Ileoscopy

Antonello TreccaEditor

Ileoscopy

Technique, Diagnosis, and ClinicalApplications

123

Foreword by Shin-ei Kudo

EditorAntonello TreccaEndoscopic and Operative Gastroenterology UnitsUSI GroupRomeItalye-mail: atrecca@alice.it

ISBN 978-88-470-2344-4 e-ISBN 978-88-470-2345-1DOI 10.1007/978-88-470-2345-1Springer Milan Heidelberg Dordrecht London New York

Library of Congress Control Number: 2011941715

� Springer-Verlag Italia 2012This work is subject to copyright. All rights are reserved, whether the whole or part of the material isconcerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting,reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publicationor parts thereof is permitted only under the provisions of the Italian Copyright Law in its current version,and permission for use must always be obtained from Springer. Violations are liable to prosecution underthe Italian Copyright Law.The use of general descriptive names, registered names, trademarks, etc. in this publication does notimply, even in the absence of a specific statement, that such names are exempt from the relevantprotective laws and regulations and therefore free for general use.Product liability: The publishers cannot guarantee the accuracy of any information about dosage andapplication contained in this book. In every individual case the user must check such information byconsulting the relevant literature.

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Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

To my father, Pasquale Trecca

Foreword

It is a great pleasure to see the publication of IIeoscopy, edited by Dr. Antonello

Trecca. Dr. Trecca studied endoscopic diagnosis and treatment of early cancers

of the gastrointestinal tract at the National Cancer Center Hospital, Tokyo,

Japan. He is an expert in magnifying endoscopy, including pit pattern diag-

nosis, and also has an excellent understanding of the importance of depressed

type early colorectal cancers.

Colonoscopy (from diagnostic to technical aspects, including magnifying

endoscopy, insertion technique, and endoscopic treatment) is an essential tool

in the gastrointestinal field. With the emergence of the magnifying colonoscope,

pit pattern analysis enables a diagnosis with a close relation to histologic

diagnosis.

Today, there are plenty of textbooks of colonoscopy, but fewer of terminal

ileoscopy. The importance of terminal ileoscopy during routine colonoscopy,

however, should not be underestimated. We can diagnose many ileal diseases

with terminal ileoscopy without using capsule endoscopy or balloon

enteroscopy.

This book is dedicated to the role of exploration of the terminal ileum in

lower gastrointestinal endoscopy. It covers both technical aspects and the

modern diagnosis and treatment of small intestinal diseases in a very accessible

format. It will be an indispensable guide not only for colonoscopists but also for

gastroenterologists and surgeons.

I hope that this book will find the wide readership it doubtlessly deserves.

Prof. Shin-ei Kudo

Digestive Disease Center

Showa University Northern Yokohama Hospital

Yokohama

Japan

vii

Preface

The challenge for the authors of a medical/scientific monograph is to com-

municate both their passionate interest in and their dedication to the subject

matter, whether a disease, a new technique, an original therapeutic approach, or

the most recent trends in clinical and experimental research. Of equal impor-

tance is to consider the scope of the audience, which may include students,

interns, and residents but also highly experienced professionals.

We have kept these goals in mind in our exploration of the difficult subject of

digestive endoscopy, specifically, of the terminal ileum, and the most important

issues related to the use of this technique in various disease settings. Each

chapter consists of a thorough discussion of a particular topic, which is illus-

trated by a large number of detailed images.

In the field ofmodern gastroenterology, digestive endoscopy continues to be the

focus of enormous interest because of the many achievements over the last several

decades: from the introduction of capsule endoscopy to the development of ent-

eroscopy. These imaging capabilities have greatly expanded our knowledge of

intestinal diseases while opening up new frontiers in their more accurate treatment.

Exploration of the terminal ileum during total colonoscopy has gained much

greater acceptance within the profession based on the diagnostic accuracy of

terminal ileoscopy with respect to ileocecal pathologies, including neoplasias of

the cecal region. In addition, terminal ileoscopy documents the completeness

of colonoscopy and points the way to the optimal procedure for further study

of the intestine. This capability is such that we provocatively refer to ileoscopy

as the fast track to the diagnosis of gut diseases.

The multidisciplinary approach taken by the authors of this volume to the

accurate study of the ileocecum is highlighted by the contributions of experts in

radiology and surgery, providing a closer look at several intestinal diseases.

Particular emphasis has been placed on endoscopic imaging of the different

disease stages and on analyzing the results obtained with the new techniques in

terms of their ability to enhance diagnostic accuracy.

We would like to thank all the authors who actively participated in realizing

this book, for their clinical efforts and scientific contributions. To our readers: we

hope that we have been able to contribute to your professional development and

to have inspired in you the same passionate interest that has resulted in this book.

Rome, September 2011 Antonello Trecca

ix

Acknowledgments

The editor would like to thank Raffaele Gurrieri, for the illustrations drawn for

Chap. 1 with passion and competence, and Astrid Gurrieri, for her unflagging

contribution to the book.

xi

Contents

1 Terminal Ileoscopy: Technique . . . . . . . . . . . . . . . . . . . . . . . . . . . 1Antonello Trecca, Giuseppe Cerno, Emilio Gentile Warschauer,Gabriele Marinozzi, and Fabio Gaj

2 The Importance of Complete Colonoscopy and Explorationof the Cecal Region . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7Kuangi Fu, Takahiro Fujii, Takahisa Matsuda, and Yutaka Saito

3 What are the Correct Indications for Ileoscopy? . . . . . . . . . . . . . . 13Antonello Trecca, Fabio Gaj, Stefano Serafini, Gabriele Marinozzi,and Marco Silano

4 Contribution of New Technologies to Endoscopic Imaging . . . . . . . 21Giuseppe Galloro, Luca Magno, Simona Ruggiero, Ferdinando Fusco,and Tiziana Rappa

5 Ileoscopy in Coeliac Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31Marco Silano, Emilio Gentile Warschauer, Gabriele Marinozzi,Giuseppe Cerno, and Antonello Trecca

6 The Role of Ileoscopy in Inflammatory Bowel Disease . . . . . . . . . . 35Bjorn Rembacken and Mohammed Thoufeeq

7 Ileoscopy in the Diagnosis of Infectious Diseases . . . . . . . . . . . . . . 41Roberto Lorenzetti, Angelo Mario Zullo, and Cesare Hassan

8 Results of Ileoscopy in Pediatric Patients. . . . . . . . . . . . . . . . . . . . 47Paola De Angelis, Erminia Romeo, Filippo Torroni, andLuigi Dall’Oglio

9 The Role of Histology in Small Bowel Diseases . . . . . . . . . . . . . . . 53Vincenzo Villanacci and Gabrio Bassotti

10 Radiological Diagnosis of Small-Bowel Diseases . . . . . . . . . . . . . . . 59Laura Maria Minordi, Amorino Vecchioli, Luigi Larosa,and Lorenzo Bonomo

xiii

11 Capsule Endoscopy: The Answer to a Challenge . . . . . . . . . . . . . . 65Emanuele Rondonotti and Roberto de Franchis

12 Double-Balloon Enteroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73Alessandro Mussetto and Tino Casetti

13 Single-Balloon Enteroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79Mauro Manno, Raffaele Manta, and Rita Conigliaro

14 Spiral Enteroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87Mauro Manno, Raffaele Manta, and Rita Conigliaro

15 Surgery for Small-Bowel Disease. . . . . . . . . . . . . . . . . . . . . . . . . . 91Ugo Grossi, Andrea Mazzari, Pasquina MC Tomaiuolo,Giuseppe Brisinda, and Antonio Crucitti

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

xiv Contents

Contributors

Gabrio Bassotti Department of Clinical and Experimental Medicine, University

of Perugia, Perugia, Italy

Lorenzo Bonomo Department of Bio-Imaging and Radiological Sciences,

Catholic University (UCSC), Radiology Institute, Rome, Italy

Giuseppe Brisinda General Surgery, Catholic University of Rome, Rome, Italy

Tino Casetti Department of Gastroenterology, Santa Maria delle Croci Hos-

pital, Ravenna, Italy

Giuseppe Cerno Department of Pathology, USI Group, Rome, Italy

Endoscopic and Operative Units, Department of Pathology, USI Group,

Rome, Italy

Histopathology Endoscopic and Operative Gastroenterological Units, USI

Group, Rome, Italy

Rita Conigliaro Gastroenterology and Digestive Endoscopy Unit, Nuovo

Ospedale Civile S. Agostino-Estense, Baggiovara di Modena (MO), Italy

Antonio Crucitti General Surgery, Catholic University of Rome, Rome, Italy

Luigi Dall’Oglio Digestive Surgery and Endoscopy Unit, Ospedale Pediatrico

Bambino Gesu, IRCCS, Rome, Italy

Paola De Angelis Digestive Surgery and Endoscopy Unit, Ospedale Pediatrico

Bambino Gesu, IRCCS, Rome, Italy

Roberto de Franchis Gastroenterology Unit, L. Sacco Hospital, University of

Milan, Milan, Italy

Kuangi Fu Department of Gastroenterology, Juntendo University Nerima

Hospital, Tokyo, Japan

Takahiro Fujii TF clinic, Tokyo, Japan

Ferdinando Fusco Department of General, Geriatric, Oncologic Surgery and

Advanced Technology, Unit of Surgical Digestive Endoscopy, University of

Naples ‘‘Federico II’’—School of Medicine, Naples, Italy

Fabio Gaj Department of General Surgery, University of Rome ‘‘La Sapienza’’,

Rome, Italy

xv

Giuseppe Galloro Department of General, Geriatric, Oncologic Surgery and

Advanced Technology, Unit of Surgical Digestive Endoscopy, University of

Naples ‘‘Federico II’’—School of Medicine, Naples, Italy

Ugo Grossi General Surgery, Catholic University of Rome, Rome, Italy

Cesare Hassan Gastroenterology Department, Nuovo Regina Margherita

Hospital, Rome, Italy

Roberto Lorenzetti Gastroenterology Department, Nuovo Regina Margherita

Hospital, Rome, Italy

Luigi Larosa Department of Bio-Imaging and Radiological Sciences, Catholic

University (UCSC), Radiology Institute, Rome, Italy

Luca Magno Department of General, Geriatric, Oncologic Surgery and

Advanced Technology, Unit of Surgical Digestive Endoscopy, University of

Naples ‘‘Federico II’’—School of Medicine, Naples, Italy

Mauro Manno Gastroenterology and Digestive Endoscopy Unit, Nuovo

Ospedale Civile S. Agostino-Estense, Baggiovara di Modena (MO), Italy

Raffaele Manta Gastroenterology and Digestive Endoscopy Unit, Nuovo

Ospedale Civile S. Agostino-Estense, Baggiovara di Modena (MO), Italy

Gabriele Marinozzi Department of Operative Endoscopy, Saint Mary Hospi-

tal, Terni, Italy

Endoscopic and Operative Gastroenterology Units, USI Group, Rome, Italy

Takahisa Matsuda Endoscopy Division, National Cancer Center Hospital,

Tokyo, Japan

Andrea Mazzari General Surgery, Catholic University of Rome, Rome, Italy

Laura Maria Minordi Department of Bio-Imaging and Radiological Sciences,

Catholic University (UCSC), Radiology Institute, Rome, Italy

Alessandro Mussetto Department of Gastroenterology, Santa Maria delle Croci

Hospital, Ravenna, Italy

Tiziana Rappa Department of General, Geriatric, Oncologic Surgery and

Advanced Technology, Unit of Surgical Digestive Endoscopy, University of

Naples ‘‘Federico II’’—School of Medicine, Naples, Italy

Bjorn Rembacken Department of Endoscopy, General Infirmary Hospital,

Leeds, UK

Mohammed Thoufeeq Department of Endoscopy, General Infirmary Hospital,

Leeds, UK

Erminia Romeo Digestive Surgery and Endoscopy Unit, Ospedale Pediatrico

Bambino Gesu, IRCCS, Rome, Italy

Emanuele Rondonotti Gastroenterology Unit, Ospedale Valduce, Como, Italy

xvi Contributors

Simona Ruggiero Department of General, Geriatric, Oncologic Surgery and

Advanced Technology, Unit of Surgical Digestive Endoscopy, University of

Naples ‘‘Federico II’’—School of Medicine, Naples, Italy

Yutaka Saito Endoscopy Division, National Cancer Center Hospital, Tokyo,

Japan

Stefano Serafini Endoscopic and Operative Gastroenterology Units, USI

Group, Rome, Italy

Marco Silano Division of Food Science, Human Nutrition and Health, Istituto

Superiore di Sanita, Rome, Italy

Pasquina M. C. Tomaiuolo General Surgery, Catholic University of Rome,

Rome, Italy

Filippo Torroni Digestive Surgery and Endoscopy Unit, Ospedale Pediatrico

Bambino Gesu, IRCCS, Rome, Italy

Antonello Trecca Endoscopic and Operative Gastroenterology Units, USI

Group, Rome, Italy

Amorino Vecchioli Department of Bio-Imaging and Radiological Sciences,

Catholic University (UCSC), Radiology Institute, Rome, Italy

Vincenzo Villanacci Department of Pathology, Spedali Civili, University of

Brescia, Brescia, Italy

Emilio Gentile Warschauer Endoscopic and Operative Gastroenterology Units,

USI Group, Rome, Italy

Angelo Mario Zullo Gastroenterology Department, Nuovo Regina Margherita

Hospital, Rome, Italy

Contributors xvii

1Terminal Ileoscopy: Technique

Antonello Trecca, Giuseppe Cerno, Emilio Gentile Warschauer,Gabriele Marinozzi, and Fabio Gaj

1.1 Introduction

The basic requirement for the intubation of theterminal ileum is knowledge of the anatomy of theileocecal region and of the main appearances ofthe ileocecal valve (ICV), accompanied by anappropriate level of technical skill in performingcolonoscopy.

1.2 Anatomy of the Ileocecal Region

The cecum is the first part of the large intestine and itoccupies the right iliac fossa. Guarding the opening ofthe ileum (the terminal portion of the small intestine)into the cecum is the ICV [1]. The cecum is locatedbelow a transversal plane running along the ileocecal-colic sphincter (Fig. 1.1). It forms a rounded sacbetween 6 and 10 cm long, with an internal diameterof 5–6 cm and a capacity of 200–300 ml. Threeteniae coli enfold this region, defined as anterior,posterolateral, and posteromedial on the basis of theirposition. The posteromedial tenia coli forms theentrance into the terminal ileum. The longitudinalaxis of the cecum and that of the right colon togethercreate an obtuse angle that opens forward and medi-ally. The cecum is lodged together with the terminalileum and is completely covered by the peritonealwall. It is separated from the ileum by the ICV (also

called the Bauhin valve), which is composed of twosegments—an upper lip and a lower lip—that areformed by intrusion of the circular muscle layer of theileum into the lumen of the large intestine. A narrowmembranous ridge continues at the ends of theaperture medially and laterally, where the lips meet,giving rise to the frenula of the valve. The circularmuscle fibers of the ileum and those of the cecumcombine to form the circular sphincter muscle of theICV, whose role is to limit the rate of food passageinto the cecum and to prevent material from returningto the small intestine. The valve acts through thecontraction of the frenula in response to overstret-ching of the cecum, but it has minimal sphinctericaction, a fact that explains the common observation ofbarium reflux into the terminal ileum during a bariumenema examination. Intestinal occlusion results in apersistent contraction of the ICV, with consequentrupture of the cecum (called diastasis rupture), or itsrelaxation, with continuous reflux of the feces and theoverstretching of the terminal ileum. The ileumcomprises three-fifths of the small intestine, althoughthere is no absolute point at which the jejunum endsand the ileum begins. In broad terms, the jejunumoccupies the upper left part of the abdomen below thesubcostal plane (that is, at the level of the 10th rib),while the ileum is located in the lower right part.It has numerous convolutions and is attached to theposterior abdominal wall by the mesentery, anextensive fold of serous-secreting membrane that ismissing at the level of the terminal ileum, therebydetermining its complete mobility in the abdominalcavity. The arterial blood supply to the large intestinecomes from branches of the superior and inferiormesenteric arteries (both of which are branches of the

A. Trecca (&)Endoscopic and Operative Gastroenterology Units,USI Group, Rome, Italye-mail: atrecca@alice.it

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_1, � Springer-Verlag Italia 2012 1

abdominal aorta) and the hypogastric branch of theinternal iliac artery (which supplies blood to thepelvic walls and viscera, the genital organs, the but-tocks, and the inside of the thighs). The vessels form acontinuous row of arcades from which vessels arise toenter the large intestine. Venous blood is drainedfrom the colon via branches that form arcades, anal-ogous to those of the arteries. The blood from theseveins eventually drains into the superior and inferiormesenteric veins, which ultimately join with thesplenic vein to form the portal vein. The ileocecalregion has both parasympathetic and sympatheticinnervation. The vagus nerve provides parasympa-thetic innervation. Sympathetic innervation is pro-vided by branches of the superior mesenteric plexus, anerve network underneath the solar plexus that fol-lows the blood vessels into the small intestine andfinally terminates in the Auerbach plexus, which islocated between the circular and longitudinal musclecoats, and in the Meissner plexus, which is located inthe submucosa. Numerous fibrils, both adrenergic(sympathetic) and cholinergic (parasympathetic),connect these two plexuses.

1.3 Ileocecal Valve Appearances

The ICV may show a spectrum of normal findings atdouble-contrast barium enema, appearing as a round,ovoid, or triangular structure with a maximum heightof nearly 4 cm. The valve may be large, asymmetric,or smoothly lobulated. In a series of 106 patients, theICV was visible in 91 (86%), being round or ovoid in

71 patients (78%) and triangular in 20 (22%).At colonoscopy, all patients with a normal valve atdouble-contrast barium enema examination had anormal valve, whereas the two patients with a valvesuspicious for tumor at barium enema examinationhad neoplasms (one carcinoma and one villousadenoma). In a comparative study between double-contrast barium enema and ileoscopy, a macroscopi-cally normal appearance of the ICV was detected in30 patients. Among these patients, 60% were diag-nosed with mild, 26.7% with moderate, and 13.3%with severe endoscopic ileal inflammation. The ICVwas affected by Crohn’s disease (CD) in 70 patients,in whom significantly more severe ileal inflammation(p \ 0.005) was detected than in patients with anormal-looking ICV. The authors of that study con-cluded that ileal exploration should be attempted inevery patient suspected of having CD, because,although the appearance of the ICV correlates withthe severity of ileal inflammation, a normal-lookingICV does not correspond to normal ileal mucosa inmany cases [2].

At endoscopy, the ICV may be classified as labial,papillary, or lipomatous based on its morphologicappearance [3, 4]. The labial type has a slit-likeopening, the papillary type is dome shaped, and thelipomatous type has a substantial deposit of fat withinits lips. However, most non-lipomatous valves willdemonstrate streaks of fat within the valve lips. EachICV subtype may vary in appearance depending onwhether the patient is prone or supine or whether thevalve is open rather than closed. Another endoscopicclassification defines the ICV with the cecum mod-erately inflated: thin lipped, when the fold has nobulge; single or double bulging, when one or twoprominent bulges of the fold are present; and volca-nic, when the fold is exuberant and the orifice isvisible. Of these, the thin lipped morphology is themost difficult to intubate (Fig. 1.2).

1.4 Ileoscopy: Technique

The correct positioning of the colonoscope in theileocecal region is an essential step in the intubationof the ICV. Straightening the colonoscope in the leftbut also in the transverse colon guarantees its goodmaneuverability, allowing easy passage into the ileum(Fig. 1.3). Once the ICV is reached, its position in the

Fig. 1.1 The anatomy of the ileocecal region

2 A. Trecca et al.

intestinal lumen must be considered as well as thedecubitus of the patient. With the patient supine andthe ICV at the 9 o’clock position, downward deflec-tion is recommended to stretch the lower lip, andanti-clockwise torque with the left hand gentlyaccompanying the scope toward the left (Fig. 1.4).When the patient is in left lateral decubitus, the ICVappears in the 6- or 7-o’clock position and passageinto the ileum can be achieved with the samemaneuvers. Sometimes the ICV is positioned in the12- to 1-o’clock position and a combination ofupward deflection and clockwise torque (oppositefrom that described above) may be necessary. In caseof a thin-lipped valve, which, as noted above, is themost difficult one to intubate, due to difficult visual-ization of the upper and lower lips, a retroversion ofthe tip of the scope in the cecal region can help toidentify the valve. In this case, the scope is withdrawnand the tip is straightened, before the instrument isadvanced into the ileum (Fig. 1.5). Once the endo-scope has entered in the ileal lumen, the ileum must

be insufflated with a good amount of air in order toposition the scope, avoiding its retreat into the cecum[5, 6]. The use of hyoscine-n-butyl bromide reducesbowel motion and may also facilitate ileal intubation[7]. Exploration of the last 10–15 cm of the ileum isalways possible, with advancement of the scopefacilitated by abdominal compression. The reportedincidence of complications during ileoscopy isessentially null, both in unsedated and sedatedpatients, especially if the use of biopsy forceps tointubate a difficult valve or insufflating large amountsof air in the ileocecal region is avoided [8–11]. Oncethe scope is in the ileal lumen, its withdrawal,accompanied by a moderate insufflation of air,

Fig. 1.2 The ileocecal valve morphology. a Thin-lipped or labial. b Single-bulge or papillary. c Double-bulge or papillary.d Volcanic or lipomatous

Fig. 1.3 The correct position of the colonoscope for ileoscopy

Fig. 1.4 a, d, g Manipulation of the scope using the left handduring ileal intubation. b, e, h Position of the patient andmanipulation of the scope using the right hand during ilealintubation. c, f, i Position of the colonoscope within theintestinal lumen during the different steps of the procedure

1 Terminal Ileoscopy: Technique 3

enables an accurate evaluation of the endoscopicappearance of the terminal ileum, searching for thepresence of hyperemia, aphthoid lesions, erosions, orulcers. The standard view cannot describe the mor-phology of the general villous architecture, whichinstead can be outlined only after the injection of10–15 ml of saline through the biopsy channel, asconfirmed in a prospective, observational study on216 consecutive completed colonoscopies in whichthe images of the terminal ileum were significantlymore likely than cecal images to be considered con-vincing in order to verify the extent of colonoscopy(p \ 0.0001 for all reviewers). The instillation ofsterile water in the intestinal lumen was considered bythe authors as a prerequisite to obtain accuratephotodocumentation [12].

1.4.1 Magnified Ileoscopy

The important clinical results obtained with magnify-ing endoscopy for the detection and definition of earlycolorectal cancer led us to reproduce this technique for

the study of the terminal ileum (magnified ileoscopy,Table 1.1) [13]. The steps of the procedure are similarto those followed for the colon, including washing themucosa with mucolytic agents in order to enhance thevillous profile and then spraying the lumen with dye(5–8 ml of indigo carmine 0.4%). The dye, with itscapacity to pool in any minimal depression, furtherenhances the villous profile, highlighting the presenceof lymphoid follicles and the subtotal or total atrophy ofthe terminal ileum. The endoscopist, after an accurateevaluation of the sprayed mucosa, can scan the region,identifying the pathological area for study and per-forming a target biopsy. Magnified ileoscopy allows amuch more accurate study of the terminal ileum. It canbe used to determine the presence of even subtlechanges of the mucosa, such as hyperemia, and of smallaphthoid or erosive lesions, which can be missed atconventional view. It also reveals the villous mor-phology, including the size of the villi, and potentialatrophy of the terminal ileum, neither of which are seenon conventional endoscopy. Caution must be exertedby the endoscopist to avoid spraying too much dye,because it can alter the visualization of the mucosa withbackflow to the ileocecal region, thus compromisingthe inspection of this area.

1.4.2 Virtual Chromoendoscopy

Virtual chromoendoscopy, called narrow-band imag-ing (NBI), represents another aid to the endoscopist.The NBI system makes use of optical filters within the

Fig. 1.5 a, d, g Manipulation of the scope using the left handduring ileal intubation. b, e, h Position of the patient andmanipulation of the scope using the right hand during ilealintubation. c, f, i Position of the colonoscope within theintestinal lumen during the different steps of the procedure

Table 1.1 Magnified ileoscopy technique

Step 1: Washing the mucosa with a mucolytic agent

Step 2: Dye-spraying with a solution of 5–8 ml of indigocarmine 0.4%

Step 3: Magnifying view

Step 4: Endoscopic evaluation

Table 1.2 Virtual magnified ileoscopy technique

Step 1: Washing the mucosa with a mucolytic agent

Step 2: Filling the lumen with saline

Step 3: Activating virtual chromoendoscopy

Step 4: Magnifying view

Step 5: Endoscopic evaluation

4 A. Trecca et al.

light source of a videoendoscope, selecting light inshort and limited wavelengths within the hemoglobinabsorption band. The most recent development iscomputed virtual chromoendoscopy imaging, inven-ted by Yoichi Miyake (Faculty of Engineering,Chiba University, Chiba, Japan) and introduced byFujinon as Fujinon Intelligent Color Enhancement(FICE). FICE is based on the same physical princi-ple as NBI, but due to a new computed spectralestimation technology it is not dependent on opticalfilters. The FICE technology takes an ordinaryendoscopic image from the video processor andarithmetically processes the reflected photons toreconstitute virtual images by increasing the relativeintensity of narrowed blue (B) light to a maximumand decreasing narrowed red (R) and green (G) lightto a minimum. FICE successfully realizes enhance-ments and real-time observations of mucosal andmicrovascular patterns [14–17]. By cutting off the

longer wavelengths, FICE improves the contrast ofthe capillary patterns and enhances the structure ofthe mucosal surface. Virtual chromoendoscopy thusprovides dyeless contrast and constitutes an easy-to-use diagnostic technology. The digital processingsystem allows switching between conventional ima-ges and FICE-NBI images by a simple push of abutton on the endoscope [18, 19] (virtual magnifiedileoscopy; Table 1.2, Figs. 1.6 and 1.7).

1.5 Conclusions

Terminal ileoscopy during colonoscopy is of pivotalimportance for the detection and definition of ilealpathology. The endoscopist should be familiar withthe ileocecal anatomy and with the different possiblemorphologies of the ICV. Following brief but indis-pensable training, proficiency in ileal intubation can

Fig. 1.6 Normal villousmorphology. a Conventionalview of the terminal ileumwith normal finding. b,c Virtual magnified ileoscopyshows the normal villouspattern, with evidence of asingle lymphatic follicle.d–f Histology of the normalvillous morphology

Fig. 1.7 Normal villousmorphology with evidence ofmultiple lymphatic follicles.a Conventional view of theterminal ileum, showingdiffuse hyperemia. b,c Virtual magnified ileoscopywith normal villous patternand multiple lymphaticfollicles. d, e Histology showsnon-specific ileitis

1 Terminal Ileoscopy: Technique 5

be achieved after 50 procedures. The principles of thetechnique should be kept in mind by both the traineeand the expert in order to simplify intubation of thelast 20 cm of the ileum. A broad spectrum of ilealdiseases can be excluded during investigation of thisregion, which has been significantly improved by thecontribution of recent technological advances, mainlymagnified ileoscopy.

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13. Kudo S, Tamura S, Nakajima T et al (1996) Diagnosis ofcolorectal tumorous lesions by magnifying endoscopy.Gastrointest Endosc 44:8–14

14. Gono K, Yamazaki K, Doguchi N et al (2003) Endoscopicobservation of tissue by narrow band illumination. Opt Rev10:1–5

15. Machida H, Sano Y, Hamamoto Y et al (2004) Narrow-band imaging in the diagnosis of colorectal mucosallesions: a pilot study. Endoscopy 36:1094–1098

16. Konerding MA, Fait E, Gaumann A (2001) 3D microvasculararchitecture of pre-cancerous lesions and invasivecarcinomas of the colon. Br J Cancer 84:1354–1362

17. Skinner SA, Frydman GM, Obrien PE (1995)Microvascular structure of benign and malignant tumorsof the colon in humans. Dig Dis Sci 40:373–384

18. Chiu HM, Chang CY, Chen CC et al (2007) A prospectivecomparative study of narrow-band imaging, chromoendoscopyand conventional colonoscopy in the diagnosis of colorectalneoplasia. Gut 56:373–379

19. Pohl J, Nguyen-Tat M, Pech O, May A, Rabenstein T, Ell C(2008) Computed virtual chromoendoscopy forclassification of small colorectal lesions: a prospectivecomparative study. Am J Gastroenterol 103:562–569

6 A. Trecca et al.

2The Importance of Complete Colonoscopyand Exploration of the Cecal Region

Kuangi Fu, Takahiro Fujii, Takahisa Matsuda,and Yutaka Saito

2.1 The Importance of a CompleteColonoscopy

Ever since case-control studies demonstrated theability of flexible sigmoidoscopy (FS) to decreasecolon cancer mortality by 60–70%, it has become themost frequently recommended modalities for coloncancer screening [1]. Recent reports, however, haveshown that FS may miss proximal neoplasms orcancers [2]. Moreover, the National Polyp Studyfound that the incidence of colorectal cancer (CRC) inan adenoma-bearing cohort that had undergoneclearing colonoscopy was reduced by 76–90% com-pared to reference populations [3]. It is obvious thatexamination of the left colon alone misses right-sidedlesions. Thus, while colonoscopy is more time-con-suming and resource-demanding, in addition tocausing greater patient discomfort and with a higherrate of complications due to bowel cleansing and theendoscopic procedure, it is widely appreciated as themost sensitive colonic imaging test for adenomas. Anadditional advantage of colonoscopy is that it allowsthe removal of precancerous polyps at the time oftheir detection.

A right-sided aging-related shift in the location ofthe initial development of colorectal adenomas wasrecently reported, based on repeated colonoscopies insubjects with no neoplasms [4]. Recurrent adenomasafter polypectomy also tend to develop at locations

proximal to the initial adenomas [5]. Accordingly,total colonoscopy is needed for surveillance, regard-less of the initial adenoma site. Moreover, the distri-bution of carcinoma and of adenomatous polyps in thecolorectum likewise shows a proximal shift with ageand female gender [6, 7]. Clinically, right-sided can-cer is likely to be detected at a more advanced stage,with severe symptoms such as passage trouble orabdominal mass. Morphologically, the frequency oftumors with a flat-type appearance is significantlyhigher in right-sided than in left-sided colon cancers,while polypoid-type lesions are substantially moredominant in the left colon [8]. Histopathologically,poorly differentiated, mucinous, and signet-ring celltumors are frequently seen in the right colon [9].From a molecular aspect, the right-sided tumors thatpredominate in the elderly are those with a high fre-quency of CpG island methylation and those withmicrosatellite instability (MSI), in which there isoften methylation of the promoter region of thehMLH1 mismatch repair gene [10]. A newly pro-posed disease entity, serrated polyps, compriseshyperplastic polyps, traditional serrated adenomas(TSAs), and sessile serrated adenomas (SSAs), whichhave also been described as sessile serrated polyps(SSPs) [11]. SSAs/SSPs are more prevalent in theproximal colon and lack classic dysplasia but mayhave mild cytologic atypia, whereas TSAs are moreprevalent in the rectosigmoid and have cytologicdysplasia. SSAs/SSPs, particularly those with foci ofclassic histologic dysplasia, are considered the likelyprecursor lesions to sporadic MSI-H colon cancer, asdetermined in studies of their molecular profiles,which have shown inactivation through methylationof genes such as the MLH-1 DNA repair genes and/or

K. Fu (&)Department of Gastroenterology, Juntendo UniversityNerima Hospital, Tokyo, Japane-mail: fukuangi@hotmail.com

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_2, � Springer-Verlag Italia 2012 7

0-6-methylguanine DNA methyltransferase (MGMT)[12]. The presence of SSAs/SSPs (C10 mm in size) isalso reported to be a risk factor for CRC, particularlyof the proximal colon [13].

2.2 The Importance of Exploringthe Cecum

It has been known for many years that colorectaladenoma and CRC have different distributions in thecolon. The anatomic distribution of adenomas in thecolon was described in previous reports (e.g., [14])that included autopsy and endoscopic studies.Autopsy studies show a relatively even distribution ofadenomas throughout the colon whereas cancer ismore frequent in the distal colon and rectum. In thosestudies, the incidence of adenomas located in thececum varied from 2 to 67%. However, in somereports fewer than 200 cases were evaluated. Bycontrast, endoscopic studies evaluated more than 200cases (one was based on 6,942 cases), reporting cecaladenomas in 2–20%. Based on data from the NationalCancer Center, the incidence of early colorectalneoplasia involving the cecum, as determined fromtumors resected endoscopically, is 6.0% (Table 2.1)whereas the incidence of CRCs located in the cecum,as determined from surgically removed tumors, is6.8% (Table 2.2). Although the incidence of colo-rectal neoplasia in the cecum is lower than in othersites, it should be kept in mind that some non-pol-ypoid neoplasias, including SSAs/SSPs or laterallyspreading tumor, can occur at this site, especially atthe periphery of the appendiceal orifice, and areendoscopically detectable. Obviously, visualization ofthe appendiceal orifice and ileocecal valve confirms acomplete total colonoscopy.

2.3 Case Presentation

2.3.1 Case 1

A 74-year-old woman underwent total colonoscopybecause of a positive fecal occult blood test. Duringconventional endoscopic observation, a superficiallyreddish area was detected on the ileocecal valve(Fig. 2.1a). Narrow-band imaging revealed a flatbrownish lesion (Fig. 2.1b). Chromoendoscopy, per-formed using indigo-carmine spraying, further dem-onstrated a non-granular type of laterally spreadingtumor (LST-NG), 20 mm in diameter, on the ileocecalvalve (Fig. 2.1c). Magnification with chromoendos-copy using indigo-carmine and crystal-violet stainingshowed a type IIIL pit pattern, according to Kudo’sclassification, which is a good indication for endo-scopic resection (Fig. 2.1d, e). The tumor was com-pletely removed en bloc with endoscopic submucosaldissection (Fig. 2.1f). Histologically, the lesion wasidentified as a tubular adenoma with high- and low-grade atypia, with the cut end free of adenoma.

2.3.2 Case 2

A 48-year-old man underwent total colonoscopybecause of a positive fecal occult blood test. A flatelevated lesion was detected in the cecum near theorifice of the appendix (Fig. 2.2a). Chromoendoscopyusing indigo-carmine day spraying showed a lesioncovered by a small amount of mucus, even after vitalwater washing (Fig. 2.2b). Magnification after chro-moendoscopy revealed an elongated type II pit patternat the periphery, with features similar to those of a typeIIIL pit pattern (Fig. 2.2c). A dilated type II pit pattern

Table 2.1 Endoscopic treatment at the National Cancer Center Hospital, Tokyo, Japan (January 1998 until September 2006)

Adenoma (14,285) M-Ca (1,717) SM-Ca (302) Total (%)

Cecum 860 (87.2%) 119 (12.1%) 7 (0.7%) 986 (6.0)

Ascending 2,942 (90.2%) 283 (8.7%) 35 (1.1%) 3,260 (20.0)

Transverse 4,004 (93.3%) 244 (5.7%) 42 (1.0%) 4,290 (26.3)

Descending 1,723 (92.8%) 122 (6.6%) 11 (0.6%) 1,856 (11.4)

Sigmoid 3,298 (84.2%) 513 (13.1%) 104 (2.7%) 3,915 (24.0)

Rectum 1,458 (73.0%) 436 (21.8%) 103 (5.2%) 1,997 (12.3)

Total (%) 14,285 (87.6) 1,717 (10.5) 302 (1.9) 16,304 (100.0)

8 K. Fu et al.

Table 2.2 Surgery at theNational Cancer CenterHospital, Tokyo, Japan(January 1998 untilSeptember 2006)

Early (618) Advanced (2,651) Total (%)

Cecum 39 183 222 (6.8)

Ascending 73 322 395 (12.1)

Transverse 58 215 273 (8.4)

Descending 26 117 143 (4.4)

Sigmoid 166 660 826 (25.3)

Rectum 256 1,154 1,410 (43.0)

Total (%) 618 (18.9) 2,651 (81.1) 3,269 (100.0)

Fig. 2.1 a–f A non-granulartype of laterally spreadingtumor (LST-NG), 20 mm indiameter, is seen on theileocecal valve

2 The Importance of Complete Colonoscopy and Exploration of the Cecal Region 9

was detected in the central flat area (Fig. 2.2d). Theseendoscopic results suggested a large hyperplasticpolyp, or an SSA/SSP. The lesion was completelyremoved en bloc with endoscopic mucosal resection(the conventional lift and cut technique). Histologi-cally, the lesion was identified as an SSA/SSP.

