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Small-bowel capsule endoscopy in patients with unexplained chronic abdominal pain: a systematic review
ORIGINAL ARTICLE
Small-bowel capsule endoscopy in patients with unexplained chronic abdominal pain: a systematic review Meng Xue, PhD,1,2 Xueqin Chen, MD,1,2 Liuhong Shi, MD,3 Jianmin Si, MD,1,2 Liangjing Wang, MD, PhD,2,4 Shujie Chen, PhD1,2 Hangzhou, China
Background: Patients frequently consult primary care physicians and gastroenterologists when experiencing chronic abdominal pain. Although its diagnostic efficacy in these settings is uncertain, small-bowel capsule endoscopy (SBCE) has been used to evaluate the unexplained reasons for abdominal pain. Objective: To evaluate the diagnostic yield of SBCE in patients with unexplained chronic abdominal pain. Design: We performed a retrospective review of publications reporting the diagnostic yield of SBCE in patients with unexplained chronic abdominal pain and calculated the overall diagnostic yield. Setting: Two investigators independently searched studies from databases and analyzed the results. Patients: A total of 1520 patients from 21 studies were included. Interventions: Small-bowel capsule endoscopy. Main Outcome Measurements: Per-patient diagnostic yield, with 95% confidence intervals (CI), was evaluated by a random-effect model. Clear categorical analysis also was performed. Results: The pooled diagnostic yield of SBCE in patients with unexplained chronic abdominal pain was 20.9% (95% CI, 15.9%-25.9%), with high heterogeneity (I2 Z 80.0%; P ＜ .001). Inflammatory lesions were the most common (78.3%) positive findings, followed by tumors (9.0%). Limitations: Heterogeneity among studies, retrospective design, variable chronicity of abdominal pain, and different previous examinations before SBCE. Conclusion: SBCE provides a noninvasive diagnostic tool for patients with unexplained chronic abdominal pain, but the diagnostic yield is limited (20.9%). Among patients with positive findings, inflammatory lesions are the most common. (Gastrointest Endosc 2014;-:1-8.)
A previous survey in the United States showed that 28.6% of outpatients complained of lower abdominal pain or stomach pain.1 Most cases were accompanied with pathologic lesions occurring in the GI tract. Despite numerous endoscopic advancements, the small intestine was considered the last frontier of endoscopy until the
arrival of small-bowel endoscopy, including small-bowel capsule endoscopy (SBCE), device-assisted enteroscopy with single or double balloons, and spiral enteroscopy.2 As an invasive diagnostic tool, device-assisted enteroscopy examination will inevitably induce certain mucosal injury or even intestinal perforation. Because the small
Abbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; QUADAS, Quality Assessment of Diagnostic Accuracy Studies; SBCE, small-bowel capsule endoscopy.
Received August 29, 2013. Accepted April 30, 2014.
DISCLOSURE: This work was supported by the National Natural Science Foundation of China (81302070, 81272678) and National Basic Research Program of China (973 Program) (2012CB945004). All other authors disclosed no financial relationships relevant to this article. Copyright ª 2014 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2014.04.062
www.giejournal.org
Current affiliations: Department of Gastroenterology, Sir Runrun Shaw Hospital, School of Medicine (1); Institute of Gastroenterology (2); Department of Ultrasound, the Second Affiliated Hospital, School of Medicine (3); Department of Gastroenterology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China (4). Reprint requests: Shujie Chen, Department of Gastroenterology, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China and Liangjing Wang, Department of Gastroenterology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
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intestine is relatively long, tortuous, and highly mobile, this endoscopic modality is time consuming and labor intensive.3 Many patients could not bear the long-lasting discomfort without the use of sedatives,2 which, however, would bring anesthesia-related adverse events. Given these disadvantages of device-assisted enteroscopy, SBCE has been widely used since its introduction into clinical practice in 2001.4 SBCE makes it possible to inspect the entire small bowel without causing any obvious discomfort or need for sedation.5 The value of SBCE in obscure GI bleeding, recurrent iron deficiency anemia, and Crohn’s disease has already been confirmed by the National Institute of Clinical Excellence in the United Kingdom.6 However, the utility of SBCE in chronic abdominal pain is still controversial.7 The diagnostic yield rate of SBCE was documented as 4% and 44%, respectively, in 2 studies.8,9 This systematic review aims to evaluate the overall diagnostic yield of SBCE in patients with unexplained chronic abdominal pain.
