2A® capsule is being ingested, a wellpapillated normal appearing tongue is seen.

Figure 3.2a Pharynx.

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

Figure 3.2c EG junction.

M2A® M2A®

M2A® M2A®

Normal M2Aß AnatomyChapter 3

Page 25: Atlante Immagini Pillcam

26

Figure 3.2d Detailed view of the Z line.

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

Figure 3.2e View of normal proximal gastric folds.

Figure 3.3b View of gastric antrum.

M2A® M2A®

M2A® M2A®

Normal M2Aß AnatomyChapter 3

Page 26: Atlante Immagini Pillcam

27

Figure 3.4a Typical stellate-like appearance of normalpyloric opening as seen by capsule.

Figure 3.5a Normal jejunum.

M2A®

M2A®

Normal M2Aß AnatomyChapter 3

Figure 3.4c Normal proximal small bowel.

M2A®

Figure 3.4b Brunner’s gland hyperplasia with suspectedectopic gastric mucosa within duodenal bulb.

M2A®

Page 27: Atlante Immagini Pillcam

28

Figure 3.5c Histological appearance of normal villi.

Figure 3.6a The Ampulla of Vater. Not commonlyvisualized by the M2A® capsule.

Figure 3.6b Detailed view of the normal vasculatureof the small bowel.

M2A® M2A®

Normal M2Aß AnatomyChapter 3

Figure 3.5b Normal jejunum with normal villi as seenin former figure.

M2A®

Page 28: Atlante Immagini Pillcam

29

Normal M2Aß AnatomyChapter 3

Figure 3.7c Capsule view of the same area showinglymphoid hyperplasia.

M2A®

Figure 3.7a Small bowel follow through showingevidence of nodular lymphoid hyperplasia in theterminal Ileum.

Figure 3.7b Ileoscopy done on same patient revealingnodular lymphoid hyperplasia.

Figure 3.8 Normal Ampulla of Vater.

M2A®

Page 29: Atlante Immagini Pillcam

30

M2A®

Normal M2Aß AnatomyChapter 3

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

M2A®

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

M2A®

Figure 3.10 M2A® capsule approaching the ileocecalvalve.

M2A®

Figure 3.11a Normal vascular pattern of the cecal wall.

M2A®

Page 30: Atlante Immagini Pillcam

31

Normal M2Aß AnatomyChapter 3

Figure 3.11b M2A® capsule imaging the right colon.

M2A®

Figure 3.11c View of the anus by the M2A® capsule.

M2A®

Page 31: Atlante Immagini Pillcam

33

position is monitored using fluoroscopy, and may often require4-6 hours until the terminal ileum is reached. The clinicianthen observes the intestinal mucosa as the endoscope isslowly withdrawn. Unfortunately, this instrument is expensive,cumbersome, and usually more than half of the intestinecannot be viewed as the tip of the instrument often becomeslodged in the intestinal folds and the image is obscured.

The primary use for the enteroscope in inflammatory boweldisease is to diagnose celiac sprue, Crohn's disease as wellas other, more uncommon forms of inflammatory boweldisease, including systemic lupus erythematosus (SLE),radiation enteritis, ischemic enteritis, eosinophilicgastroenteritis as well as infectious enteritis, includinggiardiasis, Whipple's disease, mycobacteria, and tropicalsprue. Celiac sprue, giardiasis, and Whipple's disease typicallyinvolve the proximal intestine. Crohn's disease typicallyinvolves the terminal ileum and is rarely isolated to theduodenum or jejunum in the absence of involvement of otherareas of the gastrointestinal tract. Rare cases of chronic, non-granulomatous jejunoileitis have been described. Tropicalsprue typically involves both the proximal jejunum as well asthe ileum. Mycobacterium Avium may involve any portion ofthe small intestine, although M. tuberculosis, histoplasmosis,Yersinia enterocolitis, and Behcet 's syndrome usually involvethe ileocecal region.

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

INTRODUCTION

Development of the flexible enteroscope in the 1960's allowedthe practitioner direct visualization of the intestinal tract forthe first time. Insertion of these forward-viewing fiber-opticendoscopes (now supplanted by video endoscopes) permittedvisualization of the complete duodenum. Subsequently,longer endoscopes were used and continue to be used todayin order to visualize distally to the proximal or mid-jejunum.Enteroscopes have been developed over the last 10-15 yearsthat permit visualization of the proximal and mid-jejunum.Such endoscopes utilize an overtube through which theendoscope is inserted through the stomach. This limits gastriclooping of the endoscope, permitting more distal intubation.However, even the push enteroscope does not allowvisualization of the majority of small intestine, although itdoes permit steering, re-visualization of lesions, and targetedbiopsy and therapeutic maneuvers. In addition, conventionalenteroscopes have a field of vision that approaches 110-120degrees, versus approximately 140 degrees with the M2A®

Capsule Endoscope.

The Sonde enteroscope is a very thin endoscope that is passedtransnasally into the gastrointestinal tract. This endoscopehas a balloon at its tip which is propelled via peristalsis, tothe distal extent of the small intestine. The endoscope

Chapter 4

Page 32: Atlante Immagini Pillcam

may not always be evident. Whether the stricture isinflammatory, fibrotic, or carcinogenic, cannot bedifferentiated.

In this chapter, a spectrum of new images reflectinginflammatory pathology is described. As more experienceis gained with capsule endoscopy, these abnormalitieswill redefine our approach to suspected inflammatorybowel disease.

CONCLUSION

Video capsule endoscopy permits the direct viewing of mucosathroughout the entire small intestine. Strictures and othermucosal abnormalities not evident on radiographic studiesor beyond the reach of convention endoscopy can bevisualized. This noninvasive technique avoids many of thepitfalls inherent in the use of standard push or Sondeenteroscopy, although mucosal biopsy sampling is notpossible at the present time.

34

CAPSULE EXPERIENCE

Endoscopic appearance of celiac sprue, eosinophilicgastroenteritis, and infectious enteritis may be normal,although non-specific findings may be evident. These includemucosal thickening, erythema, nodularity, or even ulceration.The endoscopic appearance of celiac or topical sprue mayinclude scalloping of the valvulae conniventes as well as amosaic pattern of the mucosa.

The endoscopic appearance of Crohn's disease may includeerythema, apthoid and linear ulceration, thickening of mucosalfolds, nodules, stenosis, and even fistula formation. The lattermay be exceedingly difficult to visualize endoscopically.Ulcers may be linear, longitudinal or transverse, and maycoalesce, forming a grid over non-ulcerated mucosa.Characteristically, there are areas of normal interveningmucosa in between areas of mucosal involved with Crohn'sdisease ("skip lesions"). Capsule Endoscopy has revealed anentirely new spectrum of inflammatory lesions allowingendoscopic diagnosis of small bowel inflammation before itis apparent by other diagnostic modalities.

Barium contrast radiographic studies, complemented bycomputerized tomography (CT) have been the primary toolfor the diagnosis of inflammatory lesions of the small intestine.The findings from these studies are often non-specific, andinclude dilated intestinal loops, separation of the intestinalloops, or mucosal spiculation which suggests the outline ofmucosal ulceration. Although CT does not detect mucosalinflammation, marked transmural thickening and signs ofextraintestinal inflammation such as peri-intestinal fatstranding and mesenteric lymphadenopathy may be evident;fistula formation may also be identified. Since barium fillsthe lumen, strictures are often readily identified, although

Inflammatory Diseases of the Small IntestineChapter 4

References and Suggested Readings

1 Sasamura H, Nakamoto H, Ryuzaki M, et al. Repeated intestinal ulcerationsin a patient with systemic lupus erythematosus and high serum antiphospholipid antibody levels. South Med J 84:515- 517, 1991

2 Mashako MN, Cezard JP, Navarro J, et al. Crohn's disease lesions in the upper gastrointestinal tract: Correlation between clinical, radiological, endoscopic, and histologic features in adolescents and children.J Pediatr Gastroenterol Nutr 8:442-446 1989

3 Cameron D. Upper and lower gastrointestinal endoscopy in children and adolescents with Crohn's disease. J Gastroenterol Hepatol 6:355-358, 1991

4 Jeffires GH, Steinberg H, Sleisenger MH. Chronic ulcerative (nongranulomatous) jejunitis. Am J Med 44:47-59, 1968

5 Baer AN, Bayless TM, Yardley JH. Intestinal ulceration and malabsorption syndromes. Gastroenterology 79:754-765, 1980

Page 33: Atlante Immagini Pillcam

6 Sayek I, Aran O, Uzunaliamoglu B, et al. Intestinal Behcet's disease: surgicalexperience in seven cases. Hepatogastroenterology 38:81-83, 1991

7 Tawil S, Brandt LJ, Bernstein LH. Scalloping of the valvulae conniventes andmosaic mucosa in tropical sprue. Gastrointestinal Endosc 37:365-366, 1991

8 Alcantara M, Rodriguez R, Potenciano JL, et al. Endoscopic and bioptic findings in the upper gastrointestinal tract in patients with Crohn's disease.

Endoscopy 25:282-286, 19939 Lescut D, Vanco D, Bonniere P, et al. Perioperative endoscopy of the whole

small bowel in Crohn's disease. Gut 34:647-649, 1993

Inflammatory Diseases of the Small IntestineChapter 4

35

Page 34: Atlante Immagini Pillcam

36

M2A®

Inflammatory Diseases of the Small IntestineChapter 4

Figure 4.3 Superficial jejunal ulcer in a patient withpatchy areas of moderate to severe enteritis.

Figure 4.2 Ulceration in the terminal ileum in a patientwith IBD.

Figure 4.1a Villous erosion with fibrosis in the jejunalarea. Presence of prominent whitish villi suggestssubmucosal fibrosis.

Figure 4.1b Area of edema, erythema and villouserosion in a patient with small bowel inflammatorydisease.

M2A® M2A®

M2A® M2A®

Page 35: Atlante Immagini Pillcam

37

Inflammatory Diseases of the Small IntestineChapter 4

Figure 4.4c The biopsy shows mild to moderateinflammation with partial villous atrophy and blunting.(H&E X 20).

Figure 4.4a Focal area of inflammation characterizedby erythema, edema, dilated lymphatics and mucosalbreakdown.

Figure 4.4b Jejunum with nodular area of inflammationand superficial ulceration.

M2A® M2A®

Figure 4.5a Jejunum of patient with Crohn’s diseaseshowing thickened infiltrated folds.

M2A®

Page 36: Atlante Immagini Pillcam

38

Inflammatory Diseases of the Small IntestineChapter 4

Figure 4.5b Ongoing infiltration, ulceration andnodularity in Crohn’s disease.

M2A®

Figure 4.5c Inflammatory process infiltrating andthickening this small bowel fold.