References

1. Selby JV, Friedman GD, Quesenberry CP Jr, Weiss NS(1992) A case control study of screening sigmoidoscopyand mortality from colorectal cancer. N Engl J Med326:653–657

2. Brenner H, Arndt V, Sturmer T, Stegmaier C, Ziegler H,Dhom G (2001) Long-lasting reduction of risk of colorectalcancer following screening endoscopy. Br J Cancer85:972–976

3. Winawer SJ, Zauber AG, Ho MN et al (1993) Prevention ofcolorectal cancer by colonoscopic polypectomy. TheNational Polyp Study Workgroup. N Engl J Med 329:1977–1981

4. Yamaji Y, Mitsushima T, Ikuma H, Watabe H, Okamoto M,Yoshida H, Kawabe T, Wada R, Omata M (2006) Right-side

shift of colorectal adenomas with aging. Gastrointest Endosc63(3):453–458 (quiz 464)

5. Yamaji Y, Mitsushima T, Yoshida H, Watabe H, OkamotoM, Ikuma H, Wada R, Kawabe T, Omata M (2007) Right-side shift of metachronous colorectal adenomas afterpolypectomy. Scand J Gastroenterol 42(12):1466–1472

6. Distler P, Holt PR (1997) Are right- and left-sided colonneoplasms distinct tumors? Dig Dis 15:302–311

7. Gonzalez EC, Roetzheim RG, Ferrante JM et al (2001)Predictors of proximal vs. distal colorectal cancers. DisColon Rectum 44:251–258

8. Nawa T, Kato J, Kawamoto H, Okada H, Yamamoto H,Kohno H, Endo H, Shiratori Y (2008) Differences betweenright- and left-sided colon cancer in patient characteristics,cancer morphology and histology. J Gastroenterol Hepatol23(3):418–423

9. Iacopetta B (2002) Are there two sides to colorectal cancer?Int J Cancer 101:403–408

10. Hawkins N, Norrie M, Cheong K et al (2002) CpG islandmethylation in sporadic colorectal cancers and itsrelationship to microsatellite instability. Gastroenterology122:1376–1387

11. Torlakovic E, Skovlund E, Snover DC, Torlakovic G,Nesland JM (2003) Morphologic reappraisal of serratedcolorectal polyps. Am J Surg Pathol 27(1):65–81

12. Snover DC (2011) Update on the serrated pathway tocolorectal carcinoma. Hum Pathol 42(1):1–10

Fig. 2.2 a–d A sessileserrated adenoma/polyp isdetected in the cecumadjacent to the orifice ofappendix

10 K. Fu et al.

13. Hiraoka S, Kato J, Fujiki S, Kaji E, Morikawa T, MurakamiT, Nawa T, Kuriyama M, Uraoka T, Ohara N, Yamamoto K(2010) The presence of large serrated polyps increases riskfor colorectal cancer. Gastroenterology 139(5):1503–1510(1510.e1-3)

14. Neugut AI, Jacobson JS, Rella VA (1997) Prevalence andincidence of colorectal adenomas and cancer inasymptomatic persons. Gastrointest Endosc Clin N Am7(3):387–399

2 The Importance of Complete Colonoscopy and Exploration of the Cecal Region 11

3What are the Correct Indicationsfor Ileoscopy?

Antonello Trecca, Fabio Gaj, Stefano Serafini,Gabriele Marinozzi, and Marco Silano

3.1 Introduction

Exploration of the terminal ileum has rapidly gainedthe interest of the international literature, startingfrom the first report in 1972 by Nagasako [1]. Overthe past few decades, technical refinements of theendoscopic equipment and the resulting improvementin knowledge have simplified intubation of the lastcentimeters of the terminal ileum. These advanceshave been confirmed in several reported experiencesin which the terminal ileum was intubated duringcolonoscopy, with a success rate in experienced handsof 74–100% [2–4].

The importance of terminal ileoscopy (TI) is that itoffers proof that a total colonoscopy has been per-formed, since previously established signs, such asvisualization of the semilunar folds of the cecal regionand transillumination of the right lower abdominalquadrant, are considered too subjective and have sincebeen abandoned.

Cherian and Singh [5] were among the first tostress the need for adequate training in TI as anessential step in becoming a proficient colonoscopist.The study demonstrated that the procedure times forcolonoscopies performed by trainees were signifi-cantly longer than those by the consultant, but thatafter adequate training, the ileum could be success-fully intubated in 85% of patients (Fig. 3.1).

Iacopini et al. [6] prospectively investigated thelearning curve and skill retention for ileoscopy,showing that competency in ileocecal valve intuba-tion, with a success rate of 80% and ileal explorationof about 16 cm, could be achieved after 50 proce-dures. Training was based on the observation of tenTIs performed by senior endoscopists and with a self-assessment made hands-on. The experience of theendoscopist and ileocecal valve morphology werethe only two independent variables influencing thesuccess of the procedure, and the tolerability of TIwas inversely proportional to the duration of theexploration (Fig. 3.2).

A useful investigation also can be defined as one inwhich the result will alter the management or addconfidence to the clinician’s diagnosis. Thus, whendebating the merits of TI we have to consider thesuccess rate, diagnostic yield, duration, and above allthe capacity to modify the clinical results [7].

3.2 Indications and Resultsof Terminal Ileoscopy

In patients with diarrhea, right lower quadrantabdominal pain, and anemia, intubation of the ter-minal ileum is of pivotal importance to excludeCrohn’s disease (CD), especially in case of a negativecolonoscopy (Table 3.1). The estimated diagnosticyield is about 20% in patients with chronic diarrheaand 40% in those in whom inflammatory bowel dis-ease (IBD) is suspected (Fig. 3.3).

Evidence was provided that intubation of the ter-minal ileum during colonoscopy can yield successrates of 74% to as high as 100% without a significant

A. Trecca (&)Endoscopic and Operative Gastroenterology Units,USI Group, Rome, Italye-mail: atrecca@alice.it

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_3, � Springer-Verlag Italia 2012 13

prolongation of the procedure. The median durationof the procedure was 55 s (55–180 s), without anincreased intra-examination risk [8–11] (Table 3.2).

Nevertheless, even if the additional time neededfor TI during colonoscopy may seem short, consid-ering the annual workload of most hospitals, insti-tuting the procedure routinely would correspond toan additional 200 colonoscopies annually, as calcu-lated in 2001 by the British Society of Gastroen-terology Working Party [12]. Thus, whether TIshould be performed in unselected patients remainsa matter of debate among the experts, although themajority seems to agree that the examination isunnecessary given the high percentage of negativefindings. All studies, including those with the bias ofbeing retrospective, found that the incidence ofpathologic findings during TI performed in asymp-tomatic patients was only 0.3–4.6%. According toYoong and Heymann, a clinical impact in terms of achange in management was noted in only half of thepatients examined [13]. Nonetheless, if we considerthe spectrum of IBD it seems obvious that a nega-tive TI examination can better validate a diagnosisof ulcerative colitis with evident colonic lesions orsupport a definitive diagnosis of indeterminate, col-lagenous, ischemic, or drug-induced colitis [14, 15].

Ileal intubation should be performed only whenabnormal findings or changes in patient managementare expected [16, 17]. As provocatively suggested byCherian and Singh, however, TI is as much a part ofcolonoscopy as the exploration of the second portionof the duodenum is during esophagogastroduodenos-copy; this is especially the case given the shortness ofthe learning curve. As summarized by Ansari et al.[2]: ‘‘Added time, technical difficulty and limitedyield are not valid reasons for choosing not to performileoscopy’’ (Fig. 3.4).

3.3 The Contribution of Histology

Another topic of discussion is TI with biopsy, whichcan add important information about the histology ofthe mucosa and thereby increase the diagnostic yieldof the procedure. Thus, the question again arises[18, 19]: should histological examination of the ter-minal ileum always be performed or should it beselective? The answer is complex if we consider that adefinitive diagnosis is based on the combinationof clinical data, laboratory values, microbiological

Table 3.1 Absolute indications for ileoscopy

• Chronic diarrhea

• Right lower quadrant abdominal pain

• Abnormal imaging findings

• Suspicion of inflammatory bowel disease

• Family history of Crohn’s disease

Fig. 3.1 Endoscopic view ofthe terminal ileum a afterimmersion with saline andb after dye spraying withindigo carmine 0.4%

Fig. 3.2 Advanced cancer located just in front of the ileocecalvalve

14 A. Trecca et al.

examinations, and radiology, endoscopy and histol-ogy findings, each of which plays a specific role.

Undoubtedly TI with biopsies provide moredetailed information than obtained by any otherradiological examination, such as small bowel follow-through (SBFT) or small-bowel enema, in detectingterminal ileal pathology. Indeed, TI has a sensitivityand specificity of 100% in the diagnosis of CD and inthe detection of microscopic inflammatory changes ofthe mucosa [20, 21]. The introduction of capsuleendoscopy into the clinical setting has revolutionizedthe diagnostic approach to the terminal ileum, asoutlined by Hara et al. in a prospective comparativestudy between capsule endoscopy, computed tomo-graphic (CT) enterography, colonoscopy with ileos-copy, and SBFT [22]. The highest diagnostic yield forCD, even if not statistically significant, was gained bycapsule endoscopy. SBFT failed to depict a stricturein one patient, which resulted in surgical removal ofthe capsule. CT enterography and SBFT depictedextra-intestinal findings (e.g., mesenteric adenopathy

in two patients, perianal and enterocolic fistulas inone patient) not detected endoscopically, confirmingthat each imaging modality has its specific role andthat patients with negative TI and suspected CDshould undergo capsule enteroscopy in order to

Table 3.2 The role of ileoscopy during colonoscopy

First author Patients (n) Ileal intubation (%) Abnormal findings (%) Ileal findings and GI symptoms (%)

Yoong [13] 2149 346 (16) 16 (4) 8 (50)

Kundrotas [4] 270 213 (79) 1 (0.3) 0

Zwas [3] 144 138 (95) 12 (5) 8 (65)

Iacopini [6] 600 –(91) 15 (5.5) 6 (2.2)

Kennedy [16] 30000 6408 (21) 68 (1) 6 (10)

Bhasin [17] 66 57 (86) 13 (22) 8 (14)

Geboes [7] 300 – 123/257 (48) Symptoms of IBD: 125/257 (49)

Cherian [5] 2537 –(71.5) IBD (16)Unselected (2.7)

IBD: 19Unselected (7.4)

Morini [26] 156 149/156 (95) 47/138 (34) CND: 8/138 (5.8)

Ansari [2] 120 117 (97) 24 (20.5) Abdominal pain 15/86 (17.4)

IBD Chronic or persistent diarrhea, CND chronic non-bloody diarrhea

Fig. 3.3 a Multiple aphthoidlesions in the terminal ileum;b magnifying view

Fig. 3.4 Meckel’s diverticulum of the terminal ileum isclearly visible after chromoendoscopy

3 What are the Correct Indications for Ileoscopy? 15

exclude lesions that may be present anywhere alongthe bowel (Fig. 3.5).

In a retrospective study by McHugh et al. [23],comprising more than 414 consecutive patients sub-mitted to ileoscopy and biopsy, TI was negative in81% and the findings were histologically normal in82%, supporting the conclusion that both proceduresare unnecessary routinely because of their high costand lengthy duration. The diagnostic yield of biopsiesvaries with the specific endoscopic findings and isgreatest when the endoscopist reports ‘‘ileitis,’’ ulcers,or erosions and discouraging in patients with a nor-mal-appearing mucosa.

A cost-effective strategy would be to include TI forpatients with suspected IBD or those with abnormalfindings involving the terminal ileum. Other reportson unselected patients seem to confirm these data,with evidence of macroscopic and/or microscopicabnormalities in 1.8–7.4% and increasing up to 19%only in patients with IBD [24].

Two major indications for ileocolonoscopy have sofar evident: in patients in whom CD is suspected andin those with diarrhea, ileocolonoscopy with biopsiesis the recommended diagnostic procedure and, inoptimal conditions, results in a final diagnosis in up to99% of the cases [25] (Fig. 3.6).

Several other clinical conditions should be kept inmind when considering the wide spectrum of IBD:backwash ileitis, which has an incidence of 6% inpatients with ulcerative colitis, a family history ofCD, and all patients in whom other imaging modali-ties raise suspicion of CD. In this setting, the

Fig. 3.5 Mucosal bridges ofthe left colon a in a patientwith chronic ulcerative colitisand b ileoscopy with negativefindings

Fig. 3.6 Diffuse nodular lymphoid hyperplasia of the terminalileum with active bleeding

Fig. 3.7 Diffuse and serpiginous ulcerative lesions of theterminal ileum in patient with Crohn’s disease

Table 3.3 Absolute indications for ileoscopy and biopsy

• Suspicion of Crohn’s disease

• Chronic diarrhea

• HIV-infected patients

• Suspicion of tuberculosis

• Ileal lesions at ileoscopy

16 A. Trecca et al.

histology of the terminal ileum is undoubtedly theonly available basis for the diagnosis.

Chronic non-bloody diarrhea should be consideredanother indication for TI and biopsy only afterit has been correctly classified on a clinical basis.In unselected patients, the diagnostic yield of TI isapproximately 5%, while in a series of 156 patientswith chronic non-bloody diarrhea, CD, nonspecificileitis, and nodular lymphoid hyperplasia were sig-nificantly more frequent in patients than in controls,confirming the ability of TI to detect alterations in thisgroup of patients such that the gain in the finaldiagnosis of CD was 5.8% [26]. The passage of bloodmakes an accurate exploration indispensable, while incase of an inflammatory condition histology cannotrule out a definitive diagnosis (Fig. 3.7).

Terminal ileoscopy should always be attemptedbut only in case of mucosal lesions integrated withbiopsy. A normal terminal ileum should be biopsiedonly in HIV-infected patients or in patients fromcountries in which intestinal tuberculosis is highlylikely [27–29] (Table 3.3).

3.4 Open Issues

A possible link between TI and histology can beprovided by the benefits gained from the most recenttechnological advances, which have opened up newhorizons for the modern endoscopist by improvingdiagnosis as well as the selection of patients for targetbiopsy [30, 31].

Conventional or virtual chromoendoscopy in com-bination with magnification accentuates the uniqueappearance of the ileal mucosa’s surface structure andcapillary vessels. Confocal laser endomicroscopy pro-vides such high resolution of the columnar villousepithelium that it is possible to observe discrete gobletcells, mononuclear cells, intraepithelial lymphocytes,and erythrocytes within the subepithelial stromalcapillary net [32, 33].

The ability to enhance the mucosal appearance ofthe terminal ileum surely provides an optimalmodality to study villous morphology and to detectany minimal reduction or shortening of the villi.

Fig. 3.8 a Severe atrophicchanges in the terminal ileumafter chromoendoscopy withindigo carmine 0.4% andb magnified view

Fig. 3.9 a Sessile polyp atterminal ileoscopy. b Thevillous structure is clearlyvisible after the instillation ofsaline

3 What are the Correct Indications for Ileoscopy? 17

The diagnostic yield can be improved particularly inpatients with celiac disease or early CD, as demon-strated in a study of 143 patients examined by mag-nification. In this study, 6 out of 10 patients withCeliac disease were correctly diagnosed by endos-copy alone. Among the four patients with CD, twohad ileal lesions detectable only on magnifying view[34] (Fig. 3.8).

Nevertheless, the exact role of these imagingmodalities should be confirmed in larger series ofpatients, which would contribute to establishing amodern diagnostic flow-chart able to increase the clini-cal results obtainable for each and every patient [35](Fig. 3.9).

3.5 Conclusions

Terminal ileoscopy currently represents an effectiveprocedure for the assessment of diseases of the terminalileum. The possibility of gaining a highly specializedexpertise after adequate training confirms that thisexamination establishes proficiency as a colonoscopist.The diagnostic yield of TI, considering the brief dura-tion of the procedure and the lowest risk of complica-tion, merit the use of this procedure in patients in whomthere is suspicion of CD, as based on right lowerabdominal quadrant pain, anemia, and suspiciousimaging results. The endoscopist should alwaysattempt TI, obtaining biopsy material when lesions tothe terminal ileum are identified. The role of emergingtechnologies, while promising, remains to be bettervalidated in clinical practice. A well-performed TIrepresents the best method to correctly select patientswho would most benefit from other procedures and itoffers a fast-track approach to diseases of the gut.

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26. Morini S, Lorenzetti R, Stella F et al (2003) Retrogradeileoscopy in chronic nonbloody diarrhea: a prospectivecase-control study. Am J Gastroenterol 98:1512–1515

27. Sato S, Yao K, Yao T, Schlemper RJ, Matsui T, Sakurai T,Iwashita A (2004) Colonoscopy in the diagnosis of intestinaltubercolosis in asymptomatic patients. Gastrointest Endosc59:362–368

28. Misra SP, Misra V, Dwivedi M (2007) Ileoscopy in patientswith ileocolonic tubercolosis. WJG 13:1723–1727

29. Misra SP, Dwivedi M, Misra V (2006) Ileoscopy in 39hematochezia patients with normal colonoscopy. WJG12:3102–3104

30. Tanaka S, Kaltenbach T, Chayama K et al (2006) High-magnification colonoscopy. Gastrointest Endosc 64:604–613

31. Technology Commitee ASGE (2009) Technology statusevaluation report on high-resolution and high-magnificationendoscopes. Gastrointest Endosc 69:399–407

32. Siegel LM, Stevens PD, Lightdale CJ et al (1997) Combinedmagnification endoscopy with chromoendoscopy in theevaluation of patients with suspected malabsorption.Gastrointest Endosc 46:226–230

33. Cammarota G, Martino A, Pirozzi GA et al (2004) Directvisualization of intestinal villi by high-resolution magnifyingupper endoscopy: a validation study. Gastrointest Endosc60:732–738

34. Trecca A, Gaj F, Gagliardi G, Calcaterra R, Battista S,Silano M (2008) Role of magnified ileoscopy in thediagnosis of cases of coeliac disease with predominantabdominal symptoms. Scand J Gastroenterol 44:320–324

35. Dionisio PM, Gurudu SR, Leighton JA, Leontiadis GI,Fleischer DE, Hara AK, Heigh RI, Shiff AD, Sharma VK(2010) Capsule endoscopy has a significantly higherdiagnostic yield in patients with suspected and establishedsmall-bowel Crohn’s disease: a meta-analysis. Am JGastroenterol 105:1240–1248

3 What are the Correct Indications for Ileoscopy? 19

4Contribution of New Technologiesto Endoscopic Imaging

Giuseppe Galloro, Luca Magno, Simona Ruggiero,Ferdinando Fusco, and Tiziana Rappa

4.1 Introduction

The importance of the earliest possible detection ofdigestive malignant lesions has fueled the develop-ment of new high-technology endoscopic systems, theso-called powerful endoscopes. Comparable to therapid development of chip technology, the opticfeatures of the new powerful endoscopes offer a res-olution able to reveal surface details of the gastroin-testinal tract. Some of these technologies increasediagnostic performance by improving resolution,others by modifying the chromatic spectrum of theendoscopic image. The augmented endoscopic visionis due to the use of either charge-coupled device(CCD) or central processing unit (CPU; endoscopicprocessor) features.

The new generation of gastric and colonic endo-scopic probes enable high-resolution endoscopy, high-magnification endoscopy (magnifying and zoom), andcomputed virtual chromoendoscopy (CVC) whereasthe enteroscopes that are currently available arerestriced to CVC types, without high-resolution ormagnifying-zoom endoscopic capabilities. Conse-quently, the only way to perform high-resolution ormagnifying-zoom endoscopy in the ileum is by usinga new-generation coloscope, inserted through the

ileocolic valve, while CVC involves the use of adedicated enteroscope. Nevertheless, Pentax hasdeveloped a new type of enteroscope, the VSB-2990iHD, able to perform high-resolution enteroscopy,although study data have yet to be reported.

4.2 High-Resolution andHigh-MagnificationEndoscopy

4.2.1 Technological Status

The video capabilities of the color images generatedby standard definition (SD) endoscopes are based ontraditional television (TV) broadcast formats [1, 2].SD signals offer images in a 4:3 aspect ratio, withimage resolutions of 640–700 pixels width by480–525 pixels or ‘‘lines’’ of height (approximately367,000 pixels) [2]. SD endoscopes are equipped withCCD chips that produce an image signal of100,000–400,000 pixels, which are displayed in SDformat. Advances in CCD technology have resulted insmaller CCDs with an increased number of pixels andhigher resolution. The CCDs used in current high-resolution or high-definition (HD) endoscopes pro-duce signal images with resolutions between 850,000and 1 million pixels.

The general definition of HD and high-resolutionimages is an image with more than 650–720 lines ofresolution (height) [3]. Moreover, images may beprogressive or interlaced. With progressive (p) images,lines are scanned consecutively and the image is cre-ated 60 times per second, whereas with interlaced (i)

G. Galloro (&)Department of General, Geriatric, Oncologic Surgeryand Advanced Technology, Unit of Surgical DigestiveEndoscopy, University of Naples ‘‘Federico II’’—Schoolof Medicine, Naples, Italye-mail: giuseppe.galloro@unina.it

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_4, � Springer-Verlag Italia 2012 21

images, every other line is scanned and the image iscreated in two passes at 30 times per second each.

HD video imaging can be displayed in either TV orcomputer monitor format. The 16:9 aspect ratio is notuseful to display images from round endoscopiclenses. Historically, endoscopic images are typicallydisplayed in a 4:3 aspect ratio, to match the standardaspect ratios of SD TV and because this ratio providesthe highest possible pixel density and resolution,given the shape of the lens. The display in computermonitor formats uses progressive scanning and is notrestricted by broadcast HD formats or aspect ratios.Monitors have traditionally had 4:3 aspect ratios butrecently 5:4 ratios have become more popular.Current high-resolution endoscopic CCDs displayimages in either 4:3 or 5:4 aspect ratios [3]. It isimportant to recognize that, to provide a true HDimage, each component of the system (e.g., endo-scope CCD, processor, monitor, and transmissioncables) must be HD compatible.

Three different high-resolution endoscope systemsare currently commercially available: (1) Olympushigh-resolution endoscopes were designed based onthe commercial availability of TVs and recorders foroutput onto HDTVs. The output from the endoscope isenhanced to 1080i; however, the endoscopic imageitself is displayed within a 1,280 9 1,024-pixel frame.(2) Fujinon high-resolution endoscopes were designedfor output onto computer monitors. The first FujinonCCD chips were 1,077 9 788 pixels and their outputwas equivalent to XGA monitors [2]; however, currentendoscopes have an output of 1,280 9 960 pixels. Theactual resolution of the CCD is proprietary informa-tion. The newest processors enhance the image to1080i. (3) Pentax Medical high-resolution endoscopeswere designed for output onto computer monitors. ThePentax CCD is 1,280 9 1,024 pixels and displays atnative resolution.

High-resolution endoscopes magnify the endo-scopic images 30–35 times. Zoom endoscopes aredefined by the capacity to perform optical zoomingthrough a movable lens in the tip of the endoscope[4]. Optical zoom provides a closer image of thetarget while maintaining image display resolution.This is distinguished from electronic magnification,which simply moves the image closer on the displayand results in a decreased number of pixels thatcompose the area of the display, with no improvementin resolution [5]. With the proper processor,

conventional endoscopes permit an electronic mag-nification of 1.5–2. Although standard endoscopesmagnify images 30–35 times, zoom endoscopes canoptically magnify images up to 150 times, dependingon the size of the monitor.

4.2.2 Implementation of High-Resolutionand High-Magnification Endoscopyin Ileoscopy

Usually, the target of high-resolution and high-magnification endoscopy is a qualitative diagnosis thatdifferentiates between neoplastic and non-neoplasticlesions, based on the study of the pit pattern (superficialorifices of the glandular crypts on the digestive mucosalsurface) [6, 7]. To date, there are limited analyses ofmagnification endoscopy in small-bowel diseases,although there have been a few promising reports oftargeting duodenal biopsies in celiac sprue or malab-sorption [8–10]. One of these studies, conducted on 34patients with either celiac or tropical sprue, found thatmagnifying chromoendoscopy was better than standardendoscopy in identifying duodenal villous atrophy andtherefore improved target biopsies [8]. Another studyshowed that high-resolution endoscopy had 95% sen-sitivity, 99% specificity, 95% positive predictive value,and 99% negative predictive value to detect the pres-ence of any duodenal villous abnormality [9].

Some authors have proposed a new role for high-resolution and high-magnification enteroscopy in thestudy of primary intestinal lymphangiectasia, i.e., toshow the dilated capillary vessels in intestinal villi andthe loss of lymph fluid into the gastrointestinal tract [11].

As in the duodenum, high-resolution and high-magnification endoscopy also could be used in theileum, i.e., in targeted biopsies and in the study ofmucosal areas where histopathologic abnormalities aremost likely to be present. However, this applicationawaits further and more specific evaluation. Moreover,cost-effectiveness studies are needed before thesetechniques can be recommended for clinical practice.

A Japanese paper [12] suggested the use of high-magnification ileoscopy (using a zoom colonscopethrough the ileocolic valve) to evaluate the presenceof Peyer’s patches, which on magnifying endoscopyare seen as irregularly shaped, granular, dome-likeelevations and irregularly arranged villi in the termi-nal ileum. The histologic finding of microgranulomas,

22 G. Galloro et al.

lymphoid hyperplasia, and the presence of M cells atscanning electron microscopy confirms that theseareas are Peyer’s patches [13]. Peyer’s patches, asdetected by magnifying endoscopy and electronmicroscopy, may provide insights into the pathogen-esis of Crohn’s disease.

Another important indication of high-resolution andhigh-magnification endoscopy of the small bowel, andthe ileum in particular, is the zoom endoscopic follow-up of transplanted patients, to monitor potentialsmall-bowel allograft rejection. In fact, with recentimprovements in surgical techniques and immuno-suppressive drugs, small-bowel transplantation hasbecome a desirable and potentially life-saving alter-native for patients with short-gut syndrome or otherproblems causing intestinal failure [14–16]. The earlydiagnosis of graft rejection is extremely importantbecause rapid progression to severe rejection can occurwithout proper treatment, and advanced stages ofrejection are associated with poor outcomes [17, 18].The technology and clinical protocols for monitoringgraft function and for treating acute rejection are still inthe early stages of development. Frequent biopsies ofthe small-bowel graft are critical for detecting thepresence of acute cellular rejection. While randommucosal biopsy provides detailed information about avery small area, the endoscopic view can provideinformation about large areas, thus allowing rapidassessment of the overall health of the graft mucosa.In addition, this approach is essential for obtaininghistologic specimens [19–21]. Unfortunately, standardendoscopy is not powerful enough to provide anaccurate view of the mild changes that occur in theearly phase of small-bowel rejection [22, 23] whereashigh-resolution and high-magnification ileoscopy,performed by a zoom colonscope through a surgicallycreated ileostomy, allows direct visualization of thevilli and crypt areas, thereby providing a more accurateoverall evaluation of the graft mucosa [22]. Indeed, inskilled hands, zoom endoscopic evaluation of villousshortening, villous blunting, background erythema,villous congestion, and mucosal friability (confirmedby histologic findings on target biopsies) has achieved asensitivity of 45%, a specificity of 98%, a positivepredictive value of 82%, and a negative predictivevalue of 88% [24]. In pediatric patients, these valuesare, respectively, 61, 84, 57, and 86%. In conclusion,the enhanced capability afforded by zoom ileoscopy inthe assessment of graft mucosal health has been shown

to provide useful information, thus enabling a rapiddiagnosis that, along with the presenting clinicalsymptoms, can determine the need to treat histologi-cally diagnosed early rejection.

4.3 Computed VirtualChromoendoscopy

4.3.1 Technological Status

Computed virtual chromoendoscopy is a real-time,on-demand endoscopic imaging technique in which thespectroscopic characteristics of the videoendoscopicsystems are adjusted by using a frame sequential lightingmethod [25], thereby allowing enhanced visualization ofthe vascular network and mucosal surface texture and, inturn, improved tissue characterization, differentiation,and diagnosis. CVC is considered a potential alternativeto traditional chromoendoscopy, providing contrastenhancement of tissue surface structures; however, it hasnot been as extensively studied as chromoendoscopy.Currently, three different CVC systems are commer-cially available: olympus narrow-band imaging (NBI),Fujinon Intelligent Color Enhancement (FICE), andPentax i-Scan.

Standard videoendoscope systems use the entirespectrum of visible light (400–700 nm). These so-calledwhite-light imaging endoscopic systems are designed tosimulate daylight and to examine tissues in their naturalcolors. The videoendoscopic images can be obtained byone of two different systems: the red–green–blue (RGB)sequential and color CCD systems [26].

In the RGB sequential system, light from a xenon arclamp is filtered through a rotating broadband RGB filterlocated between the lamp and the endoscope’s lightguide to obtain sequential bursts of red, green, and bluelight that give rise to the visual strobe effect. Aftertissue illumination, the reflected red, green, and bluetissue images are sequentially captured by a mono-chromatic CCD at the tip of the endoscope and trans-mitted to a video processor. The three images are fedinto the electron guns that illuminate the red, green, andblue phosphor dots on the monitor, respectively, tocreate a final composite image in full natural color [27].

The color CCD system uses a micromosaic colorfilter mounted over the CCD itself. Continuous white-light illumination from the xenon lamp is delivered tothe tissue by the endoscope’s light guide, with the

4 Contribution of New Technologies to Endoscopic Imaging 23

reflected light and image created on the CCD surfacethen processed by circuitry in the video processorprior to display. Similar to the RGB system, tissuestructures that heavily reflect red, green, and bluelight are displayed on the R, G, and B video channelson the video monitor, respectively [27].

The NBI system (Olympus Medical Systems,Tokyo, Japan) emphasizes the mucosal microvascu-lature and is able to identify vascular alterationsindicative of pathologic conditions [28–31]. It consistsof narrow bandpass filters placed in front of aconventional white-light source to produce a contrastbetween vascular structures and surrounding mucosa.Unlike the initial three-band NBI prototypes, currentlyavailable NBI systems use just two different narrow-band filters [27]. The first provides tissue illuminationin the blue spectrum of light at 415 nm, emphasizingcapillaries in the superficial mucosal layer and show-ing them in brown; the second provides tissue illumi-nation in the green spectrum of light at 540 nm, whichcorresponds to the secondary hemoglobin absorptionpeak, and emphasizes deeper mucosal and submucosalvenular vessels, displaying them in cyan. The NBIsystem can be coupled with electronic or optical(zoom) magnification for enhanced visualization ofmucosal details.

The FICE system (Fujinon, Saitama, Japan), ismarketed as a digital image processing technique thatenhances mucosal surface structures by using selectedwavelengths of light in reconstituted virtual images.Unlike NBI (which uses optical filters), FICE is soft-ware-driven and uses an image-processing algorithmthat is based on spectral estimation methods. In thistechnology, developed by Professor Yoichi Miyake[32], a standard image captured by a color CCDvideoendoscope is sent to a spectral estimation matrixprocessing circuit contained in the EPX 4400 videoprocessor. Here, the spectra of the various pixels cor-responding to the conventional image are mathemati-cally estimated. Since the pixels’ spectra are wellknown, it is possible to implement imaging at a singlewavelength. The single-wavelength images are ran-domly selected and assigned to red, green, and blue tobuild and display a CVC-enhanced color image. Thedigital processing system is able to immediately switchbetween an ordinary image and a FICE image by asimple push of a button on the handle of the endoscope.Moreover, the wavelengths most suitable for exami-nation can be selected because of the system’s variable

setting functions, with up to ten preselected settings.These ten presets can be customized and configuredfrom a very large number of wavelength permutationssince any of 60 wavelengths (400–695 nm, in incre-ments of 5 nm) can be used as input into any of the three(R, G, and B) channels [33]. A programmable pushbutton on the handle of the endoscope enables switch-ing between the conventional white-light image and thecorresponding FICE image of a single specified preset.FICE can also be coupled with electronic or optical(zoom) magnification for enhanced visualization ofmucosal details.

The i-Scan (Pentax, Tokyo, Japan) is the latest CVCtechnology and it is marketed as a digital-contrastmethod among endoscopic imaging techniques [34].This CVC system has three modes of image enhance-ment: (1) surface enhancement (SE), in which thestructures are enhanced through recognition ofthe edges; (2) contrast enhancement (CE), in which thedepressed areas and differences in structure areenhanced through colored presentation of low-densityareas; and (3) tone enhancement (TE), in which indi-vidual organs are enhanced by modifying the combi-nation of RGB components for each pixel. SE and CEallow switching among three enhancement levels (low,medium, and high), and TE among three objects(esophagus, stomach, and colon). Since the three modes(SE, CE, and TE) are arranged in series, two or more ofthem can be applied at one time. Switching the levels ormodes of enhancements is done on a real-time basis,without any time lag, by pushing a relevant button, thusenabling efficient endoscopic observation [35].

With SE, the difference in luminance intensitybetween the pixels concerned and the surrounding pixelsis analyzed and the edge components are enhanced.With ordinary enhancement, minor changes in structureare perceived as noise. Adjustment of the noise-erasurefunction allows more evident enhancement of the edges[36]. Compared to normal images, SE images do notdiffer in brightness and differ little in color.

With CE, areas of lower luminance intensity arecompared to surrounding pixels and identified on thebasis of pixel-wise luminance intensity data, followedby relative enhancement of the B component throughslight suppression of the R and G components in thelow-luminance area. As a result of CE, the low lumi-nance area is stained slightly bluish white and minuteirregularities on the mucosal surface are enhanced [37].There is no change in image brightness and very little

24 G. Galloro et al.

change in the color of the images, only the slight bluish-white staining of depressed areas.

With TE, the RGB components of the endoscopeimage are divided into their respective components(R, G, and B) which are converted independentlyalong the tone curve, followed by their re-synthesis toyield a reconstructed image. The tone curve isdepicted by plotting input (on the x axis) againstoutput (on the y axis) and can be changed, by modi-fication of the parameters into S and J types. If thetone curve assumes an S-type form, the highR-component area is shifted to an even higher rangeof R to enhance the color tone R, or the lowR-component area is shifted to an even lower range ofR to elevate the sensitivity to the GB components, thusallowing clear enhancement of the differences in colortone. If the tone curve assumes a J-type form, the Rcomponent is shifted completely to a low R range,thus elevating the overall sensitivity to GB compo-nents and the brightness/darkness contrast [35–38].

Thus far, no complications have been attributed tothe use of NBI, FICE, or i-Scan [27]. Endoscopicsystems equipped with CVC are more expensive thanthose with white light but formal cost analyses haveyet to be reported. Moreover, there are no uniquecurrent procedural terminology (CPT) codes for NBI,FICE, or i-Scan [27].

4.3.2 Implementation of ComputedVirtual Chromoendoscopyin Ileoscopy

The usual target of CVC systems is a qualitativediagnosis that distinguishes between non-neoplastic,dysplastic, and neoplastic lesions, based on the studyand evaluation of the superficial microvascular net-work and surface texture of the mucosa [25–27].Studies have been conducted to evaluate and assess therole of CVC enteroscopy in the characterization ofvarious small-bowel diseases. Since Fujinon doubleballoon enteroscopy (DBE) was the first balloon-gui-ded enteroscopy system on the market and it is suppliedwith FICE, most of these studies have involved thissystem. FICE was shown to be a feasible virtual chro-moendoscopy technique, enhancing surface visualiza-tion of the small-bowel mucosa [39–41]. Specifically,DBE with FICE effectively evaluated small-bowelpolyps in familial adenomatous polyposis (FAP), in

which the pit pattern resembles that of colon polyps[39]. FICE better delineates these polyps while contrastenhancement allows the detection of a greater numberof lesions. However, despite the increased visualizationof diminutive adenomatous polyps in FAP, FICE doesnot modify either the diagnosis or the mode of therapy.

