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Journal of Crohn's and Colitis (2008) 2, 107–113

REVIEW ARTICLE

Capsule endoscopy in Crohn's disease — Indicationsand reservations 2008Irit Chermesh, Rami Eliakim⁎

Department of Gastroenterology, Rambam Health Care Campus, Rappaport Medical School, Technion-Israel institute ofTechnology, Haifa, 31096, Israel

Received 25 November 2007; accepted 25 November 2007

⁎ Corresponding author. Tel.: +972 4E-mail address: r_eliakim@rambam

1873-9946/$ - see front matter © 200doi:10.1016/j.crohns.2007.11.003

Abstract

Capsule endoscopy (CE) was found to be an effective tool in diagnosis of small bowel pathology.This review will focus on its role in Crohn's disease. Its role in patients with suspected Crohn'sdisease (CD) is described. CE has an established role for diagnosing CD when other tests arenegative, though it is not a first line investigative tool in these patients. Over diagnosis is ofconcern. Its use in established CD remains an open question. It can provide exact mapping ofsmall bowel disease before surgery, and might have impact on the treatment of the disease. Itmay have role in monitoring mucosal healing, which is becoming a target of therapy, and mayhelp establish the exact diagnosis in a limited group of patients with indeterminate colitis.Retention of CEmight occur. It is of low rate in patients with suspected CD and higher in patientswith known CD but clinical obstruction is extremely rare. Economic considerations are a limit toa wider application of the CE.© 2007 European Crohn’s and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

KEYWORDSCapsule endoscopy;Crohn's disease;Suspected Crohn's disease;Indeterminate colitis;Mucosal healing;Retention;Complications

Contents

1. Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1081.1. What about Crohn's disease? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108

2. Diagnosis of Crohn's disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1083. Defining the extent of Crohn's disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1094. Indeterminate colitis (IC) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1105. Monitoring postoperative recurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1116. Assessment of mucosal healing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1117. What are the risks and how can they be minimized? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111

854 3784; fax: +972 4 854 3058..health.gov.il (R. Eliakim).

7 European Crohn’s and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

108 I. Chermesh, R. Eliakim

8. Economic considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1129. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112

1. Background

Capsule endoscopy (CE) is a minimally invasive means ofevaluating the small intestine. In this elegant technique, thepatient is given a small capsule to swallow. This is a disposable26×11 mm video capsule (Given Imaging, Yokneam, Israel)containing its own optical dome, light source, batteries,transmitter and antenna. The pictures (2 per second) aretransferred via sensor arrays to a recorder and are downloadedfor reviewing. This minimally invasive modality that took up tothe challenge of literally viewing the entire small bowel wasintroduced by Gabriel Idan in 2000.1 The capsule has been withus for seven years and over 700 publications regarding its use invarious clinical settings have been published. Recently the FDAhas approved the second-generation capsule for use. Thiscapsule has an improved angle of view, better illumination, andautomatic light control. The new Rapid 5 software contains anatlas and a scoring system for IBD (the Lewis score) incorporatedin it (Fig. 1). There are some additional small bowel capsulesystems that are approved for use in different parts of theworld,none of which is yet, to our knowledge, except the OlympusEndoCapsule (Olympus Japan) is FDA approved. These includethe Chinese OMOM pill (Jinshan science & technology, Chongq-ing, China) and the Korean MicroCam (Intromedic, Seol Korea).

This review will focus on the Given capsule endoscope andits role in Crohn's disease.

Crohn's disease is an inflammatory disease of the gastro-intestinal tract. Any part of the gastrointestinal tract from themouth to the anus could be involved. Standard endoscopyprocedures enable vision of only a small part of the smallintestine. With these procedures, only the first, second andthe beginning of the third part of the duodenum (gastro-scopy), and the terminal ileum (colonoscopy) are seen. Whenenteroscopy is preformed, some of the distal duodenum andproximal jejunum can be scoped, but the vast part of thesmall intestine cannot be reached, unless the newly intro-

Figure 1 PillCam SB2.

duced double balloon system is used. The remainder of thesmall intestine could be imaged by roentgen (CT MRI or smallbowel follow through). Up to the introduction of CE, we weresomewhat blind to a major part of the small intestine. Sinceits introduction and usage many questions have arisen. Doesthe capsule enable viewing of the whole small intestine?Will itchange patient management in Crohn's disease? If so, whenshould it be used in patients suffering from Crohn's disease, orsuspected to have Crohn's disease? Should it be used only whenthe classic techniques fail? Are there special considerations tobe taken when evaluating a patient with known Crohn'sdisease with CE compared to other indications?