M2A®

Figure 4.5d Small bowel stricture in this patient withCrohn’s disease. Note the slit-like opening of thestricture. Capsule passed easily.

M2A®

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

M2A®

Page 37: Atlante Immagini Pillcam

39

Inflammatory Diseases of the Small IntestineChapter 4

Figure 4.5f Pseudopolyp with surroundingcobblestoning in Crohn’s disease.

M2A®

Figure 4.5g Near total obliteration of lumen secondaryto inflammatory process.

M2A®

Figure 4.5h Irregular ulcer in IBD.

M2A®

Figure 4.6a M2A® Capsule entering a narrowed areawith surrounding geographic ulceration.

M2A®

Page 38: Atlante Immagini Pillcam

40

Inflammatory Diseases of the Small IntestineChapter 4

Figure 4.6b M2A® Capsule passing through thenarrowed area as depicted in 4.6a.

M2A®

Figure 4.6c Narrowed lumen with surroundingulceration in Crohn’s disease.

M2A®

Figure 4.6d Isolated ulcer in a normal surroundingarea in a patient with known IBD.

M2A®

Figure 4.6e Inflammation, ulceration and narrowingin a patient with IBD.

M2A®

Page 39: Atlante Immagini Pillcam

41

Inflammatory Diseases of the Small IntestineChapter 4

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 diseaserevealing submucosal edema and ulceration.

M2A®

Figure 4.8b Early inflammatory lesions with spectrumof abnormalities showing edema, villous erosion andulceration.

M2A®

Page 40: Atlante Immagini Pillcam

42

Inflammatory Diseases of the Small IntestineChapter 4

Figure 4.9b Same patient. View of additional ulcerwith narrowing of lumen.

M2A®

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

M2A®

Figure 4.9c At surgery Crohn’s disease was diagnosed.A deep fissure can be seen in the histologicalexamination. (H&E).

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

Page 41: Atlante Immagini Pillcam

43

Inflammatory Diseases of the Small IntestineChapter 4

Figure 4.11 Early duodenal fissuring in a patient withearly Crohn’s lesion.

M2A®

Figure 4.12 Ileal linear ulceration.

M2A®

Figure 4.10b Lymphoid hyperplasia.Figure 4.10a Lymphoid hyperplasia. This is a normalvariant and should not be interpreted as pathologicalnodularity.

M2A® M2A®

Page 42: Atlante Immagini Pillcam

44

Inflammatory Diseases of the Small IntestineChapter 4

Figure 4.14 Ileal lesion in Crohn’s disease.

M2A®

Figure 4.13c Area of proximal jejunum with erythema,edema. Note the ulcer between 6 and 7 o’clock.

M2A®

Figure 4.13b Early proximal small bowel inflammation.

M2A®

Figure 4.13a Segment of proximal small bowel withedema and erythema.

M2A®

Page 43: Atlante Immagini Pillcam

45

Inflammatory Diseases of the Small IntestineChapter 4

Figure 4.16 Crohn’s disease with mucosal fissure inproximal jejunum.

M2A®

Figure 4.15a Jejunal linear ulcerations.

M2A®

Figure 4.15b Jejunal linear ulcerations.

M2A®

Figure 4.15c Linear ulceration in Crohn’s disease.

M2A®

Page 44: Atlante Immagini Pillcam

47

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

INTRODUCTION

Tumors of the small bowel comprise 5% to 7% of allgastrointestinal tumors. With the use of more accuratediagnostic methods, diagnosis of small bowel tumors hasbecome more frequent and it is probable that the actualincidence is underestimated. The most important symptomin cases of small bowel neoplasia is undoubtedly obscurebleeding with secondary iron deficiency anemia. Indeed, smallbowel tumors are the second most common cause of obscuregastrointestinal bleeding, accounting for 5% to 10% of allcases of chronic blood loss. Among patients with obscuregastrointestinal bleeding, small bowel tumors are the singlemost common lesion in patients below 50 years of age.

Having excluded the upper and lower portions of thegastrointestinal tract, attention should be concentrated onthe small bowel as being responsible for bleeding. Thisstrategy probably affords the rapid identification of a tumoras a cause of the bleeding. The most frequent location bothfor epithelial tumors and for non-epithelial small bowel tumorsis 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 smallbowel and carcinoids are more common in the ileum.

Adenomas are the most common benign small bowel tumorswith malignant potential and adenocarcinoma is the mostcommon malignant small bowel tumor. Carcinoid tumors arethe second most frequent neoplasm encountered in the smallbowel. Primary intestinal lymphoma accounts for about 20to 30% of malignant neoplasms of the small bowel and is thethird most common small bowel neoplasm. Among vasculartumors, hemangiomas and lymphangiomas account for 3%to 8% of all benign small bowel neoplasms; Kaposi's sarcomais the most frequent neoplasm in AIDS patients. GISTs arenon-epithelial neoplasms that originate from cells located inthe wall of the stomach and small bowel and are characterizedby extreme variability of differentiaton potential. GISTs withsmooth muscle differentiation (leiomyomas) are the second-commonest benign tumors of the small bowel. GISTs withneural differentiation (schwannomas, gastrointestinalautonomic nerve tumors) are rare neoplasms that may be thecause of obscure gastrointestinal bleeding.

CAPSULE EXPERIENCE

Diagnostic methods for small bowel tumors includeenteroclysis, CT, MR imaging, arteriography, enteroscopy andcapsule endoscopy. Barium studies of the small bowel havelow diagnostic yield. In our personal experience of 24 patients

Chapter 5

Page 45: Atlante Immagini Pillcam

Neoplastic Diseases

with small bowel tumors identified enteroscopically, only 25%had enteroclysis compatible with the presence of a smallbowel tumor. Although tumors may escape diagnosis evenwith enteroscopy, in any case it appears to be superior tobarium studies of the small bowel in patients with obscurebleeding in whom tumor is suspected. The two methods areusually considered to be complementary, but it is hoped thatrecently introduced diagnostic methods such as helical CTenteroclysis, MR enteroclysis and, above all, capsuleendoscopy may modify the non invasive diagnostic approachto this important pathology.

In the two clinical trials performed in the United States andin Italy to evaluate the use of capsule endoscopy in patientswith obscure bleeding reported so far, 2 out of 36 patients(5%) were ultimately diagnosed to have a small bowel tumorand had curative surgery. This further stresses that capsuleendoscopy is an extremely promising tool for the diagnosisof small bowel tumors.

Capsule endoscopy and push enteroscopy are also extremelyimportant in the surveillance of groups of patients withincreased risk of small bowel tumors, such as the followingprecancerous conditions: celiac disease, ulcerative jejuno-ileitis, familial adenomatous polyposis (FAP), Peutz-Jegherssyndrome (PJS), juvenile polyposis, immunodeficiencysyndromes, alpha-chain disease, small bowel adenomas,hereditary non-polyposis colorectal cancer syndrome (HNPCC).In particular, in patients with FAP or PJS, whereas surveillanceof the upper and lower gastrointestinal tract is easily achievedthrough esophagogastroduodenoscopy and total colonoscopywith terminal ileoscopy, the small bowel is still an importantand challenging problem. Capsule endoscopy offers the greatopportunity to identify polyps and map their distribution.It is to be hoped that this new technique will be able to replace

the more invasive enteroclysis in the surveillance strategy forthe small bowel. A follow-up program might be based onperiodic capsule endoscopies, and the use of other techniquessuch as push enteroscopy and/or intraoperative enteroscopycould be targeted on the basis of the data acquired bythe capsule.

CONCLUSION

Capsule endoscopy is highly innovative both from thetechnological and the clinical standpoint, since it providesnon invasive visualization of areas of the small bowel thatare not easily accessible using wired endoscopy. There isalso the undoubted advantage of a simple, complication-freeprocedure that does not require hospitalization. Capsuleendoscopy opens up new horizons for the diagnosis of smallbowel tumors. It will very probably bring about the progressiveabandonment of some currently used invasive and costlydiagnostic methodologies (which also have a low diagnosticyield), which greatly increase the cost of managinggastroenterological patients.

Chapter 5

References and Suggested Readings1 Rossini FP, Risio M, Pennazio M. Small bowel tumors and polyposis

syndromes. Gastrointest Endosc Clin N Am 1999; 9: 93-1142 Lewis BS, Swain P. Capsule endoscopy in the evaluation of patients with

suspected small intestinal bleeding: the results of the first clinical trial. Gastrointest Endosc 2001; 53: 70

3 Pennazio M, Santucci R, Rondonotti E, et al. Wireless capsule endoscopy in patients with obscure gastrointestinal bleeding: preliminary results of the Italian multicentre experience. Digest Liver Dis 2001; 33: 2

4 Pennazio M, Rossini FP. Small bowel polyps in Peutz-Jeghers syndrome: management by combined push enteroscopy and intraoperative enteroscopy.Gastrointest Endosc 2000; 51: 304-8

5 Rossini FP, Pennazio M. Small bowel endoscopy. Endoscopy 2002; 34:13-20

48

Page 46: Atlante Immagini Pillcam

49

Neoplastic DiseasesChapter 5

Figure 5.1 Benign appearing polyp of small bowel.

M2A®

Figure 5.2 80 year old patient with chronic GI bloodloss requiring transfusion. CE revealed a large polypoidmass of small intestine

M2A®

Figure 5.3a Duodenal polyp in patient with familialpolyposis.

M2A®

Figure 5.3b Histology of polyp in figure 5.3a revealsa villous adenoma with high grade dysplasia. (H & E).

Page 47: Atlante Immagini Pillcam

50

Neoplastic DiseasesChapter 5

Figure 5.4b Small bowel series of same patientrevealing the polyp.

Figure 5.4a Large hamartomatous polyp in Peutz-Jegher’s Syndrome.

M2A®

Figure 5.5a Large jejunal polyp causing recurrentbleeding in a 70 year old patient.

M2A®

Figure 5.5b Surgical specimen of case 5.5a. Noticepolyp at 6 o’clock.

Page 48: Atlante Immagini Pillcam

51

Neoplastic DiseasesChapter 5

Figure 5.7a Patient with PJS. CE revealed hamar-tomatous polyp in duodenum.

M2A®

Figure 5.6a Diffuse lymphoid hyperplasia presentthroughout the entire GI tract in a patient with CommonVariable Immunodeficiency.

M2A®

Figure 5.6b Detailed view of the lymphoid nodularhyperplasia in same case.

M2A®

Figure 5.6c Small intestine. Lymphoid hyperplasia.There are hyperplastic B-cell follicles as well as aprominent interfollicular infiltrate.

Page 49: Atlante Immagini Pillcam

52

Neoplastic DiseasesChapter 5

Figure 5.7b Same patient with polyps in distal jejunum.