FICE is useful to better delineate the margin ofadenomatous polyps from healthy surrounding mucosa[40]. This is especially important in polypectomies,mucosal and submucosal resections, and argon-plasmaablation. Margin evaluation more accurately confirmscomplete eradication. However, it remains to bedetermined whether FICE, when used in the detectionof small-bowel polyps, can differentiate low- fromhigh-grade dysplasia. FICE also does not improve thedefinition of Peutz–Jeghers syndrome polyps [39]while in nodular lymphoid hyperplasia, white light andFICE seem to be equivalent in characterizing themucosa and delineating pseudopolyps [39–42].

Other studies have reported that FICE improvesthe visibility of normal mucosal vessels and aids inthe detection of vascular ectasias not seen by white-light endoscopy [42]. Specifically, FICE can be usedto clearly demarcate angioectasias, which appear ashomogeneous spots within the surrounding mucosa.The theoretical advantage of FICE is that, due to thelarge number of possible filters, the mucosa can beevaluated with various virtual dyes [39] whereas theNBI system from Olympus has only one set offilters. However, there are as yet no studies showingthat a greater number of options results in bettercharacterization of either the mucosa or mucosallesions.

In analyses of villous architecture, the color-contrast capabilities of FICE and the addition ofendoscopic magnification allow high-quality charac-terization of small-bowel villi. In addition, FICE welldemonstrates the submucosal and intravillous capil-lary network. In primary intestinal lymphangiectasia,better appreciation of engorged mucosal villi andlymphangiectasias is achieved with CVC than withwhite-light endoscopy [43].

The use of balloon-assisted enteroscopy has beenassessed in small-bowel follicular lymphoma, reveal-ing multiple nodular lesions, elevated white patches,and scattered white polypoid lesions [44]. In thiscase, either NBI [45] or FICE [46] improves the diag-nosis, demonstrating small, whitish nodules and a coiled,elongated vascular pattern within the elevated lesions.

4 Contribution of New Technologies to Endoscopic Imaging 25

The latest technological development is the imple-mentation of FICE software within the workstation ofthe video capsule system [47]. This allows the assessorto flexibly choose between standard imaging and threedifferent FICE patterns with different wavelengthselections, resulting in optimal mucosal imaging.FICE-enhanced capsule endoscopy improves the con-trast of vascular and mucosal patterns. Preliminaryclinical tests suggest that the properties of FICE are notonly of theoretical value but can also make a real dif-ference in clinical practice, in case of obscure digestivebleeding, suspected Crohn’s disease, the differentiationof neoplastic from non-neoplastic lesions, and thesurveillance of polyposis syndromes. However, thereare major differences between the application of FICEin flexible endoscopy versus capsule endoscopy, sinceimage resolution with capsule endoscopy is muchlower than with high-resolution video technology.

4.4 Confocal LASER Endoscopy

4.4.1 Technological Status

Confocal laser endomicroscopy (CLE) is a newendoscopic technology developed to obtain very-high-resolution images of the gastrointestinal mucosa.It is based on tissue illumination using low-powerlaser, with subsequent detection of the fluorescencereflected from the tissue through a pinhole [48]. Theterm confocal refers to the alignment of the illumina-tion and collection systems in the same focal plane[49]. The laser light is focused at a selected depth inthe tissue of interest and reflected light is then refo-cused onto the detection system by the same lens.Only returning light refocused through the pinholeis detected. Light reflected and scattered at othergeometric angles from the illuminated object or refo-cused out of plane with the pinhole is excluded fromdetection [50]. This dramatically increases imageresolution, providing a nearly histological examinationor ‘‘optical biopsy’’ of the superficial layer of thedigestive tract [51–53]. Confocal imaging systems canbe based on tissue reflectance or tissue fluorescence.Those based on tissue reflectance do not require theuse of contrast agents but are plagued by technicalproblems and low resolution, thus compromising theirclinical utility [54, 55], whereas systems based ontissue fluorescence use local and/or intravenous

contrast agents and generate high-quality imagescomparable with those obtained by traditional histol-ogy preparations [56, 57].

Two types of confocal endoscopes are com-mercially available. The first is integrated into thedistal tip of a conventional upper endoscope(EG-3870CIK; Pentax, Tokyo, Japan) or colonoscope(EC-3870CILK; Pentax). The second uses a dedicatedconfocal miniprobe with a laser microscope (MaunaKea Technologies, Paris, France) inserted through theaccessory channel of a traditional endoscope. Bothinstruments have CE code and US Food and DrugAdministration authorization, and both have differentdepths of imaging, field of views, and lateral resolu-tions. The Mauna Kea confocal gastrointestinalminiprobes include the CholangioFlex, GastroFlex(standard and UHD), and ColoFlex (standard andUHD). All of these probes generate dynamic images,with 12 frames per second, and are reusable forapproximately 20 studies. The depth of imaging is40–70 lm for CholangioFlex probes, 70–130 lm forGastroFlex and ColoFlex probes, and 55–65 lm forGastroFlexUHD and ColoFlexUHD probes. Themaximal field of view is 325 lm for CholangioFlexprobes, 600 lm for GastroFlex and ColoFlex probes,and 240 lm for GastroFlexUHD and ColoFlexUHDprobes. The lateral resolution is 3.5 lm for Cholan-gioFlex, GastroFlex, and ColoFlex probes, and 1 lmfor GastroFlexUHD and ColoFlexUHD [58, 59]. ThePentax confocal microscope integrated into conven-tional endoscopes collects images at a scan rate of 1.6frames per second (1024 9 512 pixels) or 0.8 framesper second (1024 9 1024 pixels), with an adjustabledepth of scanning ranging from 0 to 250 lm, a field ofview of 475 9 475 mm, a lateral resolution of0.7 lm, and an axial resolution of 7 lm [50–61].

The fluorescent contrast agents for CLE can beadministered intravenously or topically. Intravenousfluorescein (Pharmalab, Lane Cove, New SouthWales, Australia) distributes throughout the extra-cellular matrix of the surface epithelium and laminapropria but does not stain cell nuclei [49]. Topicallyadministered acriflavin (Sigma Pharmaceuticals,Clayton, Victoria, Australia), tetracycline, or cresylviolet (AnaSpec, San Jose, CA, USA) stains the cellnuclei of the surface epithelium but does not penetratethe deeper layers of the mucosa [49]. Acriflavin is amutagenic dye and a potential human carcinogen,which will no doubt limit its clinical utility [62].

26 G. Galloro et al.

After contrast administration, the tip of the confocalendomicroscope or miniprobe is positioned in gentlecontact with the area of interest to obtain high-resolution confocal images. Accumulated images canbe saved for postprocedural analysis.

4.4.2 Implementation of ConfocalLaser Endoscopy in Ileoscopy

Several studies have addressed the clinical applicationsof CLE [63]. The extreme enlargment and the high-resolution of the confocal images, providing a nearlyhistologic examination, make CLE perfectly suitablefor the study of early displastic-neoplastic changes ofthe gastrointestinal tract. Thus far, there have been nostudies on CLE applications in small-bowel diseasesbut confocal endomicroscopy will likely improve thecharacterization and diagnosis of celiac disease,Crohn’s disease, infections, vasculitis, mesentericischemia, and angiodysplasias, among others.

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4 Contribution of New Technologies to Endoscopic Imaging 27

27. Technology Commitee ASGE (2008) Technology statusevaluation report on narrow band imaging and multibandimaging. Gastrointest Endosc 67:589–589

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32. Miyake Y, Kouzu T, Takeuchi S et al (2005) Developmentof new electronic endoscopes using the spectral images ofan internal organ. In: Proceedings of the IS&T/SID’sThirteen Color Imaging Conference, Scottsdale (Ariz),7–11 November, pp 261–269

33. Burgos H, Porras M, Brenes F, Izquierdo E (2007) FujinonFICE Electronic Chromovideoendoscopy Helps Differentiatethe Type of Metaplasia in Patients with Chronic AtrophicGastritis Gastrointest Endosc 65(5):AB 353

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38. Hoffman A, Basting N, Goetz M et al (2009) High-definition endoscopy with i-Scan and Lugol’s solution formore precise detection of mucosal breaks in patients withreflux symptoms. Endoscopy 41:107–112

39. Neumann H, Fry LC, Bellutti M, Malfertheiner P,Mönkemüller K (2009) Double-balloon enteroscopy-assisted virtual chromoendoscopy for small-boweldisorders—a case series. Endoscopy 41:468–471

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28 G. Galloro et al.

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4 Contribution of New Technologies to Endoscopic Imaging 29

5Ileoscopy in Coeliac Disease

Marco Silano, Emilio Gentile Warschauer, Gabriele Marinozzi,Giuseppe Cerno, and Antonello Trecca

5.1 Introduction

Celiac disease is a permanent autoimmune enteropa-thy that is triggered, in genetically determined indi-viduals, by the ingestion of gluten, an alcohol-solubleprotein storage compound present in wheat [1, 2]. Themain protein component of wheat gluten is gliadinand there are similar proteins in rye and barley(secalin and hordein, respectively). In addition togliadin, gluten contains a second major protein,glutenin, and both are active in celiac disease [3].

Celiac disease is the most common food intoleranceworldwide and its reported incidence is increasingannually. Although 1% of the population of Europeand North America is estimated to be affected byceliac disease, the majority of celiac patients are eithernot diagnosed or are misdiagnosed [1]. This is becausethe disease manifests as a wide spectrum of gastro-and extra-intestinal signs and symptoms of broadlyvarying severity, including asymptomatic forms [3, 4].Often, the diagnosis of celiac disease is made byantibody screening among first-degree relatives of thepatient, as they are at high risk of develop the disease[5]. The presumed diagnosis is based upon the detec-tion of serum IgA anti-transglutaminase antibody andis confirmed by the histological findings of the char-acteristic lesions of the small-bowel mucosa: villousatrophy, hyperplasia of the crypts, and T-cell

infiltration of the lamina propria, along with anincrease in intraepithelial lymphocytes [4, 6].

Duodenoscopy with biopsy is still the gold standardfor the diagnosis of celiac disease, even if the diag-nostic value of serological tests is quite high. Since themucosal lesions can be patchy, multiple biopsy sam-ples should be taken during duodenoscopy [7, 8].

Presently, the only known treatment of celiac diseaseis the life-long withdrawal of gluten-containing foodsfrom the diet. In celiac patients, a gluten-free diet resultsin remission, while the re-introduction of gluten into thediet causes disease relapse [9]. Compliance with a glu-ten-free diet is difficult because of the widespread dis-tribution and consumption of cereal-based foods, butstrict adherence is necessary to reduce mortality andmorbidity. Poor adherence to a gluten-free diet increasesthe celiac patient’s risk of developing life–threateningcomplications, such as enteropathy-associated T-celllymphoma and intestinal adenocarcinoma [5, 10, 11].

5.2 Videocapsule and CapsuleEndoscopy in the Evaluationof Celiac Disease

Nowadays, imaging of the small bowel can beimproved by the use of videocapsule endoscopy, anon-invasive technique that enables the study of theentire length of the intestine and, in celiac disease,demonstrates the extent of the affected bowel seg-ments. The procedure can confirm the adequatehealing of the mucosa in response to a gluten-free dietand detect malignancies in patients at high risk. Manyauthors have reported that the most important endo-scopic signs of celiac disease, such as scalloping folds,

M. Silano (&)Division of Food and Science,Human Nutrition and Health,Istituto Superiore di Sanità, Rome, Italye-mail: marco.silano@iss.it

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_5, � Springer-Verlag Italia 2012 31

mosaicism, micronodularity, and the reduction of folds,can be detected by capsule endoscopy even if thesefindings are suggestive of villous atrophy. Rondonottiet al. [12] showed that 66.6% of patients had an exten-sion of the mucosal changes seen at capsule endoscopybeyond the proximal small bowel and 11.1% had lesionsthat involved the small bowel entirely.

The accuracy of conventional endoscopy with amagnifying view has increased with respect to thedetection of celiac disease, such that it is possible tovisualize even minimal changes in the mucosa(Fig. 5.1). In the celiac patient, patchy atrophy is easilydiagnosed, greatly facilitating target biopsy. Both the‘‘immersion technique’’ and magnifying endoscopy[13, 14] show sensitivity, specificity, and positive andnegative predictive values close to 100% in case oftotal villous atrophy, while for less severe mucosaldamage, as in Marsch I and II villous atrophy, theresults are encouraging.

An increasing numbers of patients are diagnosedwith celiac disease after showing intestinal symptomsthat result in the patients undergoing a lower endos-copy rather than an upper endoscopy. The mucosa ofthe terminal ileum (TI) of celiac patients is oftennormal and the finding of villous atrophy is rare,whereas infiltration of the lamina propria by

intraepithelial lymphocytes ([25/100 enterocytes) ismore frequently detected [15, 16].

We recently reported on a series of 143 patientswho underwent ileoscopy. TI mucosal lesions weredetermined in 21 patients. Among them, ten patientsshowed villous atrophy at ileoscopy that was clearlyvisible only with a magnifying view. Six of thosepatients had an intraepithelial lymphocyte count[25/100 enterocytes. Upper intestinal lesions con-firmed the diagnosis of celiac disease [17, 18].

These findings demonstrate that inflammation asso-ciated with celiac disease may involve the entire intes-tinal tract and that in some cases ileoscopy can drive thediagnosis of the disease. Therefore, endoscopists shouldbe aware of the possibility offinding celiac-disease-typeinflammation even during a TI endoscopic examination.As imaging techniques become increasingly sensitive,more accurate results will be achieved in the diagnosisand management of celiac disease.

References

1. Fasano A, Catassi C (2001) Curent approaches to diagnosisand treatment of celiac disease: an evolving spectrum.Gastroenterology 120:636–651

Fig. 5.1 Ileoscopy in a celiac patient a Conventional ileoscopicview showing granular appearance of ileal mucosa. b Aftervirtual chromoendoscopy and magnifying view, partial villousatrophy of ileal mucosa is clearly visible. c Ileal atrophy at high-

resolution magnification. d–f Corresponding biopsy of terminalileum (H&E stain) shows the villous atrophy, along with theincreased intraepithelial lymphocyte count (magnification1009), confirmed on immunostaining for CD3 CX10, and Dx20

32 M. Silano et al.

2. Kagnoff ME (2005) Overview and pathogenesis of celiacdisease. Gastroenterology 128:S10–S18

3. Shewry PR, Tatham AS, Kasarda DD (1992) Celiacdisease. Blackwell Scientific, London

4. Alaedini A, Green PHR (2005) Narrative review: Celiacdisease: understanding a complex autoimmune disorder.Ann Intern Med 142:289–298

5. Green PHR, Jabri B (2003) Coeliac disease. Lancet362:383–391

6. Rostom A, Dubé C, Cranney A, Saloojee N, Sy R, Garritty C,Sampson M, Zhang L, Yazdi F, Mamaladze V, Pan I,MacNeil, J, Mack D, Patel D, Moher D (2005) The diagnosticaccuracy of serological test for celiac disease: a systematicreview. Gastroenterology 128: S38–S46

7. Hopper AD, Cross SS, Sanders DS (2008) Patchy villousatrophy in adult patients with suspect gluten intolerance: isa multiple duodenal biopsy strategy appropriate?Endoscopy 40:219–224

8. Bonamico M, Mariani P, Thanasi E, Ferri M, Nenna R,Tiberti C, Mora B, Mazzilli MC, Magliocca FM (2004)Patchy villous atrophy of the duodenum in childhood celiacdisease. J Pediatr Gastroenterol Nutr 38:204–207

9. Green PH, Cellier C (2007) Celiac disease. N Engl J Med357:1731–1743

10. Catassi C, Bearzi I, Holmes GK (2005) Association ofceliac disease and intestinal lymphomas and other cancers.Gastroenterology 128:S79–S86

11. Silano M, Volta U, De Vincenzi A, Dessì M, De VincenziM (2008) Collaborating Centers of the Italian Registry ofthe Complications of Coeliac Disease. Effect of a gluten-

free diet on the risk of enteropathy-associated T-celllymphoma in celiac disease. Dig Dis Sci 53:972–976

12. Rondonotti E, Spada C, Cave D, Pennazio M, Riccioni ME,De Vitis I, Schneider D, Sprujevnik T, Villa F, Langelier J,Arrigoni A, Costamagna G, de Franchis R (2007) Videocapsule enteroscopy in the diagnosis of celiac disease: amulticenter study. Am J Gastroenterol 102:1624–1631

13. Cammarota G, Martino A, Pirozzi GA, Cianci R,Cremonini F, Zuccala G, Cuoco I, Ojetti V, Montalto M,Vecchio FM, Gasbarrini A, Gasbarrini G (2004) Directvisualization of intestinal by high-resolution magnifyingupper endoscopy: a validation study. Gastrointest Endosc60:732–738

14. Petroniene R, Dubcenco E, Backer JP, Ottaway CA, TangSJ, Zanati SA, Streutker CJ, Gardiner GW, Warren RE,Jeejeebhoy KN (2005) Given capsule endoscopy in celiacdisease: evaluation of diagnostic accuracy andinterobserver agreement. Am J Gastroenterol 100:685–694

15. Hopper AD, Hurlstone DP, Leeds JS, McAlindon ME,Dube AK, Stephenson TJ (2006) The occurrence ofterminal ileal histological abnormalities in patients withcoeliac disease. Dig Liver Dis 38:815–819

16. Dickey W, Hughes DF (2004) Histology of the terminalileum in coeliac disease. Scand J Gastroenterol 39:665–667

17. Sundar N, Muktar A, Finnie IA (2003) Ileocolonoscopicdiagnosis of celiac disease Endoscopy 35:374

18. Trecca A, Gaj F, Gagliardi G, Calcaterra R, Battista S,Silano M (2009) Role of magnified ileoscopy in thediagnosis of cases of coeliac disease with predominantabdominal symptoms. Scand J Gastroenterol 44:320–324

5 Ileoscopy in Coeliac Disease 33

6The Role of Ileoscopy in InflammatoryBowel Disease

Bjorn Rembacken and Mohammed Thoufeeq

6.1 Introduction

Total colonoscopy, including the exploration of theterminal ileum, can assure the visualization ofmucosal lesions in patients with inflammatory boweldisease (IBD) [1]. Ileocolonoscopy provides anaccurate evaluation of the early and characteristiclesions of IBD, their severity, and their extension.Other, radiological imaging modalities, i.e., ultraso-nography, computed tomography (CT) scan, andmagnetic resonance imaging (MRI), are needed todescribe the intestinal wall as they are able to identifypenetrating and stricture-related complications.Nonetheless, endoscopy plays a fundamental role,allowing not only morphological evaluation but alsoan assessment of healing of the intestinal mucosa.These parameters are very useful in the clinicalmanagement of affected and treated patients.Recently, the therapeutic arsenal for IBD has pro-gressed, with the introduction of biologics but also theimproved awareness of how and when treatmentshould be administered [2]. In particular, the step-upapproach has gained a broader consensus for thetreatment of patients with refractory disease that iseither unresponsive to conventional therapies orsteroid-dependent [3]. Moreover, endoscopy, with itscapacity to accurately describe mucosal lesions andmucosal healing, has been used to predict clinicaloutcome in patients with Crohn’s disease (CD) and

ulcerative colitis (UC), identifying those patientseligible for more aggressive therapies or even surgery.

6.2 Endoscopic Evaluationin Crohn’s Disease

Ileocolonoscopy in patients with CD can describe theminimal changes seen in the mucosa, such aserythema, swelling, nodularity, and aphthoid ulcer-ations, as well as more ‘‘advanced lesions,’’ such asulcers of variable size and depth, the cobblestoneappearance of the intestinal wall, and the presence ofstrictures (Figs. 6.1 and 6.2). These endoscopiclesions can be quantified by validated endoscopicindices of disease activity. For example, the CDendoscopic index of severity (CDEIS) is based on therecognition of elementary lesions (non-ulceratedlesions, superficial and deep ulcerations) in associa-tion with an evaluation of their surface properties,dividing the intestine in five segments (ileum, rightcolon, transverse, left colon, and sigmoid andrectum). A simple endoscopic score for CD (SES-CD)also has been proposed and correlates well with theCDEIS, which is still considered difficult to apply forclinical purposes [4–6] (Table 6.1). Both scores canbe used for the definition of disease activity and todescribe mucosal healing. In a retrospective series of78 patients submitted to surgical therapy for CD,endoscopic detection of severity correlated well withthe histology performed on colectomy specimens,whereas this was not case using clinical and biologi-cal severity criteria [7]. The most important endo-scopic criteria of severity were: (1) deep ulcerationseroding the muscle layer, (2) deep ulcerations not

B. Rembacken (&)Department of Endoscopy,General Infirmary Hospital,Leeds, UKe-mail: bj.rembacken@nteworld.com

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_6, � Springer-Verlag Italia 2012 35

eroding the muscle layer but involving more than one-third of the mucosal area; and (3) mucosal detachmentat the edge of ulcerations. At least one of these criteriawas found in 95% of patients with severe anatomiclesions as determined on colectomy specimens. TheCDEIS, however, does not correlate with the clinicalindex (CDAI) nor with the biological activity of thedisease, which is mainly determined by measuringC-reactive protein (Table 6.2). Retrospective studieshave shown that when endoscopic examination of CDpatients with active disease highlights deep andextensive ulcerations of the ileocolonic mucosa,

ileocolonoscopy predicts a more aggressive course ofthe disease with an increased number of surgicalprocedures than required by patients without severelesions (relative risk 5.43, 95% CI: 2.64–11.18) [8].

During the last decade, with the introduction ofnew treatment approaches, the concept of mucosalhealing has gained much greater relevance in theclinical setting [9]. Previously, mucosal healing wasseen only in one-third of the patients with steroid-induced clinical remissions and endoscopic recoverywas not associated with a low risk of relapse; thus,steroid-treated patients were evaluated mainly usingthe clinical index (CDAI). However, it is now rec-ognized that mucosal healing predict treatment effi-cacy and the reduced frequency of surgery andhospitalizations [10]. CD patients submitted to sur-gical resections need strict follow-up as they are at ahigher risk for disease recurrence. Rutgeerts et al.[11], in 1990, showed that ileocolonoscopy performedwithin 1 year of surgery is able to predict diseaseoutcome. Accordingly, the authors proposed a scorethat is now widely used in clinical practice and hasbeen accepted as part of the ECCO guidelines(Table 6.3).

6.3 Endoscopic Evaluationin Ulcerative Colitis

The endoscopic evaluation of patients with UC isbased on mucosal patterns, which are similar to thosealready described in CD patients. The endoscopistshould search for an abnormal vascular pattern,granularity, and ulcers. There are currently nine dif-ferent scores proposed for use in clinical practice(Table 6.4). In patients who suffer a severe attack ofUC, colonoscopy has demonstrated its utility indescribing the extensive deep ulcerations; however,the examination should be performed with cautionand only after radiological exclusion of megacolonand with minimal insufflation of air (Figs. 6.3 and6.4). Carbonnel et al. [12] showed the feasibility ofcolonoscopy without significant complications inpatients with severe UC; in that study, the presence ofdeep ulcerations was confirmed in nearly all of thepatients who subsequently underwent colectomy. Inanother series in which the response to medicaltreatment was evaluated, severe ulcerations were

Fig. 6.1 Advanced lesions in a patient with Crohn’s disease(CD): ulcers of variable size and depth are visible duringretrograde ileoscopy

Fig. 6.2 Advanced lesion in CD: a stricture of the ileocecalvalve

36 B. Rembacken and M. Thoufeeq

described more frequently in non-responders than inresponders (91 vs. 34%, respectively; OR [ 20) [13].

In UC patients, mucosal healing should always beassessed endoscopically, even if there is no agreementregarding its definition, since the disappearance of thenormal vascular pattern is considered sufficient to

determine disease progression [14]. Wright andTruelove [15] found that 40% of patients with a goodresponse to oral and rectal steroids did not experiencedisease relapse after 1 year of follow-up compared to18% of those who continued to have active endo-scopic lesions. A reduced likelihood of surgery was

Table 6.1 Simple endoscopic score for Crohn’s disease (SES-CD)

Variable 0 1 2 3

Size of ulcers None Aphthous ulcers(0.1–0.5 cm)

Large ulcers(0.5–2 cm)

Very large ulcers([2 cm)

Ulcerated surface None \10% 10–30% [30%

Affected surface Unaffected segment \50% 50–75% [75%

Strictures None Single, can be passed Multiple, can be passed Cannot be passed

Table 6.2 Crohn’s disease activity index (CDAI)

Clinical or laboratory variable Weighting factor

Number of liquid or soft stools each day for 7 days 92

Abdominal pain (graded from 0–3 on severity) each day for 7 days 95

General well being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days 97

Presence of complicationsa 920

Taking Lomotil or opiates for diarrhea 930

Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite) 910

Hematocrit of \0.47 in men and \0.42 in women 96

Percentage deviation from standard weight 91

The index consists of eight factors, each summed after adjustment with a weighting factor. The table shows the components of theCDAI and the weighting factors. The remission of Crohn’s disease is defined as a fall in the CDAI of \150. Severe disease isdefined as a value [450. Most major research studies on medications in Crohn’s disease define response as a [70 point fall ofthe CDAIa One point each is added for each set of complications:

• The presence of joint pain (arthralgia) or frank arthritis• Inflammation of the iris or uveitis• Presence of erythema nodosum, pyoderma gangrenosum, or aphthous ulcers• Anal fissures, fistulae, or abscesses• Other fistulae• Fever during the previous week

Table 6.3 Endoscopic score of activity from Rutgeerts et al. (from [11])

Grade Endoscopic findings

0 No lesions in the distal ileum

1 C5 aphthous lesions

2 [5 aphthous lesions with normal mucosa between the lesions, or skip areas of larger lesions confined to the ileocolonicanastomosis

3 Diffuse aphthous ileitis with diffusely inflamed mucosa

4 Diffuse inflammation with larger ulcers or stenosis

6 The Role of Ileoscopy in Inflammatory Bowel Disease 37

Table 6.4 Endoscopic indexes for ulcerative colitis activity

Author [reference] Description

Truelove 1995 [19] Sigmoidoscopic appearanceNormal or near-normal (only slight hyperemia or only slight granularity)ImprovedUnchanged or worse

Baron 1964 [20] Baron scoreNormal (0): matt mucosa, ramifying vascular pattern clearly visible throughout, no spontaneousbleeding, no bleeding to light touchAbnormal (1): between normal (0) and moderately hemorrhagic (2)Moderately hemorrhagic (2): bleeding to light touch, but no spontaneous bleeding seen ahead ofinstrument on initial inspectionSeverely hemorrhagic: spontaneous bleeding seen ahead of instrument at initial inspection withbleeding to light touch

Feagan 2005 [21] Modified Baron scoreNormal mucosaGranular mucosa with an abnormal vascular pattern (1)Friable mucosa (2)Microulceration with spontaneous bleeding (3)Gross ulceration

Powel-Tuck 1978 [22] Sigmoidoscopic appearanceNonhemorrhagic (0): no spontaneous bleeding or bleeding to light touchHemorrhagic (1): no spontaneous bleeding but bleeding to light touchHemorrhagic (2): spontaneous bleeding ahead of instrument at initial inspection with bleeding tolight touch

Schroeder 1987 [23] Mayo score (sigmoidoscopic evaluation)• Normal or inactive disease (0)• Mild disease (1): erythema, decreased vascular pattern, mild friability• Moderate disease (2): marked erythema, absent vascular pattern, friability, erosions• Severe disease (3): spontaneous bleeding, ulceration

Sutherland 1987 [24] Sutherland sigmoidoscopic mucosal appearance• Normal (0)• Mild friability (1)• Moderate friability (2)• Exudation, spontaneous hemorrhage (3)

Rachmilewitz 1989 [25] Rachmilewitz indexA: Granulation scattering reflected light: yes (0), no (2)B: Vascular pattern: normal (0), faded/disturbed (1), Completely absent (2)C: Vulnerability of mucosa: none (0), slightly increased (contact bleeding) (2); greatly increased

(spontaneous bleeding) (4)D: Mucosal damage (mucus, fibrin, exudates, erosions, ulcer): none (0), slight (2), pronounced (4)

Hanauer 1993 [26] Sigmoidoscopic index (0, normal; 1, mild; 2, moderate; 3, severe)A: Erythema (0–3)B: Friability (0–3)C: Granularity/ulceration (0–3)D: Mucus (0–3)E: Lack of mucosal vascular pattern

The total score is the sum of subscores A–E

Lemann 1995, Hanauer1998 [27]

Sigmoidoscopic inflammation gradeNormal mucosa (0)Edema and/or loss of visible mucosal vascularity, granularity (1)Friability (visible, contact bleeding on examination), petechiae (2)Spontaneous hemorrhage, visible ulcers (3)

38 B. Rembacken and M. Thoufeeq

also demonstrated in patients with mucosal healing at5 years of follow-up [16].

Finally, since chronic inflammation of the mucosastill represents a higher risk of colorectal cancer, theendoscopist should always search for dysplasticlesions in these patients [17]. Thus, modern endo-scopic imaging of the mucosa may also offer animportant opportunity to improve the accuracy of theearly detection of colorectal cancer in UC patients.

6.4 Conclusions

There is a increasing consensus that mucosal healingcan identify those patients with a good response to aspecific therapy. Ileocolonoscopy is of pivotalimportance for the definition of elementary lesions inIBD patients and for the evaluation of mucosal heal-ing. The assessment of mucosal morphology withrespect to disease activity may help the clinician to

intensively treat these patients with the intention ofsparing them surgery and its associated complica-tions. In conclusion, as stated by Rutgeerts et al. [18],the primary goals of endoscopy in IBD patients notreceiving steroid therapy should be to monitor theinduction and maintenance of remission and to eval-uate complete healing of the intestinal and colonicmucosa. Careful monitoring will not only allow thesepatients to avoid surgery and its complications, butcan also result in the early detection of cancer.

References

1. Classen M, Tytgat GNJ, Lightdale C (2010)Gastroenterological endoscopy. Thieme, Munchen

2. Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ,Kornbluth A, Rachmilewitz D, Lichtiger S, D’Haens G,Diamond RH, Broussard DL, Tang KL, van der Woude CJ,Rutgeerts P (2010) Infliximab, azathioprine, or combinationtherapy for Crohn’s disease. N Engl J Med 362:1383–1395

Fig. 6.3 Emergency colonoscopy; a Endoscopy shows massive bleeding in a patient with a previous diagnosis of ulcerativecolitis; b a huge flat lesion is visible at the lower rectum

Fig. 6.4 Endoscopy performed in the same patient after1 week of treatment. a A sessile lesion is visible at the hepaticflexure (tubular adenoma with low-grade dysplasia) not

detected at emergency endoscopy; b the flat rectal lesiondetected at emergency endoscopy and after chromoendoscopywith indigo carmine 0.4%

6 The Role of Ileoscopy in Inflammatory Bowel Disease 39

3. Fefferman DS, Farrell RJ (2005) Endoscopy in inflammatorybowel disease: indications, surveillance, and use in clinicalpractice. Clin Gastroenterol Hepatol 3:11–24

4. Mary JY, Modigliani R (1989) Development and validationof an endoscopic index of the severity for Crohn’s disease:a prospective multicentre study. Groupe d’EtudesThérapeutiques des Affections Inflammatoires du TubeDigestif (GETAID). Gut 30:983–998

5. Cellier C, Sahmoud T, Froguel E, Adenis A, Belaiche J,Bretagne JF, Florent C, Bouvry M, Mary JY, Modigliani R(1994) Correlations between clinical activity, endoscopicseverity, and biological parameters in colonic or ileocolonicCrohn’s disease. A prospective multicentre study of 121cases. The Groupe d’Etudes Thérapeutiques des AffectionsInflammatoires Digestives. Gut 35:231–235

6. Daperno M, D’Haens G, Van Assche G, Baert F, Bulois P,Maunoury V, Sostegni R, Rocca R, Pera A, Gevers A,Mary JY, Colombel JF, Rutgeerts P (2004) Developmentand validation of a new, simplified endoscopic activityscore for Crohn’s disease: the SES-CD. GastrointestEndosc 60:505–512

7. Nahon S, Bouhnik Y, Lavergne-Slove A, Bitoun A, Panis Y,Valleur P, Vahedi K, Messing B, Matuchansky C,Rambaud JC (2002) Colonoscopy accurately predicts theanatomical severity of colonic Crohn’s disease attacks:correlation with findings from colectomy specimens. Am JGastroenterol 97:3102–3107

8. Allez M, Lemann M, Bonnet J, Cattan P, Jian R,Modigliani R (2002) Long term outcome of patients withactive Crohn’s disease exhibiting extensive and deepulcerations at colonoscopy. Am J Gastroenterol 97:947–953

9. Rutgeerts P, Vermeire S, Van Assche G (2008) What is therole of endoscopy in predicting Crohn’s disease relapse orcourse? Inflamm Bowel Dis 14(2):S183–S184

10. Frøslie KF, Jahnsen J, Moum BA, Vatn MH (2007) Mucosalhealing in inflammatory bowel disease: results from aNorwegian population-based cohort. Gastroenterology133:412–422

11. Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R,Hiele M (1990) Predictability of the postoperative course ofCrohn’s disease. Gastroenterology 99:956–963

12. Carbonnel F, Lavergne A, Lémann M, Bitoun A, Valleur P,Hautefeuille P, Galian A, Modigliani R, Rambaud JC(1994) Colonoscopy of acute colitis. A safe and reliabletool for assessment of severity. Dig Dis Sci 39:1550–1557

13. Daperno M, Sostegni R, Scaglione N, Ercole E, Rigazio C,Rocca R, Pera A (2004) Outcome of a conservative approachin severe ulcerative colitis. Dig Liver Dis 36:21–28

14. Pineton de Chambrun G, Peyrin-Biroulet L, Lémann M,Colombel JF (2010) Clinical implications of mucosalhealing for the management of IBD. Nat RevGastroenterol Hepatol 7:15–29

15. Wright R, Truelove SR (1966) Serial rectal biopsy inulcerative colitis during the course of a controlledtherapeutic trial of various diets. Am J Dig Dis 11:847–857

16. Sandborn WJ, Rutgeerts P, Feagan BG, Reinisch W,Olson A, Johanns J, Lu J, Horgan K, Rachmilewitz D,Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D,Sands BE, Colombel JF (2009) Colectomy rate comparisonafter treatment of ulcerative colitis with placebo orinfliximab. Gastroenterology 137:1250–1260

17. Allez M, Lemann M (2010) Role of endoscopy inpredicting the disease course in inflammatory boweldisease. World J Gastroenterol 16:2626–2632

18. Rutgeerts P, Vermeire S, Van Assche G (2007) Mucosalhealing in inflammatory bowel disease: impossible ideal ortherapeutic target? Gut 56:453–455

19. Seo M, Okada M, Yao T, Okabe N, Maeda K, Oh K (1995)Evaluation of disease activity in patients with moderatelyactive ulcerative colitis: comparisons between a newactivity index and Truelove and Witts’ classification. AmJ Gastroenterol 10:1759–1763

20. Baron JH, Connell AM, Lennard Jones JE (1964) Variationbetween observers in describing mucosal appearances inproctocolitis. Br Med J 53:89–92

21. Griffiths AM, Otley AR, Hyams J, Quiros AR, Grand RJ,Bousvaros A, Feagan BG, Ferry GR (2005) A review ofactivity indices and end points for clinical trials in childrenwith Crohn’s disease. Inflamm Bowel Dis 2:185–196

22. Ritchie JK, Powell-Tuck J, Lennard-Jones JE (1978)Clinical outcome of the first ten years of ulcerative colitisand proctitis. Lancet 8074:1140–1143

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26. Hanauer SB (1993) Medical therapy of ulcerative colitis.Lancet 8868:412–417

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40 B. Rembacken and M. Thoufeeq

7Ileoscopy in the Diagnosisof Infectious Diseases

Roberto Lorenzetti, Angelo Mario Zullo,and Cesare Hassan

7.1 Introduction

Although advocated by some authors [1, 2], routineintubation of the terminal ileum during colonoscopy isnot recommended because of the expected low diag-nostic yield in the absence of clinical suspicion ofspecific ileal disease [3]. Conversely, retrogradeileoscopy is highly useful when performed in certainclinical settings, such as suspected or establishedinflammatory bowel diseases [4], seronegative spondy-larthropathy [5], lower gastrointestinal (GI)-tractbleeding [6], human immunodeficiency virus (HIV)seropositivity [7], or in cases of chronic non-bloodydiarrhea [8]. However, ileoscopy is mandatory whenan infectious disease potentially involving the ileum isclinically presumed.