MATERIALS AND METHODS Data identification and study selection We systematically searched the databases PubMed, Medline, Web of science, EMBASE, Scopus, Ovid, and the Cochrane Library from January 2001 to June 2013. The following terms were involved in the searching of the above-named databases: ("abdominal pain" OR "bellyache") AND "capsule endoscopy." Furthermore, the list of all selected articles was manually checked for additional references that were potentially suitable. Primary screening was based on titles and abstracts and then secondary screening on available full texts. All data were collected by 2 individual investigators. Opinions were fully discussed, and an agreement was reached in the end. The primary endpoint was the diagnostic yield of SBCE in patients with abdominal pain. Studies were required to fulfill the following inclusion criteria: written in English; providing sufficient data for the authors to confirm an accurate number of patients and providing either diagnostic yield or sufficient data to allow the calculation of diagnostic yield for SBCE. Those studies only available with abstracts were excluded. For the purpose of statistical analysis, 1 study presenting fewer than 10 cases was excluded.10 The population included in 2 studies11,12 overlapped (conducted by the same group in Greece, based on participants from the same hospitals, and had overlapped study periods [January 2008 to December 2009]), so only the more complete one11 was included.
Data extraction Two individual authors (M.X., X.C.) extracted data from each selected study with the following items: (1) first author’s name and the year of publication, (2) single-center or multicenter study, (3) the country where the study 2 GASTROINTESTINAL ENDOSCOPY Volume
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Take-home Message Small-bowel capsule endoscopy is of limited value in patients with unexplained chronic abdominal pain, with an overall diagnostic yield of 20.9%. In patients with a positive capsule study, inflammatory lesions were the most common finding.
was conducted, (4) prospective or retrospective study design, (5) whether consecutive patients were included, (6) the manufacturer of the capsule, (7) the total number of patients recruited, (8) the number of patients with unexplained abdominal pain, (9) male/female ratio and patient age, if available (because several studies did not record the data of pediatric or adult patients separately, different age brackets were analyzed together), and (10) the number of patients with clinically significant SBCE findings (erosions or ulcers, Crohn’s disease, tumors, etc). Patients with suspicious or uncertain SBCE findings (eg, arteriovenous malformations, lymphangiectasia, erythema, red spots, polyps, lymphoid follicular hyperplasia)13,14 were not taken into account in the calculation of diagnostic yield. Lesions including gastritis and peptic ulcer that could be reached by routine endoscopy, nonspecific lesions like lymphoid nodular hyperplasia, and those presented as others without specific descriptions also were excluded in the analysis.15 Number (11) included categories of positive findings by SBCE if available.
Risk of bias in individual studies The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) was used to assess the quality of studies and detect potential bias. Because the current work is a systematic review of diagnostic yield, and most studies lack a criterion standard (definite pathologic findings or long-term follow-up), items 3 to 11 of the QUADAS were not applicable.
Statistical analysis Data on the diagnostic yield of SBCE were extracted, pooled, and analyzed. A 95% confidence interval (CI) was equal to 2 t-fold of standard errors wide, in which t Z tinv (0.05, N-1) (tinv is a t distribution function; N: the total number of patients in each study).16 The Q statistic of I2 was used to estimate the proportion of unexplained variation across studies. I2 O50% was considered significant for heterogeneity, which would indicate that the random-effect model, DerSimonian-Laird method, instead of the Mantel-Haenszel method, should be performed to derive pooled results with corresponding 95% CI.10 Meta-regression analysis was used to investigate the possible sources of heterogeneity on the basis of the following covariates: design of studies (prospective vs retrospective), capsule manufacturer (Pillcam; Given www.giejournal.org
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Figure 1. Flow chart of the process for selecting eligible studies. SBCE, small bowel capsule endoscopy; DBE, double-balloon endoscopy; SBE, single-balloon endoscopy; DY, diagnostic yield.
Imaging [Yoqneam, Israel] vs not Given Imaging or no record), number of centers (multiple vs single), and sample size (O60 vs %60). Publication bias was assessed by using funnel plots (based on diagnostic yield vs the standard error). Statistical analysis was carried out by using the Metan, Metareg, and Metabias packages of STATA version 12.0 (StataCorp, College Station, Tex).