When evaluating the sensitivity and specificity of a newtechnique, it should be compared to a gold standard test, butno gold standard test for visualization of the small intestineexists. Studies evaluating the sensitivity and specificity of thecapsule are somewhat problematic in this sense. Another pitfallis an incomplete examination,which has been found to occur inabout 20% (15–35%) of cases.2–5 While some clinical settingssuch as obscure gastrointestinal bleeding are readily validatedand widely accepted,6 others are still under investigations.

1.1. What about Crohn's disease?

Erosions and ulcerations can be detected with a high degreeof accuracy with CE.7 Thus, in a patient with Crohn's disease,the capsule allows to diagnose the extent of disease. Themeaning of the findings in a patient with suspected Crohn'sdisease is somewhat more complicated. Does the patientwith erosions and/or ulcerations suffer from Crohn's disease,are these findings secondary to non-steroidal anti inflamma-tory drug usage, or are they just part of the “normal”spectrum with no clinical significance, as has been describedin some studies in up to 14% of normal subjects.8 Part of theanswer has been given by Maiden et al. who included healthyvolunteers in their study. They demonstrated that if 4 weeksof abstinence from NSAID were kept, no erosions were foundin the small bowel.9

We will address the following clinical situations in whichCE might be useful and relevant:

1. Diagnosis of Crohn's disease.2. Defining extant of Crohn's disease.3. Differentiating between Crohn's disease and Ulcerative

Colitis (UC) in a patient with indeterminate colitis (IC).4. Monitoring postoperative recurrence.5. Assessment of mucosal healing.6. Risks and how can they be minimized?7. Economic considerations.

2. Diagnosis of Crohn's disease

Abdominal pain, diarrhea, weight loss, anemia, and labora-tory signs of inflammation may indicate Crohn's disease.

Table 1 Diagnostic yield of CE in patients with suspected CD3,5,10–17

1st author Nopatients

Indication Diagnostic yieldfor Crohn's (%)

Comparative studies

May 50 Abdominal pain+1≥objective sign 26 Colonoscopy and gastrocopyShim 110 Abdominal pain 3 VariousDe Bona 12 Abdominal pain 8 Various

26 Abdominal pain+markers ofinflammation

46

Chong 21 Suspected CD 10 Push enteroscopy, enteroclysis, and CE — sameyield

Eliakim 35 Suspected CD 77 CTE or SBFT 26%Fireman 17 Suspected CD 71 Colonoscopy, gastroscopy and SBFT — 0%Liangpunsakul 40 Abdominal pain+/−anemia 8 Colonoscopy, gastroscopy and SBFT — 0%Herrerías 21 Suspected CD clinical+ laboratory 43 Colonoscopy — 5%, gastroscopy and SBFT — 0%Argüelles-Arias

12 Suspected CD 58 Colonoscopy, gastroscopy and SBFT — 0%

Ge 20 Suspected CD 65 Colonoscopy, gastroscopy and SBFT — 0%

CTE = CT enterography.

109Capsule endoscopy in Crohn's disease — Indications and reservations 2008

Standard, classic evaluation consists of thorough historytaking, physical examination and basic laboratory tests,where upon a decision is made as to whether the patientshould undergo further evaluation. This evaluation consistsof endoscopic examinations, colonoscopy with ileoscopy,and radiographic tests: CTor MRI enteroscopy, and/or smallbowel follow through (SBFT). When these tests are negativea decision should be made whether the signs and/orsymptoms justify further evaluation. It is this group ofpatients that most CE studies are focused on: patients withsuspected Crohn's and negative radiologic/endoscopicworkup. Of note is the fact that ileoscopy was not preformedin about 50% of the patients studied in this setting. To date,10 studies have assessed the usefulness of the capsule indiagnosing Crohn's disease10–17 (Table 1). The studies arenot uniformly designed, so it is not surprising that theoutcomes are different. Earlier studies included highlyselected patients with a high degree of suspicion. In thisgroup of patients, the yield of Crohn's diagnosis was~70%.12,13 Recent studies have included a less selectedgroup of patients. In these studies, the diagnostic yield wasmuch lower ~20% (8–60%). The yield is lowest when the onlysubjective finding is abdominal pain, as opposed to moreobjective findings (weight loss or inflammatory laboratoryfindings) are present.5,12 Whether the yield is 70% or 20%,there is a general agreement that, if there is a suspicion ofCrohn's disease and the workup is negative but the physicianperceives that further investigation is warranted, CE shouldbe considered as the next step. When CE is preformed, thereis a tradeoff — higher sensitivity but lower specificity.Therefore, we recommend that CE be done after at least1 month off NSAIDs and the results be described judicially,taking into consideration clinical presentation as well asadditional tests so that over diagnosis is avoided.7,18 Severalgroups are trying to develop a CE scoring system so that allphysicians interpreting CE results will speak the same“language”. Recently, Gralnek et al. defined three majorscoring parameters — villous edema, ulceration, andstenosis. Each parameter was defined by a numerical

score. The results are thereupon summed, according tothe sum, a conclusion of no or clinically insignificantchange, mild change, and moderate or severe change isreached.19

Algorithm formanagement of patientwith suspectedCrohn'sdisease was published by the consensus group at the interna-tional conference for capsule endoscopy (ICCE)20 (Fig. 2).