M2A®

Figure 5.8a Carcinoid tumor of small bowel.

M2A®

Figure 5.8b Histology of carcinoid tumor of small bowelshows solid nests of tumor cells in the submucosawhich were positive for neuroendocrine markers. (H&E).

Figure 5.7c Same patient with hamartomatous polyp.

M2A®

Page 50: Atlante Immagini Pillcam

53

Neoplastic DiseasesChapter 5

Figure 5.9 Ileal Carcinoid. A 45 year old patient withthree episodes of GI hemmorrhage. Multiple evaluationsdid not reveal a bleeding source. M2A® Capsuleendoscopy revealed an ileal submucosal mass.

M2A®

Figure 5.10c High magnification of GIST shows a densecellular area with pleomorphic spindle-shaped cells. (H&E).

Figure 5.10a Gastrointestinal Stromal Tumor. Thewhite mass at 5 o’clock is the submucosal portion ofa 3 cm exophytic malignant GIST causing repeated GIbleeding. The vessel coursing at its apex is beingeroded by the tumor.

M2A®

Figure 5.10b Same GIST as in former figure.

M2A®

Page 51: Atlante Immagini Pillcam

54

Neoplastic DiseasesChapter 5

Figure 5.11a A 49 year old male, suffering from weightloss, recurrent abdominal pain and diarrhea. Polypoidlesions in duodenum, with thickened mucosa and linearerosions. This lesion was proven to be a lymphoma ofthe small bowel.

M2A®

Figure 5.11b Same patient with lymphomatouspolypoid mass in jejunum.

M2A®

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

Figure 5.11c Upper GI series showing an irregularity inthe 3rd and 4th portion of the duodenum correspondingto an infiltration of the wall by the lymphoma.

Page 52: Atlante Immagini Pillcam

55

Neoplastic DiseasesChapter 5

Figure 5.11f Same patient with a small polyp in ileum.

M2A®

Figure 5.11e Histology reveals Non-Hodgkin FollicularLymphoma (grade 1). Immunohistochemical stainingshowed: CD20, bcl-2 and CD10: (+). CD3, CD5, Cyclin D: (-).

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.

M2A®

Page 53: Atlante Immagini Pillcam

56

Neoplastic DiseasesChapter 5

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

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

Figure 5.12e Endoscopy reveals lymphoma of theduodenum.

Figure 5.12f Endoscopy reveals the same area in theduodenum.

Page 54: Atlante Immagini Pillcam

57

Neoplastic DiseasesChapter 5

Figure 5.13a Images of proximal small bowel showingthickened folds with onset of ulceration.

M2A®

Figure 5.13b A narrowed lumen with a key holeconfiguration is seen in this infiltrating Non-Hodgkin’sT-Cell Lymphoma, same patient.

M2A®

Figure 5.14a Infiltrating adenocarcinoma of thejejunum with active bleeding.

M2A®

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

M2A®

Page 55: Atlante Immagini Pillcam

58

Neoplastic DiseasesChapter 5

Figure 5.15a Adenocarcinoma of small bowel in a 57year old male with a pancreatic mass. The pancreaticmass 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 patientwho underwent resection for a small boweladenocarcinoma two years prior to CE.

M2A®

Figure 5.16b Push enteroscopy of the same case.

Page 56: Atlante Immagini Pillcam

59

Neoplastic DiseasesChapter 5

Figure 5.16c Same case revealing an elongatedpolypoid lesion.

M2A®

Figure 5.16d Histological examination of one of thepolyps showing normal mucosa with no signs ofmalignancy. These polyps proved to be normal tissuein a polypoid configuration.

Figure 5.17a Submucosal jejunal mass in a patientwith GI bleeding.

M2A®

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

M2A®

Page 57: Atlante Immagini Pillcam

60

Neoplastic DiseasesChapter 5

Figure 5.18a Nodular lesion of small bowel in AIDSpatient with biopsy proven Kaposi’s.

M2A®

Figure 5.18b Submucosal nodular lesion of smallbowel in Kaposi’s sarcoma.

M2A®

Figure 5.19b Nodular bluish lesion in a patient withsuspected Kaposi’s sarcoma, same case.

M2A®

Figure 5.19a Nodular bluish lesion in a patient withsuspected Kaposi’s sarcoma.

M2A®

Page 58: Atlante Immagini Pillcam

Neoplastic DiseasesChapter 5

Figure 5.20 AIDS patient with recurrent unexplainedGI bleeding. Note bluish nodular lesion suspected tobe Kaposi’s sarcoma of the small bowel.

M2A®

Figure 5.19c Nodular bluish lesion in a patient withsuspected Kaposi’s sarcoma, same case.

M2A®

61

Page 59: Atlante Immagini Pillcam

63

particularly true in patients who use NSAIDs and who havehad radiation, because these strictures may not bedemonstratable by conventional technology includingenteroclysis. Therefore, CE should not be performed onpatients who are an unacceptable operative risk, sinceretention of a capsule in such a patient could put all concernedin a serious predicament. Retained capsules have remainedin patients for up to 14 weeks without causing symptoms,but more long-term data regarding retained capsules isneeded. The small bowel may be injured by a variety ofmedications, ionizing radiation and surgery with short and/orlong-term consequences. This chapter will review theseconditions and provide images that demonstrate each ofthese situations.

CAPSULE EXPERIENCE

NSAIDS AND OTHER MEDICATIONS

NSAIDs are well known to cause gastro-duodenal injury. Lesscommonly, injury to the more distal small bowel and colonhas been reported. Well described, but rare, are NSAIDassociated webs or strictures. How common these latterlesions are is unknown, as they will only draw attention tothemselves if they cause bleeding or iron deficiency anemia.Generally small bowel series or enteroclysis will not showthem, as they are often only more rigid versions of the normal

Iatrogenic DiseasesDavid R. Cave, M.D.

INTRODUCTION

Capsule endoscopy [CE] has provided a revolutionary andsensitive method for the visualization of the small intestinalmucosa at an 8:1 magnification with excellent resolution. Thistechnology allows us for the first time to view non-invasivelythe majority of the intestinal mucosa. Any technology issubject to the Heisenberg uncertainty principle. In brief, thisstates that, in the process of making an observation, themeasurement alters the behavior of the object of study. Inthe case of CE, the capsule behaves as a large particle of food.Because of this, the mucosal folds are in their near naturalstate unlike during conventional push enteroscopy where theinsufflation of air opens the lumen and flattens the mucosa.Furthermore, the process of mucosal flattening may obscuresubtle villous changes. Similarly diverticula are generally notseen with CE, because the lumen is collapsed and are thereforeunlikely to trap a capsule.

It is important to understand that succus entericus and partiallydigested food are liquid and rarely contain large food particles.Therefore quite tight strictures may only be revealed bypassage or retention of the video capsule that has a diameterof 11mm. The implications of this are, that the pros and consof the procedure should be carefully considered, by bothpatient and physician, prior to capsule ingestion. This is

Chapter 6

Page 60: Atlante Immagini Pillcam

64

plicae circulares. A history of NSAIDs or aspirin use shouldbe a caveat to users of CE that a normal small bowel seriesor enteroclysis does not preclude the presence of a stricturetight enough to cause retention of the capsule. Usually thecapsule will tumble around proximal to the stricture,asymptomatically, and eventually pass spontaneously.However it may produce pain and transient obstruction andeven require surgical retrieval. The stricture may or may notbe ulcerated. Ulcers may occur without strictures. It isnot clear as to whether the process of stricturing andulceration continues after the cessation of NSAID use. Othermedications have been implicated in small intestinalstrictures such as slow release potassium tablets. Thisis very rare. Chemotherapy induced mucositis is quitecommon, but usually easily detected with an endoscopein the duodenum.

RADIATION INJURY

Radiation therapy for a variety of neoplastic conditions,especially cervical and endometrial lesions, may unavoidablyradiate the small intestine, despite the radio therapist havingtaken measures to avoid this problem. The small intestineis moderately resistant to long-term injury but maynevertheless develop chronic radiation injury includingmucosal changes, strictures and ulcerations leading toobscure gastrointestinal bleeding and bacterial overgrowth.

Careful choice of patient for CE is mandatory in patients whohave received radiation. Only those who are operativecandidates should be considered for study, since capsuleretention and subsequent retrieval may entail a difficultdissection of matted loops of small bowel and a resectionof a long length of irradiated bowel. Anastomoses may healpoorly in this setting. Small bowel series may reveal stricturesbut may miss them. Limited experience using intra-operative

enteroscopy has demonstrated tight strictures not seenon small bowel series.

SURGICAL INTERVENTION

Small bowel resective surgery, unless for Crohn's disease, isuncommon. The blood supply to the small bowel is usuallyexcellent and hence small intestinal anastomoses rarely healwith stricturing. Ileo-colonic anastomoses also usually healwell. Anastomoses as well as staples and sutures can bevisualized by CE. Development of small bowel adhesions isquite common after any abdominal surgery. The role of CE inthis setting remains to be determined. In any patient whopresents with presumed adhesions and intermittent or partialsmall bowel obstruction, a small bowel series should be anecessary prelude to CE. The patient and physician shouldclearly understand the potential for retention of the capsuleand possible need for surgical retrieval of the capsule, priorto embarking on the study.

CONCLUSION

Iatrogenic small intestinal mucosal abnormalities, ulcers andstrictures may be found with much higher frequency than waspossible with conventional endoscopy and radiology. Theseoften-unanticipated small intestinal strictures may lead tocapsule retention. The capsule passes the majority ofstrictures uneventfully within a few hours or days. A smallproportion of these patients may need surgical removal ofthe capsule and the related lesions.

Chapter 6 Iatrogenic Diseases

Page 61: Atlante Immagini Pillcam

65

Figure 6.1a Ulcer secondary to NSAID use. Patientwas on COX-1 inhibitors.

M2A®

Figure 6.1b Membranous stricture caused by NSAIDuse, same case.

M2A®

Figure 6.1c NSAID induced membranous stricture,same case.

M2A®

Figure 6.1d NSAID induced small intestinal ulcer, samecase.

M2A®

Chapter 6 Iatrogenic Diseases

Page 62: Atlante Immagini Pillcam

66

Figure 6.1e Membranous stricture with ulcerationsecondary to NSAID use.

M2A®

Figure 6.3 Surgical staples at an anastomosis.

M2A®

Figure 6.2 NSAID induced small bowel stricture.

M2A®

Figure 6.4 NSAID induced small bowel stricture.

M2A®

Chapter 6 Iatrogenic Diseases

Page 63: Atlante Immagini Pillcam

67

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 milderythema were found in a patient on COX-2 inhibitors.