RESULTS Description of studies A total of 1193 articles were initially identified with the aforementioned search strategies, and 21 were eligible for final analysis. Detailed reasons for exclusion are outlined in Figure 1. A total of 1520 patients with unexplained abdominal pain who were investigated with SBCE were enrolled. The main characteristics of enrolled studies are shown in Table 1. Five studies were from the United States,13,17-20 2 studies each from China,21,22 Greece,11,23 Italy,24,25 the United Kingdom,9,26 and Israel,27,28 and 1 study from each of the following countries: New Zealand,29 Germany,14 Korea,30 Norway,8 Spain,15 and Canada.31 Fifteen studies were retrospectively designed, whereas 6 other studies were prospective. Seventeen studies reported the manufacturer of the capsule, 15 of which were from Given Imaging Ltd and 2 from Jinshan Group (Chongqing, China).
Quality of studies The quality of each selected study was evaluated by using the QUADAS tool (Table 2). Collectively, 1 study8 www.giejournal.org
achieved 3 of the 5 quality items, and the remaining 20 studies achieved 4 or 5, suggesting a moderate-togood quality of most studies. The cohort of patients in one of the studies14 could not represent the patients receiving SBCE in practice, so item 1 was marked with “no.” Item 13 was labeled as “no” because the study8 neither reported the intermediate suspicious diagnostic yield (based on suspicious/inconclusive findings) nor detailed categories of the positive findings. Three studies9,15,28 did not report any incomplete examinations, and 5 studies8,17,21,24,25 reported incomplete cases without any explanation.
Diagnostic yield of SBCE There was a statistically significant heterogeneity among the 21 included studies (I2 Z 80.0%; P ! .001). The pooled diagnostic yield of SBCE was 20.9% (95% CI, 15.9%-25.9%) in study participants by a random-effect evaluation model (Fig. 2). By using a multivariable metaregression model, we found that the design of the study (P Z .981), capsule type (P Z .692), the number of centers (P Z .171), and sample size (P Z .893) were not the source of heterogeneity. The Begg funnel plot of diagnostic yield versus standard error showed symmetry (P for bias Z .274), indicating that there was no significant publication bias in this meta-analysis (Fig. 3). Fifteen articles9,11,13,15,17,18,20-22,25-28,30,31 reported clear categorizations of the significant findings by SBCE. Among the 1223 patients in those 15 studies, 23.7% (290 of 1223) had definitive pathologic findings, including inflammatory lesions (78.3%, 227 of 290; eg, erosion, Crohn’s disease, nonsteroidal anti-inflammatory drug/ radiation–induced enteritis), tumor/mass lesions (9.0%, Volume
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TABLE 1. Characteristics of selected studies
Study
No. of Sex, No. of Capsule patients male/ centers manufacturer with AP female
Age, mean (range)
Diagnostic yield, no.
N/A
N/A
2
62
27/35
43 (20-78)
9
N/A
72
N/A
45.3 (14-81)
30
Design
Consecutive
Country
Retrospective
Yes
New Zealand
Single
Giveny
10
Retrospective
Yes
China
Single
OMOMz
Katsinelos11
Prospective
Yes
Greece
Multiple
Rondonotti24
Khan29 21
Zhang
Retrospective
Yes
Italy
Multiple
Giveny
155
N/A
N/A
23
22
Retrospective
Yes
China
Multiple
OMOMz
642
N/A
49 (9-91)*
137
FritscherRavens26
Prospective
Yes
United Kingdom
Multiple
Giveny
12
N/A
6.3 (4.5-7.9)
4
Retrospective
Yes
USA
Single
Giveny
30
N/A
55.7 (18-91)*
7
Buscaglia
Retrospective
Yes
USA
Multiple
Giveny
54
N/A
51.8*
23
14
May
Prospective
Yes
Germany
Multiple
Giveny
50
16/34
41 (18-72)
18
Shamir27
Prospective
Yes
Israel
Single
Giveny
10
5/5
13 (10-17.5)
2
Spada25
Prospective
Yes
Italy
Single
Giveny
16
6/10
42.7 (18-75)
1
Retrospective
Yes
Korea
Multiple
N/A
110
70/40
50.8
18
Retrospective
Yes
United Kingdom
Single
N/A
16
N/A
39.5 (7-86)*
7
Retrospective
Yes
USA
Single
Giveny
50
22/28
42 (20-83)
4
Liao
Toy17 18
30
Shim
9
Makins Fry13
8
Prospective
Yes
Norway
Single
N/A
25
N/A
58 (14-90)*
1
19
Tatar
Retrospective
Yes
USA
Single
Giveny
41
N/A
61.5*
5
Carlo20
Retrospective
Yes
USA
Single
Giveny
81
N/A
N/A
33
Kalantzis23
Retrospective
Yes
Greece
Single
Giveny
16
N/A
N/A
1
15
Retrospective
Yes
Spain
Single
Giveny
29
16/13
47.2
7
Retrospective
Yes
Canada
Single
Giveny
19
N/A
N/A
3
Retrospective
Yes
Israel
Single
Giveny
20
8/12
34.5 (21-70)
5
Qvigstad
Caunedo 31
Enns
28
Bardan
AP, Abdominal pain; N/A, not applicable. *Age of patients with abdominal pain was not recorded separately in these studies; presented here is the average age (age range) of patients, including those with indications other than abdominal pain. yPillCam, Given Imaging, Yoqneam, Israel. zOMOM capsule endoscopy system, Jinshan Science and Technology Company, Chongqing, China.