Most studies evaluating the diagnostic yield ofretrograde ileoscopy have been performed either inasymptomatic patients or in patients in whom specificileal disease is not suspected. Therefore, acute infec-tious ileitis has been rarely observed in these series, asthe condition is usually symptomatic. Disappointingly,the role of retrograde ileoscopy in infectious diseasesthat may involve the terminal ileum has not been sys-tematically addressed. Nonetheless, the relevant role ofcolonoscopy with ileoscopy in the diagnosis of intes-tinal tuberculosis has been recently emphasized, inresponse to epidemiological changes in the distributionof this disease during the last several decades. In fact,

intestinal tuberculosis, traditionally common only indeveloping countries, is now observed even in manydeveloped countries, especially among immigrants, inHIV-infected individuals, and those patient treatedwith biological therapies [9, 10].

7.2 Intestinal Tuberculosis

Several reports have demonstrated that colonoscopywith targeted biopsies of the observed lesions is themost valuable procedure to diagnose intestinaltuberculosis [11–16]. In a review of 297 patients withintestinal tuberculosis, the distal ileum and cecumwere the most frequent localizations, involved in over40% of the cases [17]. Since mucosal lesions may beconfined to the distal ileum in some patients, ileos-copy is recommended in this setting to increase thediagnostic yield of endoscopy. Indeed, in a studycomprising 53 patients with suspected ileocolonictuberculosis, the distal ileum was involved in 11(21%) [18] and was the exclusive disease localizationin two (3.8%). Other case reports confirmed thisobservation [16, 19]. Therefore, a diagnosis of intes-tinal tuberculosis may be overlooked if retrogradeileoscopy is not performed when the disease is clini-cally suspected. In those geographic areas wheretuberculosis is endemic, ileoscopy may have a rele-vant role even when the symptoms suggestive of thisinfection are vague. Of note, in an Indian series of 39patients undergoing colonoscopy for bleeding inwhom no colonic lesions were detected, two (5.1%)cases of ileal tuberculosis were identified by ileos-copy, with a further patient diagnosed with ilealtyphoid ulcers [6]. Therefore, in those clinical settings

R. Lorenzetti (&)Gastroenterology Department, Nuovo ReginaMargherita Hospital, Rome, Italye-mail: rlorenzetti2004@yahoo.it

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_7, � Springer-Verlag Italia 2012 41

in which the prevalence of tuberculosis is increased,such as immigrant patients or those with immunode-ficiency, ileoscopy should be performed even in theabsence of specific symptoms.

The endoscopic features of tuberculosis observedin the colon vary and include transverse or linearulcers, nodules, strictures, polypoid lesions, andirregular fibrous bands forming pockets. In rare cases,an ulcerative-colitis-like picture may be present[14, 20]. Conversely, in the terminal ileum, only non-specific ulcerations with or without nodularity areusually observed. On video capsule endoscopy, ulcersof the small bowel in patients with intestinal tuber-culosis are characteristically shallow, with extensiveirregular ‘‘geographic’’ borders, usually not largerthan 1–2 cm, and transverse rather than the typicallongitudinal ulcers seen in Crohn’s disease [21].

The diagnostic yield of biopsies for intestinaltuberculosis could be a matter for concern. Indeed,given that the specific lesions are located in the sub-mucosa, the sensitivity of the procedure is poor.However, histological alterations are seen more oftenin ileal specimens than in colon biopsies, with non-caseous granulomas and collections of epithelioidcells detected in 45 and 36% of patients with ileallesions, respectively [18]. A very low diagnostic yield(8%) is achieved when biopsies are taken from thenormal-appearing colonic or ileal mucosa of patientsin whom ileo-colonic involvement of tuberculosis isclinically suspected, with noncaseating granulomasobserved only in the ileal specimens [22].

Diagnostic uncertainties may arise at histologicalassessment in geographic areas where both intestinaltuberculosis and Crohn’s disease are high prevalent[23]. In India, intestinal tuberculosis is very common,but Crohn’s disease is also increasingly reported, sothat it may be difficult to rule out one or the otherdisease [24]. Since treatment distinctly differs, diag-nostic doubt must be opportunely resolved, by takinginto account clinical data, endoscopic features, andradiological findings [25, 26]. Diagnostic uncertain-ties may persist when only ileal lesions are detected,since the endoscopic alterations and mucosal inflam-matory feature seen in Crohn’s disease and intestinaltuberculosis are similar. However, the colonic lesionsare well-defined and a scoring system is available.Indeed, as shown in Table 7.1, several endoscopicfeatures are suggestive of Crohn’s disease, whilstothers are evocative of intestinal tuberculosis [25].

By following such a classification, a positivepredictive value for Crohn’s disease of 94.9% and forintestinal tuberculosis of 88.9% can be achieved. Inaddition, certain histological peculiarities may beuseful in distinguishing the two conditions. Typically,granulomas are smaller in Crohn’s disease than inintestinal tuberculosis, where they are multiple, con-fluent, and show central caseating necrosis [23, 27].However, the small sample size and an examinationrestricted to the superficial portion of the mucosacould make a differential pathological diagnosisdifficult.

7.3 Ileal Bacterial Infections

Acute ileitis describes a clinical picture characterizedby right lower quadrant abdominal pain, diarrhea, andfever, in which ileal participation is identified orsuspected. Infections or infestations are a leadingcause of ileitis, and these conditions should be firstlyconsidered in the differential diagnosis. In a recentstudy performed in Spain [28], a diagnostic protocolwas systematically used in patients with clinicallysuspected ileitis. This included abdominal ultrasoundand computed tomography performed in theemergency departments, and retrograde ileoscopy assecond-line diagnostic tool. By following such aprocedure, infectious ileitis was eventually diagnosedin one-third of the patients. Early identificationavoided unnecessary laparotomies when the differ-ential diagnosis included acute appendicitis, extra-uterine pregnancy, etc. The importance of thisprocedure is further strengthened given the frequentfalse-negative results of stool culture, which can leadto an underestimation of infectious ileitis or to anincorrect diagnosis.

Yersinia enterocolitica and Y. pseudotuberculosisare the most commonly detected pathogens in acuteileitis. The infection is generally acquired by the

Table 7.1 Endoscopic feature differentiating colonic Crohn’sdisease from colonic tuberculosis

Crohn’s disease Tuberculosis

Anorectal lesions Involvement of \4 segments

Longitudinal ulcers Transverse ulcers

Aphthous ulcers Patulous ileocecal valve

Cobblestone aspect Pseudopolyps

42 R. Lorenzetti et al.

ingestion of contaminated foods or water, anddiagnosis is usually based on the isolation ofY. enterocolitica in feces and/or by elevated serumantibody titers against the bacterium. Endoscopicfeatures of Yersinia ileitis include round or ovalmucosal elevations with or without ulcers, while on theileocecal valve and in the cecum aphthoid erosions aremore frequently detected [29]. Differently fromCrohn’s disease, ulcers are mostly uniform in both sizeand shape. The lesions invariably involve the terminalileum, with frequent extension to both the ileocecalvalve and the cecum, whilst the ascending colon is less

frequently involved. These findings are observed even4–5 weeks following the onset of symptoms of acuteileitis, suggesting a relatively long course of the dis-ease [30].

The Mycobacterium avium-intracellulare complexis another pathogen that can cause acute ileitis inpatients with immunodeficiency, either of congenital(i.e., common variable immunodeficiency) or acquired(HIV infection) origin [7]. Although the most com-monly affected site is the duodenum, involvement ofthe terminal ileum has been shown in 6% of the HIVpatients with Mycobacterium infection [31]. Diffuse

Fig. 7.1 Anisaki is clearlyvisible in gastric lumen (a);the head of nematode is fixedin the wall of the posteriorgastric body (b). (Picture byA. Trecca)

Fig. 7.2 Enlargedsubmucosal follicole in theterminal ileum (a); ascariasisappears after biopsy (b).(Picture by A. Trecca)

Fig. 7.3 Many worms ofossiuri occupy the cecal sac(a), younger specimens in thececal region (b). (Picture byA. Trecca)

7 Ileoscopy in the Diagnosis of Infectious Diseases 43

mucosal ulcerations, mucosal-fold thickening, and,less frequently, strictures are the most frequent findingsat ileoscopy [32, 33].

Abdominopelvic infection with the filamentous,Gram-positive bacteria Actinomyces spp. frequentlyincludes the ileocecal region, most likely due tophysiological stasis. Although actinomycosis diag-nosis at colonoscopy has been reported [34], virtuallyall patients are diagnosed at laparotomy with ileocecalresection [35]. Therefore, in this setting, endoscopicexamination of the affected terminal ileum plays amarginal role.

7.4 Ileal Protozoal Infections

Chronic diarrhea is a common problem in immuno-compromised patients [36]. Examination of stoolsamples for bacterial and protozoal pathogens is thefirst diagnostic step; if these studies are negative, thenthe next step is colonoscopy. While the usefulness andcost-effectiveness of colonoscopy have been clearlydemonstrated [37], the diagnostic yield of ileoscopyhas not been systematically investigated. In patientswith HIV, especially those with advanced disease,diarrhea is frequently caused by Cryptosporidiumparvum. The inclusion of ileoscopy and biopsy of theterminal ileum during colonoscopy results in a sig-nificant yield in the diagnosis of microsporidiosis[38]. In a study enrolling 79 HIV patients, the addi-tional diagnosis of microsporidiosis was made in five(6.3%) by biopsy of the terminal ileum [39]. Of note,in these cases, the coccidian infection was confined tothe terminal ileum, with no additional diagnosisperformed by upper endoscopy including duodenalbiopsies. However, ileal microsporidiosis was also

detected in three (23%) out of 13 patients withduodenal evidence of infection [40]. These observa-tions suggest that ileoscopy with biopsies in HIVpatients with diarrhea increases the microsporidiosisdetection rate, especially when duodenal infectionis ruled out. The usefulness of random ilealbiopsies in HIV patients with chronic diarrhea, evenin the presence of a grossly appearing mucosa, isfurther strengthened by the possibility of detectingcytomegalovirus ileitis [41].

7.5 Ileal Fungal and ParasiticInfections

Histoplasma capsulatum is a dimorphic fungus thatcan cause ileitis. In the disseminated form of histo-plasmosis, the terminal ileum is commonly affecteddue to dissemination of the fungus, via the reticulo-endothelial system, by macrophages that accumulatein lymphoid aggregates and Peyer’s patches [42]. Inthese patients, retrograde ileoscopy may lead to thediagnosis, demonstrating lesions ranging from seg-mental or continuous superficial mucosal ulcerationswith erythema or edema to deep ulcers, with orwithout frank perforation [43].

Anisakis simplex is a nematode acquired by humansafter the ingestion of raw fish infected with third-stagelarvae. The infestation may involve the ileocecalregion [29]. Since no specific therapy is available,prompt endoscopic removal of the parasite is the onlyapproach, before it penetrates the small-bowelmucosa, causing a vigorous eosinophilic granuloma-tous response. Anisakis is generally removed duringupper endoscopy (Fig. 7.1a, b) [44], but capsuleendoscopy has also demonstrated enteric anisakiasis

Fig. 7.4 A case of amoebiasis: the left colon shows many scars of the mucosa (a) and atrophic changes (b). Histology shows largenumbers of trophozoites (HE and PAS stained) are clearly visible (c). (Picture by A. Trecca)

44 R. Lorenzetti et al.

[45]. A case report by Trecca et al. [46] provided adetailed description of ascariasis detection by magni-fied ileoscopy. A worm emerging from the ilealmucosa was captured during biopsy of an enlargedsubmucosal follicle in a patient referred for severeweight loss and asthenia (Fig. 7.2a, b).

7.6 Conclusions

Endoscopic examination of the terminal ileum mayplay an important role in the diagnosis of infectiousdisease affecting the ileocecal region (Figs. 7.3a, band 7.4a–c). This is of particular relevance in patientswith suspected intestinal tuberculosis but is manda-tory when the differential diagnosis includes Crohn’sdisease. Moreover, in immunocompromised patientswith HIV infection and diarrhea, ileoscopy may helpin the diagnosis of several opportunistic infections ofthe terminal ileum, especially microsporidiosis, whichcan be successfully treated. Finally, the substantialdiagnostic yield of ileoscopy in the presence of aclinical picture of acute ileitis should be taken intoaccount in the decision-making process.

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16. Sato S, Yao K, Yao T et al (2004) Colonoscopy in thediagnosis of intestinal tuberculosis in asymptomaticpatients. Gastrointest Endosc 59:362–368

17. Marshall JB (1993) Tuberculosis of the gastrointestinaltract and peritoneum. Am J Gastroenterol 88:989–999

18. Misra SP, Misra V, Dwivedi M (2007) Ileoscopy in patientswith ileocolonic tuberculosis. World J Gastroenterol13(11):1723–1727

19. Leung VK, Tang WL, Cheung CH et al (2001) Importanceof ileoscopy during colonoscopy for the early diagnosis ofileal tuberculosis: report of two cases. Gastrointest Endosc53:813–815

20. Misra SP, Misra V, Dwivedi M et al (1998) Colonictuberculosis mimicking ulcerative colitis. J AssocPhysicians India 46:309–310

21. Cello JP (2004) Capsule endoscopy features of humanimmunodeficiency virus and geographical diseases.Gastrointest Endosc Clin N Am 14:169–177

22. Misra SP, Dwivedi M, Misra V et al (2004) Endoscopicbiopsies from normal-appearing terminal ileum and cecumin patients with suspected colonic tuberculosis. Endoscopy36:612–616

23. Epstein D, Watermeyer G, Kirsch R (2007) Review article:the diagnosis and management of Crohn’s disease inpopulations with high-risk rates for tuberculosis. AlimentPharmacol Ther 25:1373–1388

24. Ouyang Q, Tandon R, Goh KL et al (2005) The emergenceof inflammatory bowel disease in the Asian Pacific region.Curr Opin Gastroenterol 4:408–413

25. Lee YJ, Yang SK, Byeon JS et al (2006) Analysis ofcolonoscopic findings in the differential diagnosis betweenintestinal tuberculosis and Crohn’s disease. Endoscopy38:592–597

26. Amarapurkar DN, Patel ND, Rane PS (2008) Diagnosis ofCrohn’s disease in India where tuberculosis is widelyprevalent. World J Gastroenterol 14:741–746

27. Almadi MA, Ghosh S, Aljebreen AM (2009) Differentiatingintestinal tuberculosis from Crohn’s disease: a diagnosticchallenge. Am J Gastroenterol 104:1003–1012

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28. Garrido E, Sanroman AL, Rodriguez-Gandia MA et al(2009) Optimized protocol for diagnosis of acute ileitis.Clin Gastroenterol Hepatol 7:1183–1188

29. Di Lauro S, Crum-Cianflone NF (2010) Ileitis: when it isnot Crohn’s disease. Curr Gastroenterol Rep 12:249–258

30. Matsumoto T, Iida M, Matsui T et al (1990) Endoscopicfindings in Yersinia enterocolitica enterocolitis. GastrointestEndosc 36:583–587

31. Sun HY, Chen MY, Wu MS et al (2005) Endoscopicappearance of GI mycobacterosis caused by theMycobacterium avium complex in a patient with AIDS:case report and review. Gastrointestinal Endosc 61:775–779

32. Schneebaum CW, Novick DM, Chabon AB et al (1987)Terminal ileitis associated with Mycobacterium aviumintracellulare infection in a homosexual man with acquiredimmune deficiency syndrome. Gastroenterology 92:1127–1132

33. Cappell MS, Gupta A (1992) Gastrointestinal hemorrhage dueto gastrointestinal Mycobacterium avium intracellulare oresophageal candidiasis in patients with the acquiredimmunodeficiency syndrome. Am J Gastroenterol 87:224–229

34. Morini S, Hassan C, Lorenzetti R et al (2004) Submucosalnodules containing purulent fluid: a colonoscopic sign ofactinomycosis? Gastrointest Endosc 59:319–321

35. Cintron JR, Del Pino A, Duarte B et al (1996) Abdominalactinomycosis. Dis Colon Rectum 39:105–108

36. Committee AGAPC (1996) AGA technical review:malnutrition and cachexia, chronic diarrhea, and hepato-biliary disease in patients with human immunodeficiencyvirus infection. Gastroenterology 111:1722–1752

37. Bini EJ, Cohen J (1998) Diagnostic yield and cost-effectiveness of endoscopy in chronic human immuno-deficiency virus-related diarrhea. Gastrointest Endosc 48:354–361

38. Oldfield EC 3rd (2002) Evaluation of chronic diarrhea inpatients with human immunodeficiency virus infection. RevGastroenterol Disord 2:176–178

39. Kearney DJ, Steuerwald M, Koch J et al (1999) Aprospective study of endoscopy in HIV-associateddiarrhea. Am J Gastroenterol 94:596–602

40. Michiels JF, Hofman P, Saint Paul MC et al (1993)Pathologic features of intestinal microsporidiosis in HIVpositive patients. A report of 13 new cases. Pathol ResPract 189:377–383

41. Shah RJ, Fenoglio-Preiser C, Bleau BL et al (2001)Usefulness of colonoscopy with biopsy in the evaluation ofpatients with chronic diarrhea. Am J Gastroenterol96:1091–1095

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46 R. Lorenzetti et al.

8Results of Ileoscopy in Pediatric Patients

Paola De Angelis, Erminia Romeo, Filippo Torroni,and Luigi Dall’Oglio

8.1 Traditional Ileoscopy

Ileoscopy is considered one of the most importantdiagnostic procedures, even in pediatric patients pre-senting with abdominal pain, obscure bleeding,chronic diarrhea, and suspicion of inflammatory boweldisease (IBD). The practice of pediatric colonoscopyand ileoscopy has evolved and improved over the past20 years, both in terms of technique and technologicaladvances [1]. It has become an important component ofa complete traditional colonoscopy, with the ability toexplore the cecal region and the small bowel and toperform multiple biopsies of the terminal ileum. Datafrom retrospective studies assessing the diagnosticvalue of terminal ileum biopsies suggest that they aremainly helpful in patients with inflammatory diarrheaand/or suspected IBD [2].

Despite the fact that the distal 15–40 cm of theterminal ileum is not always displayed, routineendoscopy of the terminal ileum is, nonetheless,suggested in all patients with established IBD and/orpersistent diarrhea, lower gastrointestinal tractbleeding, severe irritable bowel syndrome, or sus-pected neoplastic disease [3].

Correct indications for terminal ileoscopy in pedi-atric patients are the suspicion of inflammatory (IBD,allergic enterocolitis, and autoimmune enteropathy),infectious (Yersinia, tuberculosis), congenital (chronic

granulomatous disease, glycogen storage disease types1b and 1c, defective neutrophil chemotaxis) andneoplastic (lymphoma) diseases, for which the histol-ogy of biopsied specimens is essential to complete thediagnosis. The correlation between endoscopic andhistologic findings is high, but accurate microscopicand electronic study of biopsies of normal ileum mustbe included, especially in patients with abdominal painand/or chronic diarrhea, to establish the presence ofalterations and confirm the diagnosis [4].

The clinical results of ileoscopy in the diagnosis ofIBD are excellent and the role of histology is crucial toreach a diagnosis, together with clinical data and otherexaminations. Endoscopy contributes to establishingthe best diagnostic definition of type, location, extent,and severity of disease, to beginning or adjustingmedical therapy, and to performing endoscopic dila-tion through a guide wire under radiologic monitoring.Examination of the entire colon with intubation of thedistal ileum provides the best chance of reaching adiagnosis; it can detect evidence of Crohn’s diseaseand thus help to distinguish between IBD and lym-phoid nodular hyperplasia, which is very common inchildren [1]. The utility of repeat endoscopy for themanagement of pediatric IBD is that it can be used toevaluate the effects of medical treatment, sincemucosal healing is an important endpoint [5]. Despiteseveral diagnostic investigations available to performthe complex diagnosis of IBD, colonoscopy withileoscopy remains the gold-standard, also in children.

Colonoscopy and ileoscopy with ileal biopsiescombined with upper endoscopy achieve the highestdiagnostic yields in the diagnosis of gastrointestinalgraft-versus-host-disease (GVHD) [6]. The endoscopeis an essential tool also in assessing the intestinal

P. De Angelis (&)Digestive Surgery and Endoscopy Unit,Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italye-mail: paola.deangelis@opbg.net

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_8, � Springer-Verlag Italia 2012 47

allograft after intestinal transplantation. In thesepatients, frequent postoperative surveillance ileos-copies with biopsies are highly recommended [7].

Magnified ileoscopy with histological examinationof macroscopic mucosal abnormalities facilitates therecognition of strongly suspected mucosal villoussubtotal or total atrophy [8]. This diagnostic oppor-tunity should be strongly considered in pediatricpatients due to the high frequency of celiac diseasewithout typical symptoms in children and adolescents.

Colonoscopy and retrograde ileoscopy are routinelyperformed in many pediatric centers but the success ofthe procedure in terms of quality, extent, and durationdepends on many factors [9]. Visualization of theintestinal mucosa, completion of the examination withoptimal detection of pathological lesions, and thera-peutic maneuvers are a function of the quality of bowelpreparation. While there is no ideal preparation,several agents with different palatability and severalprotocols (e.g., sodium phosphate and stimulantlaxative based protocols), both aimed at improvingcompliance in children, are available [10, 11].

Extreme care should be taken in performing acomplete colonoscopy and ileoscopy in children witha known or suspected diagnosis of severe ulcerativedisease or Crohn’s colitis, due to the high risk ofperforation and hemorrhage [1]. For pediatric endos-copy, the technical rules to perform colonoscopy untilthe ileum are the same as in adults, involving thesame general principles, patient positioning, loopformation, manual compression, withdrawal of theinstrument, etc., but greater caution is required,regardless of the endoscope used (pediatric colono-scope or adult instrument down to 3 years or 15 kg).

Training in pediatric traditional ileoscopy mustinclude not only technical knowledge of endoscopybut also gastroenterology and a background in pedi-atrics, which is useful in approaching children withdigestive disease and their families especially whenfurther diagnostic steps and therapeutic measuresmust be proposed.

8.2 Capsule Endoscopy and Small-Bowel Enteroscopy

The small bowel remains the last frontier in terms ofendoscopic visualization, as it is beyond the length ofcurrent endoscopes. The use of enteroscopy, or small-

bowel endoscopy, has been limited in the pediatricage group. Currently, intraoperative enteroscopy isthe only method to investigate the small bowel,including in children, but it requires abdominallaparotomy or laparoscopy and thus has a limited usein pediatrics.

The recent development of a swallowable, wirelesscapsule endoscope provides the unique opportunity tonon-invasively visualize the entire small bowel. Studiesin adult patients have demonstrated that the disposablecapsule is innocuous and highly effective [12].

Given Imaging’s capsule endoscopy consists of adisposable plastic capsule (Pillcam SB) weighing3.7 g and measuring 11 mm in diameter and 26 mmin length. It contains a battery-powered flashing lightsource, the capsule chip camera sensor, and a microtransmitter that allows the acquisition of high-qualityimages of the bowel and their transmission viadigital radiofrequency. The battery permits an aver-age total recording time of approximately 8 h, gen-erating over 100,000 images. The disposable capsuleis then eliminated in the stool and discarded. Alimitation of wireless capsule endoscopy (WCE) inchildren is the size of the capsule, which precludesits use in infants and very young children [13, 14].In children unable to swallow the capsule, it can bepositioned endoscopically through specific devices(Fig. 8.1). The Pillcam SB has been approved by the

Fig. 8.1 Capsule delivery device

48 P. De Angelis et al.

US Food & Drug Administration for visualization ofthe small-bowel mucosa in adults and in childrenage 10 years and older. However, there is clinicalexperience regarding its use in children as young as3 years of age, after endoscopic placement. Themost common indications for WCE are:• Obscure gastrointestinal bleeding, including iron-

deficiency anemia• Suspected Crohn’s disease• Suspected small intestinal tumors and surveillance

in patients with polyposis syndrome (Peutz-Jeghers,juvenile polyposis)

• Suspected or refractory malabsorption syndrome(celiac disease, intestinal lymphangiectasia, protein-losing enteropathies, etc.).Other indications are:

• Food allergy or eosinophilic enteropathies• Drug-induced mucosal injury• Chronic abdominal pain with high suspicion of

small-bowel pathology• Transplantation (rejection of intestinal graft,

GVHD in bone-marrow transplant recipients).Contraindications include:

• Known or suspected gastrointestinal obstruction,strictures

• A cardiac pacemaker or other implanted electro-medical devices [15].The risk of retention in an adult is 0.75%. There

has been one report in the pediatric field of a delay inelimination of the capsule, which resolved after theadministration of corticosteroids [16]. Two furtherreports described capsule retention requiring urgentsurgical intervention due to acute intestinal obstruc-tion (vomiting and abdominal pain) in patients withCrohn’s disease who were radiologically negative forsmall-bowel stenosis [17].

The experience of the Digestive Surgery andEndoscopy Unit of Ospedale Pediatrico BambinoGesù, (IRCCS, Rome), acquired over the last 5 years,consists of 207 WCE procedures performed in 207patients (age range: 18 months–25 years; smallestbody weight: 8 kg). One patient with Crohn’s diseaseexperienced capsule retention, resolved by theadministration of corticosteroids. In two patients (onewith insulin-dependent diabetes mellitus), the capsuledid not pass the stomach following 8 h of procedure(eliminated 36 h later). In one patient, the capsuleimpacted in the esophagus due to peptic stenosis andit was urgently removed.

The immediate future in the pediatric fieldwill be the combination of WCE and a companiontherapeutic procedure, such as double-/mono-balloonenteroscopy. In adult patients, the diagnostic andtherapeutic possibilities of small-intestinal diseasedrastically improved with the advent of double-balloon enteroscopy (DBE). This allowed biopsysamples to be acquired and therapeutic procedures(polypectomies, hemostasis, dilations) to be success-fully performed [18].

The small bowel has always been a difficult area toexplore. DBE was introduced at the beginning of2001 for small-bowel studies, by Yamamoto et al.[19]. This procedure is now available for routineclinical use in adults. The largest reported pediatricsexperience was published in 2007 by Leung, whodescribed 30 DBE procedures in 24 pediatric patients[20]. Recently, a novel single balloon enteroscopy(SBE) system was developed to examine the smallintestine. The procedure is simpler than DBE and isindicated for suspected gastrointestinal bleeding,Crohn’s disease, abdominal pain, intestinal polyposis,and suspected intestinal tumor (Figs. 8.2, 8.3 and 8.4).The use of SBE in children is well known, includingin newborns and infants [21]. The SBE system(Olympus XSIF-Q 260Y) has a working length of200 cm, an outer diameter of 9.2 mm, a workingchannel of 2.8 mm and a soft overtube (OlympusXST SB1) with a distal silicon balloon loaded ontothe endoscope, and a pressure-controlled pump(Olympus XMAJ 1725), which is used to inflate theovertube balloon.

Fig. 8.2 Medium ileum: large polyp

8 Results of Ileoscopy in Pediatric Patients 49

Working together, an endoscopist, his or herassistant, and an anesthesiologist generally performSBE with the aid of fluoroscopy and the patient undergeneral anesthesia. The patient’s position is left lat-eral for the oral approach and prone for the anal route;however, in the pediatric population, the analapproach is technically more complex due to the riskof overrun of the colon and passage through theileocecal valve. The most appropriate approachshould be decided according to the position of thelesions previously found on WCE. Enteroscopycombined with WCE provides excellent diagnosticand therapeutic yields during polypectomy for intes-tinal polyps, dilation of stenosis in Crohn’s disease,biopsies in suspected tumor lesions, and hemostasis ofbleeding lesions of the small bowel [22].

Rare complications following SBE in a large adultseries of 166 procedures consisted of one perforation,which occurred after dilation of a benign stricture,whereas no serious complications have thus far beenreported in pediatric patients [23]. Thus, in general,SBE appears to be a safe and effective method for thedetection of small-bowel pathology. Contraindicationsto the procedure include previous abdominal surgery.Pediatric gastroenterologists should be appropriatelyand specifically trained in this procedure.

8.3 Intraoperative Ileoscopyand Indications for Surgeryin Small-Bowel Diseases

The most frequent indications in which a combinedendoscopic and surgical approach is indicated ormandatory are:• To allow endoscope progression• To perform endoscopic operative procedures in

high-risk patients and situations• Coagulopathies• Large-pedicle ([1 cm) polyps• Underweight children• Portal hypertension• In patients with large venous malformations.

In some patients, it may be impossible to progress tothe medium and distal ileum, despite the use of modernenteroscopes. While modern endoscopic accessorieshave enabled more procedures than ever before, inchildren, the need for surgical support, either tradi-tional or laparoscopic, in exploration of the smallbowel is more frequent than in adults. This is due to thethinness of the jejunal and ileal walls, with a high riskof perforation in polypectomy, mucosectomy, or thetreatment of vascular malformations.

8.4 Surgically Assisted Ileoscopy

Through a laparotomy, the surgeon can easily controlthe tip of the endoscope, inserted above the ligament ofTreitz. The endoscopist pushes the scope while thesurgeon essentially invaginates the bowel on the scope,thus allowing the endoscope to reach the distal ileus.

In case of lesions that should be endoscopicallytreated, the surgeon uses a dermographic pen to markthe correct site to be treated following the withdrawal

Fig. 8.3 Single-balloon enteroscopy: polypectomy

Fig. 8.4 Single-balloon enteroscopy: jejunal mass

50 P. De Angelis et al.

of the endoscope. This strategy is very important inorder to avoid traction or manipulations at the poly-pectomy site or banding of a vascular malformation,such as blue rubber bleb nevus syndrome [24].In these patients, who have frequent and sometimesmassive bleeding, the only treatment is a combinationof wedge resection, polypectomy, suture-ligation,segmental bowel resection, and band ligation, all ofwhich are possible and safe with a surgically assistedendoscopic approach. After therapeutic endoscopy,the surgeon can correctly verify the procedure’seffectiveness and the absence of complications, suchas a burn or perforation. In the latter, the treatment ofchoice involves the use of resorbable suture, withsuturing preferably restricted to the serosal layer.

Although endoscopic progression is easier with theopen technique, the well-trained pediatric surgeon canperform all of the above-mentioned procedures usinglaparoscopy. In some cases, it is possible to grasp theaffected intestinal segment and extract it through theenlarged trocar site, to perform a resection or otherprocedures.

The most important and frequent pediatric indica-tions for ileal surgery are:• Jejunostomy in patients with a history of abdominal

surgery• Ileal strictures• Ileal tumors• Large venous malformations.

It is important to note not only the indications forileal surgery but also the role of surgery, either lap-aroscopic or traditional, depending on the surgeon’sexperience, with respect to the possibility of endo-scopic treatment. However, in patients with previoussurgery, an endoscopic jejunostomy could be haz-ardous because of adhesions and possible boweloverlap, with the risk of intestinal fistulas. In suchcases, a surgical approach, even if endoscopicallysupported, is the safest strategy.

In patients with Crohn’s disease and ileal strictureslonger than 10 cm, and especially strictures not easilyreached by the endoscope, surgery is used to performa resection and anastomosis or a strictureplasty [25].Dissection of the affected bowel is often very difficultdue to adhesions and mesentery thickening, whichcomplicate retraction.

In case of ileal tumors, which are rare in thepediatric population, endoscopy plays a role only inthe early diagnosis of superficial lesions suitable for

mucosectomy. Due to the non-specific symptomatol-ogy, a late diagnosis generally indicates the need for asurgical approach to these patients.

References

1. Thompson M, Murphy MS (2006) Diagnostic colonoscopy.In: Winter HS et al (eds) Pediatric gastrointestinalendoscopy, textbook and atlas. BC Decker, Hamilton

2. Geboes K (2007) The strategy for biopsies of the terminalileum should be evidence based. Am J Gastroenterol102(5):1090–1092

3. Börsch G, Schmidt G (1985) Endoscopy of the terminalileum. Diagnostic yield in 400 consecutive examinations.Dis Colon Rectum 28(7):499–501

4. Melo MM, Cury PM, Ronchi LS et al (2009) Terminalileum of patients who underwent colonoscopy: endoscopic,histologic and clinical aspects. Arq Gastroenterol46(2):102–106

5. Thakkar K, Lucia CJ, Ferry GD et al (2009) Repeatendoscopy affects patient management in pediatricinflammatory bowel disease. Am J Gastroenterol 104(3):722–727

6. Thompson B, Salzman D, Steinhauer J et al (2006)Prospective endoscopic evaluation for gastrointestinalgraft-versus-host disease: determination of the bestdiagnostic approach. Bone Marrow Transplant 38(5):371–376

7. Sigurdsson L, Reyes J, Putnam PE et al (1998) Endoscopiesin pediatric small intestinal transplant recipients: five yearsexperience. Am J Gastroenterol 93(2):207–211

8. Trecca A, Gaj F, Gagliardi G et al (2009) Role of magnifiedileoscopy in the diagnosis of cases of coeliac disease withpredominant abdominal symptoms. Scand J Gastroenterol44(3):320–324

9. Israel DM, McLain BI, Hasall E (1994) Successfulpancolonoscopy and ileoscopy in children. J Pediatr GastrNutr 19(3):283–289

10. Hunter A, Mamula P (2010) Bowel preparation forpediatric colonoscopy procedures. J Pediatr Gastr Nutr51:254–261

11. Turner D, Levine A, Weiss B et al (2010) Evidence-basedrecommendations for bowel cleansing before colonoscopyin children: a report from a national working group.Endoscopy 42:1063–1070

12. Gong F, Swain P, Mills T (2000) Wireless capsuleendoscopy. Gastrointest Endoscopy 51(6):725–729

13. Barth BA, Donovan K, Fox VL (2004) Endoscopicplacement of the capsule endoscope in children.Gastrointest Endosc 60(5):818–821

14. de’ Angelis GL, Fornaroli F, de’ Angelis N et al (2007)Wireless capsule endoscopy for pediatric small boweldisease. Am J Gastroenterol 102:1749–1757

15. Seidman E, Sant’Anna AM, Dirks MH (2004) Potentialapplication of WCE in the pediatric age group. GastrointestEndosc Clin N Am 14:207–217

16. Sant’Anna AM, Doubois J, Miron MC et al (2005) Wirelesscapsule for obscure small bowel disorder: final results of

8 Results of Ileoscopy in Pediatric Patients 51

the first pediatric controlled trial. Clin GastroenterolHepatol 3:264–270

17. Barkin J, Friedman S (2002) Wireless capsule endoscopyrequiring surgical intervention. Am J Gastroenterol 97:A907

18. Chong A, Chin B, Meredith C (2006) Clinically significantsmall-bowel pathology identified by double-balloonenteroscopy but missed by capsule endoscopy. GastrointestEndosc 64(3):445–449

19. Yamamoto H, Sekine Y, Sato Y et al (2001) Totalenteroscopy with a nonsurgical steerable double-balloonmethod. Gastrointest Endosc 53:210–220

20. Leung YK (2007) Double balloon endoscopy in pediatricpatients. Gastrointest Endosc 66(Suppl):S54–S56

21. Kramer RE, Brumbaugh DE, Soden JS, Capocelli KE,Hoffenberg EJ (2009) First successful anterograde single-balloon enteroscopy in a 3 year-old with occult GIbleeding. Gastrointest Endosc 70(3):546–549

22. Ramchandani M, Reddy DN, Gupta R et al (2009)Diagnostic yield and therapeutic impact of single-balloonenteroscopy: series of 106 cases. J Gastroenterol Hepatol24:1631–1638

23. Aktas H, de Ridder L, Haringsma J et al (2010)Complications of single-balloon enteroscopy: a prospectiveevaluation of 166 procedures. Endoscopy 42(5):365–368(Epub 2010, Feb 22)

24. Fishman SJ, Smithers CJ, Folkman J et al (2005) Bluerubber bleb nevus syndrome: surgical eradication ofgastrointestinal bleeding. Ann Surg 241(3):523–528

25. Wibmer AG, Kroesen AJ, Gröne J et al (2010) Comparisonof strictureplasty and endoscopic balloon dilatation forstricturing Crohn’s disease review of the literature. Int JColorectal Dis 25:1149–1157

52 P. De Angelis et al.

9The Role of Histology in Small BowelDiseases

Vincenzo Villanacci and Gabrio Bassotti

9.1 Introduction

The role of histology in the diagnosis of differentpathologies of the terminal ileum and cecal region(TICR) is one of the most difficult aspects of surgicalpathology for two important reasons: (1) the site of theTICR, and thus the dependence on the ability of theendoscopist to obtain an adequate number of speci-mens and a correct orientation of the biopsy samples,and (2) the complexity of the pathological conditionsinvolving this site. Therefore, to achieve a correctdiagnosis, good working relationships between gast-roenterologists, radiologists, endoscopists, and pathol-ogists are of paramount importance, together with acorrect methodological approach.

