Capsule endoscopy for abdominal pain - is it of value or just another test for doctors to do?

Chronic abdominal pain represents a true diagnostic challenge to both gastroenterologists and primary care physicians. The underlying etiologies are diverse, including but not limited to inflammatory bowel disease, gastrointestinal infections, ischemic diseases, malabsorption syndromes, malignancies, and functional disorders. Irritable bowel syndrome (IBS), functional abdominal pain and functional dyspepsia account for up to 50 % of referrals for the gastroenterological evaluation of abdominal pain and associated gastrointestinal symptoms [1]. The positive yield of diagnostic testing in patients with IBS is only 2 %, which is equivalent to the yield in the general healthy population [2]. According to a systematic review, the pretest probability of organic diseases, including inflammatory bowel disease, infectious diarrhea and colorectal cancer was found to be less than 1 % in patients with suspected IBS [3]. The only exception was celiac sprue, which was associated with a pretest probability of 5 %, compared with < 1 % in healthy controls. The presence of alarm features of age greater than 50 years, gastrointestinal bleed, weight loss, and anemia have been reported as independent predictors of organic disease in patients with suspected functional disorders [4]. There is a huge financial burden related to chronic abdominal pain, with an estimated $ 8 billion spent annually in the US on patients with IBS alone [5]. Better stratification of patients with chronic abdominal pain would lead to a more appropriate and cost-effective use of resources.

Video capsule endoscopy (VCE) (Given Imaging Ltd., Yoqneam, Israel) has been unequivocally established as an effective noninvasive endoscopic modality in the evaluation of obscure gastrointestinal bleed, nonstricturing Crohn’s disease and polyposis syndromes [6] [7] [8]. In contrast, this diagnostic modality has not been found to be of much value in patients with chronic abdominal pain or diarrhea. Barden et al. evaluated the yield of VCE in 20 patients with chronic abdominal pain, and noted only insignificant findings in the small intestine in 30 %, and normal findings in the remaining majority of patients [9]. Similarly, Spada et al. used VCE to evaluate a cohort of 16 patients with chronic abdominal pain, and found a specific cause in only 6.3 %, with insignificant findings in 19 %, and normal findings in 75 % of patients [10]. An additional study by Fry et al. reported a slightly higher diagnostic yield from VCE in patients with both abdominal pain and diarrhea (13 %), or diarrhea alone (14 %), compared with those with only abdominal pain (6 %) [11]. Although, VCE is a relatively noninvasive test and the complication rate is low, it is crucial to identify patients who would benefit from VCE, and those for whom the risks outweigh the benefits.

In the current issue of Endoscopy, May et al. present the results of a multicenter prospective study (the CEDAP-Plus Study) evaluating the diagnostic yield of VCE in patients with chronic abdominal pain, who had additional alarm signs or laboratory anomalies (“plus signs”). Fifty patients with chronic abdominal pain, in the presence of alarm signs (≥ 10 % body weight loss within 3 months, suspected small-intestinal bleed, or chronic anemia) and/or laboratory parameters indicative of inflammation (elevated erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], thrombocytosis or leucocytosis), and a negative prior diagnostic evaluation, were included in this trial. In addition to abdominal pain, 34 patients had diarrhea of at least 3 months’ duration. Positive findings on VCE, suggestive of Crohn’s disease, celiac disease or neoplasm, were detected in 36 % and 40 % of patients by two independent examiners, and potentially relevant findings were identified in 14 % and 24 % respectively, with good interobserver agreement for specific diagnoses and exclusion of nonrelevant findings. The most common relevant finding was small-bowel Crohn’s disease. The investigators report that the only significant “plus sign” was an elevation in markers of inflammation, associated with a threefold greater chance of a relevant finding on VCE. Interestingly, there was no increase in the likelihood of positive findings in the presence of more than one “plus sign”.

The investigators of the study are to be commended on undertaking the task of answering this important and challenging question regarding appropriate utilization of VCE in patients with chronic abdominal pain and/or diarrhea, and for conducting the first prospective study. In an earlier retrospective study, Shim et al. analyzed findings in 110 patients, and found that VCE was helpful in establishing a diagnosis in 17 %, if abdominal pain was accompanied by weight loss or elevated markers of inflammation [12]. Similarly, results from another study showed that the presence of concomitant signs of inflammation, malabsorption, or obstruction were predictive of positive VCE findings in patients with abdominal pain, with or without diarrhea [13]. The current study confirms these observations, and the results would indicate that a careful selection of patients, based on alarm signs, may increase the diagnostic yield of VCE to as high as 40 %.

Despite the important findings reported in the study, it has certain limitations, which in turn necessitate careful interpretation of the results. Despite the fact that this was a multicenter trial performed in 13 centers, there were only 50 patients enrolled in the study over a 2-year period. The presence of selection bias may have resulted in overestimation of the diagnostic yield of VCE. It is surprising that the only significant “plus sign” was inflammation, which showed a high variability and small significance. The investigators do not indicate whether one or more of the inflammatory markers were associated with positive small-bowel findings on VCE. It would be interesting to establish whether abdominal pain itself added any diagnostic value over the presence of inflammatory markers; this cannot be determined with the current study design. The limited sample size may have led to a failure to show diagnostic significance of other alarm signs, including weight loss or gastrointestinal bleed. In addition, the investigators do not explain the importance of “potentially relevant findings” and whether additional diagnostic testing was performed in these patients to resolve VCE findings.