26 of 290), and other findings (12.8%, 37 of 290; eg, celiac disease, parasites, ischemic ileitis, stricture) (Table 3).
DISCUSSION Abdominal pain is a common symptom but becomes a diagnostic challenge in the primary care setting. Numerous disorders in the small intestine could cause abdominal pain. Patients with unexplained abdominal pain will generally undergo a series of examinations including US, radiography, gastroduodenoscopy, and colonoscopy. However, the diagnostic value of SBCE in 4 GASTROINTESTINAL ENDOSCOPY Volume
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those patients is controversial.7 SBCE is an effective tool in evaluating small-bowel pathology, with obscure GI bleeding as the primary indication. A systematic review showed that small-bowel lesions in nearly half of patients with iron deficiency anemia could be confirmed by SBCE to explain the anemia.32 National Institute of Clinical Excellence guidelines did not recommend SBCE as a routine examination for patients with abdominal pain,6 but several studies focusing on the application of SBCE revealed the existence of small-bowel tumors and indicated that judicious use of SBCE might result in the negligence of significant pathologic findings.9 Previous clinical studies have reported the efficacy of SBCE in patients www.giejournal.org
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TABLE 2. Quality of studies by using the QUADAS* tool Study
Item 1
Item 2
Items 3-11
Item 12
Item 13
Item 14
Khan29
Y
Y
N/A
Y
Y
Y
Zhang21
Y
Y
N/A
Y
Y
N
Katsinelos11
Y
Y
N/A
Y
Y
Y
Rondonotti24
Y
Y
N/A
Y
Y
N
Y
Y
N/A
Y
Y
Y
Y
Y
N/A
Y
Y
Y
Y
Y
N/A
Y
Y
N
Buscaglia
Y
Y
N/A
Y
Y
Y
14
N
Y
N/A
Y
Y
Y
Y
Y
N/A
Y
Y
Y
Y
Y
N/A
Y
Y
N
Y
Y
N/A
Y
Y
Y
Y
Y
N/A
Y
Y
U
Y
Y
N/A
Y
Y
Y
Qvigstad
Y
Y
N/A
Y
N
N
Tatar19
Y
Y
N/A
Y
Y
Y
Carlo20
Y
Y
N/A
Y
Y
Y
Kalantzis23
Y
Y
N/A
Y
Y
Y
15
Y
Y
N/A
Y
Y
U
Y
Y
N/A
Y
Y
Y
Y
Y
N/A
Y
Y
U
22
Liao
26
Fritscher-Ravens 17
Toy
18
May
27
Shamir
25
Spada
30
Shim
9
Makins 13
Fry
8
Caunedo 31
Enns
28
Bardan
Y, Yes; N/A, not applicable; N, no. *QUADAS, Quality Assessment of Diagnostic Accuracy Studies.
Item Item Item Item Item
1. Was the spectrum of patients representative of the patients who will receive the test in practice? 2. Were selection criteria clearly described? 12. Were the same clinical data available when test results were interpreted as would be available when the test is used in practice? 13. Were uninterpretable/intermediate test results reported? 14. Were withdrawals from the study explained?