In this chapter, we begin with a consideration ofthe normal histological aspect of the TICR and thencontinue with a discussion of the different patholog-ical conditions, which can be summarized as follows:• Crohn’s disease• Backwash ileitis and pouchitis• Inflammatory conditions• Ischemia• Celiac disease• Rare pathological entities• Tumors.

Under normal conditions, and especially on biopsymaterial, in which it is possible to observe only themucosa, muscularis mucosae, and superficial part ofthe submucosa, the pathologist should pay particularattention to the following elements:1. The morphology and the architecture of the villi.

Normally, the villous/crypts ratio is not \ 3:1.2. Intraepithelial lymphocytes (IEL). Generally, these

are T lymphocytes, CD3+ and CD8+; the normalnumber of IEL is not [25/100 epithelial cells [1].

3. Inflammatory cells in the lamina propria. Apartfrom the crypts, these cells, and particularly eosin-ophils, are usually present along with lymphoidfollicles, strictly related to Peyer’s patches [2].

4. The number of IEL in the cecal region. A valueC30 IEL/100 epithelial cells is considered patho-logical. Of equal importance is the thickness ofthe subepithelial collagen layer, which should beexamined for signs of microscopic (lymphocytic-collagen) colitis.

5. The presence of granulomas. Their presence indi-cates the need to include both Crohn’s disease andYersinia infection in the differential diagnosis.

9.2 Inflammatory Bowel Disease

The first and most important pathological form ofTICR is Crohn’s disease. Its best known and diag-nostic hallmark is the presence of sarcoid-type gran-ulomas that are Ziehl–Neelsen negative, although inmost cases no granulomas are found. The differentialdiagnosis for granulomatous disease of the TICR mustinclude Yersinia enterocolitica/pseudotubercularisand tuberculosis infections. In the absence of

V. Villanacci (&)Department of Pathology, Spedali Civili,University of Brescia, Brescia, Italye-mail: villanacci@spedalicivili.brescia.it

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_9, � Springer-Verlag Italia 2012 53

granulomas, there are other important features to beevaluated that are indicative of Crohn’s disease(Fig. 9.1), in particular the architectural distortion ofthe crypts, crypt density, a discontinuous type ofinflammatory infiltrate (especially basal plasmocyto-sis), and fissuring ulcerations, if present [3].

In patients with severe ulcerative colitis extending toall segments of the colon (pancolitis), it is sometimespossible to find an active inflammation in the distal fewcentimeters of the terminal ileum, presumably relatedto reflux of the colonic contents. This condition,referred to as ‘‘backwash ileitis,’’ can be difficult todistinguish from Crohn’s disease. In resection speci-mens, the differentiation is straightforward, becausethe continuity of the disease from the proximal coloninto the ileum, with an incompetent ileocecal valve,can be readily appreciated. However, in small mucosalbiopsies, the distinction between the two conditions ismuch more difficult; in fact, backwash ileitis canmimic active Crohn’s disease of the ileum. In thissituation, the pathologist should be informed of theendoscopic features of the disease, notably its extentin the colon, its continuity between the colon andileum, and the appearance of the ileocecal valve, asthis information will avoid an erroneous diagnosis of

Crohn’s disease. In addition, an important point is theaccurate morphological evaluation of the mucosa, inwhich it is possible to distinguish an inflammatoryinfiltrate rich in neutrophils and eosinophils fromlymphoyd aggregates normal for the biopsy sites andfew superficial erosions but with a normal architec-ture of the crypts and no fissuring ulcerations, granu-lomas, or transmural lymphoid aggregates [4, 5].

In patients treated for ulcerative colitis by totalcolectomy and creation of a continent ileo-analanastomosis, there may be inflammation of the ilealpouch. In many centers, scoring systems have beenused to grade the extent of the histopathologicalabnormalities. The amount of ulceration and acuteinflammation is usually assessed according tothe St. Mark’s scoring system, in which an acuteinflammatory score C4 usually implies pouchitis.It should be noted that only the acute inflammatoryscore correlates well with the clinical and endoscopicfeatures of pouchitis [6, 7].

Concerning dysplasia in the pouch mucosa, astudy by Heuschen et al. [8] showed a strong asso-ciation of backwash ileitis with the development ofcolorectal cancer in patients with ulcerative colitiswho underwent proctocolectomy. In patients with

Fig. 9.1 Crohn’s disease.a Biopsy of the terminal ileum(H&E, 49), b crypt abscess(H&E 209), c granulomas,d negative Ziehl Neelsenstaining (c and d, 409)

54 V. Villanacci and G. Bassotti

pancolitis, colorectal cancer was found in 29% of the107 patients with backwash ileitis compared to 9%of the patients without and 1.8% of the patients withlimited left-sided colitis. However, discrete patho-logical criteria for backwash ileitis were not defined.In view of the reports of dysplasia and carcinoma inthe pouch mucosa and in the columnar cuff, someform of surveillance of the ileal reservoirs is rec-ommended. Importantly, biopsies should be takenfrom several different sites in the pouch, accordingto standardized methodology, due to the evolvinghistological changes in the colonic phenotypic andthus the patchy inflammation of the pouch mucosa[9, 10].

9.3 Ischemia–Actinic Ileocolitis

Ischemia in the TICR displays the typical features ofcoagulative necrosis. In so-called actinic ileitis, there isa previous history of radiotherapy. Morphologically,the features of the disease include fibrosis in the laminapropria, bizarre radiation fibroblasts more frequent inthe submucosa, and telangiectatic mucosal bloodvessels. Indeed, telangiectatic mucosal blood vesselsmay be a prominent feature of this condition and areoften the only diagnostic feature seen in a small biopsy

(Fig. 9.2). The thick hyaline walls of the vessels willdistinguish them from the thin-walled angioma-likedilated vessels of angiodysplasia [11, 12].

9.4 Celiac Disease

Particular attention must be paid to the possible diag-nosis of celiac disease during evaluation of the TICR.At present, the gold standard for the diagnosis of celiacdisease is the histological evaluation of duodenalbiopsies, with the assumption that the most frequentand most severe lesions are present in the proximal partof the small intestine [13, 14]. However, an importantproblem is the correct identification of the earlylesions, in particular type 1 and 2, as scored using theMarsh–Oberhuber classification [15, 16], correspond-ing to grade A of the newly proposed classification[17]. Recognition of the early lesions in celiac diseaseis one of the major pitfalls in its histological diagnosis,as the only morphological alteration in the presence ofnormal villi is a pathological increase of IEL [18–21].However, as recently stressed by Rostami ‘‘…mostEuropean pathologists (and not only European) do notroutinely count the intraepithelial lymphocytes induodenal biopsies. Minor intestinal changes compati-ble with [celiac disease] are, therefore, overlooked in

Fig. 9.2 a, b Histological(H&E staining) examinationof ischemic colitis, shown at109 and 209 magnification,respectively. c, d Histological(H&E staining) examinationof actinic colitis, with fibrosisand typical hyaline dilatedvessels, shown at 209 and109, respectively

9 The Role of Histology in Small Bowel Diseases 55

many symptomatic cases and subsequently labeled as[inflammatory bowel syndrome] or functional’’ [22].

In the TICR, the clinician is confronted with a sim-ilar problem, the difference being that the alterations aremore infrequent and in some cases are confused withthose of the other, above-described pathologies. In anearly study by Dickey and Hughes [23], biopsies takenfrom the terminal ileum during colonoscopy/ileoscopywere examined for features of gluten-sensitive enter-opathy. The authors studied 30 patients with duodenalvillous atrophy consistent with celiac disease and 60controls with no evidence of the disease or of inflam-matory bowel disease. The results demonstrated thatonly one patient, in the celiac disease group, had partialvillous atrophy with crypt hyperplasia in the terminalileum. IEL counts were significantly higher in the celiacgroup than in controls. An ileal IEL count C25 IEL/100enterocytes had a sensitivity for duodenal villousatrophy of 60% and a specificity of 100%.

Similar results were obtained by Hopper et al. [24],who investigated 20 patients newly diagnosed withceliac disease and four control groups: celiac disease ongluten-free diet, inflammatory bowel disease, chronic

diarrhea, and polyp surveillance. The results showedthat the IEL count in the terminal ileum was signifi-cantly higher in patients with celiac disease than in thecontrol groups, and that IEL count as a test for thisdisease using a cut-off of[25 IEL/100 enterocytes hada sensitivity of 45% and a specificity of 97%. Thus,these two studies underline the fact that celiac diseasemay involve the entire small bowel.

An increased IEL density in the TICR is associatedwith duodenal villous atrophy and should prompt asearch for celiac disease by serology and duodenalbiopsy. Conversely, a normal IEL count does notallow the exclusion of celiac disease with confidence;for this reason, quantifying IELs in terminal ileumbiopsies may be of limited clinical/pathological value.However, the subjective recognition of IEL on a ter-minal ileum biopsy should alert the referring clinicianto the possibility of underlying celiac disease.

The same caveat can be made in cases of so-calledlymphocytic gastritis, in which a possible associationwith celiac disease is present in 38% of the cases, and inso-called lymphocytic colitis, which may be indicativeof the presence of celiac disease (Fig. 9.3) [25, 26].

Fig. 9.3 Celiac disease. Thelow atrophy of the villi in theterminal ileum are shown inthis H&E-stained histologicalsample at a 109 and b 209

magnification. A pathologicalincrease in T lymphocytes canbe seen with immunostainingfor CD3 at c 109 and d 209

magnification

56 V. Villanacci and G. Bassotti

The take-home message is the importance of acorrect evaluation of the morphological features. Thepathologist must be able to provide the clinician witha precise description of the small-bowel mucosa inorder to allow an accurate diagnosis.

9.5 Rare Pathological Entities

Among the rare pathological entities involving theTICR, two conditions in particular should be noted:angiodysplasia and vasculitis. Angiodysplasia isrelated to an abnormal proliferation, congenital oracquired, of small vessels prevalent in the submucosa.More difficult to diagnose on biopsy material is thesecond condition, vasculitis. In fact, the diagnosis,apart from the epiphenomenon of ischemia in themucosa, is possible only on total thickness biopsies orsurgical specimens (Fig. 9.4) [27, 28].

9.6 Tumors

Tumors in the TICR are rare but include precancerouslesions and epithelial tumors, endocrine tumors, gas-trointestinal stromal tumors (GISTs), and lymphomas.As for the other pathological conditions discussedherein, their diagnosis is based on a correct histopa-thological evaluation [27, 28].

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Fig. 9.4 Vasculitis withinfiltration of inflammatorycells in the vessel walls, asseen in this H&E stainedhistological sample ata 409 and b 29

magnification.Angiodysplasia with typicaldilated vessels in thesubmucosa in this H&Estained sample shown atc 109 and d 409

magnification

9 The Role of Histology in Small Bowel Diseases 57

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25. Olesen M, Eriksson S, Bohr J, Jarnerot G, Tysk C (2004)Lymphocytic colitis: a retrospective clinical study of 199Swedish patients. Gut 53:536–541

26. Villanacci V, Bassotti G, Liserre B, Lanzini A, Lanzarotto F,Genta RM (2006) Helicobacter pylori infection in patientswith celiac disease. Am J Gastroenterol 101(8):1880–1885

27. Greenson JK (ed) (2010) Diagnostic pathology:gastrointestinal, 1st edn. Amirsys Inc, Salt Lake City

28. Fenoglio C (2008) Preiser gastrointestinal pathology.An atlas and text, 3rd edn. LWW, Philadelphia

58 V. Villanacci and G. Bassotti

10Radiological Diagnosis of Small-BowelDiseases

Laura Maria Minordi, Amorino Vecchioli, Luigi Larosa,and Lorenzo Bonomo

10.1 Introduction

The small bowel has been a subject of intense interestin radiology. Over the past several years, manytechniques have been standardized and their applica-tions verified for the diagnosis of a wide range ofpathologies. Currently, these techniques includedirect radiography, barium studies, ultrasonography(US), computed tomography (CT), and magneticresonance imaging (MRI).

10.2 Direct Abdominal Radiography

Direct abdominal radiography is the first exam to beperformed in patients with acute abdominal disease,especially when obstruction is suspected. Even if aspecific correct interpretation is not always possible,radiography usually provides adequate informationfor the subsequent diagnostic approach [1].

10.3 Small-Bowel Follow-Through Studyand Peroral Pneumocolon

At present, the most commonly used radiologicmethod is the small-bowel follow-through study(SBFT), in which the patient is administered a

low-density barium dose and a series of radiographsare subsequently acquired to follow barium progres-sion to the ileocecal region. However, this method isburdened by a high rate of false negatives due tooverlapping intestinal loops, which can mask evengross organic lesions [2]. The SBFT can be completedby a peroral pneumocolon (PP): when the barium hasreached the right colon, air or CO2 is insufflated bythe rectal route to obtain its reflux into the ileum. In aprevious study [3], we demonstrated the superiority ofPP over SBFT in the evaluation of patients withsuspected Crohn’s disease.

10.4 Enteroclysis

With the introduction of enteroclysis, all the disad-vantages of the previously described techniques havebeen overcome. In enteroclysis, contrast media (bar-ium and methylcellulose or air) are administered bynaso-jejunal tube to obtain a double-contrast study ofthe small-bowel loops [4]. The disadvantages of theprocedure are the need for intubation, patient dis-comfort during the intubation, and the higher radia-tion dose than in a conventional follow-through study.

In patients with Crohn’s disease, the initial intes-tinal alterations are plical thickening and aphthousulcerations [5]. The latter appear as superficialdepressions, 1–2 mm in diameter, often surroundedby a halo. They may be the only radiologic abnor-mality or they may be associated with larger ulcers ormore extended alterations that form a characteristiccobblestone pattern (Fig. 10.1). The association ofaphthous ulcerations with plical thickening andgranulomas confirms the early stage of the disease [5].

L. M. Minordi (&)Department of Bio-Imaging and Radiological Sciences,Catholic University (UCSC) Radiology Institute,Rome, Italye-mail: lmminordi@rm.unicatt.it

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_10, � Springer-Verlag Italia 2012 59

Linear ulcers along the mesenteric margin areanother important signs of Crohn’s disease. Theseulcers can be over 15 cm long and typicallydevelop parallel to the shortest concave or straightmesenteric margin. Deep ulcers cause luminal nar-rowing, resulting in concentric or asymmetricalstenosis. In addition, stenosis of small-bowel loopsfrequently occurs from the combination of fibrosis,mural thickening, and spasm. During contraststudies, true stenosis should be distinguished fromnarrowing caused by ulceration and spasm; how-ever, in some cases this distinction can be verydifficult [5]. Also, contrast studies show fistuloustracts in approximately 20–40% of patients withCrohn’s disease.

In Crohn’s disease the choice between SBFT andenteroclysis should be made by the radiologist basedon the clinical situation, while enteroclysis should bethe first exam in patients with suspected small-boweltumors [6].

Nonetheless, these radiological techniques provideonly indirect information on the intestinal wall andadjacent extraintestinal structures (Fig. 10.2a)whereas US, CT (Fig. 10.2b) and MRI allow directvisualization of wall (thickness and structure) andthe adjacent extraintestinal structures (mesentery,perivisceral fibrofatty cells, lymph nodes, peritonealspaces).

10.5 Ultrasound Appearance of Crohn’sDisease and Malignancies

As a non-invasive procedure free of exposure toionizing radiation or conventional radiologic contrastmedium, US is ideal for use in patients with chronicinflammation, in children, and in some small-boweldisorders to prove or rule out a clinical suspicion.The tone and contractile activity of the small-bowelloops under physiologic conditions can be readilyvisualized on US.

The most important ultrasound finding indicativeof Crohn’s disease is the symmetrical mural thick-ening, with preserved stratification or diffuse hypo-echogenicity. US can evaluate the residual motility ofthe pathological loops, the grade of luminal stenosisand dilatation of proximal segments, and the presenceof fistulae, abscesses, and lymphadenopathies. Thespecificity of US in the identification of the Crohn’sdisease is 88–94% while its sensitivity is 73–95% [7].In the detection of complications, sensitivity andspecificity are, respectively, 50–87% and 90–94% forfistulae, 84–100% and 91–97% for stenosis, and83–100% and 92–94% for abscesses [7].

The morphologic and Doppler appearance of localhypervascularization, resulting from the increasedflow in the superior mesenteric artery, correlates wellwith the severity of the endoscopic and histologicalterations and with inflammatory activity scores [8].The characteristic of malignant neoplasms of thesmall bowel are similar to those of the stomach andcolon: asymmetrical mural thickening, loss of normalstratification, stenosis, and luminal deformation(Fig. 10.3).

10.6 Computed Tomography Studiesof Small-Bowel Disease

The primary requirements of CT imaging of the smallbowel are visualization of the entire small bowel,adequate visceral distension, elimination of respira-tory motion and peristalsis, and i.v. administration ofiodinated contrast agent to evaluate the extent andpattern of wall enhancement.

Different types of contrast agents and differentmodes of administration are used to obtain distensionof the small bowel [9]. Hyperdense contrast media

Fig. 10.1 Enteroclysis shows a cobblestone pattern andstenosis of the last ileal loop (arrows)

60 L. M. Minordi et al.

(1–2% barium sulfate suspension or a 2–3% water-soluble iodinated solution) are the best known andmost well studied. They allow intestinal loop delim-itation and the determination of whether an intestinalformation is intraluminal or extraluminal. However,their high density precludes accurate evaluation of thecharacteristics of the wall of the small intestine.Instead, hypodense contrast agents (oral water, oral oilemulsions, air, low-density barium suspensions, poly-ethyleneglycol (PEG) solution) ensure better definitionof the internal aspect of the small bowel, especiallythe degree of parietal contrast enhancement afterintravenous contrast bolus infusion (Fig. 10.4) [10].

We recommend PEG for oral use [11, 12] and usuallyadminister 1.5–2.0 L of PEG in doses of 100 mlstarting 45 min before the CT examination.

Oral contrast agents have the disadvantage of aninadequate, non-uniform distension of all small-bowelloops, particularly the jejunal loops. The problem isovercome, albeit at the expense of higher invasive-ness, time, and cost, with CT-enteroclysis. In thismethod, developed in the early 1990s, variableamounts (2,000–2,750 ml) of low-density (methyl-cellulose or water) or high-density (4–5% sodiumdiatrizoate, 1% barium sulfate) are administered via anaso-jejunal tube [9, 10, 13].

Fig. 10.2 Small-bowelfollow-through examination.a A small-bowel loop isseparated from adjacent loops(encircled). b CT confirms asmall-bowel mass (arrows).Surgical report: stromal tumor

Fig. 10.3 Ultrasound shows asymmetrical mural thickening,with deformation of one small-bowel loop and the loss of normalstratification and stenosis. Surgical report: adenocarcinoma

Fig. 10.4 Enterography CT performed after oral administra-tion of hypodense contrast material (PEG) shows muralthickening of the last ileal loop, with target sign (arrow). Goodvisualization of the normal wall of the ileal loops (I) revealsa linear and homogeneous hyperdense appearance betweenthe endoluminal low-density solution and the extraparietalhypodensity of the peritoneal fat

10 Radiological Diagnosis of Small-Bowel Diseases 61

On CT, the finding of parietal thickening isthe main criterion for the diagnosis of small-boweldisease. Malignant tumors of the small bowel,including adenocarcinomas, carcinoid tumors, lym-phoma, stromal tumors (Fig. 10.2b), and metastases,cause asymmetrical mural thickening, loss of normalstratification, stenosis, and luminal deformation.

The CT criteria for the diagnosis of small-bowelCrohn’s disease are the essential finding of parietalthickening ([3 mm) and at least one extraparietalinflammatory involvement. CT findings in thesepatients are listed in Table 10.1, with two examplesdepicted in Figs. 10.4 and 10.5.

10.6.1 CT and Clinical Disease Activity

The CT findings correlate with the clinical activity ofthe disease. In a previous study [14], we found asignificant correlation between mural thickening andthe levels of C reactive protein (CRP) and fibrinogen.The target sign and fibrofatty proliferation werepresent more frequently in patients with a Crohn’sdisease activity index (CDAI) score [150 than inthose with a CDAI score \150. There was also astatistically significant correlation between the combsign and abnormal values of CRP, while perientericstranding correlates with abnormal CRP and fibrino-gen levels. Similarly, we found a positive correlation

between the CT relief of fistulas and abnormal ESRand fibrinogen values [14].

10.6.2 CT Versus Ileocolonoscopyin Evaluating Recurrent Crohn’sDisease

The evaluation of patients with Crohn’s disease afterintestinal resection is another application of CT.In fact, even if medical therapy is the main method oftreating patients with Crohn’s disease, approximately

Table 10.1 CT findings in Crohn’s disease

CT finding Definition

Diameter of the small-bowel lumen

Diameter of the loop excluding the thickness of the wall

Diameter of the loop Diameter of the loop including the thickness of the wall

Stenosis Decreased diameter of the lumen

Mural enhancement Hyperdensity of the involved segments

Target sign Alternating rings of high and low density

Comb sign Hypervascularity of the involved mesentery manifesting as mesenteric arterial dilation, tortuosity,prominence, wide spacing, and dilation of the vasa recta

Perienteric stranding Loss of the normally sharp interface between the bowel wall and mesentery

Fibrofatty proliferation Increased attenuation of the mesenteric fat (-20–60 H.U.)

Fistulas Communication between two epithelial lined organs (internal fistula) or communication with theskin surface (external fistula)

Lymphadenopathy Diameter [1 cm

Abscesses Rounded or oval fluid-density masses delimited by hyperdense wall

Fig. 10.5 PEG-CT (with maximum-intensity projection MIPreconstruction) shows symmetrical thickening of some small-bowel loops (black arrows) and the comb sign (white arrows)

62 L. M. Minordi et al.

70% of them will undergo surgical intestinal resectionat least once in their lives, although disease recur-rence is common. Ileocolonoscopy is still the goldstandard among the methods for evaluating diseaserecurrence in patients who have undergone ileal-colicresection. The endoscopic Rutgeerts’ score is anestablished clinical score for the staging of Crohn’sdisease and provides guidelines for further therapeuticstrategies. Nevertheless, endoscopy is an invasivemethod that frequently requires sedation or anesthe-tization of the patient. Moreover, it can be incompletein the presence of stenosis not surmountable by theendoscope, and vision is often restricted to the ileal-colic anastomosis, with or without the neo-terminalileum. In a recent study [15], the sensitivity, speci-ficity, and diagnostic accuracy of CT in the evaluationof the ileal-colic anastomosis were 97, 100, and 97%,respectively. A comparison between CT signs andendoscopic scores in that study shows positive cor-relations between a score of 4 and the following CTsigns: target sign, peri-enteric stranding, comb sign,and fibrofatty proliferation. Moreover, a score of 1positively correlates with mucosal hyperdensitywithout wall thickening, and a score of 2 withmucosal hyperdensity with wall thickening.

10.7 MRI Evaluation of Small-BowelDisease

In patients undergoing MRI for the investigation ofsmall-bowel disease, bowel distension can beachieved with different oral contrast media (water,methylcellulose, PEG, mannitol, superparamagneticiron particles-SPIO). In enteroclysis-MRI, boweldistension requires duodenal intubation, largevolumes of contrast agent (1,500–2,000 ml), and aconstant injection rate (80–150 ml/min).

Pulse sequences are basically T1- and T2-weigh-ted, although the latter are reserved for assessments ofthe mucosa and valvulae conniventes, with imagessimilar to those obtained with X-ray. T1-weightedsequences are used in the assessment of the wall andextraluminal space [16]. In Crohn’s disease, thefindings are similar to those seen on X-ray. Linearulcers are recognized on T2-weighted images ashyperintense, fine lesions within the walls. Muralthickening is readily documented both on T2-weigh-ted and post-contrast T1-weighted images [16].

Submucosal edema is visualized as mural thickeningwith high signal intensity depending on the amount ofwater (Fig. 10.6) [16]. The cobblestone pattern ofCrohn’s disease can be appreciated especially on T2-weighted sequences. With optional bowel distension,stenosis and loop dilatation are more accuratelyassessed than is the case following CT with the oraladministration of contrast medium. Fibrofatty mes-enteric proliferation appears as irregular, linear, andnodular thickening of adipose tissue, best depicted onT2-weighted images (Fig. 10.6). Fistulae are seen aslinear images in the mesentery; they are hyperintenseto their water contents on T2-weighted sequences.Abscesses are also hyperintense on T2-weightedimages and show wall enhancement on post-contrastT1-weighted sequences [16].

Similar to luminal stenosis, intestinal masses arereadily detectable on MRI. They are typically hypo-isointense compared to the normal wall. On T2-weightedand pre-contrast T1-weighted images, various patterns ofcontrast enhancement are seen after Gd administration[17]. Adenocarcinomas, carcinoid tumors, and smoothmuscle tumors are usually hypervascularized, showinghigh-grade contrast enhancement.

10.8 Conclusions

The availability of different procedures requires anin-depth knowledge of their diagnostic possibilities,to be able to select the one best able to specificallyreveal a lesion whose presence is suspected based on

Fig. 10.6 T2-weighted axial scan with fat saturation showsmural thickening of the last ileal loop with hyperintensity of thewall (short arrow). A collection (long arrow) and fibrofattyproliferation (arrowhead) are also evident

10 Radiological Diagnosis of Small-Bowel Diseases 63

clinical and laboratory findings. Correct imaging ofthe small bowel should enable the diagnosis of smalland early structural alterations as well as the reliabledocumentation of the normal intestinal morphology.

References

1. Lappas JC, Reyes BL, Maglinte DDT (2001) Abdominalradiography findings in small bowel obstruction: relevanceto triage for additional diagnostic imaging. Am JRoentgenol 176:167–174

2. Maglinte DDT, Burney BT, Miller RE (1982) Lesionsmissed on small bowel follow-through: analysis andrecommendation. Radiology 144:737–739

3. Minordi LM, Vecchioli A, Dinardo G et al (2006) Thevalue of the per oral pneumocolon in the study of the distalileal loops. Clin Radiol 61:1016–1022

4. Herlinger H, Maglinte DDT, Yao Tsuneyosi (1998)Enteroclysis technique and variations. In: Helinger H,Maglinte DDT, Birnbaum BA (eds) Clinical imaging of thesmall intestine. Springer, New York, pp 95–123

5. Berstein CN, Boult IF, Greenberg HM et al (1997) Aprospective randomized comparison between small bowelenteroclysis and small bowel follow-through in Crohn’sdisease. Gastroenterology 113:390–398

6. Gourtsoyiannis NC, Papaionnou, Bays et al (1993) Benigntumours of the small intestine: preoperative evaluation witha barium infusion technique. Eur J Radiol 16:115–125

7. Maconi G, Bollani S, Bianchi Porro G (1996)Ultrasonography detection of intestinal complications inCrohn’s disease. Dig Dis Sci 41:1643–1648

8. Giovagnorio F, Diacinti D, Vernia P (1998) Dopplersonography of the superior mesenteric artery in Crohn’sdisease. Am J Roentgenol 170:123–126

9. Bender GN, Timmons JH, Williard WC et al (1996)Computed tomographic enteroclysis: one methodology.Invest Radiol 31:43–49

10. Maglinte DD, Sandrasegaran K, Lappas JC et al (2007) CTEnteroclysis. Radiology 245:661–671

11. Minordi LM, Vecchioli A, Mirk P et al (2007)Multidetector CT in small-bowel neoplasms. Radiol Med112:1013–1025

12. Minordi LM, Vecchioli A, Mirk P et al (2010) CTenteroclysis with polyethylene glicol solution vs CTenteroclysis in small bowel disease. Br J Radiol 84(998):112–119

13. Minordi LM, Vecchioli A, Guidi L et al (2006)Multidetector CT enteroclysis versus barium enteroclysiswith methylcellulose in patients with suspected smallbowel disease. Eur Radiol 16:1527–1536

14. Minordi LM, Vecchioli A, Guidi L et al (2009) CT findingsand clinical activity in Crohn’s disease. Clin Imaging33:123–129

15. Minordi LM, Vecchioli A, Poloni G et al (2009)Enteroclysis CT and PEG-CT in patients with previoussmall bowel surgical resection for Crohn’s disease: CTfindings and correlation with endoscopy. Eur Radiol19:2432–2440

16. Gourtsoyiannis NC, Papanikolau N, Rieber A et al (2002)Evaluation of the small intestine by magnetic resonanceimaging. In: Gourtsoyiannis NC (ed) Radiological imagingof the small intestine. Springer, New York, pp 157–170

17. Semelka RC, John G, Kelekis N et al (1996) Small bowelneoplastic disease: demonstration by MRI. J Magn ResonImaging 6:855–860

64 L. M. Minordi et al.

11Capsule Endoscopy: The Answerto a Challenge

Emanuele Rondonotti and Roberto de Franchis

11.1 Introduction

A look at the number of papers focused on the studyof the small bowel that have been published in the last20 years readily reveals a continuous increase.Nevertheless, beginning in 2000–2001, a clear changein the trend of these publications is apparent(Fig. 11.1). This change is not related to an increasedprevalence of small-bowel diseases but mainly to theintroduction into clinical practice of new diagnosticdevices for the study of the small bowel.

Before 2001, the main diagnostic tools used toevaluate the small bowel were the small-bowelfollow-through (SBFT) study and small-bowel enter-oclysis. These two techniques, although specificallydesigned to evaluate the small bowel, have low sen-sitivity and specificity in recognizing small and flatlesions. Additionally, both are often poorly toleratedby patients and the results are sometimes difficult tointerpret. Indeed, prior to 2001, push enteroscopy wasthe only way to endoscopically evaluate the smallbowel; but, as is well-known, this technique is limitedby the depth of insertion of the instrument to theproximal jejunum (about 90–150 cm by the oralroute) and to the terminal ileum (50–80 cm by theanal route) and, despite sedation, is poorly tolerated.On the other hand, intra-operative enteroscopy is themost complete but it is also the most invasive meansof examining the small bowel [1].

After 2001, several new endoscopic and non-endoscopic techniques became widely available. Theformer includes capsule endoscopy and device-assistedenteroscopy, and the latter CT- and MRI-enteroclysis.Among these new devices, capsule endoscopy, mainlydue to its technical characteristics, is revolutionary andhas resulted in a tremendous shift from insensitive andinvasive techniques to a sensitive and patient-friendlyexamination. Thus, capsule endoscopy is now consid-ered the cornerstone for the evaluation of the smallbowel in several clinical conditions.

In this chapter, we summarize, based on currentevidence and recently released guidelines, the resultsof capsule endoscopy applications in clinical practice.We also highlight the risks and limitations of thisdevice, an awareness of which has emerged in the10 years of its use in this setting.

11.2 Indications and Results

The most important feature of capsule endoscopy isthe possibility to acquire and transmit more than50–80,000 images of the small-bowel mucosa with-out any cable connection. In addition, the capsule iseasily swallowed with a single sip of water bypeople of almost any age (older than 8 years). Oncethe capsule is swallowed, the examination can beginwithout the need for further intervention. And, lastbut not least, the quality of the images acquired ishigh and, with the help of specific software, they canbe easily evaluated by a dedicated physician. For allthese reasons, capsule endoscopy, at least theoreti-cally, is ideal in the diagnosis of any diseaseaffecting the small bowel. However, 10 years after

E. Rondonotti (&)Gastroenterology Unit, Ospedale Valduce,Como, Italye-mail: emanuele.rondonotti@unimi.it

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_11, � Springer-Verlag Italia 2012 65

the introduction of capsule endoscopy into clinicalpractice, it has become apparent that its use islimited to a few clinical conditions (Fig. 11.2), withthe most common indications being obscure gastro-intestinal bleeding (OGIB), known or suspectedCrohn’s disease, small bowel tumors, and celiacdisease [2–4].

11.2.1 Obscure Gastrointestinal Bleeding

So far, OGIB is the main clinical indication for capsuleendoscopy, and 70–80% of patients undergoing theprocedure suffer from this condition. The majority ofstudies initially published on this application reported ahigh, although widely variable, diagnostic yield, with a

Fig. 11.2 Indications for capsule endoscopy in clinicalpractice. The data were derived from a systematic review,published by Liao et al. [3], of more than 2,000 capsule

endoscopy procedures performed worldwide in the last 7 years.OGIB Obscure gastrointestinal bleeding

Fig. 11.1 Trend of original papers published over timeconcerning the diagnosis of small-bowel diseases. Searchengine: www.pubmed.org. Red line publications addressing thediagnosis of small-bowel tumors (keywords for research:‘‘small bowel tumors’’). Blue line publications addressing thediagnosis of obscure gastrointestinal bleeding and small bowel

(keywords for search: ‘‘obscure gastrointestinal bleeding’’AND ‘‘small bowel’’). Green line publications addressing thediagnosis of Crohn’s disease involving the small bowel (key-words for search: Crohn’s disease AND small bowel). Blackline overall. The x axis shows the number of papers published;the y axis is the timeline (October 1990–2009)

66 E. Rondonotti and R. de Franchis

range of 40–90%, and typically 75–80% [5]. Thesestudies, mainly performed in tertiary referral centers,included highly selected patients with a long-standinghistory of OGIB and low levels of hemoglobin at thetime of the examination who had undergone an enor-mous number of prior examinations, with negativeresults. Subsequent series comprising larger popula-tions similar to those undergoing capsule endoscopy ineveryday clinical practice reported a slightly lowerdiagnostic yield (50–60%) [3, 4]. Nonetheless, severalof those studies (both head to head comparisons andmeta-analyses) clearly demonstrated that, in patientswith OGIB, capsule endoscopy is superior to traditionalradiological techniques (SBFT and small-bowel enter-oclysis) and push enteroscopy [6, 7]. At the presenttime, there have been no comparisons of capsuleendoscopy with other recently introduced radiologicaltechniques (CT-enteroclysis, MRI-enteroclysis); how-ever, despite the improved spatial resolution offered bythe latter, they remain relatively insensitive in the visu-alization of small flat lesions. This is particularly the casefor angioectasias, which are the most frequent findingidentified with capsule endoscopy in patients withOGIB. The factors potentially improving the diagnosticyield of capsule endoscopy include active bleeding at thetime of examination, a short interval between the lastepisode of acute bleeding and capsule endoscopy, lowlevels of hemoglobin, and a high transfusion require-ment [8, 9].

