Video Capsule Endoscopy of the Small Bowel

[David in Seattle]

Rami Eliakim

Curr Opin Gastroenterol. 2010;26(2):129-133. © 2010 Lippincott Williams & Wilkins

Abstract and Introduction
Abstract

Purpose of review It is now over 8 years since small bowel capsule endoscopy (SBCE) was first introduced to the gastrointestinal community. The original capsule (Given Imaging, YoKneam, Israel) – a disposable 26 × 11 mm video capsule containing its own optical dome, light source, batteries, transmitter and antenna – is swallowed with water after a 12 h fast. The capsule is propelled via peristalsis through the gastrointestinal tract and is excreted naturally. We will review all recent work concerning SBCE.
Recent findings At present there are three other SBCEs in the market. SBCE has become a first-line tool to detect abnormalities in the small bowel, as all other imaging technologies are rather ineffective, or very tedious.
Indications for SBCE include obscure gastrointestinal bleeding, suspected small bowel tumor, suspected Crohn's disease, surveillance of inherited polyposis syndromes, drug-induced small bowel injury or any abnormal small bowel imaging and new ones are emerging like small bowel motility. Since most of the articles in the literature relate to the PillCam small bowel capsule the data presented will refer mainly to this capsule endoscopy.
Summary SBCE has shed new light into our knowledge of the small bowel, paving the way for new modalities to come.
Introduction

Capsule endoscopy was first introduced nine years ago by Iddan et al.,[1] and was accepted with great enthusiasm. Since then, it has become an important tool in the investigation of small bowel abnormalities. In the few years since its marketing over 1000 studies have been published looking at its efficacy versus other modalities in various indications, and preparation aiming to improve the diagnostic yield and technical aspects.

Technical Aspects of Small Bowel Capsule Endoscopy

The original PillCam small bowel video capsule endoscope is a wireless capsule (11 × 26 mm) comprised of a light source, lens, CMOS imager, battery and a wireless transmitter. The slippery coating of the capsule allows easy ingestion and prevents adhesion of contents, whereas the capsule moves via peristalsis from the mouth to the anus. The battery provides 7–8 h of work in which the capsule photographs two images per second (around 60 000 images all together), in a 140 degree field of view and 8: 1 magnification. The second generation of the capsule (PillCam SB2) has been available for over 2 years. It has the same size, but has a broader angle of view (156 degrees) and better optics with an advanced automatic light control, allowing 120% better visualization of the small bowel mucosal area. The pictures are transmitted via an eight lead sensor array, arranged in a specific fashion on the patient's belly, to a recorder, which is worn on a belt. Recently the company released a new sensor array in a belt, with no attachments to the belly. The recorder is downloaded into a Reporting and Processing of Images and Data computer workstation (RAPID 6) and seen as a continuous video film. Since its development additional support systems have been added. These include a localization system, a blood detector, a double and quadri picture viewer, a quick viewer, single picture adjustment mode, incorporation of the Fuji intelligent color enhancement (FICE) system, an inflammation (Lewis) scoring system and an atlas, all meant to assist the interpreter.

For the patient, this is an easy, well tolerated, noninvasive and ambulatory procedure. Typically, the patient swallows the capsule with water after a 12 h fast. The patient can drink clear fluids, 2 h after capsule ingestion and eat a light lunch after 4 h. During the procedure he is free to do his daily activities. In some places, the patient is connected at home and disconnected at work, allowing a regular daily schedule.

Some investigators have suggested the addition of a bowel preparation in order to improve the rate of complete small bowel endoscopy and visualization of distal small bowel. A meta-analysis looking at the efficiency of bowel preparation concluded that preparation improves the quality of visualization, but has no effect on transit times or percentage of capsules reaching the cecum. There was no agreement whether there was an effect on the diagnostic yield.[2•] Two recent prospective studies have found no advantage for bowel preparation with oral sodium phosphate, or for the use of bowel purgatives or/and prokinetic agents.[3,4] Incomplete small bowel transit while doing the examination is about 20%. A recent retrospective study found previous small bowel surgery, hospitalization, moderate or poor bowel cleansing and gastric transit time longer than 45 min as independent risk factors for incomplete small bowel capsule endoscopy (SBCE) procedures.[5]

There are some additional small bowel capsule systems that are approved for use in different parts of the world. These include the Olympus EndoCapsule (Olympus, Japan), which was compared head to head to the old generation PillCam small bowel and found to be as good,[6•] the Chinese OMOM pill (Jinshan Science & Technology, Chongqing, China) and the Korean Miro pill[7••] (Fig. 1). The characteristics and comparison between the capsules are given in Table 1.