with abdominal pain, but the results differ vastly among them. In the present study, we systematically reviewed the existing medical literature in evaluating the utility of SBCE in patients with unexplained abdominal pain. The pooled diagnostic yield is relatively low at 20.9% from 21 studies with a total of 1520 patients. Exclusion of suspicious and potentially relevant findings was partially responsible for the low diagnostic yield by SBCE. In addition, some of the patients with negative findings based on SBCE examinations actually might have functional symptoms or irritable bowel syndrome. Moreover, the relatively high heterogeneity (I2 Z 80.0%) across all studies reflected the variability in the reported diagnostic yield. www.giejournal.org
Several studies have reported that patients who had additional symptoms besides abdominal pain might have a higher positive diagnostic yield from SBCE examinations. Studies showed that SBCE could be more useful in patients with abdominal pain accompanied by weight loss.33 A Korean multicenter study found that abdominal pain accompanied by weight loss increased the diagnostic yield of SBCE by 17.6-fold.30 Delvaux et al34 revealed that the diagnostic yield of SBCE was significantly higher in patients with abdominal pain and alarm signs (weight loss, fever, or positive fecal occult blood test), compared with those with abdominal pain alone (41.7% vs 18%). However, such consistent results were not observed in a prospective multicenter trial, where patients with Volume
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Figure 2. Forrest plot of the diagnostic yield of small-bowel capsule endoscopy in patients with unexplained chronic abdominal pain. AP, abdominal pain; SBCE, small-bowel capsule endoscopy; DY, diagnostic yield; CI, confidence interval.
abdominal pain as well as weight loss failed to benefit from SBCE.14 We reviewed studies that reported definite findings by SBCE and found that inflammatory lesions (78.3%) were the predominant reason for unexplained abdominal pain among 290 patients. Inflammation is the most common lesion in the small-intestinal tract, including small-bowel Crohn’s disease and nonsteroidal anti-inflammatory drug/ radiation–induced enteritis.35,36 Laboratory signs of inflammation will greatly increase the diagnostic yield of SBCE in evaluating unexplained abdominal pain. A 3-fold greater chance of a relevant finding was identified if there were signs of inflammation (elevated erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP] level, thrombocytosis, and leukocytosis).14 In addition, another study indicated that the diagnostic yield of SBCE was increased to 62.5% in patients with elevated CRP levels when compared with 18% in those with abdominal pain alone.34 Univariate analysis in one study showed that positive findings by SBCE were significantly associated with elevated ESR and CRP levels, with odds ratios of 11.5 and 5.0, respectively, whereas multivariate analysis failed to demonstrate a significant difference.30 Small-bowel tumors account for approximately 3% to 6% of all digestive tract neoplasms.37 Patients with smallbowel tumors typically remain asymptomatic for years or present only with nonspecific symptoms such as abdominal pain.38 A systematic review showed that the prevalence of small-bowel tumors in patients undergoing 6 GASTROINTESTINAL ENDOSCOPY Volume
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Figure 3. Funnel plot comparing diagnostic yield versus standard error of diagnostic yield (Begg asymmetry test). Open circles represent studies included. Two-pair studies have equal diagnostic yields and standard errors inside each pair, so the funnel presents only 19 circles. The symmetrical funnel indicates no significant publication bias (P for bias Z .274). DY, diagnostic yield; s.e., standard error.
SBCE is about 4.0%.39 Our results showed that 2.1% of the patients with unexplained abdominal pain were diagnosed with a small-bowel tumor/mass lesion by SBCE, accounting for 9.0% of all positive findings. In the study conducted by Shim et al,30 2 patients were diagnosed with tumors by SBCE and confirmed later by surgical resection of the intestinal lesion or biopsy of the lymph node. These studies suggest that its ability to detect malignancy may justify its use in certain situations, www.giejournal.org
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TABLE 3. Categorical diagnostic yield in studies with detailed findings reported Diagnostic yield categories No. of patients
No. of significant findings
No. of inflammatory lesions
No. of tumor/ mass lesions
No. of other significant lesions
62
9
4
3
2
Katsinelos
72
30
24
5
1
Liao22
642
137
121
4
12
Fritscher-Ravens26
12
4
3
0
1
Toy17
30
7
6
1
0
54
23
20
0
3
10
2
2
0
0
16
1
1
0
0
110
18
10
2
6
Makins
16
7
7
0
0
13
50
4
3
1
0
81
33
18
10
5
29
7
7
0
0
19
3
2
0
1
20
5
3
0
2
1223
290
227
26
37
23.7
18.6
2.1
3.0
Authors Zhang21 11
18
Buscaglia 27
Shamir
25
Spada
30
Shim
9
Fry
20
Carlo
15
Caunedo 31
Enns
28
Bardan
Total (no.) Total (%)
despite the overall low diagnostic yield of SBCE. Besides, the diagnostic yield would become higher in patients with abdominal pain accompanied by weight loss and signs of inflammation. These additional conditions might be the optimal indications when SBCE could exhibit a higher diagnostic yield. The present study has some limitations. First, we limited our analysis to those studies written in English. Second, the majority of the studies included were retrospectively designed. Therefore, errors associated with the retrospective retrieval of information from databases were inevitable. Third, the time for which the abdominal pain persists and the previous examinations before SBCE in each study were not well-documented. Fourth, this review included patients of all ages. Children usually are less tolerant of device-assisted enteroscopy,40 and the elderly usually are less tolerant of the anaesthetic agents41 during deviceassisted enteroscopy, thus SBCE examinations are more likely to be performed. Moreover, different age groups have different disease spectrums.42 Finally, analysis was restricted to lesions defined as clinically significant by authors. The criteria of significant or relevant might be variable among providers. These limitations likely explain www.giejournal.org
the high heterogeneity of the studies included. Further subgroup analysis and prospective, multicenter studies with appropriately selected patients, clear inclusion criteria, and follow-up are needed to confirm the value of SBCE in patients with unexplained abdominal pain. In conclusion, this review indicates that SBCE is of limited value in patients with unexplained chronic abdominal pain. The overall diagnostic yield was about 20.9%, and inflammatory lesions occurred most frequently among those positive findings.