Based on these observations and experience, a‘‘Standard of practice’’ paper was recently publishedon behalf of the American Society of GastrointestinalEndoscopy (ASGE) [10], In this paper, the ASGEStandard of Practice Committee Members reviewedthe available evidence and suggested the best diag-nostic approach to OGIB. The authors clearlyunderlined that a careful examination of both theupper and lower gastrointestinal tract, mainly in caseof overt GI bleeding, is still mandatory (evenrepeating an upper GI endoscopy) before addressingthe small bowel. However, if the bleeding is correctlydefined as obscure (overt or occult) and is suspectedof originating from a small-bowel mucosal lesion,then the best way to evaluate the small bowel iscapsule endoscopy.

For those patients in whom capsule endoscopy isable to show small-bowel findings that clearly explainthe reason for referral, a further specific diagnosticand therapeutic workup, such as by means of device-

assisted enteroscopes, is warranted. In those patientsin whom capsule endoscopy is negative, conservativemanagement is often sufficient [11], e.g., by means ofiron supplementation in the presence of establisheddeficiency. Alternatively, further investigations maybe deemed necessary, in which case the authorssuggested repeat capsule endoscopy, especially whenthe clinical presentation changes; for example,when occult bleeding becomes overt bleeding orwhen there is a significant drop in hemoglobin levels(at least 4 g/dL).

Despite the large experience with capsule endos-copy in clinical practice, studies evaluating the impactof this examination on long-term outcomes are lacking.Indirect evidence shows a positive impact of capsuleendoscopy in terms of decreasing the number offurther examinations, the need for new hospitaliza-tions, and transfusion requirements, but larger studiesare warranted.

11.2.2 Crohn’s Disease

The results of a recent consensus meeting, in whichexperts from the European Crohn’s and ColitisOrganisation (ECCO) and the World Organisation ofDigestive Endoscopy (OMED) participated, have beenpublished, addressing the role of capsule endoscopy inpatients with Crohn’s disease. Specifically, the authorsevaluated the use of capsule endoscopy in the followingclinical situations: in patients with suspected Crohn’sdisease in whom other diagnostic techniques failed, inpatients with established Crohn’s disease, in patientswith disease recurrence after surgical intervention, andin those with inflammatory bowel disease unclassified(IBD-U) [12].

In patients with suspected Crohn’s disease, theauthors found that the available evidence is weak andthe quality of the published studies low. In fact, themajority of studies aimed at evaluating the role ofcapsule endoscopy in patients with suspected Crohn’sdisease: (a) included a heterogeneous group of patients,(b) seldom verified over time the final diagnosis bymeans of other independent diagnostic techniques(e.g., histology), and (c) often used different criteria toclassify the lesions identified. Nevertheless, despitethese limitations, capsule endoscopy seems to besuperior to other diagnostic tools, including SBFTand CT-enterography, in identifying small mucosal

11 Capsule Endoscopy: The Answer to a Challenge 67

lesions. However, the specificity for mucosal lesions islow and Crohn’s disease cannot be diagnosed basedonly on the appearance of the small bowel at capsuleendoscopy. Therefore, in case of suspected small-bowel Crohn’s disease, a cross-sectional imagingexamination should precede capsule endoscopy.

In patients with established Crohn’s disease theauthors found a limited role for capsule endoscopydue to the high risk of complications, particularlycapsule retention (see below). In these patients,capsule endoscopy should be reserved for those withunexplained symptoms when other investigations areinconclusive, if this will alter management. Accord-ingly, radiographic imaging takes precedence oversmall-bowel capsule endoscopy because it canpotentially identify obstructive strictures, extraluminaldisease, and the transmural nature and/or the ana-tomical distribution of the disease. Nevertheless,these statements may need to be revised in the future.

In general, there is growing interest in identifyingpossible predictors of patient outcome in Crohn’s dis-ease, in order to choose the most effective therapeuticstrategy, mainly when biologic drugs are concerned(i.e., top-down vs. step-up strategy). The predictorsthus far identified are young age at onset, specific dis-ease pattern, and small-bowel involvement. Therefore,in the future, at the time of their diagnosis patients withCrohn’s disease may receive a complete and accurateevaluation of the small bowel. In this case, after smallbowel strictures (see below) have been excluded, cap-sule endoscopy would be the tool of choice.

It should be noted that the role of capsule endos-copy also seems to be limited in patients with recur-rence of Crohn’s disease after surgical intervention.Indeed, capsule endoscopy is often not feasiblebecause of the development of de novo or anastomoticstrictures. Thus, for the assessment of postoperativerecurrence of Crohn’s disease, capsule endoscopyshould only be considered if ileocolonoscopy is con-traindicated or unsuccessful.

In patients with IBD-U, capsule endoscopy is betterthan SBFT or enteroclysis in identifying mucosal lesionsconsistent with Crohn’s disease; in this subset ofpatients, there are no data comparing capsule endoscopyand either CT- or MRI-enteroclysis. Therefore, it canonly be stated that capsule endoscopy can be helpful inidentifying mucosal lesions compatible with Crohn’s

disease—although a negative capsule endoscopy doesnot exclude a future diagnosis of the disease.

Recently, capsule endoscopy also has been pro-posed, in the setting of Crohn’s disease, to evaluatemucosal healing after therapy. At the present time,there are several problems with this application: thespecificity of mucosal lesions, problems in locatingfindings along the small bowel, difficulties in sizingfindings, etc.; but this truly exciting and promisingfield deserves further exploration.

11.2.3 Small-Bowel Tumors

When compared with gastric or colonic neoplasms,small-bowel tumors are a rare disease, accounting for1–3% of all primary gastrointestinal tumors. Since theintroduction of capsule endoscopy into clinicalpractice, a few small studies have been published,reporting a frequency of small-bowel tumors rangingbetween 6 and 9%. However, according to larger,recently published studies the frequency is between1.6 and 2.4% among patients undergoing capsuleendoscopy for any clinical reason. In addition, allpublished series on capsule endoscopy in the diagnosisof small-bowel tumors underlined that the main clin-ical indication for the procedure in these patients wasOGIB [13].

Small-bowel tumors are seen at capsule endos-copy, regardless of their histological type (i.e.,adenocarcinomas, lymphomas, neuroendocrine tumors,gastrointestinal stromal tumors), either as stenoses,polyps, or masses. Therefore, it is not possible todistinguish between different tumors based on theirappearance at capsule endoscopy.

Although there are no studies formally evaluatingthe role of capsule endoscopy in the diagnosticalgorithm of small-bowel tumors, in light of the abovedata it can be argued that when there is high clinicalsuspicion of a small-bowel tumor, such as in case ofweight loss and/or obstruction and/or severe anemia, across-sectional imaging study of the small bowelshould be preferred. Conversely, in reading a capsuleendoscopy, when the leading symptom is OGIB, itshould be kept in mind that in about 3% of thepatients a small-bowel tumor can be identified only bymeans of this modality.

68 E. Rondonotti and R. de Franchis

11.2.4 Celiac Disease

A few studies explored the performance of capsuleendoscopy versus the histological evaluation of small-bowel biopsies taken during gastroscopy in patientswith suspected celiac disease. Although all of thesestudies showed high agreement between these twotechniques (sensitivity of capsule endoscopy 85–90%),traditional gastroscopy with duodenal biopsies remainsthe method of choice to assess mucosal atrophy inpatients with suspected celiac disease [14]. However,capsule endoscopy can be a suitable tool in patients withhigh clinical suspicion of celiac disease who are unableor unwilling to undergo traditional endoscopy. Cur-rently, the main obstacle to the extensive use of capsuleendoscopy in the diagnosis of celiac disease is the highcost of the procedure, but also, as highlighted by severalauthors, the difficulty in grading mucosal atrophy.

Capsule endoscopy has also been used in patientswith established celiac disease who have maintained agluten-free diet but with symptoms of recurrence/persistence or with poor histological recovery, thusnecessitating a small-bowel evaluation. While theresults of these studies are controversial, the key pointseems to be patient selection. For patients with severesymptoms or the appearance of new symptoms suchas anemia, capsule endoscopy can play a role indiagnosing the complications of celiac disease,including ulcerative jejunitis, or in identifying otherdiseases, e.g., small-bowel angioectasias. Conversely,in celiac disease patients on a gluten-free diet withmild symptoms such as abdominal pain but withoutany alarm symptoms, the role of capsule endoscopy islimited since it shows only the different extents ofmucosal atrophy and does not seem to significantlyimpact further management strategies.

Capsule endoscopy does, however, add significantclinical information affecting further managementmostly in patients with refractory celiac disease(which is a very rare condition). In these patients,capsule endoscopy can easily identify enteropathy-associated T-cell lymphomas or ulcerative jejunitis,but it does not allow the acquisition of biopsies toconfirm the diagnosis. In these cases, the combinationof a diagnostic procedure, such as capsule endoscopyor cross-sectional imaging, with device-assistedenteroscopy or other therapeutic procedures allows afinal diagnosis to be reached and any further thera-peutic strategy to be planned.

11.2.5 Miscellanea

Abdominal pain as a possible indication for capsuleendoscopy is still largely debated. Although small-bowel tumors have sometimes been identified inpatients undergoing capsule endoscopy for unex-plained abdominal pain, in these patients the findingsare negative in about 80% of cases [15]. By contrast,when chronic abdominal pain is associated with othersigns or symptoms (weight loss[10% of body weight,inflammation shown by laboratory tests, chronicanemia, or suspected mid-gastrointestinal bleeding),relevant, or potentially relevant, findings are diagnosedby capsule endoscopy in about 60% of cases [16].

Capsule endoscopy has also been used withpromising results in other rare clinical conditions,such as small-bowel transplantation, graft versus hostdisease, protein-losing enteropathy, primitive lymph-angectasia (mostly in the pediatric population),Whipple disease, and irritable bowel syndrome (withclinical suspicion of celiac disease).

11.3 Open Issues

In the last 10 years, as the use of capsule endoscopyhas become routine in clinical practice, the technicaland clinical limitations of this technique have becomeapparent. In fact, at the present time, capsule endos-copy is a passive imaging modality that cannot bedriven by the operator. Furthermore, it is unable totake biopsies and has a limited power supply (8–12 h,depending on the equipment). Unfortunately, thesetechnical aspects significantly impact the clinicalperformance of capsule endoscopy.

Findings identified at capsule endoscopy aregenerally not disease-specific and have to be inter-preted in the context of the clinical setting, thereason for the referral, and the medications taken bythe patients. In addition, in 10–13% of healthysubjects undergoing capsule endoscopy small non-specific mucosal lesions (such as mucosal breaks orerosions) are found [17].

Several studies clearly demonstrated that capsuleendoscopy can miss small-bowel lesions and, some-times, even large small-bowel tumors. There are noobvious explanations for this inconvenience but theangle of view (140–156�), the quick passage of thedevice through some tracts of the small bowel,

11 Capsule Endoscopy: The Answer to a Challenge 69

especially the proximal small bowel, and the presenceof food and debris inside the lumen have beensuggested.

As far as the cleanliness of the small bowel isconcerned, despite more than 10 years of experiencewith capsule endoscopy there is still no standardprotocol for bowel preparation. A recently publishedmeta-analysis suggested the administration of 2 L ofPEG-based solutions the day before the proce-dure [18]. However, the weaknesses of the studiesincluded in the meta-analysis and the results of newrecently published studies significantly decrease thestrength of this recommendation.

Even when capsule endoscopy identifies small-bowel lesions, the inter-observer agreement amongreaders in describing these findings is quite low,especially for relevant findings such as polyps ormasses [19]. These discrepancies often necessitatefurther diagnostic examinations in order to betterclarify the diagnosis, thus increasing the number ofprocedures performed and the costs.

Last, but not least, in about 1–2% of patientsundergoing capsule endoscopy for any clinical reasonthe capsule can be retained at the site of a previouslyunknown small-bowel stricture. Table 11.1 shows thefrequency of capsule retention depending on theclinical indication for the procedure [20]. Unfortu-nately, it is extremely difficult to prevent this com-plication, including by the routine use of radiologicalexaminations before capsule endoscopy. Clearly, toavoid this complication, patients at risk must beidentified, i.e., those with known Crohn’s disease,and, when possible, they should be tested with a blinddissolvable capsule (Agile Patency Capsule, GivenImaging Ltd., Yoqneam, Israel). Once the AgilePatency Capsule is excreted intact, the small-bowelexamination with the ‘‘regular’’ capsule can be safely

performed. Nevertheless, in performing this test itmust be noted that the size of this particular dissolv-able capsule is compatible with only three of the fourcapsules currently available on the market.

11.4 Conclusions

The advent of capsule endoscopy was a revolution inthe field of endoscopy providing high-quality endo-scopic images of the small bowel. In the 10 years inwhich capsule endoscopy has been used in clinicalpractice for studies of the small bowel, this devicehas established its superiority over other diagnostictools previously used for this purpose. Capsuleendoscopy does not require sedation, can be easilyperformed, and is well tolerated and safe; yeteveryday experience has also highlighted its limita-tions (low specificity for mucosal lesions, potentialcapsule retention). In view of these advantages anddisadvantages, capsule endoscopy can be granted adefinitive place for some clinical conditions, espe-cially OGIB and clinically suspected Crohn’sdisease. In other applications, the device is eitherstill under evaluation (established Crohn’s disease)or not recommended (in the diagnosis of celiacdisease). It is important to keep in mind that, whencapsule endoscopy was introduced into clinicalpractice, it was the first imaging modality able toperform studies of the small bowel.

References

1. Rondonotti E, Villa F, Mulder CJ et al (2007) Small bowelcapsule endoscopy in 2007: indications, risks andlimitations. World J Gastroenterol 14(13):6140–6149

2. Liao Z, Gao R, Li F et al (2010) Fields of applications,diagnostic yields and findings of OMOM capsule endos-copy in 2400 Chinese patients. World J Gastroenterol16:2669–2676

3. Liao Z, Gao R, Xu C et al (2010) Indications and detection,completion, and retention rates of small-bowel capsuleendoscopy: a systematic review. Gastrointest Endosc7:280–286

4. Rondonotti E, Soncini M, Girelli C et al (2010) Smallbowel capsule endoscopy in clinical practice: a multicenter7 year survey. Eur J Gastroenterol Hepatol 22:1380–1386

5. Scapa E, Jacob H, Lewkowicz S et al (2002) Initialexperience of wireless-capsule endoscopy for evaluatingoccult gastrointestinal bleeding and suspected small bowelpathology. Am J Gastroenterol 97:2776–2779

Table 11.1 Frequency of capsule retention as a function of theclinical indications for capsule endoscopy (Modified from [20])

Indication for capsule endoscopy Retention rate (%)

Healthy controls 0

Obscure GI bleeding 1–2

Suspected Crohn’s disease 1–3

Established Crohn’s disease 5–13

Small-bowel tumors 10–25

Intestinal obstruction 20

70 E. Rondonotti and R. de Franchis

6. Raju GS, Gerson L, Das A et al (2007) Americangastroenterological association (AGA) institute technicalreview on obscure gastrointestinal bleeding. Gastroen-terology 133:1697–1717

7. Marmo R, Rotondano G, Piscopo R et al (2005) Meta-analysis: capsule enteroscopy vs. conventional modalitiesin diagnosis of small bowel diseases. Aliment PharmacolTher 22:595–604

8. Sidhu R, Sanders DS, Kapur K et al (2009) Factorspredicting the diagnostic yield and intervention in obscuregastrointestinal bleeding investigated using capsuleendoscopy. J Gastrointestin Liver Dis 18:273–278

9. Carey EJ, Leighton JA, Heigh RI et al (2007) A single-center experience of 260 consecutive patients undergoingcapsule endoscopy for obscure gastrointestinal bleeding.Am J Gastroenterol 102:89–95

10. ASGE Standards of Practice Committee, Fisher L, LeeKrinsky M et al (2010) The role of endoscopy in themanagement of obscure GI bleeding. Gastrointest Endosc72:471–479

11. Lai LH, Wong GL, Chow DK et al (2006) Long-termfollow-up of patients with obscure gastrointestinal bleedingafter negative capsule endoscopy. Am J Gastroenterol101:1224–1228

12. Bourreille A, Ignjatovic A, Aabakken L et al (2009) Role ofsmall-bowel endoscopy in the management of patients withinflammatory bowel disease: an international OMED-ECCO consensus. Endoscopy 41:618–637

13. Pennazio M, Rondonotti E, de Franchis R (2008) Capsuleendoscopy in neoplastic diseases. World J Gastroenterol14:5245–5253

14. El-Matary W, Huynh H, Vandermeer B (2009) Diagnosticcharacteristics of given video capsule endoscopy in diag-nosis of celiac disease: a meta-analysis. J LaparoendoscAdv Surg Tech A 19:815–820

15. Spada C, Pirozzi GA, Riccioni ME et al (2006) Capsuleendoscopy in patients with chronic abdominal pain. DigLiver Dis 38:696–698

16. May A, Manner H, Schneider M et al (2007) Prospectivemulticenter trial of capsule endoscopy in patients withchronic abdominal pain, diarrhea and other signs andsymptoms (CEDAP-plus study). Endoscopy 39:606–612

17. Goldstein JL, Eisen GM, Lewis B et al (2005) Videocapsule endoscopy to prospectively assess small bowelinjury with celecoxib, naproxen plus omeprazole, andplacebo. Clin Gastroenterol Hepatol 3:133–141

18. Rokkas T, Papaxoinis K, Triantafyllou K et al (2009) Doespurgative preparation influence the diagnostic yield ofsmall bowel video capsule endoscopy? A meta-analysis.Am J Gastroenterol 104:219–227

19. Pezzoli A, Cannizzaro R, Pennazio M et al (2011)Interobserver agreement in describing video capsuleendoscopy findings: a multicentre prospective study. DigLiver Dis 43:126–131

20. Pennazio M (2006) Capsule endoscopy: where are we after6 years of clinical use? Dig Liver Dis 38:867–878

11 Capsule Endoscopy: The Answer to a Challenge 71

12Double-Balloon Enteroscopy

Alessandro Mussetto and Tino Casetti

12.1 Enteroscopy: An Overview

The twentyfirst century has marked the onset of arevolution in the approach to small-bowel diseases. Inparticular, the introduction of capsule endoscopy [1]and double-balloon enteroscopy [2, 3] has enabled theendoscopic examination of the entire small bowel,a task that has always been difficult because of thelength of the small bowel and its tortuous anatomy inthe abdominal cavity.

Along with the increasingly widespread use of cap-sule endoscopy, the increased interest in this technol-ogy, and the recognition of its numerous applications,has been the acknowledgement of its limitations: firstly,capsule endoscopy does not allow for therapeutic pro-cedures. Secondly, the examination can be limited byincompleteness, poor bowel preparation or limitedmucosal visualization, rapid transit through particularsegments, and the unidirectional field of view.

Enteroscopy, orally or trans-rectally, can obtainbiopsies and/or allows for simultaneous therapeuticintervention, such as the treatment of bleedinglesions, the removal of foreign bodies (often retainedcapsules), polypectomy, and stricture dilation.Lesions can be tattooed to target subsequent surgicalinterventions. In addition, enteroscopy can be appliedto the treatment and diagnosis of biliary-tract diseasesthrough the bypassed tract, such as a Roux-en-Y

afferent limb. Minor indications are: persistent irondeficiency anemia and/or bleeding in patients afternegative capsule endoscopy; unexplained malab-sorption or diarrhea; refractory celiac disease; orradiographic abnormalities of the small bowel.

Early enteroscopic procedures, such as rope-wayenteroscopy and sonde enteroscopy, have largelybeen abandoned because of their invasive and time-consuming nature. Instead, they have been replacedby balloon-assisted enteroscopy (double- or single-balloon or NaviAid BGE method) and spiral enter-oscopy. Intraoperative enteroscopy, long consideredthe gold standard of enteroscopy, is also performedless frequently. However, not all lesions can be trea-ted with endoscopic therapy, and a guide to thesurgical approach can be useful.

Most of the published literature has examineddouble-balloon enteroscopy, which was the first of thenew procedures to be introduced. It is also the subjectof this chapter.

12.2 Double-Balloon Enteroscopy

The first report of double-balloon enteroscopy (DBE)appeared in 2001 [2] followed by the introduction of adedicated system (Fujinon Inc.) in 2003 [3]. DBE isnow available worldwide. The first internationalworkshop on DBE was held in Japan in August 2006,with the first Italian DBE workshop held in Cervia inthe same year and planned by our G.I. Unit.

The principle of DBE starts from the knowledgethat insertion would be easier if the intestinal tractcould be straightened. In fact, when the endoscopebends in complex fashion or forms a loop, the force

T. Casetti (&)Department of Gastroenterology,Santa Maria delle Croci Hospital, Ravenna, Italye-mail: t.casetti@ausl.ra.it

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_12, � Springer-Verlag Italia 2012 73

applied to the shaft of the instrument is nottransmitted to the tip, which, therefore, cannot beadvanced further.

12.2.1 Double-Balloon Endoscopy Systems

The DBE system (Fig. 12.1) comprises an endoscopeto which an inflatable balloon can be attached at thetip, a flexible overtube with a second balloon, alwaysat the tip, and a balloon controller (automatic pressurecontrol) that controls the inflation/deflation of bothballoons. A light source and a monitor are alsorequired.

Two types of DBE systems are currently available.The standard system consists of a thin endoscope withan 8.5 mm diameter and a 200 cm working lengthwith a 2.2 mm operating channel (Fujinon EN-450P5),a 145 cm soft overtube with an outer diameter of12.2 mm, and a specifically designed pump. A thera-peutic double-balloon endoscope (Fujinon EN-450T5)is also available. The Fujinon EN-450T5 has a largerouter diameter (9.4 mm), in order to accommodate alarger channel (2.8 mm in diameter), with a dedicatedovertube.

12.2.2 Technique

The DBE procedure can be peformed using either theoral or the anal approach, with the patient under deepor conscious sedation (deep sedation is recommended,

particularly for the oral approach). From the oralroute, the depth of insertion and the diagnostic yieldare greater than obtained with push enteroscopy(230 vs. 80 cm) [4].

In the oral approach, a single operator initiatesinsertion of the endoscope. When the endoscope ispassed from the incisura to the antrum, the assistantmoves the overtube to the white line marked on theendoscope. The line represents a stopping pointbeyond which the overtube should not be advanced orthe endoscope withdrawn: this prevents the overtubefrom shearing off the endoscope balloon. Next, theoperator inserts the endoscope from the descendinglimb of the duodenum to the third portion of theduodenum and inflates the balloon at the tip ofthe endoscope. The second operator then moves theovertube along the endoscope to the region of thewhite line and inflates the overtube balloon, so thatthe entire apparatus is secured in the intestine, withboth balloons inflated. The endoscope is furtherinserted after its balloon is deflated, with the balloonagain inflated at the deepest point (in many patients,this is over the ligament of Treitz); again, the secondoperator moves the overtube along the endoscope tothe white mark and inflates the overtube balloon.After this second stroke, shortening of the smallintestine is performed, withdrawing the scope andovertube together, pleating the bowel ‘‘concertina-style’’ over the overtube. Subsequent inflation anddeflation of the two balloons allows the instrument tobe advanced (Fig. 12.2).

When the desired insertion distance is achieved,the intestine can be marked with a tattoo if there issuspicion of more distal lesions. Withdrawal is initi-ated with the endoscope balloon inflated, and theovertube balloon deflated. The overtube is retractedand then the overtube balloon is reinflated. Endoscoperetraction is always performed with the overtubesecured by its balloon, to prevent uncontrolled lossof depth.

For the anal approach, a colonoscopy preparationis required. The endoscope and the overtube areadvanced to the cecum using the double-balloonpush–pull system described above. Then, with theovertube balloon inflated, the endoscope is advancedacross the ileocecal valve and its balloon is inflatedwithin the ileum. The overtube is then advanced alongthe endoscope and into the ileum and the push–pullprocedure continued [5] (Fig. 12.3).

Fig. 12.1 Double-balloon endoscopy (DBE) system ofFujinon Inc

74 A. Mussetto and T. Casetti

DBE is usually performed under fluoroscopicguidance, if the operator is not familiar with thetechnique. In a recent article, Manner et al. concludedthat, compared with non-fluoroscopically guidedprocedures, fluoroscopy during DBE via the oral routedoes not provide a significant gain in insertion depth,advancement time, or diagnostic yield [6].

12.3 Indications

• DBE following capsule endoscopy or radiologicalimaging: the most common indication and gener-ally performed for obscure gastrointestinal bleeding(OGIB) in patients in whom further diagnostic testsor treatment are indicated.

• Mid-gastrointestinal bleeding: in patients withknown mid-gastrointestinal bleeding for endo-scopic hemostasis.

• Diagnosis and treatment of known or suspectedstenoses (e.g., Crohn’s disease).

• Mass lesions: endoscopic diagnosis and histologicconfirmation of tumors or masses detected by otherimaging modalities.

• Pre-surgical tattooing for patients undergoing,e.g., small-bowel resection.

• Removal of foreign bodies from the small intestine(e.g., retained endoscopy capsule).

• Endoscopic access in patients with postoperativealtered anatomy: including endoscopic retrogradecholangiopancreatography after Billroth II orRoux-en-Y operation.

• In difficult colonoscopy cases.

12.4 Results Obtained in the MajorIndications

12.4.1 Obscure Gastrointestinal Bleeding

According to large published studies, the diagnosticyield of DBE in OGIB ranges from 50 to 75%.Recently, a study of 108 patients with OGIB

Fig. 12.3 DBE technique for anal insertion (Courtesy ofTomonori Yano, Jichi Medical University, Japan)

Fig. 12.2 DBE technique for oral insertion (Courtesy ofTomonori Yano, Jichi Medical University, Japan)

12 Double-Balloon Enteroscopy 75

suggested that early DBE is critical to identify thesource of bleeding in these patients; yields were sig-nificantly higher when the indication was overtongoing OGIB (100%) than with overt previous(48.4%) or occult OGIB (42.1%) [7]. The causes ofbleeding in series studied in Eastern countries areoften ulcers or tumors [8], whereas in European andNorth/South American studies the most commondiagnostic finding is a vascular lesion [9, 10](Fig. 12.4).

In a recent retrospective study from Japan, DBEdetected bleeding sources in 155 of 200 patients(78%) with OGIB [11]. Small-intestinal ulcers anderosions were the most frequent finding. The timeelapsed between the bleeding episode and the endo-scopic evaluation was crucial: the yield was higher inthe patients who underwent DBE within one month ofan episode of overt bleeding compared with patientswho did not (84 vs. 57%). The overall rate of bleedingcontrol was 64%. However, the diagnostic yield wassimilar in DBE and capsule endoscopy in a recentmeta-analysis considering small-bowel disease,including OGIB, with a pooled overall yield of 57 and60%, respectively [12]. Another study [13] comparedconcordance between capsule endoscopy and DBE inOGIB and showed agreement between the two tech-niques, especially for polyps or tumors.

12.4.2 Crohn’s Disease

Crohn’s disease can be diagnosed using DBE, ashistological corroboration is available. Nonetheless,

there are not enough data to recommend DBE in thissetting, unless conventional studies (ileocolonoscopyand radiographic imaging) have been inconclusiveand an accurate histological diagnosis would alterdisease management. Thus, DBE only has a place inpatients with obstructive Crohn’s disease, as it allowsdilation to be performed [14].

12.4.3 Celiac Disease and UnexplainedMalabsorption

One paper specifically described the value of DBE inrefractory celiac disease [15]; the authors found majorlesions (enteropathy-associated T-cell lymphoma orulcerative jejunitis) in 33% of the patients. Fry andcolleagues [16] used DBE to explain the etiologyof malabsorption in 42% of a small population(12 patients).

12.4.4 Tumors

Small-bowel tumors were found in 2.4% of a large seriesrecently studied with video capsule endoscopy [17]. In ameta-analysis, the diagnostic yield for small-bowellesions was comparable using DBE and capsuleendoscopy [12]; however, DBE is an effective tool forobtaining biopsies for histological diagnosis, formarking lesions before surgery, and for performingtherapeutic interventions such as polyp resection orstenting (Fig. 12.5).

Fig. 12.4 AngiodyplasiaFig. 12.5 Ileal adenocarcinoma

76 A. Mussetto and T. Casetti

12.5 Route Selection

The localization of a lesion identified at capsuleendoscopy is challenging. If DBE is needed, thedecision must be made whether to reach the lesionfrom an oral or a trans-rectal approach. There arecurrently few published data to guide clinicaldecision-making. Gay and colleagues [18] found thatcapsule endoscopy reliably indicated the need for atrans-rectal DBE approach if the transit time to reacha lesion was C75% of the total transit time. Li et al. [19]suggested instead a ratio based on a percentage of thepylorus to ileocecal valve time. Lesions with a timeratio [0.6 were assumed to be located in the middleor distal ileum and should therefore be readilyreached by a trans-rectal route.

Clearly, the choice of the endoscopic insertionroute remains an important issue and can be difficulteven with information provided by video capsuleendoscopy and/or radiological imaging.

12.6 Complications

With the increasingly widespread use of DBE, com-plications ensuing from the procedure have beenreported. In a large multicenter study, the incidence ofcomplications was 0.8% for diagnostic DBE and 4.3%for therapeutic DBE; there were no fatal cases. Theonset of pancreatitis, albeit of unknown etiology,following DBE was reported in 0.3% of cases [20].A recent review concluded that the most probablecause of pancreatitis in this setting is mechanicalstraining of the endoscope with the overtube on thepancreas or in the papillary area [21]. The usualrecommendation is to avoid inflating the balloonswithin the duodenum.

12.7 Future Perspectives

With further technological advances and increasingexperience, DBE is expected to be useful not only in thediagnosis and treatment of intestinal diseases but also inclarifying their underlying etiologies. Since DBE alsocan be used to obtain biopsy tissue, its applicationsinclude not only histological but also microbiologicaland molecular biological investigations. Furthermore,

DBE will likely contribute to the development of newmedical agents for treating small-intestinal disease [22].

References

1. Iddan G, Meron G, Glukhovsky A et al (2000) Wirelesscapsule endoscopy. Nature 405:417

2. Yamamoto H, Sekine Y, Sato Y et al (2001) Totalenteroscopy with a nonsurgical steerable double-balloonmethod. Gastrointest Endosc 53:216–220

3. Yamamoto H, Yano T, Kita H et al (2003) New system ofdouble-balloon enteroscopy for diagnosis and treatment ofsmall intestinal disorders. Gastroenterology 125:1556

4. May A, Nachbar L, Schneider M, Ell C (2006) Prospectivecomparison of push enteroscopy and push-and-pullenteroscopy in patients with suspected small-bowelbleeding. Am J Gastroenterol 101(9):2016–2024

5. May A, Nachbar L, Wardak A et al (2003) Double-balloonenteroscopy: preliminary experience in patients withobscure gastrointestinal bleeding or chronic abdominalpain. Endoscopy 35:985–991

6. Manner H, May A, Pohl J et al (2010) Impact offluoroscopy on oral double-balloon enteroscopy: results ofa randomized trial in 156 patients. Endoscopy42(10):820–826

7. Tanaka S, Mitsui K, Yamada Y et al (2008) Diagnosticyield of double-balloon endoscopy in patients with obscureGI bleeding. Gastrointest Endosc 68(4):683–691

8. Chen LH, Chen WG, Cao HJ et al (2010) Double-balloonenteroscopy for obscure gastrointestinal bleeding:a singlecenter experience in China. World J Gastroenterol16(13):1655

9. Madisch A, Schmolders J, Brückner S et al (2008) Lessfavorable clinical outcome after diagnostic and inter-ventional double balloon enteroscopy in patients withsuspected small-bowel bleeding? Endoscopy 40(9):731–734

10. May A, Nachbar L, Wardak A et al (2003) Double-balloonenteroscopy: preliminary experience in patients withobscure gastrointestinal bleeding or chronic abdominalpain. Endoscopy 35(12):985–991

11. Shinozaki S, Yamamoto H, Yano T et al (2010) Long-termoutcome of patients with obscure gastrointestinal bleedinginvestigated by double-balloon endoscopy. ClinGastroenterol Hepatol 8(2):151–158

12. Pasha SF, Leighton JA, Das A et al (2008) Double-balloonenteroscopy and capsule endoscopy have comparablediagnostic yield in small-bowel disease: a metaanalysis.Clin Gastroenterol Hepatol 6(6):671–676

13. Marmo R, Rotondano G, Casetti T et al (2009) Degree ofconcordance between double-balloon enteroscopy andcapsule endoscopy in obscure gastrointestinal bleeding:a multicenter study. Endoscopy 41(7):587–592

14. Bourreille A et al (2009) Role of small-bowel endoscopy inIBD: international OMED–ECCO consensus. Endoscopy41:618–637

15. Hadithi M, Al-toma A, Oudejans J et al (2007) The value ofdouble-balloon enteroscopy in patients with refractoryceliac disease. Am J Gastroenterol 102(5):987–996

12 Double-Balloon Enteroscopy 77

16. Fry LC, Bellutti M, Neumann H et al (2008) Utility ofdouble-balloon enteroscopy for the evaluation ofmalabsorption. Dig Dis 26(2):134–139

17. Rondonotti E, Pennazio M et al (2008) Small-bowelneoplasms in patients undergoing video capsule endoscopy:a multicenter European study. Endoscopy 40(6):488–495

18. Gay G, Delvaux M, Fassler I (2006) Outcome of capsuleendoscopy in determining indication and route for push andpull enteroscopy. Endoscopy 38:49–58

19. Li X et al (2009) Predictive role of capsule endoscopy onthe insertion route of double-balloon enteroscopy.Endoscopy 41:762–766

20. Mensink PB, Haringsma J, Kucharzik T et al (2007)Complications of double balloon enteroscopy:a multicenter survey. Endoscopy 39:613–615

21. Kopacova M, Tacheci I, Rejchrt S et al (2010) Doubleballoon enteroscopy and acute pancreatitis. World JGastroenterol 16(19):2331–2340

22. Sunada K, Yamamoto H (2009) Double-balloonendoscopy: past, present, and future. J Gastroenterol44:1–12

78 A. Mussetto and T. Casetti

13Single-Balloon Enteroscopy

Mauro Manno, Raffaele Manta, and Rita Conigliaro

13.1 Background

The small bowel was long considered a black box forendoscopists because it could not be routinely exam-ined by way of endoscopic techniques. Standardendoscopy using traditional upper endoscopes canreach up to the first, second, or third portions of theduodenum while push enteroscopy typically reachesdistances of about 80 cm past the ligament of Treitz.Colonoscopy may cover a distance of 10–20 cmbeyond the ileocecal valve. Thus, most of the smallbowel is inaccessible by traditional endoscopic means.In addition, radiographic studies have significant lim-itations with regard to diagnostic yield, and surgery isan invasive alternative. These limitations have beenovercome through the development of balloon enter-oscopy, which has since become established throughoutthe world for diagnostic and therapeutic examinationsof the small bowel. Compared with other imagingprocedures (e.g., capsule endoscopy and CT scan), themain advantages of balloon enteroscopy are that itallows histologic sampling and endoscopic therapy.With appropriate patient selection, a diagnostic yieldfor relevant pathologic findings of 70–80% is achieved,while endoscopic therapy can be performed in morethan 50% of patients.

13.2 The Single-Balloon EnteroscopeSystem

The single-balloon enteroscope (SBE; Olympus,Tokyo, Japan) system was developed in 2006 andintroduced into the commercial market in 2007. Therationale behind its development was: (1) to reducethe learning curve for balloon-assisted enteroscopy,(2) to avoid the difficulty encountered in double-bal-loon enteroscopy (DBE) of attaching the enteroscopeballoon to the distal tip of the scope, and (3) toeliminate the requirement of inflating and deflatingtwo balloons in multiple steps, as is the case with thecurrent DBE insertion technique.