M2A®

Chapter 6 Iatrogenic Diseases

Page 64: Atlante Immagini Pillcam

Figure 6.9a NSAID stricture with active bleeding.

M2A®

Figure 6.9c Microscopic examination showingulceration of stricture depicted in Fig. 6.9a (H&E).

Figure 6.9b Histology showing fibromuscularhyperplasia of stricture depicted in Fig. 6.9a (H&E).

68

Figure 6.10a Minor erosion secondary to NSAID use.

M2A®

Chapter 6 Iatrogenic Diseases

Page 65: Atlante Immagini Pillcam

Figure 6.10b NSAID induced erosions. Patient was onCOX-2 inhibitors.

M2A®

Figure 6.10c Mucosal erythema and edema secondaryto NSAIDs.

M2A®

69

Figure 6.11a Radiotherapy induced stricture. Notecoffee grounds.

M2A®

Figure 6.11b Radiotherapy induced stricture. Noteabnormal villous pattern.

M2A®

Chapter 6 Iatrogenic Diseases

Page 66: Atlante Immagini Pillcam

Figure 6.12a CE reveals edematous erythematousmucosa with early neo-vascularization. This patientunderwent abdominal radiotherapy within the last 12months.

M2A®

70

Figure 6.12c Above patient showing active bleeding.

M2A®

Figure 6.12b Same case as previous image.

M2A®

Chapter 6 Iatrogenic Diseases

Page 67: Atlante Immagini Pillcam

73

allows diagnostic exploration of the whole small intestinewith very low risk and high comfort for the patient.

CAPSULE EXPERIENCE

AVMs of the small bowel are lesions that occur with increasingfrequency secondary to aging. These lesions are presumedto be degenerative in nature, secondary to either intermittentobstruction of the submucosal veins or hypoxemia of themicrocirculation resulting from cardiac or pulmonary disease.They can appear as small red spots, sometimes slightlyelevated. They may be large and flat or even spider like. Incontrast to congenital or neoplastic vascular lesions such ashemangioma and arteriovenous malformations they are notassociated with dermal angiomas. The differential diagnosesof AVMs of the GI tract should include post-radiationtelangiectasia and lesions of Hereditary HemorrhagicTelangiectasia and Osler-Weber-Rendu.

Small bowel AVMs are a source of significant morbidity frombleeding and are the most common cause of obscure GIbleeding, regardless of presentation (obscure-occult orobscure-overt) or mode of investigation. They were identifiedas the source of bleeding by push-enteroscopy in 8%-45%by sonde enteroscopy in 7%-27% and by combination of both

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

INTRODUCTION

Vascular abnormalities in the small bowel have beenincreasingly recognized as important causes of bleeding.They may affect any section of the small bowel and in somepatients with hereditary conditions are associated withvascular anomalies elsewhere, particularly in the skin. Termsused to describe these lesions include telangiectasias,phlebectasias, angioectasias and angiodysplasias orarteriovenous malformations (AVMs).

Obscure bleeding typically refers to recurrent or persistentiron deficiency anemia, positive FOBT, or visible bleedingwith no bleeding source found at original endoscopy (EGDand colonoscopy). These cases pose difficult diagnosticand management problems. They require numeroustransfusions, repeated hospital admissions and multipleendoscopic procedures. Up to 25% of lower intestinalbleeding causes remain undiagnosed after initial andsometimes exhaustive investigation. The main problem is,that not all parts of the small bowel can be reached byconventional endoscopy and flat lesions like AVMsangioectasia cannot be detected by radiologicalexaminations. Invasive intraoperative enteroscopy with itsrisk for complications was the only possibility for totalvisualization of the small bowel. Today, the M2A® capsule

Chapter 7

Page 68: Atlante Immagini Pillcam

74

diagnostic tools in 31% of obscure bleeding cases. In largestudies involving intraoperative enteroscopy angiodysplasiaswere identified in 34%-40% of patients.

We performed capsule endoscopy in 28 patients with obscure-occult or obscure-overt bleeding and we found bleedingsources in 72% of these patients. In 11 cases the capsulefound AVMs: one or multiple flat telangiectasias in 10 patientsand jejunal varices in one case. 7 patients showed sites of ableeding source, in these cases AVMs are also a probableorigin of bleeding. Many authors have reported on theincreased incidence of AVMs in patients with aortic stenosis(Heyde-syndrome), renal failure, von Willebrand’s disease,cirrhosis and pulmonary disease. Association with aorticstenosis and decrease of bleeding after aortic valvereplacement is widely described, but because ofmethodological flaws of these mostly retrospective studiesa clear relationship has not yet be confirmed. Three of our 10patients with small bowel telangiectasias suffered fromadditional aortic stenosis. Not all of the other associationshave been subjected to critical analysis, but available evidencedoes not support a strong relationship in most instances.

Therapeutic options for vascular abnormalities of the GI tractinclude interventional-endoscopic procedures like electro- orlasercoagulation, argon plasma coagulation, sclerotherapyand ligation. According to a recent multicenter, randomizedclinical trial hormonal replacement therapy does not seem tobe useful in the prevention of rebleeding from gastrointestinalangiodysplasia.

Vascular abnormalities of the small bowel other than acquiredAVMs are rare. Some case reports describe phlebectasia orvarices of the small bowel, solitary jejunal or ileal vascularabnormalities or jejunal Dieulafoy’s lesions as gastrointestinal

bleeding sources. In one of our younger patients (36 yearsold) with recurrent obscure-overt bleeding capsuleexamination could reveal a short part of the jejunum withextensive varices. After successful surgery the patient did notbleed any more.

Syndromes like Hereditary Hemorrhagic Telangiectasia (HHT),von Willebrand’s disease, the Blue Rubber Bleb NevusSyndrome or Klippel-Trenaunay syndrome can be associatedwith gastrointestinal vascular malformations. Hereditaryhemorrhagic telangiectasia is transmitted in an autosomaldominant way and is characterized by multiple telangiectasiasof the skin, mucous membranes, extremities, lung and brain.The prevalence of typical telangiectases throughout thegastrointestinal tract is estimated to be about 15 to 44% ofpersons affected with HHT. Intestinal bleeding occurs in 10- 40% of these patients, mostly in the older patients with thisdisorder. Epistaxis is found more frequently in the young.

CONCLUSION

Vascular abnormalities are important causes of gastrointestinalbleeding, especially obscure bleeding. The lesions can occurthroughout the whole intestine and can often not be reachedby conventional endoscopic examinations. In these casesvisualization of the total intestine as provided by the M2A®

Capsule is a crucial addition to our diagnostic approach tothese cases.

Vascular AbnormalitiesChapter 7

Page 69: Atlante Immagini Pillcam

75

Vascular AbnormalitiesChapter 7

References and Suggested Readings

1 Zuckerman GR, Prakash C, Askin MP, Lewis BS. AGA technical review on theevaluation 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 patientsand associated with cardiac, vascular and pulmonary disease.Gastrointest Endosc 1980;26:134-138

5 Foutch PG, Sawyer R, Sanowski RA. Push-enteroscopy for diagnosisof 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, CouturierD, Barbier JP, Cellier C. Diagnostic yield of push-type enteroscopy in relationto 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 diagnosisof obscure gastrointestinal bleeding. Am J Gastroenterol 1994;89:2139-2142

10 Szold A, Katz LB, Lewis BS. Surgical approach to occult gastrointestinal bleeding. Am J Surg 1992;163:90-92

11 Ress AM, Benacci JC, Sarr MG. Efficacy of intraoperative enteroscopy in diagnosis and prevention of recurrent, occult gastrointestinal bleeding.Am J Surg 1992;163:94-98

12 Imperiale TF, Ransohoff DF. Aortic stenosis, idiopathic gastrointestinal bleeding and angiodysplasia: is there an association, Gastroenterology 1988;95:1670-1676

13 Sharma R, Gorbien MJ. Angiodysplasia and lower gastrointestinal tract bleeding in elderly patients. Arch Intern Med 1995;155:807-812

14 Krevsky B. Detection and treatment of angiodysplasias. Gastrointest EndoscClin N Am 1997;7:509-524

15 Junquera F, Feu F, Papo M, Videla S, Armengol JR, Bordas JM, Saperas E, Piqué JM, Malagelada J-R. A multicenter, randomized, clinical trial of hormonaltherapy in the prevention of rebleeding from gastrointestinal angiodysplasia.Gastroenterology 2001;121:1073-1079

16Kumar P, Salcedo J, al-Kawas FH. Enteroscopic diagnosis of bleeding jejunalphlebectasia: a case report and review of literature. Gastrointest Endosc 1997;46:185-7

17 Chen JJ, Changchien CS, Lin CC. Dieulafoy’s lesion of the jejunum. Hepatogastroenterology 1999;46:1699-701

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

Page 70: Atlante Immagini Pillcam

76

Vascular AbnormalitiesChapter 7

Figure 7.1a Patient with phlebactasia. Work-up forvarices, 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.

M2A®

Page 71: Atlante Immagini Pillcam

77

Vascular AbnormalitiesChapter 7

Figure 7.2 74 year old female with severegastrointestinal bleeding. A repeat deep ileo-colonoscopy revealed the vascular malformation. Itwas treated by argon plasma coagulation. No bleedingepisodes occurred in follow-up.

M2A®

Figure 7.4a Arteriovenous malformation of jejunumas a source of recurrent bleeding.

M2A®

Figure 7.4b Histology of AVM (same case as 7.4a)showing mucosal and submucosal dilated vessels withfresh superficial bleeding (H&E).

Figure 7.3 36 year old male with lower gastrointestinalbleeding and asplenia. Capsule endoscopy revealedshort jejunal segment with varices. Section wassuccessfully resected.

M2A®

Page 72: Atlante Immagini Pillcam

78

Vascular AbnormalitiesChapter 7

Figure 7.6 Angiodysplasia of small intestine.

M2A®

Figure 7.5a Duodenal angiodysplasia in 73 year oldmale with recurrent massive bleeding.

M2A®

Figure 7.5b Same case as Fig. 7.5a showing ileocecalangiodysplasia at 6 o’clock.

M2A®

Figure 7.7 Angiodysplasia of small bowel.

M2A®

Page 73: Atlante Immagini Pillcam

79

Vascular AbnormalitiesChapter 7

Figure 7.8a Small angiodysplasia of jejunum.

M2A®

Figure 7.9 Venous malformation in a patient with BlueRubber Bleb Nevus Syndrome.

M2A®

Figure 7.10 Giant ileal angiodysplasias.

M2A®

Figure 7.8b Histology of Fig. 7.8a revealing prominentand congested vessels (PAS stain, 50 X).