3. Defining the extent of Crohn's disease

Crohn's disease can involve any part of the gastrointestinaltract. Up to the invention of CE, there was no good way todirectly visualize the small intestine. While the capsulemighthave added value in providing a better view of the smallintestine, one needs to ask himself whether this is important,i.e., does it have an impact on patient management andwhen. The main medical treatment for Crohn's consists of 5-ASA, steroids, antibiotics, immunosuppressants, and anti TNFmedications. The decision regarding treatment relies onthorough clinical evaluation. In most patients, the exact‘mapping’ of involvement will not change management.Voderholzer et al. described a change in management of 10out of 56 patients due to the findings of CE.21 In another studyby Mow et al., 17 of 20 patients with definite findings on CEimprovedwith increased IBD-directedmedical therapy, as did7 of 10 patients with suspicious study results.22 The majorindication for the use of CE in this group of already diagnosedCrohn's patients is limited to a few situations: One might bewhen there are abdominal complaints in the face of normallaboratory results (to seeweather there is inflammation or itsIBS). Another setting might be to view the small bowel whenthere is unexplained anemia/blood loss in patients withCrohn's colitis. A 3rd setting might be to monitor small bowelmucosal healing after various treatments, or as a prognostictool, perhaps guiding treatment (mainly in research settingsat this point). A 4th setting might be when surgical treatmentis considered, when it might be important to “map” the exact

Figure 2 Algorithm of suspected Crohn's disease.

110 I. Chermesh, R. Eliakim

extent, and diagnose relevant strictures. In specific cases itcan be perceived as a “stress test” for strictures, as othernon-invasive tests, such as SBFTor CT, are less reliable for thediagnosis of strictures. If the patient has obstructivesymptoms suggestive of strictures and other tests arenegative, CE can indicate if there is a stricture and give apresumptive localization.

The only complication of CE described so far is retention,which might occur when a stricture exists (see the sectionregarding complications). In these specific scenarios, if thecapsule is not expelled, it should not be perceived as a

complication, but rather as a guide to the surgeon to definethe location of a significant stricture so that it can be treatedadequately.23,24 Another subgroup where CE might be helpful,indeterminate colitis will be discussed separately.

4. Indeterminate colitis (IC)

There is no generally accepted definition for IC.25 All currentapplications of the termrely onexclusionary criteria and there isno confirmatory diagnostic test. Nevertheless, the diagnosis of

111Capsule endoscopy in Crohn's disease — Indications and reservations 2008

IC appears to be found in about 10% of patients with IBD,suggesting that this group represents a uniquephenotype. In thisgroup of patients, there's an unclear inflammatory involvementin the colon while other tests are negative. CE may show smallbowel involvement, thereby defining the disease as Crohn's asopposed to UC or IC. Mow et al. were the first to investigate thiscondition. They investigated 22 patients — 17 fitting into theabove description and five with ileo-anal anastomosis (IAA).Relevant findings on CE suggestive or diagnostic of Crohn'sdisease, leading to a change inmanagement, were found in halfthe patients.22 Recently, Maunoury et al. 26 reported on CEfindings in 30patientswith IC. Elevenwereeventually diagnosedwith Crohn's disease, five with the help of CE, and six afterrepeat endoscopy with ileoscopy. In another study sixteenpatients considered to have UC underwent colectomy. Aftersurgery, they suffered from chronic pouchitis. Fifteen of themwere examined by CE. All 15 were found to have lesionsconsistent with Crohn's disease.27

5. Monitoring postoperative recurrence

Four studies assessed the utility of the CE in assessingpostoperative recurrence of Crohn's disease.28–31 They wereperformed 6–12 months after surgery. The studies in which CEwas preformed one year after surgery showed postoperativerecurrence in the small bowel in nearly 100% of patients. In thestudyperformed6months after surgery, involvementwas seen ina smaller portion of patients. CE results were inferior toileoscopy in the neo-terminal ileum in most studies, but weresuperior and gave new information regarding the upper smallbowel, as expected. On the whole, if endoscopic recurrencereaches 100% one year postsurgery, it could be argued that noendoscopic evaluation of any sort is needed at this stage, andmanagement should be given accordingly or if there are clinicalindications. Unless re-operation is considered ormucosal healingis sought as a means of treatment follow-up (see section onmucosal healing), the capsule does not seem to be indicated inthis group of patients.