The SBE system consists of the SIF-Q180 entero-scope, an over tube balloon control unit (OBCU,Olympus balloon control unit), and a disposable siliconesplinting tube with balloon (ST-SB1) (Figs. 13.1, 13.2,and 13.3). The enteroscope is a high-resolution videoendoscope that works with current Olympus EVIS pro-cessors and the EVIS EXERA II system to allow narrow-band imaging. It has an outer diameter of 9.2 mm, aworking length of 2,000 mm, and a wide operatingchannel size of 2.8 mm. The field of view is 140�.

The splinting tube is an over tube with an inflatableballoon affixed at its distal tip, both in latex-freesilicone. Radiopaque material is used in the distal endof the ST-SB1 to allow confirmation of the splintingtube’s tip under fluoroscopy, further enhancing inser-tion performance into the deep small intestine. Theinner diameter of the tube is 11 mm, the outer diameteris 13.2 mm, the working length is 1,320 mm, and thetotal length is 1,400 mm. The addition of a smallamount of water through a small port on the proximalend of the splinting tube activates the hydrophilic

M. Manno (&)Gastroenterology and Digestive Endoscopy Unit,Nuovo Ospedale Civile S. Agostino-Estense,Baggiovara di Modena (MO), Italye-mail: m.manno@ausl.mo.it

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_13, � Springer-Verlag Italia 2012 79

coating, thus avoiding friction between the over tubeand the enteroscope. Additional water can be flushedinto a dedicated port throughout the procedure, in orderto reduce friction or wash away debris collectedbetween the enteroscope and the splinting tube. Theballoon is inflated and deflated by a balloon control unitwith a safety pressure setting range from -6.0 to+5.4 kPa, allowing atraumatic traction on the smallbowel mucosa. The OBCU has one button for inflation,one button for deflation, and a third control for thepause/cancel feature. The balloon pump controller

should be turned on before the procedure is started toensure that the balloon inflates correctly.

13.3 Preparation

No preparation is generally recommended in mostcases for SBE performed using an oral approach,except a minimum 12 h fast by the patient. However, inthe author’s institution, patients are administered 2 Lof a polyethylene glycol (PEG) bowel preparationsolution for the anterograde approach and the standard4 L bowel preparation for retrograde examinations.Limited bowel preparation for oral examinations couldimprove visibility in the small bowel, where dark bileand debris may compromise deep enteroscopy, as forcapsule examinations.

13.4 Sedation

For anterograde SBE, deep monitored sedation (e.g.,with propofol) or general anesthesia with intubation iswidely accepted. For the retrograde approach, con-scious sedation as for colonoscopy is sufficient inmost cases. During withdrawal of the endoscope andduring therapeutic interventions, the administration ofspasmolytics might improve visualization of the smallbowel mucosa by reducing motility [1].

Fig. 13.2 Disposable silicone splinting tube with balloon(ST-SB1) (Image courtesy of Olympus Medical SystemsCorporation, Japan, with permission)

Fig. 13.3 Single-balloon enteroscope with over tube (Imagecourtesy of Olympus Medical Systems Corporation, Japan, withpermission)

Fig. 13.1 The Olympus single-balloon enteroscope system(Image courtesy of Olympus Medical Systems Corporation,Japan, with permission)

80 M. Manno et al.

13.5 Insufflation of Gas

As balloon enteroscopies are lengthy procedures,large volumes of air are usually insufflated, leading tosignificant distension of the small bowel. Indeed, oneof the main technical challenges of balloon-assistedenteroscopy is the increasing amount of intraluminalgas, which leads to failure of the procedure. Carbondioxide (CO2), unlike standard air, is rapidly absorbedfrom the bowel. Preliminary data indicate that bowelinsufflation with CO2 instead of air enhances patientcomfort and decreases the need for sedation [2].Indeed, a randomized, double-blind trial showed thatinsufflation with CO2 is safe, reduces patient dis-comfort, and significantly improves intubation depth[3]. However, these results need to be confirmed byother studies before CO2 can be recommended as thestandard insufflation gas in balloon enteroscopy.

13.6 Determination of the PrimaryInsertion Route

The choice of an oral versus anal route for the pri-mary procedure depends on the suspected location ofthe pathology within the small bowel. In patients inwhom balloon-assisted enteroscopy is performedsecondary to pathological findings at capsule endos-copy, the latter can obviously indicate the route forballoon-assisted enteroscopy, thus avoiding doubleprocedures. Findings located in the upper two-thirdsaccording to the capsule endoscopy recording indicateballoon-assisted enteroscopy via the oral route, and inthe lower third via the anal approach [4].

13.7 Fluoroscopic Control

Fluoroscopy can be beneficial during the initial 10–20DBE cases, to observe advancement and reduction ofthe enteroscope and as an aid to determine whenlooping is present and how to solve it; however, noclinical benefits in the use of fluoroscopy have beendemonstrated past the initial learning cases [5]. Forsome patients with a surgically modified anatomy and

for those undergoing therapeutic procedures such asdilations, flexible enteroscopy usually requires fluo-roscopic guidance.

13.8 Procedure

13.8.1 Balloon-Assisted Enteroscopyby the Anterograde Approach

The enteroscope, without over tube, is initially passedinto the esophagus with the same technique used for astandard upper endoscopy. After intubation of thepylorus, the enteroscope is pushed into the duodenumuntil forward advancement is no longer possible. Byangulating the tip of the enteroscope in order to hookthe intestine, the operator can gently advance the overtube over the enteroscope to the point of maximalinsertion, located at 155 cm, where a white line ispresent on the scope. In order to shorten the intestineand to advance the endoscope into the small bowel,the endoscope and the over tube, with inflatedballoon, are withdrawn together. Then, with the bal-loon still inflated in order to maintain position, theendoscope is pushed maximally into the small bowel.Balloon inflation allows the pushing force applied bythe operator to the endoscope to be transmitted to thedistal end of the endoscope without further stretchingof the intestine. The repetition of these maneuversguarantees progression of the endoscope and explo-ration of the small bowel. This is the conventionaltechnique for advancing the endoscope into the smallbowel [6] (Fig. 13.4).

Modifications of the SBE insertion technique havebeen proposed. Hartmann and colleagues described analternative method of SBE insertion (simultaneoustechnique) that consists of withdrawing only theinflated over tube in order to shorten the intestine, andsimultaneously pushing the endoscope as deep aspossible into the small bowel. When the splinting-tube balloon is near the end of the endoscope, ratherthan performing the ‘‘pull back maneuver’’ with thesplinting tube and angulated scope tip, the angulationis released and the endoscope steered to find thelumen. The over tube, with the balloon still inflated, is

13 Single-Balloon Enteroscopy 81

pulled back while the endoscope is simultaneouslypushed forward. These investigators found that thismethod works best with two examiners and is moreefficient, without sacrificing the depth of insertion orsafety [7]. Although arriving at this alternativemethod independently, the author and his colleagueshave performed four procedures using the conven-tional technique described by Tsujikawa and fourprocedures using the alternative simultaneous tech-nique, with the aim of prospectively evaluating them.We found that the alternative method allowed a lowermean procedure time (58.3 vs. 65.9 min for the oralapproach and 66.4 vs. 74.1 min for the anal approach,using the alternative technique and the conventionaltechnique, respectively). Moreover, the depth ofinsertion did not differ significantly between theconventional and alternative techniques (240 vs.250 cm for the oral approach and 180 vs. 160 cm forthe anal approach, using the alternative technique andthe conventional techniques, respectively). Theseresults did not correlate with the skill of the operators,

who were the same two operators already experiencedin DBE [8]. Of course, these two techniques can bealternately used in the same exam.

During the majority of examinations, forwardadvancement is at some point no longer possible. Themaximal depth of insertion will be reached earlier inpatients with adhesions from prior surgeries or due toother inflammatory disorders. At the point of maximalinsertion, the area should be marked with a tattoo ofIndia ink, injected with a sclerotherapy needle;alternatively, a clip can be positioned. This markercan then be visualized during subsequent capsuleendoscopy examination or balloon-assisted enteros-copy performed during the opposite approach. Totalenteroscopy is achieved when a balloon- assistedenteroscopy examination performed from the oppo-site approach visualizes the marker placed during theinitial examination.

To estimate the depth of insertion, the methodproposed by May et al. can be used, recording dataon a standardized documentation sheet. This method

Fig. 13.4 Representativescheme of single-balloonenteroscopy techniques.(Illustration provided by theauthor)

82 M. Manno et al.

was validated in an animal model during trainingcourses and shown to be accurate, with a meandeviation of less than 10%. For each advancementof the enteroscope, the distance traversed, usuallybetween 20 and 40 cm, is recorded. Any portion ofan advancement that is lost during a reductionmanoeuvre is then subtracted from this value.Alternatively, counting folds in 10 cm incrementscan estimate the depth of insertion during with-drawal [9].

Once the point of maximal insertion is reachedand a marker is placed, the enteroscope can begradually withdrawn with use of the SBE system.The over tube is gently withdrawn backward towardthe proximal end of the enteroscope without movingthe enteroscope until the over tube is at the shaft ofthe enteroscope. Next, the over tube balloon isinflated and the enteroscope slowly withdrawn untilit reaches the distal end of the over tube. With thistechnique, the enteroscope can be withdrawn in acontrolled fashion. It is recommended that anycondition visualized during advancement be treated,particularly angiodysplasia because it could be dif-ficult to distinguish arteriovenous malformationsfrom the mild mucosal trauma incurred by theenteroscope during the withdrawal process.

13.8.2 Balloon-Assisted Enteroscopyby the Retrograde Approach

The retrograde SBE route is challenging, even forexpert endoscopists. While the learning curve foranterograde procedures is estimated to be approxi-mately 10 cases [5], for the retrograde approach it istypically 20–30 cases. Even when performed byexperienced endoscopists, ileal intubation has failurerates of 20–30%, especially in the presence ofadhesions from prior pelvic surgeries and appen-dectomy and due to the flexible nature of the enter-oscope, which creates advancement through the colonand subsequent difficult intubation of the ileum [10].Accordingly, it is recommended to start using theSBE system, performing reduction manoeuvres whenlooping is first appreciated in the colon.

Initial attempts at ileocecal valve intubation shouldbe conducted with the patient in the left lateral orsupine position in order to achieve an ideal location ofthe valve between the 3 and 9 o’clock positions. In

case of failure, the patient’s position should bechanged (prone or right lateral decubitus position) [11].If these manoeuvres are unsuccessful, use of a ‘‘triple-balloon technique’’ with an inflated balloon dilatorinserted through the channel of the SBE has beendemonstrated to be useful in some cases [12].

13.9 Complications

The complications of SBE may be the result of theprocedure itself or they may be secondary toanesthesia. Relevant complications in diagnosticballoon-assisted enteroscopy can be expected inapproximately 1% of cases. As in conventionalendoscopy, the risk is higher (3–4%) in therapeuticenteroscopy [13].

Among the 484 SBE procedures published to date,only one perforation (0.21%) occurred during diag-nostic SBE (in a patient with postoperative ulcerativecolitis), and only one perforation (0.41% of the totalSBE) occurred during therapeutic enteroscopy (bal-loon dilation) [6, 14–18]. However, scrupulous care isrequired when moving the endoscope past a small-intestinal lesion or when treating patients with knownadhesions or strictures.

In contrast to per oral DBE, acute pancreatitis hasnot been reported following SBE. In DBE, thehypothesized mechanisms of acute pancreatitis onsetare: (1) the inflation of the two balloons in the duo-denum, resulting in an increase of intraluminal pres-sure, leading to the reflux of duodenal fluids into thepancreatic duct and (2) the repeated ‘‘push-and-pull,’’with stretching of the small intestine [19, 20]. In ouropinion, the lower incidence of acute pancreatitisafter SBE is mainly due to the differences in the twotechniques. In the proposed SBE technique, after theenteroscope is passed into the third duodenal portion,the over tube is advanced and the balloon is inflatedaway from the papilla. Inflating the balloon too closeto the papilla may obstruct the pancreatic duct, eitherdirectly or due to post-traumatic edema, resulting inthe onset of pancreatitis [18].

13.10 Clinical Cases

Specific cases of small bowel disease are presented inFigs. 13.5, 13.6, 13.7, 13.8, 13.9, and 13.10.

13 Single-Balloon Enteroscopy 83

Fig. 13.5 Bleeding jejunal arteriovenous malformation

Fig. 13.6 Ischemic enteritis

Fig. 13.7 Jejunal adenocarcinoma

Fig. 13.8 Intestinal lymphoma

Fig. 13.9 Intestinal metastasis of a kidney adenocarcinoma

Fig. 13.10 Intestinal metastasis of a bladder sarcoma

84 M. Manno et al.

13.11 Summary

Single-balloon enteroscopy is a viable alternative toDBE in the management of small bowel disease.Technically, it is easier to perform, may be moreefficient, and, according to the literature data, pro-vides similar diagnostic and therapeutic yields asachieved with DBE.

References

1. Pohl J, Delvaux M, Ell C et al (2008) European Society ofGastrointestinal Endoscopy (ESGE) Guidelines: flexibleenteroscopy for diagnosis and treatment of small-boweldiseases. Endoscopy 40:609–618

2. Hirai F, Matsui T, Yao K et al (2007) Efficacy of carbondioxide insufflation in endoscopic balloon dilation therapyusing double balloon endoscopy. Gastrointest Endosc66:26–29

3. Domagk D, Bretthauer M, Lenz P et al (2007) Carbondioxide insufflation improves intubation depth in double-balloon enteroscopy: a randomized, controlled, double-blind trial. Endoscopy 39:1064–1067

4. Gay G, Delvaux M, Fassler I (2006) Outcome of capsuleendoscopy in determining indication and route for push andpull enteroscopy. Endoscopy 38:49–58

5. Mehdizadeh S, Ross A, Gerson L et al (2006) What is thelearning curve associated with double-balloon enteroscopy?Technical details and early experience in 6 U.S. tertiarycare centers. Gastrointest Endosc 64:740–750

6. Tsujikawa T, Saitoh Y, Andoh A et al (2008) Novel single-balloon enteroscopy for diagnosis and treatment of thesmall intestine: preliminary experiences. Endoscopy40:11–15

7. Hartmann D, Eickhoff A, Tamm R et al (2007) Balloon-assisted enteroscopy using a single-balloon technique.Endoscopy 39(Suppl 1):E276

8. Manno M, Mussetto A, Conigliaro R (2008) Preliminaryresults of alternative simultaneous technique for single-balloon enteroscopy. Endoscopy 40:538

9. May A, Nachbar L, Schneider M et al (2005) Push-and-pullenteroscopy using the double-balloon technique: method ofassessing depth of insertion and training of the enteroscopytechnique using the Erlangen Endo-Trainer. Endoscopy37:66–70

10. Mehdizadeh S, Han NJ, Cheng DW et al (2007) Successrate of retrograde double-balloon enteroscopy. GastrointestEndosc 65:633–639

11. Gerson LB, Flodin JT, Miyabayashi K (2008) Balloon-assisted enteroscopy: technology and troubleshooting.Gastrointest Endosc 68:1158–1167

12. Ross AS, Waxman I, Semrad C et al (2005) Balloon-assistedintubation of the ileocecal valve to facilitate retrogradedouble-balloon enteroscopy. Gastrointest Endosc 62:987–988

13. May A (2009) Balloon Enteroscopy: single and double-balloon enteroscopy. Gastrointest Endoscopy Clin N Am19:349–356

14. Aktas H, de Ridder L, Haringsma J et al (2010)Complications of single-balloon enteroscopy: a prospectiveevaluation of 166 procedures. Endoscopy 42:365–368

15. Kawamura T, Yasuda K, Tanaka K et al (2008) Clinicalevaluation of a newly developed single-balloon enteroscope.Gastrointest Endosc 68:1112–1116

16. Ramchandani M, Reddy DN, Gupta R et al (2009)Diagnostic yield and therapeutic impact of single-balloonenteroscopy: series of 106 cases. J Gastroenterol Hepatol24:1631–1638

17. Mensink PB, Haringsma J, Kucharzik T et al (2007)Complications of double balloon enteroscopy: a multicentersurvey. Endoscopy 39:613–615

18. Manno M, Barbera C, Dabizzi E et al (2010) Safety of single-balloon enteroscopy: our experience of 72 procedures.Endoscopy 42:773

19. Groenen MJ, Moreels TG, Orlent H et al (2006) Acutepancreatitis after double-balloon enteroscopy: an oldpathogenetic theory revisited as a result of using a newendoscopic tool. Endoscopy 38:82–85

20. Heine GD, Hadithi M, Groenen MJ et al (2006) Double-balloon enteroscopy: indications, diagnostic yield, andcomplications in a series of 275 patients with suspectedsmall-bowel disease. Endoscopy 38:42–48

13 Single-Balloon Enteroscopy 85

14Spiral Enteroscopy

Mauro Manno, Raffaele Manta, and Rita Conigliaro

14.1 Background

The introduction of capsule endoscopy in 2001,followed by balloon-assisted enteroscopy a few yearslater, radically changed the way the small bowel isdiagnosed and treated. Nonetheless, balloon-assistedenteroscopy, designed to facilitate anterograde small-bowel enteroscopy, remains a technically challengingprocedure, often requiring extensive time and resources.

Spiral enteroscopy is a new technique for endo-scopic evaluation of the small bowel. Akerman firstproposed the concept and, together with Cantero, in2006, performed the first procedure. Indeed, develop-ment of the Endo-Ease Discovery SB (SB = smallbowel; Spirus Medical, Bridgewater, MA) overtubesystem has revolutionized enteroscopy procedures,which can now be performed more efficiently. Thedevice consists of a smooth, compliant spiral, located atthe distal end of the tube, that rapidly gathers and pleatsthe small bowel. Rotation of the overtube beyond theligament of Treitz (LOT), i.e., the fixed portion of smallbowel, allows the spiral to pleat the intestine in a rapidand controlled manner. With the Endo-Ease DiscoverySB, the enteroscope is independently manoeuveredwhile the overtube remains in place.

14.2 Endo-Ease Discovery SB Overtube

The Discovery SB (DSB) has an outer diameter of14.5 mm, an internal diameter of 9.8 mm, an overalllength of 118 cm, a spiral height of 5.5 mm, and aspiral length of 22 cm. It includes a locking device thatfixes the DSB overtube to the endoscope but still allowsrotation of the overtube at the other end. The proximalend of the DSB has two foam handles to assist rotation.The DSB is designed to be used with 200 cm-longenteroscopes with an outer diameter of 9.1–9.5 mmand an endoscope that is 9.4 mm in diameter or less.Specifically, the DSB can be used with the 9.2 mm200 cm Olympus SIF-Q180 and the 9.4 mm 200 cmFujinon EN-450T5 enteroscopes, i.e., single- anddouble-balloon enteroscopes (Fig. 14.1).

14.3 Endo-Ease Vista Retrograde

The Endo-Ease Vista Retrograde (Spirus Medical) isan innovative overtube system that helps endoscopistsperform challenging colonoscopies and enables effi-cient intubation of the terminal ileum.

The Vista is 90 cm long with a raised 5.5 mmspiral at the distal end. The spiral is 20 cm in length;the Vista’s outer diameter is 18 mm and its innerdiameter 11.5 mm. The Vista fits endoscopes withan outer diameter measuring 10.5–11.6 mm, whichallows its use with a pediatric colonoscope or withthe 260 cm enteroscope by Olympus (SIF-140). Theproximal end of the Vista has a locking collar such

M. Manno (&)Gastroenterology and Digestive Endoscopy Unit,Nuovo Ospedale Civile S.Agostino-Estense,Baggiovara di Modena (MO), Italye-mail: m.manno@ausl.mo.it

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_14, � Springer-Verlag Italia 2012 87

that rotation of the Vista locked to the endoscope ispossible. The Vista is rotationally advanced overthe endoscope to the cecum. For ileal intubation,the coupled device is unlocked and the endoscopeis then pushed through the overtube through theileocecal valve into the ileum (Fig. 14.2).

14.4 Anterograde Spiral Enteroscopy:Technique

The DSB overtube is a sterile single-use device. Twooperators are usually required to perform the exami-nation. Before the DSB is installed onto the entero-scope, a small amount of the recommended lubricantshould be squeezed into the overtube via the DSB’sproximal coupler. The lubricated DSB is then installedon the enteroscope (Olympus SIF-Q180 or FujinonEN-450T5). To begin the procedure, the device islocked on the enteroscope at 145 cm, leaving approx-imately 27 cm of enteroscope past the distal tip of theovertube. This allows the enteroscope to travel throughthe fixed portions of the upper gastrointestinal tract.

The fixed overtube and enteroscope are advancedslowly, with gentle rotation of the overtube, until theenteroscope typically passes the LOT. It is importantto minimize insufflations of air; alternatively carbondioxide can be used instead of standard air to reducingthe formation of a loop in the stomach and to allowbetter apposition of the spiral with the small bowel.

Advancement of the spiral enteroscope begins bypassing the spiral past the LOT, whereby the mobilesmall bowel can be easily pleated on the enteroscope.Early resistance to rotation is almost always due to theformation of a loop in the stomach. In this case, it ishelpful to slowly rotate the overtube while gentlewithdrawing it; this ‘‘Cantero’’ maneuver may help toadvance the scope and to begin engagement of thespiral enteroscope. If this manuever is repeated withabdominal pressure and rotation is still not possible,shortening and straightening the DSB are recom-mended. The DSB is then unlocked from the entero-scope and the enteroscope is maximally advanced intothe small bowel. Next, the overtube is advanced overthe enteroscope with gentle slow rotation. This usuallyinstalls the spiral past the LOT, allowing the overtube tobe straightened and rotated to initiate spiral advance-ment. Once the maximal depth of insertion has beenreached with spiral advancement, it is sometimespossible to pleat additional small bowel by unlockingthe enteroscope so that it advances to the maximalinsertion depth. With a hook and suction maneuverperformed with the enteroscope, the DSB is then rota-ted and the enteroscope is slowly withdrawn. This canbe repeated several times as long as additional depths ofsmall bowel are visualized. When the maximal inser-tion depth is reached, the withdrawal process begins.The overtube is slowly rotated counter-clockwise, withperiodic pauses to allow the small bowel to be carefullyvisualized. In order to maintain the DSB’s position andto avoid its rapid withdrawal, a slight forward pressureon the DSB should be applied during the counter-clockwise withdrawal. Once counter-clockwise rota-tion is no longer effective, the overtube is returned to60 cm at the bite block. The enteroscope is thenunlocked, slowly drawn back through the proximaljejunum and duodenum, and then fixed to the overtube,with the device withdrawn by applying a slow counter-clockwise rotation [1] (Fig. 14.3).

Fig. 14.2 Endo-ease vista retrograde. (Image courtesy ofSpirus Medical, with permission)

Fig. 14.1 Endo-ease discovery SB. (Image courtesy of SpirusMedical, with permission)

88 M. Manno et al.

14.5 Sedation

For anterograde spiral enteroscopy, the use of pro-pofol and general anesthesia with intubation isstrongly recommended. When the overtube spiral ispassed through the esophagus during both initialinsertion and withdrawal, the endotracheal tubeballoon must be deflated in order to minimize anytrauma to the tissue between the balloon and theDSB.

In the retrograde approach, conscious sedation asfor colonoscopy is sufficient in most cases.

14.6 Spiral Enteroscopy Studies

As noted above, Akerman and Cantero were the first toperform a DSB study, using the 200 cm enteroscopesuch as available from Olympus (SIF Q180) and Fujinon(EN-450T5) [2–4]. Seventy-five patients were pro-spectively enrolled in the study. The average estimateddepth of insertion of the enteroscope past the LOT was*250 cm, with an average total procedure time of29 min. The diagnostic yield was low (about 26%),which was attributed to the overall young age of thecohort and the lack of a pre-evaluation capsule study.

Fig. 14.3 Representativescheme of the spiralenteroscopy technique.(Scheme courtesy of SpirusMedical, with permission)

14 Spiral Enteroscopy 89

Spiral enteroscopy is a rapidly performed technique:deep small-bowel intubation is reached within20–30 min, reducing the duration of the procedure byalmost 50% compared with balloon-assisted enteros-copy. The first reports of anterograde spiral enteros-copy series showed good depths of insertion, withmeans of 176–247 cm, but with relatively low diag-nostic yields (27–36%). Recent clinical trials in tertiaryreferral centers in Europe and the USA reported similarresults in terms of performance parameters [5].

Safety issues were addressed in a large cohort studyof 1,750 procedures, published by Akerman et al. in2009 [6]. Major complications were reported in 0.4% ofthe patients undergoing spiral enteroscopy procedures.In a recent US study in 61 elderly patients undergoingspiral enteroscopy procedures, mild complicationsoccurred in 7% of the patients and there were no majorcomplications [7]. So far, the complication rate of spiralenteroscopy seems to be comparable with that of dou-ble- and single-balloon enteroscopy (DBE and SBE,respectively) systems. Surprisingly, in contrast to theDBE system, there have been no cases of acutepancreatitis after spiral enteroscopy.

Thus far, there have been only two head-to-headcomparative studies between spiral enteroscopy andballoon-assisted enteroscopy. In the first, a recentlypublished retrospective study comparing anterogradespiral enteroscopy with SBE in 92 patients [8], themean insertion depth was significantly deeper withspiral enteroscopy than with SBE, 301 and 222 cm,respectively. Other performance parameters werecomparable, including total duration of the procedure.The second study prospectively compared antero-grade spiral enteroscopy with DBE in 35 patients [9].The results showed the two techniques to be compa-rable in terms of performance, including insertiondepth, diagnostic yield, and duration.

There are as yet only two published Abstracts onretrograde spiral enteroscopy. In the first, a study of11 patients, retrograde small-bowel enteroscopy wasperformed using the Vista-SB overtube (outerdiameter 18.5 mm) and the Olympus SIF Q-140260 cm enteroscope. The average total proceduretime was 29 min and the estimated maximum depthof insertion 125 cm [10]. In the second study, theVista SB and a pediatric colonoscope were used ineight patients. The average procedure time was39 min and the estimated average depth of small-bowel insertion was 113 cm [11].

14.7 Summary

Spiral enteroscopy is a new technique for deep small-bowel intubation. To date, the performance of spiralenteroscopy has been at least comparable to that ofSBE and DBE, thus recommending its use as aninteresting alternative technique to balloon-assistedenteroscopy. However, further studies are needed todetermine its actual value in patients with suspectedsmall-bowel pathology.

References

1. Akerman PA, Cantero D (2009) Spiral enteroscopy andpush enteroscopy. Gastrointest Endosc Clin N Am 19:357–369

2. Akerman P, Agrawal D, Cantero D et al (2008) Spiralenteroscopy with the new DSB overtube: a novel techniquefor deep peroral small-bowel intubation. Endoscopy40:974–978

3. Akerman P, Cantero D, Avila J et al (2008) A pilot study ofspiral enteroscopy using a new design 48F Discovery SBovertube and the Olympus 200 cm–9.2 mm enteroscope.Gastrointest Endosc 67:AB264

4. Akerman P, Cantero D, Avila J et al (2008) A pilot study ofspiral enteroscopy using a new design 48F Discovery SBovertube and the Fujinon 200 cm–9.4 mm enteroscope.Gastrointest Endosc 67:AB264

5. Mensink PBF (2010) Spiral enteroscopy: from ‘‘new kid onthe block’’ to established deep small-bowel enteroscopytool. Endoscopy 42:955–956

6. Akerman PA, Cantero D (2009) Severe complications ofspiral enteroscopy in the first 1750 patients. GastrointestEndosc 69:AB127

7. Judah JR, Draganov PV, Lam Y et al (2010) Spiralenteroscopy is safe and effective for an elderly UnitedStates population of patients with numerous comorbidities.Clin Gastroenterol Hepatol 8:572–576

8. Khashab MA, Lennon AM, Dunbar KB et al (2010)A comparative evaluation of single-balloon enteroscopyand spiral enteroscopy for patients with mid-gut disorders.Gastrointest Endosc 72:766–772

9. Frieling T, Heise J, Sassenrath W et al (2010) Prospectivecomparison between double-balloon enteroscopy (DBE)and spiral enteroscopy (SE). Endoscopy 42:885–888

10. Akerman P, Cantero D, Pangtay J et al (2009) Retrogradesmall bowel enteroscopy using the Olympus SIF-140260 cm enteroscope and the Vista-SB spiral overtube.Gastrointest Endosc 69:AB201

11. Akerman P, Cantero D, Agrawal D et al (2007) Novelmethod of enteroscopy using Endo-ease Discovery SBovertube. Gastrointest Endosc 65(5):AB125

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15Surgery for Small-Bowel Disease

Ugo Grossi, Andrea Mazzari, Pasquina MC Tomaiuolo,Giuseppe Brisinda, and Antonio Crucitti

15.1 Congenital Malformations

Embryological development of the digestive tract issuch that it may be entirely or segmentally involvedin congenital malformations. These include all thetopographic abnormalities: intestinal atresia, gastros-chisis and omphalocele, duplications, disorders ofintestinal rotation, and small-bowel diverticula,including Meckel’s diverticulum. Patients with any ofthese conditions are at risk for volvulus, intussus-ceptions, or bowel obstruction and are thus candidatesfor early surgical resection [1], with end-to-endanastomosis as the procedure of choice. Laparoscopicprocedures are also frequently performed [2–4].

Intestinal atresia describes a partial (stenosis) orcomplete (atresia) obstruction, the latter with a con-genital absence of the bowel lumen. In case of duodenalatresia (prevalence rate of one in 5,000–10,000 births)or jejuno-ileal atresia (prevalence rate of one in 1,000births), due to the early age of the patient, immediatesurgery is required [5]; in fact, bowel distension quicklyleads to ischemic necrosis of the bowel. Prenataldiagnosis with fetal echo-tomography can alert theparents as well as the surgeon to the need for postnatalsurgery. The end-to-end anastomosis typically involvesthe resection of 4 cm before the proximal loop and2 cm from the distal one [6]. Moreover, mucosal neu-rogangliar lesions are often present in patients withatresia. Only in case of severe peritonitis or prematurity

is a temporary ileostomy the preferred approach.In case of non-critical stenosis, surgery can be post-poned for months or even years after birth.

Gastroschisis and omphalocele are among thecongenital anomalies most frequently encountered bypediatric surgeons. Their combined incidence is onein 2,000 births. If the abdomen is closed during theneonatal period, routine pediatric care may suffice;however, if the abdominal-wall defect is one com-ponent of a multifaceted anomaly, further care byspecialists who are familiar with the child’s particularproblems may be required. An infant who is born withgastroschisis may have associated malabsorption,either from in utero injury to the intestine or due topartial bowel obstruction. Anomalies of intestinalfixation accompany the abdominal-wall defects, andmidgut volvulus is possible. Atypical appendicitismay occur if the abnormally located appendix is notremoved. In addition, these children may have gas-troesophageal reflux and their clinical course may becomplicated by Hirschsprung disease.

Bowel duplications are rare malformations ofunknown origin. They generally involve the smallbowel, with clinical manifestations mostly evident inthe first 2 years of life. The most common site ofinvolvement is the ileum, followed by the esoph-agus and duodenum [7]. Obstruction, ischemia, andnecrosis are the most frequent causes for surgicalresection of the affected bowel. Bleeding usuallyindicates a long communicating duplication, such thatthe abnormal gastric mucosa causes ulceration of thedistal intestinal mucosa.

The embryologic development of the midgut canarrest at any phase, with variable consequences: non-rotation, incomplete rotation, and reversed rotation.

A. Crucitti (&)General Surgery, Catholic University of Rome,Rome, Italye-mail: acrucitti@rm.unicatt.it

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_15, � Springer-Verlag Italia 2012 91

While the early failure of rotation yields the pattern ofnonrotation, the latter is a misnomer because the initial90� of rotation has occurred, with the duodenum lyingto the right and the distal colon to the left of the superiormesenteric artery (SMA). Without further rotation, thesmall bowel is located on the right and the colon on theleft. Incomplete rotation represents a failure occurringduring the final 180� counterclockwise rotation of thesmall bowel and/or that of the colon. The resultantabnormality varies from complete non-rotation to anormal anatomy. In reversed rotation, the caudalmidgut returns to the abdomen first and the duodenumrotates clockwise rather than the normal counter-clockwise. As a result, in reversed rotation the duode-num courses anterior rather than posterior to the SMAand the colon courses posterior rather than anterior tothe artery. Rarely, reversed duodenal rotation isaccompanied by normal colonic rotation, which mayresult in an internal hernia. Treatment should beaddressed case by case according to the degree ofmalrotation and the timing of the diagnosis. Explor-atory laparotomy may be considered for patientswith intestinal obstruction. At surgery, the volvulusshould be reduced and any nonviable bowel resected.Treatment of the underlying malrotation includes lysisof all adhesions and abnormal bands, appendectomy,and widening of the small-bowel mesentery [8].

15.2 Diverticula

The following describes two distinct diseases:Meckel’s diverticulum and congenital or acquireddiverticulosis.

15.2.1 Meckel’s Diverticulum

Meckel’s diverticulum is a true diverticulum origi-nating from the persistence of the onphalomesentericduct. It was first reported by Fabricus Heldanus in 1650[9] and thoroughly described by Johann FriedrickMeckel in 1808. This abnormality is mostly asymp-tomatic and is generally detected incidentally duringsurgery for other reasons or during a radiologicalinvestigation. Patients present with non-specificsymptoms. Complications occur in 30–40% andinclude diverticulitis, peptic ulcer, intestinal intussus-ceptions, bowel occlusion, hernia, and intestinal

strangulation [10]. Although reported, the presence oftumor is uncommon. The most controversial issue inthe management of Meckel’s diverticulum is thedecision whether to perform surgical resection inpatients who are asymptomatic, i.e., in whom thecondition was discovered incidentally. Postoperativemorbidity and mortality depend on the indications forremoval. While mortality after surgical excision isalmost zero, morbidity in asymptomatic patients is8.6%, which is close to the 8.3% morbidity reported insymptomatic patients (8.5% overall) [11]. Advocatesof incidental excision claim that the relatively highmortality and morbidity rates associated with symp-tomatic disease justify the associated morbidityresulting from elective excision. The opponents ofincidental excision quote the low (4.2%) lifetime riskof symptom development. In addition, according to arecent systematic review, there is no compelling evi-dence to support prophylactic resection [12]. In fact,resection of incidentally detected Meckel’s diverticu-lum has a significantly higher early morbidity rate thanwould occur by leaving the diverticulum in situ (5.3 vs.1.3%) [13]. Nowadays, with the advent of laparoscopy,this scenario has no doubt changed. Laparoscopypermits complete abdominal exploration, increasingthe number of incidentally found diverticula. Thetechnique has the advantage that it permits the removalof an incidentally found diverticulum using a gastro-intestinal stapling device. Nevertheless, laparoscopyalso has been performed to treat patients with Meckel’sdiverticulum complicated by intestinal obstructionor bleeding caused by heterotopic gastric mucosa.In adult patients, the following criteria should beevaluated:• Age of the patient: the risk of complications is

lower with increasing age• Presence of peritonitis• Condition of the small bowel: healthy, ischemic, or

inflamed• Patient condition: ASA score• Elective or emergency surgery• Coincident major surgery or presence of tumor:

both are contraindications for removalAn additional consideration is the characteristics of

the diverticulum: whether it is long and narrow,or there is a possibility of suppuration, whether a massis palpable or an umbilication present, if there is a riskof intussusception, or the diverticulum is connected tothe umbilicus by adhesion bands. All of these are

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conditions for mandatory surgery. A recent perfora-tion could be treated by a resection and immediatebowel reconstruction. A temporary diversion has to befashioned in case of diffuse peritonitis and if thebowel closure has not been scheduled within the next3 weeks. Segmentary bowel resection with a termino-terminal anastomosis is the most reliable technique.Ileal resection is an option only if the bowel isperfectly healthy and heterotopic mucosa is notpresent; generally, a mechanical terminal anastomosisis sufficient. A laparoscopic excision through either acompletely intracorporeal approach followed byanastomosis or a mixed approach are other options.It should be highlighted that the procedure does notrule out major surgical resection to avoid the risksassociated with the above mentioned complications.Particular attention should be paid to avoid reducingthe small-bowel lumen, as this is a frequent cause ofpostoperative leakage or obstruction.