Page 74: Atlante Immagini Pillcam

80

Vascular AbnormalitiesChapter 7

Figure 7.13 Dilated and tortouous vein in a patientwith portal hypertension. This lesion may representan early stage of small bowel varices.

M2A®

Figure 7.12 Jejunal Dieulafoy’s lesion with activebleeding.

M2A®

Figure 7.11a Venous malformation in Blue RubberBleb Nevus Syndrome.

M2A®

Figure 7.11b Venous malformation in Blue RubberBleb Nevus Syndrome, same case.

M2A®

Page 75: Atlante Immagini Pillcam

83

PARTIAL (HYPOBETALIPOPROTEINEMIA) OR COMPLETE

(ABETALIPOPROTEINEMIA) DEFICIENCY IN ß-LIPOPROTEIN.

Hypobetalipoproteinemia (HBL) and abetalipoproteinemia(ABL) are the consequence of various genetic disorders andare characterized by low, almost undetectable plasma levelof Apo-B or Apo-B containing lipoproteins: chylomicrons, verylow density lipoproteins (VLDL) and light density lipoproteins(LDL) and consequently, of triglycerides and cholesterol.

In ABL, the genetic defect affects the synthesis and secretionof VLDL in the liver and of the chylomicrons in the intestinedue to the absence of microsomal triglyceride transfer protein(MTP). In HBL, the disorder is caused by a mutation or deletionof the apo-B gene, which produces a truncated Apo-B protein.The biological and clinical pictures are similar to those inabetalipoproteinemia. The diagnosis can be evoked in patientswith hypocholesterolemia. Endoscopic examination of thesmall intestine shows a whitish or yellow discoloration of theintestinal mucosa (Figures 8.1a, 8.1b, 8.1c). This aspect issimilar when observed with the wireless endoscopic capsuleand is characterized by a marked mucosal swelling thatinvolves the whole intestine (Figures 8.1d, 8.1e, 8.1f). Theadvantage of the wireless capsule is that it investigates

INTRODUCTION

The clinical work-up of patients with intestinal malabsorptionneeds a precise medical history and detailed physicalexamination. In addition, laboratory tests for biochemistry,hematology and immunology will provide the physicianwith an initial diagnostic orientation. In most cases, thisinitial set of tests will allow the choice of morphologicalinvestigations that will firmly establish the diagnosis.Gastroduodenoscopy with duodenal biopsies and now,Capsule Endoscopy (CE) help in determining the cause ofmalabsorption. The wireless endoscopic video capsule (GivenImaging M2A®, Yoqneam, Israel) allows a safe and completeexamination of the small bowel, not requiringpatient sedation.

CAPSULE EXPERIENCE

Available reports are mainly isolated clinical cases of patientswith intestinal diseases that are responsible for markedmalabsorption of nutrients.

MalabsorptionGerard Gay, M.D.Isaac Fassler, M.D.Christian Florent, M.D.Michel Delvaux, M.D.

Chapter 8

Page 76: Atlante Immagini Pillcam

the ileum and does not need to be followed by retrogradeileoscopy (Figures 8.1f, 8.1g).

CELIAC DISEASE

The diagnosis of celiac disease is usually based upon thepresence of villous atrophy on endoscopic duodenal biopsies.The endoscopic pattern is characterized by a decrease inheight or a disappearance of Kerckring folds, the presenceof swollen mucosal folds, a mosaic pattern and a markedvascular pattern (Figures 8.2a, 8.2b, 8.2c). Again, the wirelessendoscopic capsule will observe the same aspect (Figure8.2d) 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 firstdescribed by Jeffries as an idiopathic ulcerative sprue ofunknown origin. The condition might be a pre-lymphomatousstate like refractory sprue. The clinical picture is one of amalabsorption syndrome, possibly associated with a protein-losing enteropathy. Its evolution is characterized by a highmortality rate, more than 70 %, due to chronic bleeding,intestinal perforation or obstruction. Gluten-free diet,corticosteroids and other immunosuppressive medicationsare usually ineffective. VPE shows a swollen inflammatorypattern of the mucosa, ulcerations, and plaques of atrophicmucosa (Figures 8.3a, 8.3b). Pathological examination ofintestinal biopsies is not specific and shows a thickened wall,inflammatory infiltrate and variable mucosal atrophy but nospecific granuloma. The wireless endoscopic capsule showspatterns 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 conditionsmay become pre- lymphomatous, as shown byimmunohistochemical and molecular biology studies,

84

patients will require repeated examinations for surveillance.The capsule could make these repeated procedures lessinvasive and thus, more acceptable to the patient.Repeated investigations with the capsule could then allowmonitoring of the response to treatment in patients onimmunosuppressive therapy or specific diet, without repeatingPE (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 importantrole in the diagnostic strategy and follow-up of patients withintestinal malabsorption. Advantages that need to beevaluated in clinical trials include its ease of use, excellenttolerance, and the possibility of investigation of the wholesmall intestine. Presently one may outline two clinicalsituations where Capsule Endoscopy is indicated: 1) inmalabsorptive disease patients with complex clinicalconditions like gastrointestinal manifestations of systemicdiseases involving the whole small bowel, 2) follow-up ofpatients with celiac disease to exclude ulcerative jejunitisand potential lymphoma. In any case, one should carefullyexclude an intestinal obstruction that might impedeprogression of the capsule before it is used.

MalabsorptionChapter 8

Page 77: Atlante Immagini Pillcam

85

MalabsorptionChapter 8

References and Suggested Readings

1 RICEY SA, MARSH MN. Maldigestion and malabsorption in : Sleisenger MH,Fordtran JS Eds. Gastrointestinal disease. Pathophysiology, diagnosis, management, Philadelphia, WB Saunders 1998 : 1501-1522

2 GAY G, PENNAZIO M, DELMOTTE JS, ROSSINI FP. Push enteroscopy in Atlasof enteroscopy, Eds FP Rossini, G Gay. Springer Verlag Milan 1998 : 51-55

3 SCOAZEC JG, BOUMA ME, ROCHE JF, BLACHE D, VERTHIER N, FELDMANN G,GAY G. Liver fibrosis in a patient with familial homozygous hypobetalipoproteinemia : possible role of vitamin supplementation.Gut 1992 ; 32 : 414-417

4 WETTEREAU JR, AGGERBECK LP, BOUMA ME, EISENBERG C, MUNCK A, HERMIER, SCHMITZ J, GAY G, RADER DJ, GREGG RE. Absence of microsomaltriglyceride transfer proteins in individuals with abetalipoproteinemia. Science 1992 ; 258 : 99-101

5 GAY G, DELMOTTE JS. Abeta and hypobetalipoproteinemias in Atlas of Enteroscopy. Eds FP ROSSINI, G. GAY. Springer Verlag Eds 1998 : 119-120

6 CORAZZA GR, DI STEPHANO M, PISTOIA MA. Celiac disease in Atlas of enteroscopy, Eds FP Rossini, G Gay. Springer Verlag Milan 1998 : 93-96

7 DAUMS S, WEISS D, HUMMEL M, ULRICH R, HEISE W, STEIN H, RIECKEN E O, FOSS HD and the intestinal lymphoma group. Frequency of clonal intraepithelial T lymphocyte proliferations in enteropathy-type intestinal Tcell lymphoma, coeliac disease, and refractory sprue. Gut 2001 ; 49 : 804-812

Page 78: Atlante Immagini Pillcam

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

86

MalabsorptionChapter 8

Page 79: Atlante Immagini Pillcam

87

MalabsorptionChapter 8

Endoscopic management of patients with intestinal malabsorption

Suspected intestinal diseasee.g. celiac disease

EGD + Duodenal Biopsies

Abnormal

Specific treatment

Inconclusive

Abnormal

Push video enteroscopy +duodenal and jejunal biopsies

if jejunal lesions

Inconclusive

Repeat examinations ?

Page 80: Atlante Immagini Pillcam

88

Figure 8.1a Yellow and snowy jejunal mucosaand blood acanthocytosis in a patient withHypobetalipoproteinemia.

Figure 8.1b Yellow and snowy jejunal mucosa withoutatrophic area in same patient.

Figure 8.1d CE shows yellow and snowy mucosa withlymphatic stasis without atrophic area of the duodenaland jejunal mucosa in this same patient.

Figure 8.1c Yellow and snowy ileal mucosa in samepatient.

M2A®

MalabsorptionChapter 8

Page 81: Atlante Immagini Pillcam

89

Figure 8.1e CE reveals yellow and snowy mucosa withlymphatic stasis without atrophic area of the duodenaland jejunal mucosa in same patient.

Figure 8.1f CE reveals yellow and snowy mucosa withlymphatic stasis without atrophic area of the ilealmucosa in same patient.

Figure 8.2a Enteroscopy reveals scalloped folds,atrophic area, mosaic pattern in the duodenum andjejunum in patient with celiac disease.

Figure 8.1g Additional view of same case.

M2A®

M2A® M2A®

MalabsorptionChapter 8

Page 82: Atlante Immagini Pillcam

90

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

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

Figure 8.2e Same diagnosis as Fig. 8.2d.Figure 8.2d CE reveals scalloped folds, atrophic area,mosaic pattern in the duodenum in this patient.

M2A® M2A®

MalabsorptionChapter 8

Page 83: Atlante Immagini Pillcam

91

Figure 8.3a Enteroscopy performed revealspathological aspect before treatment: ulcers, lymphaticstasis, and atrophic area in a patient with Chronic NonGranulomatous Ulcerative Jejuno-ileitis.

Figure 8.3b Enteroscopy in same patient as in previousfigure.

Figure 8.3d CE reveals same diagnosis as in previousimage.

Figure 8.3c CE reveals same aspect as PE beforetreatment along the jejunum but also along the lengthof the ileum.

M2A® M2A®

MalabsorptionChapter 8

Page 84: Atlante Immagini Pillcam

92

Figure 8.3e CE reveals same aspect as PE beforetreatment along the jejunum but also along the lengthof the ileum.

Figure 8.3f Chronic Non Granulomatous UlcerativeJejuno-ileitis, same case.

Figure 8.3h Additional view of same case.Figure 8.3g Note presence of small bowel diverticulaand telangiectasia, same case.

M2A® M2A®

M2A® M2A®

MalabsorptionChapter 8

Page 85: Atlante Immagini Pillcam

93

Figure 8.3i CE reveals same aspect as PE beforetreatment.

Figure 8.3j Different view of same case.

Figure 8.3l Additional view of enteroscopy performedin same patient.

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

M2A® M2A®

MalabsorptionChapter 8

Page 86: Atlante Immagini Pillcam

94

Figure 8.3m CE post-therapy reveals persistance oflesions as ulcers, atrophic area with no bleeding.No lymphatic stasis along the jejunum and the ileumis seen.

