Video Capsule Endoscopy: A Window on the Spectrum of Small Intestinal Disease

Ritu Sachdev, M.D.
Faisal Bhinder, M.D.
David Cave, M.D.

Keywords

Crohn's disease, gastrointestinal bleeding, small intestine, video capsule endoscopy.

Introduction

The clinical application of video capsule endoscopy (VCE) started in August 2001 with the FDA approval of the M2A™ (now marketed as PillCam SB™) video capsule as a primary diagnostic device for small intestinal disease [Given Imaging: developed and produced by Given Imaging]. Three years later, there is still no competition for the device, once viewed with considerable skepticism by some. VCE has now become a primary device for the detection of small bowel disease, instead of the adjunctive device that was its initial status. Approximately 1,000 VCE sites are established in the United States and a similar number worldwide, a remarkable rate of acceptance for a new technology. The M2A™ (now marketed as PillCam SB™) capsule takes about 55,000 digital images over an 8-hour period and provides good quality images of the small intestine and variably useful images of the esophagus, stomach, and colon. Detection of pathologies is about 70% as compared with 40% for conventional radiology and endoscopy.

The peer-reviewed literature is beginning to evolve with reports on small series of patients relating to obscure gastrointestinal bleeding and Crohn’s disease (1). The literature demonstrates that the device is not just a high tech toy but has a real impact on improving patient management and outcome. In this paper, we present a series of images that demonstrate the spectrum of abnormalities that are detectable by VCE.

Non-pathological Mucosal Abnormalities

A common problem with video capsule endoscopy is the lack of pathological confirmation, despite its visual detection of lesions. This is due to our inability to reach some lesions by push enteroscopy, and the fact that not all patients in whom there is a finding need surgical or endoscopic intervention. This problem may be resolved by the increasing availability of a double balloon push enteroscope, which, at least theoretically, can be passed through the entire length of the small intestine (2). Furthermore, mucosal abnormalities provide a daily diagnostic challenge to those who are new to VCE and even to experts. The gastric aspect of the pylorus is usually easy to define (Figures 1A and 1B, Video Clip 1), but the duodenal aspect of the pylorus can cause confusion, particularly in the uncommon event of the capsule moving retrograde after having passed well in the duodenum (Figure 2). Another example is that villi may be colorless (Figure 3); white, either as isolated villi in patches (Figures 3 and 4, Video Clip 2); or diffusely white. The condition congenital lymphangectasia is an extreme example of disease at the far end of the normal spectrum, where the villi are all white. A typical example of normal villi is shown in Figure 5. Vascular anomalies of the small bowel are common and sometimes difficult to know whether they can bleed or not (Figure 6).

Figure 1A	Figure 1B	Video Clip 1: Capsule view of normal pylorus. Larger Versions: Low Resolution High Resolution	Figure 2

Figure 3	Video Clip 2: Capsule view of lymphoid hyperplasia. Larger Versions: Low Resolution High Resolution	Figure 4	Figure 5	Figure 6

Obscure Gastrointestinal Bleeding

Obscure gastrointestinal bleeding (OGIB) (3,4) has been a challenge to the endoscopist since the advent of flexible endoscopy and is emblematic of a broader issue that what one cannot see tends to be ignored or at least rationalized. The capsule can detect gastric sources of bleeding such as gastric antral venous ectasia (GAVE) (Figure 7), angioectasia (Figure 8), Dieulafoy’s lesions (Figure 9), erosions, peptic ulcers, and Cameron’s lesions (Figure 10, Video Clip 3). In the small intestine, the list of potential sources of bleeding is quite long (Table 1). The limitation of VCE in that the diagnosis is purely visual; it does not provide the ability to maneuver for a better view, biopsy, or treat. Thus, the capsule diagnosis is one of operator interpretation, which has obvious limitations. Conventional endoscopy may have the same problem, although less frequently. The issue of interpretation should gradually lessen as more experience is gained and pathological backup is provided to support VCE images. One of the most common findings is active bleeding from an anatomic area without a specific source being identified (Figure 11). This is not problematic, if it is within range of push enteroscopy. If it is beyond range of push enteroscopy and requires intra-operative endoscopy, it may be very difficult to localize, since the lesion may stop bleeding under anesthesia and be impossible to find. In general terms, VCE has reduced endoscopic rationalization and now permits, along with an EGD and colonoscopy, complete evaluation of the length of the gastrointestinal tract.