Figure 1.

Endoscopic capsules available in the market

 

[David in Seattle]

Indications

The indications for the use of capsule endoscopy are as follows:

1. occult gastrointestinal bleeding,
2. suspected Crohn's disease,
3. suspected small bowel tumor,
4. surveillance of inherited polyposis syndromes,
5. evaluation of abnormal small bowel imaging,
6. evaluation of drug-induced small bowel injury and
7. partially responsive celiac disease.

Obscure Gastrointestinal Bleeding

The primary indication for which the FDA, following the report by Lewis and Swain,[8] approved SBCE was obscure gastrointestinal bleeding (OGIB). Since then many studies have shown a statistically significant increased diagnostic yield of SBCE over push enteroscopy and other modalities in the range between 39 and 90%[9,10] and a similar diagnostic yield to balloon-assisted enteroscopy.[11••,12] It has been shown that the closer SBCE is done to the bleeding episode, the higher the diagnostic yield.[10] The sensitivity of SBCE ranges between 89 and 92%, and the specificity is around 95%. On the basis of these results the new algorithm suggests SBCE as the initial investigation after a negative upper and lower endoscopy, followed by push, double balloon, or intraoperative enteroscopy as therapeutic procedures. A negative capsule endoscopy study in patients with obscure bleeding is associated with low rate of recurrent bleeding in the long term, making it reasonable to use SBCE expectantly with these patients, avoiding the need for unnecessary additional investigations.[13]
Crohn's Disease

Initial studies evaluating the use of SBCE in suspected Crohn's disease suggested that SBCE has a higher diagnostic yield compared to other modalities.[14] A meta-analysis reviewing 11 prospective comparative studies comparing SBCE to other modalities, found SBCE to have a better incremental yield ranging between 15 and 44% compared to other modalities. This was true for both known and suspected Crohn's disease.[15] Recently, an OMED-ECCO consensus on the role of small bowel endoscopy in the management of patients with inflammatory bowel disease (IBD) was published.[16••] It stated that SBCE is able to identify lesions compatible with Crohn's disease in some patients in whom conventional endoscopic and radiographic imaging modalities have been nondiagnostic, may be better than small bowel follow through or enteroclysis, and that a normal capsule study has a high negative predictive value for active small bowel Crohn's.

In patients with known Crohn's, SBCE may alter disease management, assess mucosal healing after medical therapy, and assess early postoperative recurrence and thus guide therapy. Studies comparing SBCE to ileo-colonoscopy in the detection of early postoperative recurrence, gave contradictory results with either ileoscopy or SBCE being the better initial tool for distal small bowel recurrence. SBCE detected more lesions in the proximal small bowel in both studies.[17,18] SBCE was found to be potentially clinically useful for categorizing patients with indeterminate colitis, although negative SBCE study did not exclude further diagnosis of Crohn's.[19] Moreover SBCE found patients with chronic refractory pouchitis to have diffuse lesions from the duodenum to the ileum (apthae, erosions, etc.).[20] The nature of this enteropathy is yet unknown. It is those patients with a few aphtous lesions in the small bowel on SBCE who create a problem, as other causes such as nonsteroidal anti-inflammatory drugs (NSAIDs) can macroscopically look similar. Thus it is advised to abstain from use of NSAIDs for at least 1 month prior to capsule examination.
Inherited Polyposis Syndromes

SBCE can be used as a surveillance tool for small bowel polyps in patients with inherited (familial) polyposis syndromes. SBCE has been found to have a better diagnostic capability to reveal small bowel polyps compared to barium follow-through in patients with Peutz-Jeghers syndrome.[21,22] The duodenum is a potential pitfall as the capsule passes it very fast and thus may give false-negative results.[23] Size estimation is another problem. This was seen in a prospective study in which SBCE was compared to push enteroscopy and lower endoscopy. In that study, SBCE detected less polyps and underestimated the size of large polyps.[24] The coupling of SBCE with double balloon enteroscopy and polypectomy may offer an ideal method of follow-up and treatment of these patients, possibly avoiding surgery.[25]
Small Bowel Tumors

The utility of SBCE has more than doubled the rate of diagnosing small bowel tumors from around 3% to 6–9%. Most of the tumors were found in patients undergoing SBCE for OGIB, and 50–60% were malignant tumors.[26–28] As the outcome of small bowel tumors depends on their early diagnosis, a more liberal use of SBCE for gastrointestinal symptoms might lead to improved management and survival of these patients, but this needs to be proven.
Celiac Disease