M2A®

MalabsorptionChapter 8

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.

M2A®

Page 87: Atlante Immagini Pillcam

95

MalabsorptionChapter 8

Figure 8.4c Villous atrophy, same case as Fig. 8.4a.Note AVM at 6 o’clock.

M2A®

Figure 8.4a Celiac sprue with active jejunal bleeding.Note AVM at 4 o’clock.

M2A®

Figure 8.4b Note AVM at 5 o’clock, same case asprevious Fig. 8.4a.

M2A®

Figure 8.5 Primary lymphangiectasia of GI tract withpoor villous formation and disarray.

M2A®

Page 88: Atlante Immagini Pillcam

96

MalabsorptionChapter 8

Figure 8.6a Eosinophilic enteritis in a 32 year oldfemale with asthma, iron deficiency, anaemia andhypoproteinaemia. Patient has eosinophilia in peripheralblood and positive anti nuclear antibodies. No diarrhea.

M2A®

Figure 8.6b Eosinophilic enteritis. Note thickenedinfiltrated folds, same case as in Fig. 8.6a.

M2A®

Figure 8.6c Eosinophilic enteritis. Note thickenedinfiltrated folds, same case as in Fig. 8.6a.

M2A®

Figure 8.6d Eosinophilic enteritis. Note thickenedinfiltrated folds, same case as in Fig. 8.6a.

M2A®

Page 89: Atlante Immagini Pillcam

97

MalabsorptionChapter 8

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

Figure 8.6f Higher magnification of the base of thecrypts of the jejunum with Paneth cells, lymphoid cellsand eosinophils (x500, H&E), same case.

Figure 8.6g Tip of the villi of jejunum showing discreteeosinophilic infiltration in lamina propria consistentwith 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.

M2A®

Page 90: Atlante Immagini Pillcam

98

MalabsorptionChapter 8

Figure 8.7b Diffuse bleeding was observed duringcapsule endoscopy procedure, same case.

M2A®

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

M2A®

Figure 8.7d Note lymphangiectasia, same case.

M2A®

Figure 8.7e Histologic view of atrophic villi. Note thehypertrophic crypts, the “normal¢ basal membrane andthe dense lymphoid cell infiltrate. (Reticulin stain, x50).

Page 91: Atlante Immagini Pillcam

99

MalabsorptionChapter 8

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

Figure 8.7g Microscopic overview showing villousatrophy, 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.

Page 92: Atlante Immagini Pillcam

100

MalabsorptionChapter 8

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

M2A®

Figure 8.8a 42 year old male with primary amyloidosis(Light chain Type) of GI tract. Note thickened infiltratedfolds with poor villous formation.

M2A®

Figure 8.8c Thickened infiltrated folds with erythemaand early mucosal breakdown, same case.

M2A®

Figure 8.8d Small erosion seen in same case.

M2A®

Page 93: Atlante Immagini Pillcam

101

MalabsorptionChapter 8

Figure 8.9a 38 year old female with AIDS and chronicdiarrhea. M2A® Capsule examination reveals significantlythickened infiltrated folds with villous blunting.

M2A®

Figure 8.9b UGI series of small bowel follow throughof same case showing thickened small bowel folds anderosions.

Page 94: Atlante Immagini Pillcam

CAPSULE EXPERIENCE

The first study to examine the diagnostic value of the videocapsule in comparison with other imaging techniques inchildren with obscure small bowel disease is currentlyunderway in our Montreal center.

Pediatric patients (more than 10 years of age) suspected ofhaving small bowel disorders were included in the studyin one of the following study groups: a) occult GIbleeding/vascular malformations, b) polyposis, c) obscureCrohn's disease. The first group was evaluated usingabdominal arteriography as the "gold standard" examination.The second group was evaluated either with a bariumsmall 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 beeninvestigated with barium small bowel follow throughand colonoscopy/gastroscopy before the capsule procedure,without a confirmed diagnosis. Strictures of the bowelwere first excluded in view of their potential to precludepassage of the capsule. The investigators reviewing the videocapsule results were blinded to the patients' case records orimaging results.

INTRODUCTION

Since its introduction over four decades ago, flexible fiberopticendoscopy has become an indispensable tool for the diagnosisof a wide variety of gastrointestinal disorders in children, asin adults. In addition to enabling direct visualization of muchof the gastrointestinal tract, endoscopic procedures affordbiopsy sampling of lesions. As well, endoscopy can be usedtherapeutically to localize and treat bleeding, dilate strictures,and to remove polyps. Despite advances in other imagingtechniques, endoscopy remains the most cost-effectivestrategy to determine the type, extent and severity ofinflammatory bowel disease, particularly for colitis. A majorlimitation of current endoscopic procedures is the inability toevaluate small bowel disorders beyond the range of currentlyavailable endoscopes. Experience with enteroscopy or smallbowel endoscopy has been limited in children. This techniquerequires a large overtube (15mm), limiting its applicability inthe pediatric age group. Intraoperative enteroscopy is analternative technique, albeit much more invasive. Althoughthe entire small bowel can be visualized, this approachnecessitates abdominal laparotomy or laparoscopy.

The recent development of wireless video endoscopy usinga capsule provides the opportunity to evaluate the entiresmall bowel in a completely non-invasive manner.

PediatricsErnest Seidman, M.D.Gian L. de’ Angelis, M.D.Ana Maria Sant Anna, M.D.

Chapter 9

103

Page 95: Atlante Immagini Pillcam

Our preliminary data includes evaluations on 14 patientsbetween 10 and 16 years. Among the group with occultbleeding, the capsule exam confirmed a diagnosis ofarteriovenous malformations in two cases. The one remainingcase stopped bleeding spontaneously, and no diagnosis wasmade with any modality of investigation. Among the threewith polyposis disorders, the video capsule confirmed thepresence of small bowel polyps in all cases. Among the eightpatients suspected to have Crohn's disease, the diagnosiswas confirmed with the video capsule in five. The exam wasnegative in one other case with a functional bowel disorder.Among the two others, one was ultimately diagnosed with aneosinophilic gastroenteropathy. The capsule revealed edemaand erythema of the small bowel mucosa, with pit-like lesions.In the one remaining case with a history of perianal abscesstwo years ago, no evidence of small bowel Crohn's diseasewas found.

All the video capsule studies (M2A®) were well tolerated,without any adverse events. All patients were able to resumetheir usual activities during the examination.

The results of this preliminary study confirm the high diagnosticaccuracy of this extraordinary, novel diagnostic technique.Moreover this non-invasive exam was well tolerated in allcases. The children were able to return to school during theexam. This imaging procedure is likely to become one of theinitial diagnostic procedures to be carried out where smallbowel pathologies are suspected, but not otherwisedocumented.

PediatricsChapter 9

References and Suggested Readings

1 Seidman EG. Role of endoscopy in inflammatory bowel disease.Gastrointest Endosc N Am 2001; 11: 641-57.

2 Deutsch DE, Olson AD. Colonoscopy or sigmoidoscopy as the initial evaluationof pediatric patients with colitis: a survey of physician behavior and a costanalysis. J Pediatr Gastroenterol Nutr 1997; 25: 26-31.

3 Lewis BS. Enteroscopy. Gastrointest Endosc Clin N Am 2000; 10: 101-16.4 Mackenzie JF. Push enteroscopy. Gastrointest Endosc Clin N Am 1999; 9:

29-36.5 Seidman E. Wireless Capsule Video-endoscopy: An Odyssey Beyond the

End of The Scope. J Pediatr Gastroenterol Nutr 2002; 34: 333-4.

104

CONCLUSION

Wireless capsule endoscopy appears to permit a more accurateand non-invasive approach for diagnosing occult lesions inthe small bowel distal to duodenum in children.

Page 96: Atlante Immagini Pillcam

Figure 9.1a Celiac disease in the descending duodenumof a 10 year old girl.

Figure 9.1b Jejunum in this patient begins to showrecovery of villi.

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

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

M2A® M2A®

M2A® M2A®

PediatricsChapter 9

105

Page 97: Atlante Immagini Pillcam

Figure 9.2a Capsule endoscopy reveals gastric fundicpolyps in a 9 year old child with Peutz-Jegher’s.

Figure 9.2b Same patient with PJ. Note gastric fundicpolyps.

Figure 9.2d Multiple small hamartomatous polyps inproximal ileum in same patient with Peutz-Jegher’s.

Figure 9.2c Small hamartomatous polyp in ileum inpatient with Peutz-Jegher’s.

M2A® M2A®

M2A® M2A®

PediatricsChapter 9

106

Page 98: Atlante Immagini Pillcam

Figure 9.2e Hamartomatous polyps in Peutz-Jegher’s. Figure 9.2f Large hamartomatous polyp in mid-ileumin patient with Peutz-Jegher’s.

Figure 9.3b Same case as 9.3a. Adenomatous polypsare seen in the mid ileum.

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

M2A® M2A®

M2A® M2A®

PediatricsChapter 9

107

Page 99: Atlante Immagini Pillcam

PediatricsChapter 9

Figure 9.4a 11 year old girl, frequent episodes of melena.Required repeated transfusions and previous surgery. Capsuleendoscopy diagnosed vascular malformation observed inthe terminal ileum. This is a normal area in this patient.

M2A®

108

Figure 9.4b Note abnormal venous pattern in theterminal ileum of this same patient.

M2A®

Figure 9.5a 14 year old male with 8 months of chronic abdominalpain and negative evaluation. Capsule endoscopy reveals triangularulcer in mid jejunum consistent with Crohn’s disease.

M2A®

Figure 9.5b Same patient as in Figure 9.5a. A collarbutton ulcer in mid small bowel is present at 4 o’clock.

M2A®

Page 100: Atlante Immagini Pillcam

Standard trans-stomal terminal ileoscopy or jejunoscopyperformed in SBTx recipients are invasive, and may be unsafein frail patients. In addition, they allow only incompleteexploration of the transplanted graft, which may beunsatisfactory, since the distribution of the immunological orinfectious lesions is often patchy or segmental. Theswallowable M2A® endoscopic capsule developed by Given®,allows noninvasive examination of the entire small bowel.The technique has been proven to be safe and extremely welltolerated by the patients. In this chapter, we present the firstimages obtained by preliminary experience with the use ofthe Given® capsule endoscope in SBTx recipients.

CAPSULE EXPERIENCE

Five patients who underwent isolated small bowel transplantor multivisceral transplant between December, 2000 andSeptember, 2001 were studied at various intervals post

TransplantationRoberto 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.