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23. Kalantzis N, Papanikolaou IS, Giannakoulopoulou E, et al. Capsule endoscopy; the cumulative experience from its use in 193 patients with suspected small bowel disease. Hepatogastroenterology 2005;52:414-9. 24. Rondonotti E, Soncini M, Girelli C, et al. Small bowel capsule endoscopy in clinical practice: a multicenter 7-year survey. Eur J Gastroenterol Hepatol 2010;22:1380-6. 25. Spada C, Pirozzi GA, Riccioni ME, et al. Capsule endoscopy in patients with chronic abdominal pain. Dig Liver Dis 2006;38:696-8. 26. Fritscher-Ravens A, Scherbakov P, Bufler P, et al. The feasibility of wireless capsule endoscopy in detecting small intestinal pathology in children under the age of 8 years: a multicentre European study. Gut 2009;58:1467-72. 27. Shamir R, Hino B, Hartman C, et al. Wireless video capsule in pediatric patients with functional abdominal pain. J Pediatr Gastroenterol Nutr 2007;44:45-50. 28. Bardan E, Nadler M, Chowers Y, et al. Capsule endoscopy for the evaluation of patients with chronic abdominal pain. Endoscopy 2003;35: 688-9. 29. Khan MI, Johnston M, Cunliffe R, et al. The role of capsule endoscopy in small bowel pathology: a review of 122 cases. N Z Med J 2013;126: 16-26. 30. Shim KN, Kim YS, Kim KJ, et al. Abdominal pain accompanied by weight loss may increase the diagnostic yield of capsule endoscopy: a Korean multicenter study. Scand J Gastroenterol 2006;41:983-8. 31. Enns R, Go K, Chang H, et al. Capsule endoscopy: a single-centre experience with the first 226 capsules. Can J Gastroenterol 2004;18: 555-8. 32. Koulaouzidis A, Rondonotti E, Giannakou A, et al. Diagnostic yield of small-bowel capsule endoscopy in patients with iron-deficiency anemia: a systematic review. Gastrointest Endosc 2012;76:983-92. 33. Juckett G, Trivedi R. Evaluation of chronic diarrhea. Am Fam Physician 2011;84:1119-26. 34. Delvaux M, Kharasse G, Frederic M, et al. Diagnostic yield of small bowel capsule endoscopy in patients with unexplained chronic abdominal pain. Gastroenterology 2011;140:S613. 35. Leighton JA. Capsule endoscopy in the evaluation of small-bowel inflammation. Gastroenterol Hepatol (NY) 2008;4:771-2. 36. Smale S, Tibble J, Sigthorsson G, et al. Epidemiology and differential diagnosis of NSAID-induced injury to the mucosa of the small intestine. Best Pract Res Clin Gastroenterol 2001;15:723-38. 37. Abu-Hamda EM, Hattab EM, Lynch PM. Small bowel tumors. Curr Gastroenterol Rep 2003;5:386-93. 38. Talamonti MS, Goetz LH, Rao S, et al. Primary cancers of the small bowel: analysis of prognostic factors and results of surgical management. Arch Surg 2002;137:564-70. 39. Achour J, Serraj I, Amrani L, et al. Small bowel tumors: What is the contribution of video capsule endoscopy? Clin Res Hepatol Gastroenterol 2012;36:222-6. 40. Barth BA. Enteroscopy in children. Curr Opin Pediatr 2011;23:530-4. 41. Priebe HJ. The aged cardiovascular risk patient. Br J Anaesth 2000;85: 763-78. 42. Miller SK, Alpert PT. Assessment and differential diagnosis of abdominal pain. Nurse Pract 2006;31:38-45; 47.