Interestingly, the presence of relevant findings, including suspected Crohn’s, was seen in fewer patients with diarrhea, as compared with those without diarrhea. It is certainly possible that this finding may be related to a larger number of patients with irritable bowel syndrome in the diarrhea group, as the authors suggested. Utilization of the Rome II or Manning criteria for the exclusion of IBS patients could have overcome this potential limitation of the study. Moreover, the compromised visualization in the distal third of the small bowel, and failure of VCE to reach the cecum in 16 % of the patients, may have led to Crohn’s lesions being missed, given its predilection to affect the distal ileum.

VCE has played a key role in the recent evolution of gastrointestinal diagnostics, and one would anticipate that its ability to visualize the entire gastrointestinal tract would result in “obscure” becoming an obsolete term in gastroenterology. This exciting technology has shown tremendous potential in the diagnosis of a wide array of organic diseases, such as Barrett’s esophagus, esophageal varices, and angiodysplasias, polyps, and tumors in the small bowel, and its use in colorectal cancer screening is currently being investigated. It may hold additional promise in the investigation of gastrointestinal functional disorders. Factors implicated in IBS include gastrointestinal dysmotility, visceral hypersensitivity, microscopic inflammation, and bacterial overgrowth, among others [14] [15]. VCE is an evolving technology, with existing capsules being modified and new ones being developed. An example is the SmartPill capsule, which is a new wireless system designed to measure intraluminal pH, bacterial overgrowth, and temperature and pressure throughout the gastrointestinal tract. This may substantially improve our knowledge of the pathophysiology of various gastrointestinal disorders [16]. Additional developments in VCE can be envisioned, including a confocal capsule that allows real-time microscopy and earlier detection of microscopic inflammation in the small intestine; incorporation of a manometer that would detect subtle changes in gastrointestinal pressure; or an endoscopic ultrasound transducer that would allow both transmural and extramural evaluation throughout the gastrointestinal tract. These innovations may further revolutionize our understanding of the diagnosis and treatment of functional disorders, which have been poorly understood thus far.

The authors acknowledge that a larger number of patients would have been beneficial, and larger prospective studies would be helpful in further defining the role of VCE in this group of patients. Given the importance of this topic, and the obvious difficulty encountered by the investigators in recruiting patients despite the participation of 13 prestigious European centers, it might be worthwhile for the International Conference on Capsule Endoscopy (ICCE) to consider coordination or prioritization of international studies to address this important question of the appropriate utilization of VCE.

Competing interests: None

References

• 1 Fass R, Longstreth G F, Pimental M. et al . Evidence- and consensus-based practice guidelines for the diagnosis of irritable bowel syndrome.  Arch Int Med. 2001;  161 2081-2088
• 2 Hamm L R, Sorrells S C, Harding J P. et al . Additional investigations fail to alter the diagnosis of irritable bowel syndrome in subjects fulfilling Rome criteria.  Am J Gastroenterol. 1999;  94 1279-1282
• 3 Cash B D, Schonfeld P, Chevy W D. The utility of diagnostic tests in irritable bowel syndrome patients: a systematic review.  Am J Gastroenterol. 2002;  97 2812-2819
• 4 Thompson W G, Longstreth G F, Drossman D A. et al . Functional bowel disorders and functional abdominal pain.  Gut. 1999;  45 (Suppl 2) 1143-1147
• 5 Talley N J, Gabriel S E, Harmsen W S. et al . Medical costs in community subjects with irritable bowel syndrome.  Gastroenterology. 1995;  109 1736-1741
• 6 Triester S L, Leighton J A, Sharma V K. A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with obscure gastrointestinal bleeding.  Am J Gastroenterol. 2005;  100 2407-2418
• 7 Pennazio M. Capsule endoscopy: where are we after 6 years of clinical use?.  Dig Liver Dis. 2006;  38 867-878
• 8 Triester S L, Leighton J A, Leontiadis G I. et al . A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with nonstricturing small bowel Crohn’s disease.  Am J Gastroenterol. 2006;  101 954-964
• 9 Barden E, Nadler M, Chowers Y. et al . Capsule endoscopy for evaluation of chronic abdominal pain.  Endoscopy. 2003;  35 688-689
• 10 Spada C, Pirozzi M E, Riccioni F. et al . Capsule endoscopy in patients with chronic abdominal pain.  Dig Liver Dis. 2006;  38 696-698
• 11 Fry L C, Carey E J, Shiff A D. et al . The yield of capsule endoscopy in patients with abdominal pain or diarrhea.  Endoscopy. 2006;  38 498-502
• 12 Shim K N, Kim Y S, Kim K Y. et al . Abdominal pain accompanied by weight loss may increase the diagnostic yield of capsule endoscopy: A Korean multicenter study.  Scandinavian J Gastroenterol. 2006;  41 983-988
• 13 Keuchel M, Thaler C, Neumann-Grutzeck C. et al .M2A video capsule endoscopy in chronic diarrhea. Abstracts of the Second International Conference on capsule endoscopy. Berlin Mar 23 - 25; 2003: 129
• 14 Camilleri M, Heading R C, Thompson W G. et al . Clinical perspectives, mechanisms, diagnosis and management of irritable bowel syndrome.  Aliment Pharmacol Ther. 2002;  16 1407-1430
• 15 Foxx-Orenstein A. IBS - review and what’s new.  MedGenMed. 2006;  8 20
• 16 Kuo B, McCallum R W, Kock K. et al . Smartpill, a novel ambulatory diagnostic test for measuring gastric emptying in health and disease.  Gastroenterology. 2006;  130 A434