Chapter 10

INTRODUCTION

Small bowel transplantation (SBTx) has recently become aclinical reality, owing to major progress in harvesting andpreservation procedures, surgical techniques andimmunosuppression. However, major immunological orinfectious complications still continue to pose threateningproblems in SBTx recipients. As a consequence, post-operativemonitoring and management of these patients require a veryaggressive and multidisciplinary approach. In particular, post-operative monitoring is crucial for the early detection of post-transplant complications and for the assessment of the graft'sanatomical and functional integrity. In this setting, intestinalgraft enteroscopy plays a key role. The indications forenteroscopy in SBTx recipients are routine surveillance, andthe onset of clinical symptoms or physical signs suggestiveof the occurrence of major complications. Routine surveillanceenteroscopies are done twice a week for the first month afterSBTx, once a week for the next 2 months, monthly for thenext 3 months and every 3-6 months thereafter.

111

Page 101: Atlante Immagini Pillcam

transplant. Indications for SB transplantation were: intestinalpseudo-obstruction, post-surgical short bowel syndrome andradiation enteritis. All patients had both ileostomy and naturalcanalization and were on immunosuppressive, antibiotic andantimycotic drugs.

Ileoscopy is poorly tolerated in these patients, as theycomplain of bloating and discomfort. The capsule is swallowedeasily and passed naturally in all patients without adverseevents. Standard ileoscopy revealed that the ileal mucosawas normal in all patients. Ileal histology showed mildinflammatory infiltrate and edema in the lamina propria in allcases. Using capsule endoscopy, it was demonstrated thatthe mucosa in the ileal segments reached by ileoscopy wasnormal. However, mucosal changes were observed in moreproximal segments in 3 of the 4 patients in whom capsuleenteroscopy yielded small bowel images. These changeswere: diffuse blunted or ridge-shaped villi and isolatedhyperemic spots in a patient examined 20 days aftertransplantation (Figure 10.1a); small areas with blunted andridge-shaped villi and isolated petechiae (Figure 10.2a, 10.2b)in a patient examined at 6 weeks; diffuse blunted edematousvilli and isolated small erosions in a patient examined at 2months. In the fourth patient, studied 6 months after smallbowel transplantation, normal well-shaped long villi wereobserved (Figure 10.5a).

CONCLUSION

Capsule enteroscopy is better tolerated than retrogradeileoscopy, and allows a complete examination of thetransplanted small bowel. Proximal mucosal changes missedby retrograde ileoscopy were identified in 3/4 patients.Whether these findings seen at different time intervals after

transplantation represent the normal evolution of the graftover time, or were early signs of immunological or infectiouscomplications, or represent the normal evolution of the graftis unknown. Owing to its excellent tolerability, capsuleenteroscopy could become the first step in the endoscopicmonitoring of patients after SBTx. Standard ileoscopywith biopsy could be reserved for further assessmentin the patients in whom mucosal lesions are identified bycapsule enteroscopy.

TransplantationChapter 10

References and Suggested Readings

1 Hassainen T, Schade RR, Soldevilla-Pico C, Tabasco-Minguillan J, Abu-ElmagdK, Furukawa K, Kadry Z, Demetris A, Tzakis A, Todo S. Endoscopy Is Essentialfor Early Detection of Rejection in Small Bowel Transplant Recipients. Transplantation Proceedings 1994;26:1414-15

2 Scotti-Foglieni T, Tinozzi SD, Abu-Elmagd K, Starzl TE. Enteroscopy of the transplanted small bowel. In Rossini FP, Gay G (editors) Atlas of Enteroscopy.Springer, Milan, 1998:151-169

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

4 Lewis BS, Swain P Capsule endoscopy in the evaluation of patients with suspected small intestinal bleeding: the results of the first clinical trial. Gastrointestinal Endoscopy 2001;53:AB70

5 Pennazio M, Santucci R, Rondonotti E, Abbiati C, Beccari G, Luchetti R, DeziA, Capurso L, de Franchis R, Rossini FP. Wireless capsule endoscopy in patients with obscure gastrointestinal bleeding: preliminary results of theItalian multicentre experience. Digest Liver Dis. 2001;33 (Suppl. 1): A2

112

Page 102: Atlante Immagini Pillcam

TransplantationChapter 10

Figure 10.1a 20 days post-transplant.Blunted and ridge-shaped whitish villi and hyperemicspot 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 aftertransplantation.

M2A®

113

Page 103: Atlante Immagini Pillcam

TransplantationChapter 10

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 patientas before.

M2A®

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

M2A®

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

M2A®

114

Page 104: Atlante Immagini Pillcam

TransplantationChapter 10

Figure 10.4b 183 days post-transplant.Normal small bowel with two small areas oflymphangiectasia.

M2A®

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

M2A®

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

M2A®

Figure 10.3a 64 days post-transplant.Slight villous blunting with ulcer at 8 o’clock.

M2A®

115

Page 105: Atlante Immagini Pillcam

TransplantationChapter 10

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

M2A®

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

M2A®

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

M2A®

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

M2A®

116

Page 106: Atlante Immagini Pillcam

INTRODUCTION

Capsule Endoscopy has revolutionized the gastroenterologist'sability to diagnose and treat small bowel disease. However,it has become apparent that in the process of performingsmall bowel capsule endoscopy, high quality, clinicallymeaningful images can be recorded from the esophagus,stomach and colon as well. It is important forgastroenterologists to recognize these abnormalities as theymay have implications in the treatment of their patients. Inthis chapter, we highlight some of the findings outside thelimits of the small bowel that may be encountered in thecourse of Capsule Endoscopy.

CAPSULE EXPERIENCE

As the capsule is swallowed, it rapidly enters the esophagus.The striated muscle of the proximal esophagus contracts andrapidly propels the capsule to the mid and distal part of theesophagus. For this reason with the present design of thevideo capsule, one can expect to see just a few images of thedistal esophagus. However the capsule may at times besignificantly delayed in the distal esophagus allowing a numberof clear images of the distal esophagus and of the z-line. Inthese cases, findings of esophagitis are readily identified.

Non Small Bowel PathologySamuel Adler, M.D.Steven Kadish, M.D.

Just prior to swallowing the capsule, the patient should beasked to drink a glass of water slowly with repeated swallowsto clear the distal esophagus from accumulated saliva.

The capsule transmits images from the stomach before ittraverses the pylorus into the small bowel. Presently it isdifficult to visualize the fundus with adequate reliability.Nevertheless, the gastroenterologist should remain alertto the possibility of pathology in the fundus and body ofthe stomach as that area of the RAPID video is scanned.The capsule is far more trustworthy in reference to pathologyin the distal body, antrum and pylorus. It is noteworthy thatthe acquisition of images with the stomach in its normalphysiologic state (i.e., not altered by the insufflation of airthat occurs during endoscopy) may allow for resolutionand reproduction of mucosal detail that is superior to theimages obtained by standard commercial endoscopes.It is therefore not surprising that cases of occult GI bleedingwere identified as actively bleeding lesions on capsuleendoscopy whereas they were missed on conventionalendoscopy. One frequently observes gastric mucosal detailsuch as the areae gastricae. The ability to observe the areagastricae likely corresponds to a six to eight fold magnification.Minute focal erythema, mini erosions and even early atrophicgastritis have been identified on capsule endoscopy andmissed on video endoscopy .

Chapter 11

119

Page 107: Atlante Immagini Pillcam

Non Small Bowel PathologyChapter 11

CONCLUSION

During the course of small bowel capsule endoscopy,gastroenterologists may be provided with important diagnosticinformation in areas outside the small bowel. The RAPIDviewer should scan the area of the GI tract outside the smallbowel and report any abnormal findings.

120

Page 108: Atlante Immagini Pillcam

Non Small Bowel PathologyChapter 11

121

Figure 11.1 Distal esophagitis seen as capsule passesthrough.

M2A®

Figure 11.2 CE revealed Watermelon stomach in apatient with chronic bleeding.

M2A®

Figure 11.3a Low-grade-malt lymphoma, confined tostomach.

M2A®

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

Page 109: Atlante Immagini Pillcam

Non Small Bowel PathologyChapter 11

Figure 11.4a Kaposi’s sarcoma of the stomach in anHIV positive patient.

M2A®

Figure 11.4b Same case as before.

M2A®

Figure 11.6 Mild atrophic changes of gastric folds.

M2A®

122

Figure 11.5 Capsule endoscopy in a patient with GIbleeding of unknown etiology, Cameron’s lesion seenin a hiatal hernia.

M2A®

Page 110: Atlante Immagini Pillcam

Non Small Bowel PathologyChapter 11

Figure 11.7a Colon polyp seen as capsule passesthrough cecum.

M2A®

Figure 11.8 Appearance of stomach mucosa afterbiopsy was taken.

M2A®

123

Figure 11.7b Colon polyp. After the patient underwentprep and colonoscopy, the polyp was confirmed.

Page 111: Atlante Immagini Pillcam

Contributors

Carla Abbiati, M.D.

University of Milan and IRCCS

Ospedale Maggiore Policlinico

Milan, Italy

Samuel Adler, M.D.

Bikur Cholim Hospital

Jerusalem, Israel

Mark Appleyard, M.D.

Royal Brisbane Hopital

Herston, Queensland, Australia

Jeffrey P. Baker, M.D.

St. Michael's Hospital

Toronto, ON, Canada

Jamie Barkin, M.D.

University of Miami

Mount Sinai Medical Center

Miami, Florida, USA

Gizela Beccari, M.D.

University of Milan and IRCCS

Ospedale Maggiore Policlinico

Milan, Italy

Rhonda Cole, M.D.

Veterans Affairs Medical Center

Houston, Texas, USA

Felice Consentino, M.D.

S. Paolo Hospital

Milan, Italy

Guido Costamagna, M.D.

Catholic University of Rome

Rome, Italy

Ingrid Davies, R.N.

South Shore Gastroenterology PC &

South Nassau Communities Hospital

Oceanside, NY , USA

Gian L. de’Angelis, M.D.

Instituto Di Clinica Pediatrica

Parma, Italy

Roberto De Franchis, M.D.

University of Milan and IRCCS

Ospedale Maggiore Policlinico

Milan, Italy

Brett Bernstein, M.D.

Beth Israel Medical Center

New York, NY USA

Luigi Berreta, M.D.

Ospedaliera S.Gerardo

Monza , Italy

Faisal Bhinder, M.D.

St Elizabeth s Medical Center

Boston, MA , USA

Edmund Bini, M.D.

NYU Medical Center

New York, NY, USA

Alain Bitoun, M.D.

CHU Paris

Paris, France

Peter D. Bloom, M.D.

University School of Medicine &

Atlanta Veterans Admin. Med. Ctr.

Atlanta, GA, USA

Alan L. Buchman, M.D.

Northwestern University

Chicago, IL, USA

Carol A. Burke, M.D.