Celiac disease affects almost 1% of the western population. SBCE provides high-resolution magnified view of the mucosa, easily identifying the endoscopic changes found in celiac such as scalloping, mosaic pattern, flat mucosa, loss of folds and nodularity. SBCE can provide information on the distribution of the disease in specific individuals, be a surveillance tool in partial or nonresponders, or for initial diagnosis in patients with positive serology who refuse conventional endoscopy. Initial studies have shown SBCE to be very sensitive in patients with proven celiac disease.[29] The celiac disease consensus group concluded that there was adequate evidence to support the use of SBCE as a prognostic tool in patients with proven celiac who develop symptoms and possibly in the future as an initial diagnostic test for confirming atrophy in sero-positive patients.[30]
Monitoring Drug Effects or Side Effects

Another potential use for SBCE is to monitor deleterious effects of drugs (e.g. NSAIDs) on small bowel mucosa. SBCE clearly demonstrated NSAIDs induced small bowel damage by both COX1 and COX2 antagonists. Lesions included erythema, erosions, small ulcerations and web-like strictures.[31] SBCE may be used as a monitoring tool as well. It can be used to monitor the effect of drugs (prostaglandins or others) on small bowel injury induced by NSAIDS,[32] to monitor the small bowel in transplant patients, in the management of graft versus host disease and possibly to monitor mucosal healing of small bowel Crohn's disease after various medical treatments.[33,34]
Motility

Recently progress has been made in the evaluation of small bowel motility using capsule endoscopy. Endoluminal image analysis by means of computer vision and machine-learning techniques was shown to constitute a reliable, noninvasive and automated diagnostic test of intestinal motor disorders.[35••]

 

[David in Seattle]

Complications

Capsule retention is the major and for practical purposes the only complication of SBCE (Table 2). Capsule retention is the indefinite presence of the capsule in the small bowel unless an intervention of any sort is initiated, as opposed to slow transit or incomplete transit through the small bowel during the examination, which occurs in up to 20% of examinations. Retention can potentially lead to symptomatic small bowel obstruction and surgery or to surgery if not eventually evacuated. The rate of indefinite retention appears to depend on the indication for the examination. High risk of retention occurs in patients with known Crohn's disease, NSAID stricture, radiation enteritis and small bowel tumors. A normal small bowel series does not protect from having capsule retention. Li et al. [36] reported a 1.4% retention rate in a single-center experience with 1000 patients, the main reason for retention being NSAID enteropathy. The risk of retention in patients with OGIB is around 5%, in suspected Crohn's it is around 1.4%, whereas in known Crohn's disease it can reach 8% or more. No retention (0%) was reported in 773 capsule ingestions by healthy volunteers. As of today, a case or two of acute small bowel obstruction due to capsule endoscopy was reported in the literature in more than one million swallows.[37] Once retention is suspected, an abdominal radiograph should be obtained after 2 weeks. Once retention is diagnosed, endoscopic (double balloon enteroscopy) or surgical removal has been shown to be effective. There is no time limit for instituting management unless the patient becomes symptomatic. The intervention not only allows removable of the capsule, but also of the offending abnormality. The use of the Agile patency capsule (Given Imaging, Yokneam, Israel) can dramatically reduce retention rate when the pretest suspicion is high, and the traditional capsule can be safely used once the patency capsule was excreted undamaged.[38••]

Conclusion

In the years since its introduction, SBCE proved to be the preferred modality for mucosal imaging of the small bowel. There is now a consensus that it should be initiated early in the work-up of OGIB, when by its high diagnostic yield it can guide treatment. Moreover, it can aid in making the best decision as to the use of balloon-assisted enteroscopy and thus potentially alter the decision tree. In the right clinical setting it is a wonderful tool to diagnose Crohn's disease with no inconvenience and minimal risk, though there is yet much to be learned regarding the appearance of the normal small bowel mucosa of healthy volunteers. SBCE along with double balloon enteroscopy is becoming the primary mode of small bowel surveillance in patients with inherited polyposis syndromes, and the preferred mode of monitoring mucosal integrity in various diseases, and new indications like small bowel motility are starting to emerge. The European multicenter study using the first-generation bidirectional colonic capsule with prolonged battery time, have just been published[39] and studies with an improved second-generation colon capsule are on their way. With these, one may easily dream of a pan-endoscope, a real mouth to anus (M2A) endoscopy with just one pill that will be a perfect initial tool for patients with iron deficiency anemia, or suspected IBD, with targeted biopsies and or drug delivery.