Figure 7	Figure 8	Figure 9

Figure 10	Video Clip 3: Capsule view of Cameron's lesions. Larger Versions: Low Resolution High Resolution	Figure 11

Tumors

Tumors of the small intestine are more common than previously assumed. Figure 12 is an example of lymphoid hyperplasia. Several recent studies from around the world have consistently reported a prevalence of 6-8%. The problem is that it is not possible with the capsule alone to categorize these as benign or malignant. Large ulcerated, bleeding lesions are easy to manage as it is apparent that surgery is needed (Figures 13A and 13B, Video Clips 4 and 5). However, small lesions, such as the carcinoid in Figure 14, are much more difficult in terms of the decision making process. In general, tumors are the most challenging lesions for the capsule endoscopist to deal with. Establishing what may be a submucosal mass as opposed to an indentation from an abdominal structure may be very difficult to resolve (Figure 15). Since the resolution of the capsule is so good, it is clear that we can now detect tiny tumors such as carcinoids, much earlier in their natural history than has previously been possible.

Figure 12	Figure 13A	Video Clip 4: Capsule view of of melanoma. Larger Versions: Low Resolution High Resolution	Figure 13B	Video Clip 5: Capsule view of ischemic stricture. Larger Versions: Low Resolution High Resolution

Figure 14	Figure 15

NSAIDs

The possibility that NSAIDs can cause injury to the small intestinal mucosa has long been suspected but difficult to prove. The video capsule has been used in two contexts. First, a number of observers have detected NSAIDs associated webs in patients with obscure GI bleeding and or abdominal pain (5,6). There is a relatively high frequency of capsule retention with these lesions. Unfortunately, antecedent small bowel series or enteroclysis usually failed to detect these lesions prior to capsule endoscopy. These lesions are often associated with ulceration (Figures 16A and 16B, Video Clip 6). The discontinuation of NSAIDs does not necessarily result in cessation of bleeding. These lesions appear to be rare and are probably idiosyncratic. More recently, a clinical trial comparing nonselective NSAIDs with COX 2 inhibitors and placebo has demonstrated that the nonselective NSAIDs, even with a two week course of treatment, cause significantly more lesions than COX 2 inhibitors. The lesions induced by short-term courses of NSAIDs are mainly small mucosal breaks (Figure 17). 

Figure 16A	Video Clip 6: Capsule view of NSAID stenosis. Larger Versions: Low Resolution High Resolution	Figure 16B	Figure 17

Crohn’s Disease

The role of the video capsule in the detection of suspected Crohn's disease is beginning to be defined. There is a population of patients with abdominal pain and or diarrhea associated with anemia, low serum albumin, raised sedimentation rate, and/or weight loss in whom Crohn's disease is suspected but conventional technology cannot define. Two small series have been published on this topic (7,8). Figures 18-20 show examples of Crohn’s disease. In addition, one paper on obscure GI bleeding and our own and data suggest that in a population with obscure bleeding, about seven percent of these patients have unsuspected Crohn's disease. In addition to its role in defining unsuspected Crohn's disease, the capsule will probably have a role in defining extent of disease and activity of disease. Furthermore, capsule studies, before and after therapeutic intervention, with new agents undergoing clinical trials are likely to become commonplace.

Figure 18	Figure 19	Figure 20

Celiac Disease

Celiac disease has a common genotype but an uncommon phenotype. The reasons for this disparity are clear. Furthermore, the disease may be missed endoscopically because of this atrophy may be difficult to see if air insufflation is used. Flooding the duodenum with water provides a much better demonstration of the presence or absence of villi. It is currently unclear as to whether the video capsule will have a role in the management of celiac disease, but it has already provided a means of defining the extent of disease non-invasively (Figures 21A-21C, Video Clip 7). It may also have a role to play in the detection of neoplasia in this condition and in the detection of the source of guaiac positive stools, which may occur in as many as 25% of patients. Studies are underway to assess the relationship all of celiac disease serology, conventional endoscopy and biopsy and capsule endoscopy.