The Cleveland Clinic Foundation

Cleveland, OH, USA

Marcus J. Burnstein, M.D.

St. Michael's Hospital

Toronto, ON, Canada

Lucio Capurso, M.D.

S. Filippo Neri Hospital

Rome, Italy

Angel Caunedo, M.D.

Virgen Macarena University Hospital

Seville, Spain

David R. Cave, M.D.

St. Elizabeth’s Medical Center

Boston, MA , USA

125

Page 112: Atlante Immagini Pillcam

Contributors (continued)

Michel Delvaux, M.D.

CHU Nancy

Nancy, France

Ingrid Demedts, M.D.

University Hospital of Gasthuisberg

Leuven, Belgium

Jacques Deviere, M.D.

Hopital Erasme

Brussels, Belgium

Angelo Dezi, M.D.

S. Filippo Neri Hospital

Rome, Italy

Elena Dubcenco, M.D.

St. Michael's Hospital

Toronto, ON, Canada

Jose Dubois, M.D.

Ste Justine Hospital

University of Montreal

Montreal, Canada

David Fleischer, M.D.

Mayo Clinic Scottsdale

Scottsdale, Arizona, USA

Christian Florent, M.D.

CHU Paris

Paris, France

Frans T. Fork, M.D.

Malmô University Hospital

Malmô, Sweden

Francesca Foschia, M.D.

Catholic University of Rome

Rome, Italy

Erik Francois, M.D.

Hopital Erasme

Brussels, Belgium

Diniz Freitas, M.D.

University Hospital of Coimbra

Coimbra, Portugal

Gareth Dulai, M.D.

CURE VA

Greater L.A. Health Care System

Los Angeles, CA, USA

Frank Duperier, M.D.

The Cleveland Clinic Foundation

Cleveland, OH, USA

Rami Eliakim, M.D.

Rambam Medical Center

Haifa, Israel

Christian Ell, M.D.

HSK

Wiesbaden, Germany

Douglas Faigel, M.D.

Portland VA Medical Center

Portland, WA, USA

Kent Farris, M.D.

Gastrointestinal Assoc.

Knoxville, TN, USA

Isaac Fassler, M.D.

CHU Nancy

Nancy, France

Jay Fenster, M.D.

South Shore Gastroenterology

Center Cedarhurst

Cedarhurst, NY,USA

Pedro Figueiredo, M.D.

University Hospital of Coimbra

Coimbra, Portugal

Zvi Fireman, M.D.

Hillel-Yaffe Medical Center

Hadera, Israel

Babak Firoozi, M.D.

NYU Medical Center

New York, NY, USA

Doron Fischer, M.D.

Rambam Medical Center

Haifa, Israel

126

Page 113: Atlante Immagini Pillcam

Contributors (continued)

Sandor Joffe, M.D.

Beth Israel Medical Center

New York, NY, USA

Enrico Jovine, M.D.

University of Modena

and Regio Emilia

Modena, Italy

Renee Jovine, M.D.

St. Elizabeth’s Medical Center

Boston, MA , USA

Steven Kadish, M.D.

South Shore Gastroenterology PC &

South Nassau Communities Hospital

Oceanside, NY, USA

Dalia Katz, M.D.

Rambam Medical Center

Haifa, Israel

Martin Keuchel, M.D.

Medizinische Abteilung

Allgemeines Krankenhaus Altona

Hamburg, Germany

Gavriel Meron, Ph.D.

Given Imaging Ltd.

Yoqneam, Israel

Marie Claude Miron, M.D.

Ste Justine Hospital

University of Montreal

Montreal, Canada

Roger Mitty, M.D.

St. Elizabeth’s Medical Center

Boston, MA , USA

Danette Musil, M.D.

Mayo Clinic Scottsdale

Scottsdale, Arizona, USA

Massimiliano Mutignani, M.D.

Catholic University of Rome

Rome, Italy

Colm O’ Loughlin, M.D.

University of Miami

Mount Sinai Medical Center

Miami, Florida, USA

Devon Klein, M.D.

Beth Israel Medical Center

New York, NY, USA

Yehudith Kraizer, Ph.D.

Given Imaging Ltd.

Yoqneam, Israel

Jonathan A. Leighton, M.D.

Mayo Clinic Scottsdale

Scottsdale, Arizona, USA

Gavin Levinthal, M.D.

The Cleveland Clinic Foundation

Cleveland, OH, USA

Blair S. Lewis, M.D.

Mt. Sinai Hospital

New York, NY, USA

Shlomo Lewkowicz, D.Sc.

Given Imaging Ltd.

Yoqneam, Israel

David Lieberman, M.D.

Portland VA Medical Center

Portland, Oregon, USA

Ramona Lim, M.D.

University of Miami

Mount Sinai Medical Center

Miami, Florida, USA

Roberto Luchetti, M.D.

S. Filippo Neri Hospital

Rome, Italy

Pasquale Marano, M.D.

Catholic University of Rome

Rome, Italy

Andrea May, M.D.

HSK

Wiesbaden, Germany

Alberto Merighi, M.D.

University of Modena

and Reggio Emilia

Modena, Italy

128

Page 114: Atlante Immagini Pillcam

Contributors (continued)

Antone R. Opekun, M.D.

Baylor College of Medicine

Houston, Texas, USA

Guillermo Payeras, M.D.

Hospital del Aire

Madrid, Spain

Francisco J. Pellicer, M.D.

Virgen Macarena University Hospital

Seville, Spain

Marco Pennazio, M.D.

S.Giovanni A.S. Hospital

Turin, Italy

Vincenzo Perri, M.D.

Catholic University of Rome

Rome, Italy

Rima Petroniene, M.D.

St. Michael's Hospital

Toronto, ON, Canada

Antonio Pinna, M.D.

University of Modena

and Regio Emilia

Modena, Italy

Javier P. Piqueras, M.D.

Hospital del Aire

Madrid, Spain

Thierry Ponchon, M.D.

CHU Lyon

Lyon, France

Massimo Primignani, M.D.

University of Milan and IRCCS

Ospedale Maggiore Policlinico

Milan, Italy

Marlene Rackson , M.D.

Beth Israel Medical Center

New York, NY, USA

Stefanie Remke, M.D.

HSK

Wiesbaden, Germany

Maria Elena Riccioni, M.D.

Catholic University of Rome

Rome, Italy

Jürgen F. Riemann, M.D.

Klinikum Ludwigshasen

Ludwigshasen, Germany

Jean-Francois Roche, M.D.

CHG Verdun

Verdun, France

Manuel Rodriguez-Tellez, M.D.

Virgen Macarena University Hospital

Seville, Spain

Rafael Romero, M.D.

Virgen Macarena University Hospital

Seville, Spain

Emanuele Rondonotti, M.D.

University of Milan and IRCCS

Ospedale Maggiore Policlinico

Milan, Italy

129

Marc Rosenberg, M.D.

University School of Medicine &

Atlanta Veterans Admin. Med. Ctr.

Atlanta, GA, USA

Steven Rosenblatt, M.D.

The Cleveland Clinic Foundation

Cleveland, OH, USA

Francesco P. Rossini, M.D.

S.Giovanni AS Hospital

Turin, Italy

Paul Rutgeerts, M.D.

KU. Leuven

Leuven, Belgium

Manuel Jimenez-Saenz, M.D.

Virgen Macarena University Hospital

Seville, Spain

Miguel A. Saez, M.D.

Hospital del Aire

Madrid, Spain

Page 115: Atlante Immagini Pillcam

Contributors (continued)

Ana Sant Anna, M.D.

Ste Justine Hospital

University of Montreal

Montreal, Canada

Janice M. Santisi, R.N.

The Cleveland Clinic Foundation

Cleveland, OH, USA

Renato Santucci, M.D.

S.Giovanni A.S. Hospital

Turin, Italy

Shigeru Sato, M.D.

Fukuoka University

Fukuoka, Japan

Jean-Christophe Saurin, M.D.

CHU Lyon

Lyon, France

Eitan Scapa, M.D.

Assaf-Harofe Medical Center

Zrifin, Israel

David Stolpman, M.D.

Oregon Health & Science University

Portland, Oregon, USA

Alain Suissa, M.D.

Rambam Medical Center

Haifa, Israel

Paul Swain, M.D.

Royal London Hospital

London, England

Jan Tack, M.D.

KU. Leuven

Leuven, Belgium

Ervin Toth, M.D.

Malmô University Hospital

Malmô, Sweden

Laura Toth, M.D.

St. Elizabeth’s Medical Center

Boston, MA, USA

Wolff Schmiegel, M.D.

Knappschaftskrankenhaus Bochum

Ruhr-University

Bochum, Germany

Alain Schmit, M.D.

Hopital Erasme ULB

Brussels, Belgium

Douglas Schneider, M.D.

St. Elizabeth’s Medical Center

Boston, MA, USA

Karsten Schulmann, M.D.

Knappschaftskrankenhaus Bochum

Ruhr-University

Bochum, Germany

Ernest Seidman, M.D.

Ste Justine Hospital

University of Montreal

Montreal, Canada

Warwick Selby, M.D.

Royal Prince Alfred Hospital &

University of Sydney

Sydney, Australia

Nicholas Shackell, M.D.

Royal Prince Alfred Hospital &

University of Sydney

Sydney, Australia

Saumil Shah, M.D.

Catholic University

Rome, Italy

Virender K. Sharma, M.D.

Mayo Clinic Scottsdale

Scottsdale, Arizona, USA

Nidhir Sheth, M.D.

Beth Israel Medical Center

New York, NY, USA

Sandra Smith-Ziv

Given Imaging Ltd.

Yoqneam, Israel

Jean-Christophe Souquet, M.D.

CHU Lyon

Lyon, France

130

Page 116: Atlante Immagini Pillcam

Contributors

Gert Van Assche, M.D.

KU. Leuven

Leuven, Belgium

Andre Van Gossum, M.D.

Hopital Erasme ULB

Brussels, Belgium

Maurizio Vecchi, M.D.

University of Milan & IRCCS

Ospedale Maggiore Policlinico

Milan, Italy

Amorino Vecchioli, M.D.

Catholic University

Rome, Italy

Erica Villa, M.D.

University of Modena &

Regio Emilia

Modena, Italy

Kamal Yassin, M.D.

Rambam Medical Center

Haifa, Israel

Mahmoud Yousfi, M.D.

Mayo Clinic Scottsdale

Scottsdale, Arizona, USA

Arthur H. Zalev, M.D.

St. Michael's Hospital

Toronto, ON, Canada

Johnathan Zinberg, M.D.

South Shore Gastroenterology PC

& South Nassau Communities Hosp.

Oceanside, NY, USA

131


Recommended