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Small-bowel capsule endoscopy in patients with unexplained chronic abdominal pain: a systematic review Meng Xue, PhD,1,2 Xueqin Chen, MD,1,2 Liuhong Shi, MD,3 Jianmin Si, MD,1,2 Liangjing Wang, MD, PhD,2,4 Shujie Chen, PhD1,2 Hangzhou, China
Background: Patients frequently consult primary care physicians and gastroenterologists when experiencing chronic abdominal pain. Although its diagnostic efficacy in these settings is uncertain, small-bowel capsule endoscopy (SBCE) has been used to evaluate the unexplained reasons for abdominal pain. Objective: To evaluate the diagnostic yield of SBCE in patients with unexplained chronic abdominal pain. Design: We performed a retrospective review of publications reporting the diagnostic yield of SBCE in patients with unexplained chronic abdominal pain and calculated the overall diagnostic yield. Setting: Two investigators independently searched studies from databases and analyzed the results. Patients: A total of 1520 patients from 21 studies were included. Interventions: Small-bowel capsule endoscopy. Main Outcome Measurements: Per-patient diagnostic yield, with 95% confidence intervals (CI), was evaluated by a random-effect model. Clear categorical analysis also was performed. Results: The pooled diagnostic yield of SBCE in patients with unexplained chronic abdominal pain was 20.9% (95% CI, 15.9%-25.9%), with high heterogeneity (I2 Z 80.0%; P ＜ .001). Inflammatory lesions were the most common (78.3%) positive findings, followed by tumors (9.0%). Limitations: Heterogeneity among studies, retrospective design, variable chronicity of abdominal pain, and different previous examinations before SBCE. Conclusion: SBCE provides a noninvasive diagnostic tool for patients with unexplained chronic abdominal pain, but the diagnostic yield is limited (20.9%). Among patients with positive findings, inflammatory lesions are the most common. (Gastrointest Endosc 2014;-:1-8.)
A previous survey in the United States showed that 28.6% of outpatients complained of lower abdominal pain or stomach pain.1 Most cases were accompanied with pathologic lesions occurring in the GI tract. Despite numerous endoscopic advancements, the small intestine was considered the last frontier of endoscopy until the
arrival of small-bowel endoscopy, including small-bowel capsule endoscopy (SBCE), device-assisted enteroscopy with single or double balloons, and spiral enteroscopy.2 As an invasive diagnostic tool, device-assisted enteroscopy examination will inevitably induce certain mucosal injury or even intestinal perforation. Because the small
Abbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; QUADAS, Quality Assessment of Diagnostic Accuracy Studies; SBCE, small-bowel capsule endoscopy.
Received August 29, 2013. Accepted April 30, 2014.
DISCLOSURE: This work was supported by the National Natural Science Foundation of China (81302070, 81272678) and National Basic Research Program of China (973 Program) (2012CB945004). All other authors disclosed no financial relationships relevant to this article. Copyright ª 2014 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2014.04.062
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Current affiliations: Department of Gastroenterology, Sir Runrun Shaw Hospital, School of Medicine (1); Institute of Gastroenterology (2); Department of Ultrasound, the Second Affiliated Hospital, School of Medicine (3); Department of Gastroenterology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China (4). Reprint requests: Shujie Chen, Department of Gastroenterology, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China and Liangjing Wang, Department of Gastroenterology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
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intestine is relatively long, tortuous, and highly mobile, this endoscopic modality is time consuming and labor intensive.3 Many patients could not bear the long-lasting discomfort without the use of sedatives,2 which, however, would bring anesthesia-related adverse events. Given these disadvantages of device-assisted enteroscopy, SBCE has been widely used since its introduction into clinical practice in 2001.4 SBCE makes it possible to inspect the entire small bowel without causing any obvious discomfort or need for sedation.5 The value of SBCE in obscure GI bleeding, recurrent iron deficiency anemia, and Crohn’s disease has already been confirmed by the National Institute of Clinical Excellence in the United Kingdom.6 However, the utility of SBCE in chronic abdominal pain is still controversial.7 The diagnostic yield rate of SBCE was documented as 4% and 44%, respectively, in 2 studies.8,9 This systematic review aims to evaluate the overall diagnostic yield of SBCE in patients with unexplained chronic abdominal pain.