15.2.2 Diverticulosis

Diverticulosis of the small bowel is an infrequentclinical entity; the development of these multiple sac-like mucosal herniations are in fact more typical inthe left colon. Small-bowel diverticula can be single(30%) or multiple. They are extremely rare in new-borns and in children but on rare occasions are seen inadult patients as a consequence of ischemic disease.Duodenal diverticula are approximately five timesmore common than jejuno-ileal diverticula [14] butthe true incidence of either type is unclear becausethese lesions are usually asymptomatic. The incidenceat autopsy of duodenal diverticula is 6–22%. Jejunaldiverticula are less common, with a reported inci-dence of\0.5% on upper gastrointestinal radiographsand of 0.3–1.3% at autopsy. Most cases of duodenaldiverticula involve patients older than 50 years, whilejejuno-ileal diverticula are commonly observed inpatients age 60–70 years. Complications occur in10–12% of the patients with duodenal diverticulosisand 46% of those with jejunal diverticulosis. Theyinclude diverticular pain, bleeding, diverticulitis,intestinal obstruction, perforation and localizedabscess, malabsorption, anemia, biliary tract disease,and volvulus [15]. Surgical resection is the treatmentof choice and consists of diverticulectomy or seg-mental resection. In case of multiple sites of

diverticulosis, medical treatment with antispastics anda low-fiber diet is preferred.

15.3 Small-Bowel Obstruction

Surgical treatment of small-bowel obstruction (SBO)depends on the cause, site, and presence of ischemiclesions or other visceral or parietal lesions. Since thesurgical procedures may vary in each case, the dif-ferent types of SBO are separately discussed below.

15.3.1 Occlusion

Occlusion may be adhesion-related, intraluminal, orparietal (Fig. 15.1).

Adhesion-Related OcclusionIntraperitoneal adhesions are the most frequent(90–95%) cause of occlusion after any abdominal sur-gery [16]; the first episode may occur in a very differentsetting after weeks, years, or decades after surgery.Rarely a spontaneous adhesion in patients without pre-vious surgery arises as a result of an unrecognized intra-abdominal abscess. With the exception of volvulus, theadhesion may cause occlusion in two ways: (1) acuteplication such that it involves a small-bowel loop whoseantimesenteric margin is stuck either to the abdominalwall at any point, or to a section of mesothelium, or toother abdominal viscera; (2) throttling mechanismof a small-bowel loop through an adhesion stretchedbetween two fixed points of the peritoneal cavity.The adhesion is sectioned with scissors or by electro-coagulation between ligatures wherever it appears to bevascularized.

The situation becomes more difficult if the adhe-sion is very short, with dilatation of several small-bowel loops hindering exposure of the lesion, or if itis located at a difficult site. In such cases, all of thesmall intestine should be placed outside the peritonealcavity. The presence of further adhesions or non-occlusive adhesions between small-bowel loops is acommon finding and requires a subsequent completeadhesiolysis.

Intraluminal OcclusionIn contrast to parietal occlusions, intraluminal occlu-sions are rare, accounting for only 3% of SBO. Most

15 Surgery for Small-Bowel Disease 93

are due to biliary ileus and more rare to foreignbodies. Bilary ileus commonly affects the ileum,rarely the duodenojejunal tract; a gallstone is gener-ally present at palpation and may appear as a dis-crepancy in the size of the bowel [17]. The stoneshould be gently separated from the congested boweland then removed through a cranial (not \10 cm)longitudinal enterotomy of the normal bowel wall.The small intestine is emptied upstream through theenterotomy anterogradely and the entire small bowelshould be carefully palpated to identify further calculiin the intestinal lumen, which could cause repeatedocclusions. The enterotomy is then closed trans-versely with interrupted or overlocking sutures.A short small-bowel resection anastomosis, perhapspreceded by retrograde intestinal emptying, may benecessary in case of clear damage to the bowel wall.

Bezoars are collections of indigestible matter withinthe bowel. They are commonly phytobezoars, origi-nating from plant material. Trichobezoars occur sec-ondary to the ingestion of hair and are associated withtrichotillomania. The mass may reach the small bowel,a condition described as the Rapunzel syndrome [18].

Parietal OcclusionSeveral conditions affecting the small-bowel wallmay cause occlusion. Primary malignancies of thesmall intestine, representing about 3% of tumors ofthe digestive tract, can result in acute occlusion,sometimes related to luminal stenosis but more oftento intussusception or volvulus. Cancer of the smallintestine (50% of cases) is stenosing; its grossappearance is that of a scirrhous neoplasm, verysimilar to colon cancer. Sarcoma (30%) rarely causesocclusion and is instead more often associated withtorsion and, rarely, stenosis of the lumen. Carcinoidtumors (20%) are typically multiple, whitish, andsmall and are often seen with synchronous livermetastases. Benign tumors of the small intestine

(adenomas, leiomyomas, fibromas, lipomas) rarelycause SBO except through a mechanism of intussus-ception. Basically, a wide intestinal resection-anastomosis is required, with digestive resectionsperformed at least 10 cm from the macroscopic limitsof the tumor on both sides. A complete exeresis of theaffected mesentery is performed, with removal of atriangle whose base is the resected small bowel andwhose peak corresponds to the root of the mesentery.A non-traumatic intramural hematoma of the smallintestine, without interruption of the intestinal wall, isexceptional. Usually, this lesion occurs in the contextof complications related to the use of anticoagulants,e.g., in patients treated with excessive doses of anti-vitamin K. Abstention typically suffices. Crohn’sdisease, intestinal tuberculosis and, rarely, sarcoidosiscan cause inflammatory or cicatricial small-bowelstenosis. These generally present as repeated sub-occlusive crises, but some patients may require anemergency laparotomy if the occlusion is acute.These are frequently patients whose disease goesunrecognized. However, the diagnosis of benignstenosis of the small intestine is easily made andnecessitates careful exploration of the entire digestivetract, looking for multifocal lesions. In the absence ofcomplete stenosis, it is better to refrain from perform-ing an emergency resection and instead wait for theresults of a postoperative complete evaluation. Onlycases of very tight stenosis should be treated withurgent exeresis-anastomosis, ensuring that the limits ofresection include the healthy tissue, in order to reducethe risk of postoperative anastomotic fistulization.

Successful laparoscopic surgery for bowelobstruction is being reported with increasing fre-quency, with up to 60% of the cases of SBO causedby adhesions amenable to laparoscopic therapy.The reported conversion rate is 20–51.9% and thecomplication rate (bowel injury) is 6.5–18.0%[19, 20]. Conversion to an open procedure may be

Fig. 15.1 Common causesof small-bowel obstruction inindustrialized countries

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secondary to dense adhesions, an inability to resolvethe obstruction, intestinal necrosis, intestinal perfo-ration, and conditions not amenable to laparoscopictherapy. Factors that favor laparoscopic success arepost-appendectomy SBO, with bands as the cause,patients who have undergone less than two previoussurgeries, and shorter duration of symptoms. Theconversion rate can be decreased to as low as 6.9%when surgery is guided by preoperative enteroclysis.The laparoscopic treatment of SBO appears to beeffective and results in a shorter hospital stay in ahighly selected group of patients. The literature alsosupports that patients treated with a laparoscopicintervention have a lower rate of hernia and postop-erative SBO but require the same amount of operativeintervention. Patients fulfilling the criteria for con-sideration of laparoscopic management [21] includethose with mild abdominal distention allowing ade-quate visualization, proximal obstruction, partialobstruction, or an anticipated single-band obstruction.

Currently, patients who have advanced, complete,or distal SBO are not candidates for laparoscopictreatment. Unfortunately, this includes the majority ofpatients with obstruction. Similarly, patients withmatted adhesions or those with persistent boweldistention after nasogastric intubation should bemanaged with conventional laparotomy. Therefore,the role of laparoscopic procedures in the treatment ofthese patients remains to be defined.

15.3.2 Strangulation

The consequences of mechanical SBO include stran-gulation of both the small bowel and mesentery,leading to ischemia of the bowel wall, which is oftenseverely distended, and the risk of gangrene as well asperforation. Strangulation is the most severe form ofocclusion and requires surgical treatment in cases ofextreme emergency.

Small-Bowel VolvulusSmall-bowel volvulus is due to a twist of a part or theentire small bowel along its mesenteric axis. Primaryvolvulus is encountered especially in the newborn,sometimes in children, and only rarely in adults, inwhom the cause is usually an anomaly that hasremained latent. Secondary volvulus is more commonand is usually due to an obstacle that subsequently

immobilizes a small-bowel loop. The obstaclecan be in the form of a tumor, a foreign body, aninflammation-related narrowing or scar, Meckel’sdiverticulum, a long and ectopic appendix, or anobstructed or strangulated hernia. In cases ofstraightforward irreversible ischemic injury or perfo-ration, bowel resection becomes essential and mustinclude the entire volvulated loop. The upstream anddownstream sections must be macroscopically heal-thy and extend at least 5 cm from the margins of thelesion. Resection is ideally performed beforeuntwisting the volvulus, to avoid the occurrence ofabsorption shock, and must still be followed byimmediate bowel restoration. If the loop seems to beviable, it should be untwisted and then heated afterenteric decompression. Only then can the decision bemade to spare or resect the loop, depending on thereversibility of the injury. In the particular case ofvolvulus of the entire small bowel with a commonmesenterium, requiring sub-total resection of thesmall intestine, the length of the residual small bowelmust be carefully measured, as this will determine thenutritional needs of the patient.

Strangled Primitive and Incisional HerniasInternal hernias comprise a group of disparate lesions,often intraoperatively discovered, that commonlyshow an intraperitoneal orifice that may cause small-bowel strangulation. The orifice may be abnormal(trans-epiploic, trans-mesenteric, or trans-mesocolichernias), standard (hernias of Winslow’s hiatus),or originate from a developmental abnormality, such asthe lack of adherence of the peritoneal leaflets (para-orretro-duodenal, pericolic or intersigmoid hernias).

Paraduodenal hernias are retroperitoneal, resultingfrom the abnormal adherence of the mesocolon and anexcessive rotation of the small bowel around themesenteric axis beyond the traditional 270�. Leftparaduodenal hernia is the most common. The sac canreach above the spleen and pancreas and down untilthe pelvis, to the cecum and ascending colon. Thehernial orifice is found close to the cecum. Once thecontent is reduced, the hernial orifice is closed with afew stitches. These should include only the perito-neum to avoid damage to the aorta posteriorly and theinferior mesenteric vessels anteriorly.

Pericolic hernia is located in the retrocecal recess,limited anteriorly by the cecum and the ascendingcolon, posteriorly by the peritoneum of the iliac fossa,

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and laterally by two peritoneal folds: the exteriorparieto-cecal fold and the interior mesenteric-cecalfold.

In trans-epiploic hernia, a small-bowel loop isstrangled through an epiploic orifice of congenital,post-operative, or post-traumatic origin. After reduc-tion of the loop, the epiploic orifice can be simplyclosed with sutures that avoid blood vessels.Omentectomy is usually unnecessary.

Trans-mesocolic hernia of the retroperitonealspace, the most common type, usually contains mostof the small bowel incarcerated in the retroperitonealspace of the greater omentum. Since there is no per-itoneal sac and the herniated small bowel is stoppedsecondarily from the rear or by the lesser omentumand gastrocolic ligament it instead penetrates into theperitoneal cavity, either below or above the stomachor, more rarely, through the foramen of Winslow.After reduction of the small intestine, the hernialorifice is closed by a simple suture, with care taken topreserve the mesocolic vessels or, if this is not pos-sible, by inclusion of the margins along the posteriorsurface of the stomach.

Hernia through the foramen of Winslow is theincarceration in the lesser peritoneal sac of a segmentof the intestine through this opening. The hernia mayaffect only the small intestine (ileus or jejunum) or theascending ileo-colonic tract, sometimes with theright side of the transverse colon. If gentle tractionmaneuvers through the hiatus do not result inuntwisting of the small bowel, a wider opening of thelesser peritoneal sac is required. Once hernial reduc-tion is achieved, the orifice is closed with a strip ofperitoneum carefully set at the right edge of thehepatic pedicle and anchorage of the right colonicflexure to the anterior abdominal wall.

Diaphragmatic injuries are the most common causeof occlusion as they can result in the strangulation ofthe small intestine. They may occur as post-traumaticdiaphragmatic hernias (90% of cases), in most casesdue to an unrecognized rupture of the diaphragm afterthoraco-abdominal blunt trauma, and only rarely froma diaphragmatic laceration after open thoraco-abdominal trauma. The diaphragmatic gap varieswidely in size, a peritoneal sac is almost neverinvolved and other abdominal organs are oftenstrangled together with the small bowel. Alterna-tively, there may be retro-costo-xiphoid hernia, alsoknown as the Morgagni hernia, which contains the

transverse colon more often than the small bowel; theoval orifice is usually on the right. A third source ofstrangulation hernia is the lumbocostal hernia: either aBochdalek hernia, or, more rarely, hernia of thelumbocostal foramen.

15.3.3 Intussusception

Acute intestinal intussusception in adults is rare and isusually secondary to benign or malignant tumors(50–90% of cases), inflammatory lesion (appendix,Meckel’s diverticulum), or foreign bodies within thesmall intestine [22]. Consequently, the intussuscep-tion is mostly ileo-ileal and only rarely jejuno-ileal orileo-ceco-colic. The lesion is easily highlighted atabdominal exploration, since it is usually found in theright iliac fossa and is seen as a purplish swelling,5–10 cm long, with the ileal loop upstream fittingwithin an external cylinder consisting of the down-stream ileum or the right colon. Mesentericlymphadenopathy at this level may be helpful todetermine the presence of a neoplastic lesion at theorigin of the intussusception. After the lesion isidentified, surgical disinvagination is not performed;rather a prompt resection-anastomosis of the smallbowel is mandatory.

15.3.4 Obstruction from OtherOrganic Causes

The frequency of radiation-induced SBO increaseswith the indications for abdominal-pelvic irradiation.These patients often present with severe malnutritionrelated to subocclusive episodes that preceded theacute ones; accordingly, the surgical risk is greater.Digestive fistulas are frequent and a pre-existingmalabsorption may be exacerbated by bowel resec-tion. Considerable advance preparation of the patientfor the intervention may be needed, typically5–15 days, with intensive digestive emptying andparenteral nutrition. The access route depends on theirradiation fields and high incisions are often required.In these cases, viscerolysis is particularly dangerousand difficult, often resulting in multiple injuries of thesmall bowel; these should be treated with sutures orresections. The absence of tumor recurrence should be

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ruled out. Treatment of radiation-induced SBO resultsin bowel resection.

Peritoneal carcinomatosis often leads to SBO.In most cases an internal by-pass may temporarilysolve the occlusion. The lesions may be sufficientlyimportant to prevent any therapeutic action. In thiscase, the abdominal wall must be quickly closed,without leaving any drains. Otherwise, the obstacleshould be located, such as a small-bowel loop incar-cerated within a loco-regional tumor recurrence orlocalized stenosis of the small bowel in a nodule ofperitoneal carcinomatosis. The approach in such casesis resection-anastomosis or, in case of unresectablelesions, intestinal bypass.

15.3.5 Functional Obstructions

Septic obstructions are a sign of an intraperitonealinfectious outbreak that must be treated specifically.Viscerolysis, enteric retrograde emptying, and peri-toneal cleaning with removal of the pseudomem-branes must be done cautiously, given the extremefragility of the inflamed small bowel. As for post-operative occlusions, the suture of an accidentalintestinal hole exposes the patient to an increased riskof postoperative fistula; instead a temporary enteros-tomy is often the preferred measure.

Acute idiopathic small-bowel pseudo-obstructionis an extreme situation arising in the course of anurgent laparotomy for acute SBO. In such cases, thesurgeon discovers an overall dilated small bowel, withno clear sites of occlusion. The treatment is limited toretrograde intestinal decompression.

15.4 Crohn’s Disease

The diagnosis and treatment of Crohn’s disease canbe difficult even for gastroenterologists and surgeons,due to the wide spectrum of intestinal and extra-intestinal manifestations. Patients with CD oftenrequire surgery as their disease progresses, with thetiming of surgery being one of the critical details ofthe clinical history of these patients. Generally, sur-gery becomes more likely, the longer the diseaseduration. The initial management of patients with CDis medical, until treatment fails or a complicationarises. Surgery is considered only for CD patients in

whom medical treatment has failed, or in cases ofsevere secondary effects, or in the presence ofsurgical complications such as occlusion, fistulas,or abscesses. Symptoms are precipitated by a singlestricture or multiple strictures or a lengthy disease-involved intestinal segment and differ depending onthe location of the disease in the gastrointestinal tract.Even a complete obstruction in CD tends to resolvewith nasogastric decompression, intravenous hydra-tion, and medical therapy, allowing surgery to bepostponed until resolution of the clinical pictureallows for a definitive procedure.

Intestinal fistulae occur in 33% of CD patients [23]but are the primary indication for surgery in only aminority of patients. Enterovesical fistulae are seen in2–5% of patients with CD [24] and often result inrecurrent urinary tract infections, including pyelone-phritis. While it is not mandatory to operate on allpatients with enterovesical fistulae, surgery is war-ranted to avoid the deterioration of renal function.Enterocutaneous fistulae usually drain through aprevious abdominal scar or through the umbilicus.In some cases, they are the result of surgical incisionand drainage of a subcutaneous abscess complicatingsevere intra-abdominal disease or from percutaneousdrainage of an abdominal abscess. Patients may bereluctant to undergo surgical treatment whenthe enterocutaneous fistula has a minimal output andthe underlying disease is under satisfactory control.Enterovaginal fistulae are rare complications of CDand occur only in women who have undergone aprevious hysterectomy. The vaginal discharge is asource of discomfort, social and sexual embarrass-ment, and difficulty in maintaining personal hygiene.A trial of medical therapy may be elected forenterocutaneous and enterovaginal fistulae, but mostcases require surgery and the majority of patientsreadily accept surgical intervention. Enteroduodenal,enteroenteric, and enterocolic fistulae are usuallyasymptomatic and often discovered only during acareful abdominal exploration or at examination ofthe resected specimen [25].

While less frequent than fistulae, intra-abdominalabscesses and inflammatory masses more commonlynecessitate surgical intervention. However, despitesuccessful percutaneous drainage, the abscess will verylikely recur or cause an enterocutaneous fistula, as aconsequence of the disease severity in the intestinalsegment from which it originated. Accordingly,

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surgical resection is usually recommended for thesepatients. Large intraloop abscesses are a rare occur-rence and are often successfully treated by open sur-gical drainage. Inflammatory masses point to thepresence of severe disease and commonly contain anunrecognized abscess. Thus, patients with inflamma-tory masses that do not readily respond to antibiotictreatment should be considered as candidates for sur-gical treatment. Free perforation is a rare complicationof CD, occurring in only about 1% of cases [26], but itis an obvious indication for urgent operation.

Hemorrhage is an uncommon complication inpatients with CD. It necessitates a thorough diagnosticwork up to determine the source of bleeding, which inmany cases is not related to CD. For example, patientson chronic steroid therapy may develop peptic ulcerdisease. In patients with small bowel disease,hemorrhage is rarely obvious but rather chronic,causing anemia but rarely requiring urgent surgery.Massive gastrointestinal hemorrhage occurs morefrequently against a background of colitis. Angiog-raphy can localize the site of bleeding in the presenceof brisk hemorrhage; otherwise, upper endoscopy andcapsule endoscopy can identify the bleeding source inthe duodenum and small bowel, whereas colonoscopycan be employed for the large bowel. Intraoperativelocalization is facilitated by enteroscopy or colonos-copy. The possibility of a life-threatening hemorrhagein a CD patient should not be underestimatedsince five cases of exsanguinating gastrointestinalhemorrhage have been reported in patients with CD.

CD is a preneoplastic condition with an increasedrisk for adenocarcinoma of the affected intestinalsegment. The risk of colorectal cancer in Crohn’scolitis is 4–20 times higher than in the controlpopulation [27], with an incidence between 1.4 and1.8% [28]. The preoperative diagnosis of adeno-carcinoma of the small bowel is difficult because thesymptoms and radiographic findings of a small-bowelmalignancy can be similar to those of the underlyingCD. Male patients and patients with long-standingdisease appear to be at increased risk for small boweladenocarcinoma. Defunctionalized bowel segmentsalso seem to be particularly vulnerable to malignancy.For this reason, bypass surgery should be avoidedand defunctionalized rectal stumps should either befunctionally restored or excised. Once the need forsurgical intervention has been established, the surgi-cal strategy will vary depending on the portion of the

intestine involved by CD. The Heineke–Mikuliczpyloroplasty can be used in patients with shortCrohn’s strictures of the first, second, and third por-tions of the duodenum; the Finney strictureplastylends itself better to longer strictures in the first andfourth portions of the duodenum. The jejunum andileum are involved by CD in 3–10% of patients [29].The two most common indications for surgicaltreatment are obstruction and sepsis; massive hem-orrhage and carcinoma are much less common.Chronic, high-grade, SBO may be caused by single ormultiple short or long strictures (Fig. 15.2).

These patients present with postprandial abdomi-nal cramps, nausea, and vomiting and their conditionoften progresses to a complete obstruction. Due to theneed for a second operation in as many as 30% ofpatients, short-bowel syndrome reportedly occurs inup to 12.6% of cases [30]. Currently, the Heineke–Mikulicz, the Finney, and the side-to-side isoperi-staltic approach are three most commonly performedstrictureplasty techniques. In general, the Heineke–Mikulicz strictureplasty is used for short strictures(up to 7 cm in length), the Finney strictureplasty forlonger strictures (up to 10–12 cm), and side-to-sideisoperistaltic strictureplasty for multiple sequentialstrictures. Strictureplasty is contraindicated in thepresence of active sepsis when the bowel wall is thickand unyielding or in patients with severe weight lossand marked hypoalbuminemia. Small-bowel carci-noma in patients with CD is treated with a radicalsegmental resection when feasible. The prognosis forthese patients is poor, with survival rates of 23% at3 years and 5% at 5 years [31]. Cancers in bypassed

Fig. 15.2 A long stricture in a patient with Crohn’s disease

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loops or in defunctionalized stumps can reachadvanced stages before they become symptomatic.The terminal ileum is the most common Crohn’saffected site requiring surgery and accounts forapproximately 40–50% of the CD patients referred tothe surgeon [32]. In the majority of cases, the patientspresent with symptoms of obstruction or sepsis, bothof which point to a contained perforation or anabscess with or without a fistula. For obstructiveprimary disease involving exclusively the terminalileum without septic complication, the treatment isresection, either in the form of an ileocolic resectionor a formal right hemicolectomy if there is significantinvolvement of the ascending colon. If CD is com-plicated by the presence of an abscess the method andtiming of intervention require careful decision-making. In almost half of these cases, percutaneousdrainage not only allows most patients to avoid earlysurgery but it is also associated with a shortedhospitalization stay [33]. Large intraloop abscessesare not easily approached percutaneously, thusnecessitating surgery instead. Retroperitoneal perfo-ration of the ileocecal region may give rise to a psoasabscess, which can create a chronic inflammatoryreaction at the pelvic brim featuring ureteral stenosisand right hydronephrosis. The abscess should bedrained and the diseased terminal ileum resected;these measures should relieve the compressed ureterand resolve the hydronephrosis.

15.5 Neoplasms

While the small bowel accounts for 80% of the totalintestinal length and 90% of its absorptive surface,small-bowel neoplasms (SBN) comprise just 3.1% ofall intestinal cancers [34]. In the USA, it is estimatedthat almost 7,000 cases of SBN will be diagnosed andthat in 2011 around 1,100 people will die of cancer ofthe small intestine [35]. As benign neoplasms arediscovered more often in autopsy series, malignantneoplasms make up 75% of the symptomatic lesionsthat lead to surgery. Several risk factors andassociated conditions have been identified asrelated to SBN. These include familial adenomatouspolyposis (FAP), hereditary nonpolyposis colorectalcancer (HNPCC), Peutz-Jeghers syndrome, Crohn’sdisease, and celiac disease.

15.5.1 Benign Neoplasms

The most common benign neoplasms are adenomas,benign gastrointestinal stromal tumors (GISTs), andlipomas. Among these, benign GISTs, includingleiomyomas, are the most common symptomaticbenign tumors of the small bowel. These tumors maypresent with intramural or a mixed intramural–extramural pattern of growth. SBO is common in thefirst pattern. Leiomyomas can reach considerablesizes and they often outgrow their blood supply,resulting in bleeding manifestations. In such cases,surgical resection is necessary.

Adenomas account for 15% of benign small boweltumors. Most (50%) are found in the ileum, with about30% in the jejunum and 20% in the duodenum.Malignant degeneration occurs in 35–55% of the cases,according to the literature. Adenomas are usually dis-covered secondary to abdominal pain or bleeding.Segmental resection is the treatment of choice.

Lipomas are most common in the ileum and gen-erally present as single, intramural, submucosallesions. Excision is required in symptomatic lesions(mostly SBO). As lipomas show no malignantpotential, they should be removed only if the resec-tion is simple when intraoperatively discovered.

15.5.2 Malignant Neoplasms

Of the malignant SBN, neuroendocrine tumors(NETs) comprise 36.5%, adenocarcinomas 30.9%,sarcomas and GISTs 10.0%, lymphomas 18.7%, andmiscellaneous and non-specified neoplasia 3.9%.

The only curative treatment for gastrointestinalNETs is radical surgical resection. Surgery alone orin combination with other therapeutic options maybe used as palliative treatment for patients withunresectable disease, and has been shown toincrease median survival, decrease tumor burden,facilitate symptom control, and prevent complica-tions. Surgical excision, lobectomy, or ablativetechniques (hepatic artery embolization, cryoabla-tion and radio frequency ablation) reduce tumorload in NETs with hepatic metastases. These pro-cedures are associated with clinical symptomaticimprovement and may extend 5-year survival. Livertransplantation has been utilized with success in aminority of patients.

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The only curative treatment for small-bowel adeno-carcinomas is complete surgical resection but this isoften impossible due to late diagnosis and thus localextension and extensive metastasis. Jejunal and ilealadenocarcinomas should be aggressively treated with enbloc or segmental resection and primary anastomosis.An overall increased survival for patients with small-bowel adenocarcinoma treated with combined chemo-therapy and surgery has been noted, however, furtherrandomized controlled trials are required to evaluate theeffectiveness of adjuvant chemotherapy.

The management of primary non-Hodgkinlymphoma (NHL) is debated, although surgicalexploration is initially warranted for correct diag-nosis and staging. In a Japanese study of 96 patientswith primary intestinal lymphomas, 47% were trea-ted with surgery alone, 16% chemotherapy orradiotherapy, and 35% chemotherapy plus radio-therapy. In the 2% who received no treatment,overall survival was better than that of patients whounderwent surgery, but event-free survival did notdiffer between two groups. T-cell lymphomas dis-seminate early such that complete surgical resectionis usually not feasible.

In the treatment of patients with sarcomas andGISTs, the primary aim should be complete surgicalresection with negative margins, avoiding the occur-rence of tumor spillage. Localized GISTs should beremoved en bloc, respecting a possible pseudocapsuleand avoiding intraperitoneal dissemination. Adjacentorgans adherent to the tumor should also be resecteden bloc. Medical treatment with Imatinib is indicatedin patients with unresectable, metastatic or recurrentGISTs, adjusting the dose of the drug according toresponse. Some patients may benefit from repeatsurgical excision of focal GIST progression.Leiomyosarcomas are resistant to both radio- andchemo-therapy. Surgical resection involving both thetumor and adjacent mesentery offers the only poten-tial cure.

15.6 Acute Mesenteric Ischemia

Acute mesenteric ischemia (AMI) is a life-threateningcondition with mortality rates still ranging between60 and 100% [36]. The subsets of AMI includemesenteric arterial occlusion (by embolus or

thrombosis), mesenteric venous thrombosis, and non-occlusive mesenteric ischemia.

15.6.1 Mesenteric Arterial Occlusion

Rapid operative disobliteration of the obstruction isthe standard treatment in patients with occlusivemesenteric arterial ischemia. Perfusion and viabilityof the intestine are assessed after a generous midlineincision. In embolic mesenteric artery occlusion, theproximal jejunum is usually of normal appearance.All other parts of the small intestine and the colon, upto the transverse colon, may be involved. If SMAembolus is suspected, a transverse arteriotomy in theartery’s main trunk is preferred, after the patient issystemically heparinized. The arteriotomy should beproximal to the middle colic artery. After successfulproximal and distal embolectomy, 20–30 min ofreperfusion time should be permitted before bowelresection is performed. A scrupulous intraoperativeassessment of bowel viability is necessary to mini-mize bowel resection. Inspection of intestinal color,visible arterial pulsations, and peristaltic activity, withpalpation of bowel texture and arterial pulsations areuseful parameters. Doppler signals, when present,suggest bowel viability. A ‘‘second look’’ operationmay be performed 12–24 h later to re-inspect areas ofquestionably viable intestine, aiming at reducing theextent of resection at primary exploration. Overtlynecrotic bowel, of course, has to be resected, possiblywith a stoma. If the small bowel is gangrenous,enterectomy with life-long intravenous alimentationis the only option. In patients with mesenteric arterythrombosis, the proximal jejunum is usually involvedin the ischemia. Operative revascularization is per-formed by thrombectomy, if possible, or (usually)with a bypass.

15.6.2 Mesenteric Venous Thrombosis

Anticoagulation therapy should be consideredwhenever a diagnosis of mesenteric venous throm-bosis is made. Conservative treatment is an option inpatients without peritonitis and any signs of bowelnecrosis. Conversely, all patients with localized ordiffuse peritonitis should immediately undergoexploratory laparotomy. Minimal bowel resection is

100 U. Grossi et al.

the treatment of choice, with second-look laparot-omy as a highly recommended option.

15.6.3 Non-occlusive Mesenteric Ischemia

The main pathophysiological mechanism in non-occlusive mesenteric ischemia (NOMI) is mesentericvasoconstriction, which of course cannot be cor-rected by surgery. Thus, surgical exploration inpatients with NOMI is limited to those with perito-neal signs. The treatment of NOMI is basicallypharmacological, consisting of selective infusion ofpapaverine in the SMA. Nevertheless, repeatedangiogram and the patient’s clinical symptoms andsigns should not delay surgical treatment, which maybe avoided only after the radiologically confirmedresolution of vasoconstriction and the absence ofperitoneal signs.

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Index

AAbdominopelvic infection, 44Acute mesenteric ischemia, 100Anisakis simplex, 44Ascariasis, 45Autoimmune enteropathy avium-intracelluare, 47Anemia, 13

BBack wash ileitis, 16Balloon-assisted enteroscopy, 25, 73, 79, 81, 87, 89, 90, 283Bauhin valve, 1Bowel inflammation, 56

CCapsule endoscopy, 15, 26, 31, 32, 42, 48, 65–70, 73, 75–77,

79, 81, 98Capsule retention, 49, 68, 70Cecal region, 13Cecum, 1Celiac disease, 16, 31, 51Children, 47–50Chromendoscopy, 8Chronic diarrhea, 13Chronic non-blood diarrhea, 14Colonoscopy, 13Colorectal cancer, 39, 47, 54, 55, 98Computed tomography, 14Computed Tomography Studies of Small-Bowel Disease, 60Confocal laser endoscopy, 16, 25–27Confocal laser endomicroscopy, 16Congenital malformations, 91Crohn’s disease, 13, 42, 43Cryptosporidium parvum, 44CT and Clinical Disease Activity, 62CT Versus Ileocolonoscopy, 62

DDevice-assisted enteroscopy, 65, 69Diarrhea, 13Direct Abdominal Radiography, 59

Disease, 62, 63Disease activity, 35, 39, 62Disease and Malignancies, 60Diverticulosis, 92, 93Double contrast barium enema, 2Double-balloon endoscopy, 73, 74Duodenoscopy, 31Drug-induced colitis, 14

EEariy colorectal cancer, 3Endoscopy with a magnifying, 32Endoscopy, 2, 14Enteroclysis, 59–61, 63Enteroscopy, 21, 25, 48–50, 79–83, 85, 87–90Esophagogastroduodenoscopy, 14Enterography, 14Evaluating recurrent crohn’s disease, 62

FFexible sigmoidoscopy, 7FICE, 5

GGluten, 31Granuloma, 53, 54

HHDTV, 22Histology, 14Histoplasma capsulatum, 44HIV-infected patients, 17

IIBD, 13, 14, 18, 35, 39, 47, 67, 68Ileal disease, 41Ileitis, 16Ileocecal valve, 1, 13Ileocolitis, 55Ileoscopy, 13, 22, 23, 25, 27, 47, 48, 50

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1, � Springer-Verlag Italia 2012 103

I (cont.)Ileum, 1-5, 13-18, 21-23, 32, 35, 37, 41-43, 48,

50, 56, 59, 65Infectious ileitis, 42Inflammation, 2, 32, 37-39, 54, 55, 60, 69, 95Inflammatory bowel disease, 13, 47Intestinal resection, 62, 63Intestinal tuberculosis, 16, 41, 42, 45Intra-operative ileoscopy, 32, 48, 50i-Scan, 23–25Ischemia, 91, 95, 100, 101Intraepithelial lymphocytes, 32Inderterminate, 14

LLaterally spreading tumor, 9

MMagnetic resonance, 35Magnification, 8, 17, 21–25, 32, 55–57Magnification Endoscopy, 22, 23Magnified ileoscopy, 4, 5, 48Magnifying chromoendoscopy, 22Malabsorption, 49, 76, 91, 93, 96Malformation, 91Microsatellite instability, 2MRI Evaluation of Small-Bowel, 63Mycobacterium avium-intracellulare, 43

NNarrow band imaging, 3, 8NBI, 23–25Neoplasms, 99Nonspecific ileitis, 17Nodular lymphoid hyperplasia, 16

OObscure bleeding, 47Obscure gastrointestinal bleeding, 49, 66, 75Obscure GI bleeding, 70Occlusion, 92–97, 100

PPediatrics, 48, 49PEG, 61, 63, 78Peroral pneumocolon, 59Pit pattern, 8

RRetrograde ileoscopy, 41, 42, 44Right lower quadrant abdominal pain, 13

SSessile serrated adenoma/polyp, 10Single-Balloon Enteroscopy, 85Small bowel, 91–100Small bowel enema, 14Small intestine, 1Small-Bowel Follow-Through Study Peroral

Pneumocolon, 59Small-bowel follow-through study, 14Small-bowel neoplasms, 99Small-bowel obstruction, 93Small-bowel tumors, 68-70, 76Spiral Enteroscopy, 87–90Surgery, 91–95, 97–100Surgical resection, 91–93, 98–100

TT lymphocytes, 53Terminal ileoscopy, 13Terminal ileum, 1, 13, 32, 53, 54, 56Traditional serrated adenoma, 7Tumors, 7, 8, 49, 51, 53, 57, 60, 62, 63, 66

UUlcerative colitis, 14Ultrasonograpy, 59Ultrasound Appearance of Crohn’s Disease

and Malignancies, 60

VVideocapsule endoscopy, 31Villous adenoma, 2, 32Villous atrophy, 32Villous profile, 3Virtual chromoendoscopy, 3, 16, 23, 25Virtual magnified ileoscopy, 5

WWireless capsule endoscopy, 48Wireless Capsule, 48

YYersinia enterocolitica, 42

ZZoom, 22, 24Zoom endoscopy, 22

104 Index