6. Assessment of mucosal healing

There are many clinical and laboratory markers of inflamma-tion. None is specific and their sensitivity is subject to greatvariability. On the whole, these tools are far from ideal.Immunomodulator and Infliximab have been found to inducecolonic mucosal healing at different rates; this seems to bethe most reliable tool for assessing Crohn's disease activityand has recently been associated with decreased hospita-lization and operation rate.32 There is no study that as-sessed the utility of CE to detect mucosal healing, but itssensitivity formucosal pathology has been established and itis reasonable to assume that it can be applied in this setting.Therefore, if and when mucosal healing becomes standardin assessing therapeutic interventions and disease activity,there will be a probable role for CE in this setting, butremains to be proven.

7. What are the risks and how can they beminimized?

The only complication of CE is non-natural excretion (NNE).Most impactions do not cause acute intestinal obstruction,

although this has been described on rare occasions.33,34

Impaction occurs when there is an unforeseen stricture. Therates of NNE of CE are not accurate as patients wereexcluded from studies if there was any suspicion of astricture. This could have been on clinical grounds(obstructive symptoms), or imaging modalities findings.Even with these precautions, some capsules were retained,necessitating endoscopy, sometimes with the help of adouble balloon35,36 or surgical retrieval. In many cases,surgery was more than just retrieval of the capsule, butactually therapeutic with resection of the stricture itself.The propensity for retention is different with varyingindications. In a large retrospective study consisting of733 patients referred for various reasons (mainly obscure GIbleeding), retention occurred in 14 patients (1.9%).2 Elevenof these patients had normal radiologic small bowelexaminations, demonstrating that this is not a reliablemeans of detecting strictures. The highest percentage ofNNE was observed in patients with established Crohn'sdisease. In a recently published report, retention inpatients with known Crohn's disease occurred in five of 38(13%) patients; of these, three strictures were unknownbeforehand. Retention occurred in one of 64 patients withsuspected Crohn's disease.37 The overall retention rate forpatients with suspected Crohn's is 1.4%. When retention issuspected — a plain abdominal film should be obtained after2 weeks. If retention is confirmed endoscopic or surgicalremoval should be planned. Retrieval of capsule is usuallypreformed on an elective basis, unless the patient issymptomatic.38

As radiologic examinations are unreliable for the detec-tion of strictures, and seeking for a better solution inpatients with obstructive symptoms or in high risk, broughtabout the development of the “patency capsule” (PC). ThePC consists of a biodegradable body surrounding a smallradiofrequency identification tag. If the PC is excretedintact, it is presumed that no significant stricture ispresent. In the presence of a stricture, the PC disintegratesinto small fragments and is excreted along with theradiofrequency tag. A scanner is used to detect theradiofrequency tag externally. There are five studiesassessing the yield and safety of the PC.39–43 Two mainpoints were investigated. The first is the PC's ability todetermine which patients could have the real CE per-formed, and the second is the safety of the PC itself. A totalof 134 patients were studied in these four studies. Not allthe patients who had “clearance” to perform the real CEprocedure actually did so, but the 62 patients who under-went the procedure had no complications. Four of 134patients (2.9%) had to undergo surgery due to impaction ofthe PC itself. Although it could be assumed that most ofthese patients would have needed surgery irrespective ofthe PC impaction, it is still a disturbing point to be takeninto account and explained to the patient. In order to solvethe problem outlined above, a new generation of PC hasbeen developed. This new generation PC, the AGILEcapsule, disintegrates to smaller particles, therefore isdesigned to pass even when a stricture exists. Herrerías etal. preformed a study utilizing the Agile PC in 106 patientswith evidence of intestinal stricture. In 47 patients thecapsule disintegrated, therefore stricture was established,none of which suffered from clinical obstruction.44

112 I. Chermesh, R. Eliakim

8. Economic considerations

CE is perceived an expensive test. Therefore, it is somewhatsurprising to learn that this test might actually save money.Eisen performeda thorough economic evaluation of the capsulefor various indications.45 On the whole, patients underwent6.77 negative diagnostic procedures before being referred toCE. These tests are costly, some invasive or requiring X-rayexposure. CE is non-invasive, allows visualization of the entiresmall bowel in most patients, and is accurate. It might enableearlier diagnosis and treatment which can save money, withmore days of well-being and less loss of working days.Concerning Crohn's disease specifically, it was calculated thatthe capsule is economic if the diagnostic yield is 64% or higher.

9. Conclusion

At this stage, CE should be done in patients with suspectedCrohn's disease or indeterminate colitis, a month after NSAIDstoppage, when other tests are negative. It may have an evenbigger role, in earlier stages of the investigation, when theprice is lowered andphysicians accumulate greater experience.The role of CE in patients with established Crohn's disease is yetto be defined. It will most probably serve as an indicator ofmucosal healing after treatment, or of significant stricturesbefore surgery.

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