Figure 21A	Figure 21B	Figure 21C	Video Clip 7: Capsule view of celiac disease. Larger Versions: Low Resolution High Resolution

Safety of Capsule Endoscopy

The safety record for the PillCam has been excellent. No deaths have been associated with 120,000 studies with the device. Incomplete studies have been reported about 20-25% of the time. The majority are incomplete studies with failure of the device to pass the ileo-cecal valve before the battery runs down. Retention at a stricture with surgical removal of the capsule and simultaneous treatment of the cause of the retention has been reported to occur <1% of the time. There is no evidence that the capsule causes obstruction. However, abdominal pain has been reported as the capsule passes slowly through a tight stricture. Occasionally, the capsule will be retained in the stomach in the absence of gastroparesis for no obvious reason, or in the presence of gastroparesis. Aspiration of the capsule has been reported but without adverse outcome. Transient retention has been reported in various diverticula in the esophagus and small intestine. In most cases, if the capsule is seen to be retained, and the patient does not report passage of the capsule, a plain film of the abdomen 7-14 days after ingestion is useful in determining if the capsule has been retained.

Reimbursement Issues

A CPT code 91110 has been allocated by Medicare for the indication of obscure GI bleeding. Some Medicare carriers will also reimburse for suspected Crohn’s disease and suspected small intestinal tumors. Many insurers will now pay for the PillCam but require pre-approval. It is essential to comply with each carrier's requirements in order to get reimbursed.

Conclusion

The differential diagnosis of ulceration of the small intestine is significant, to the extent that ulceration alone cannot be regarded as synonymous with Crohn's disease. Many of the lesions seen may be due to NSAIDs, possibly celiac disease, eosinophilic gastroenteritis, jejunoileitis or conditions yet undefined.

In conclusion, video capsule endoscopy has opened a window into the small intestine. Some of the observations already are making us rethink the ways in which we manage patients. Further changes in technology and diagnostic capability are sure to follow.

References

1. Lewis BS, Swain P. Capsule endoscopy in the evaluation of patients with suspected small intestinal bleeding: Results of a pilot study. Gastrointest Endosc. 2002;56(3):349-53.

2. May A, Nachbar L, Wardak A et al. Double-balloon enteroscopy: preliminary experience in patients with obscure gastrointestinal bleeding or chronic abdominal pain. Endoscopy. 2003;35(12):985-91.

3. Pennazio M, Santucci R, Rondonotti E et al. Outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy: report of 100 consecutive cases. Gastroenterology. 2004;126(3):643-53.

4. Zuckerman GR, Prakash C, Askin MP, Lewis BS. AGA technical review on the evaluation and management of occult and obscure gastrointestinal bleeding. Gastroenterology. 2000;118(1):201-21.

5. Goldstein J, Eisen G, Lewis B et al. Abnormal small bowel findings are common in healthy subjetcs screened for a multicenter double blind, randomized placebo controlled trial using capsule endoscopy. Supplement to Gastroenterology. 2003;124(4):A37.

6. Goldstein J, Bjarnason I, Spalding W et al. Long term NSAIDs but not COX 2 inhibitors are associated with anemia. Supplement to Gastroenterology. 2004;126(4):A1.

7. Eliakim R, Suissa A, Yassin K et al. Wireless capsule video endoscopy compared to barium follow-through and computerised tomography in patients with suspected Crohn's disease--final report. Dig Liver Dis. 2004;36(8):519-22.

8. Fireman Z, Eliakim R, Adler S, Scapa E. Capsule endoscopy in real life: a four-centre experience of 160 consecutive patients in Israel. Eur J Gastroenterol Hepatol. 2004;16(9):927-31.

Editor:
John C. Deutsch, M.D.
Duluth, MN

Editorial Board:
Manoop S. Bhutani, M.D.
Galveston, TX
William R. Brugge, M.D.
Boston, MA
Peter R. McNally, D.O.
Denver, CO
Thomas J. Savides, M.D.
San Diego, CA
C. Mel Wilcox, M.D.
Birmingham, AL