MATERIALS AND METHODS Data identification and study selection We systematically searched the databases PubMed, Medline, Web of science, EMBASE, Scopus, Ovid, and the Cochrane Library from January 2001 to June 2013. The following terms were involved in the searching of the above-named databases: ("abdominal pain" OR "bellyache") AND "capsule endoscopy." Furthermore, the list of all selected articles was manually checked for additional references that were potentially suitable. Primary screening was based on titles and abstracts and then secondary screening on available full texts. All data were collected by 2 individual investigators. Opinions were fully discussed, and an agreement was reached in the end. The primary endpoint was the diagnostic yield of SBCE in patients with abdominal pain. Studies were required to fulfill the following inclusion criteria: written in English; providing sufficient data for the authors to confirm an accurate number of patients and providing either diagnostic yield or sufficient data to allow the calculation of diagnostic yield for SBCE. Those studies only available with abstracts were excluded. For the purpose of statistical analysis, 1 study presenting fewer than 10 cases was excluded.10 The population included in 2 studies11,12 overlapped (conducted by the same group in Greece, based on participants from the same hospitals, and had overlapped study periods [January 2008 to December 2009]), so only the more complete one11 was included.
Data extraction Two individual authors (M.X., X.C.) extracted data from each selected study with the following items: (1) first author’s name and the year of publication, (2) single-center or multicenter study, (3) the country where the study 2 GASTROINTESTINAL ENDOSCOPY Volume
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Take-home Message Small-bowel capsule endoscopy is of limited value in patients with unexplained chronic abdominal pain, with an overall diagnostic yield of 20.9%. In patients with a positive capsule study, inflammatory lesions were the most common finding.
was conducted, (4) prospective or retrospective study design, (5) whether consecutive patients were included, (6) the manufacturer of the capsule, (7) the total number of patients recruited, (8) the number of patients with unexplained abdominal pain, (9) male/female ratio and patient age, if available (because several studies did not record the data of pediatric or adult patients separately, different age brackets were analyzed together), and (10) the number of patients with clinically significant SBCE findings (erosions or ulcers, Crohn’s disease, tumors, etc). Patients with suspicious or uncertain SBCE findings (eg, arteriovenous malformations, lymphangiectasia, erythema, red spots, polyps, lymphoid follicular hyperplasia)13,14 were not taken into account in the calculation of diagnostic yield. Lesions including gastritis and peptic ulcer that could be reached by routine endoscopy, nonspecific lesions like lymphoid nodular hyperplasia, and those presented as others without specific descriptions also were excluded in the analysis.15 Number (11) included categories of positive findings by SBCE if available.
Risk of bias in individual studies The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) was used to assess the quality of studies and detect potential bias. Because the current work is a systematic review of diagnostic yield, and most studies lack a criterion standard (definite pathologic findings or long-term follow-up), items 3 to 11 of the QUADAS were not applicable.
Statistical analysis Data on the diagnostic yield of SBCE were extracted, pooled, and analyzed. A 95% confidence interval (CI) was equal to 2 t-fold of standard errors wide, in which t Z tinv (0.05, N-1) (tinv is a t distribution function; N: the total number of patients in each study).16 The Q statistic of I2 was used to estimate the proportion of unexplained variation across studies. I2 O50% was considered significant for heterogeneity, which would indicate that the random-effect model, DerSimonian-Laird method, instead of the Mantel-Haenszel method, should be performed to derive pooled results with corresponding 95% CI.10 Meta-regression analysis was used to investigate the possible sources of heterogeneity on the basis of the following covariates: design of studies (prospective vs retrospective), capsule manufacturer (Pillcam; Given www.giejournal.org
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Small-bowel capsule endoscopy
Figure 1. Flow chart of the process for selecting eligible studies. SBCE, small bowel capsule endoscopy; DBE, double-balloon endoscopy; SBE, single-balloon endoscopy; DY, diagnostic yield.
Imaging [Yoqneam, Israel] vs not Given Imaging or no record), number of centers (multiple vs single), and sample size (O60 vs %60). Publication bias was assessed by using funnel plots (based on diagnostic yield vs the standard error). Statistical analysis was carried out by using the Metan, Metareg, and Metabias packages of STATA version 12.0 (StataCorp, College Station, Tex).
RESULTS Description of studies A total of 1193 articles were initially identified with the aforementioned search strategies, and 21 were eligible for final analysis. Detailed reasons for exclusion are outlined in Figure 1. A total of 1520 patients with unexplained abdominal pain who were investigated with SBCE were enrolled. The main characteristics of enrolled studies are shown in Table 1. Five studies were from the United States,13,17-20 2 studies each from China,21,22 Greece,11,23 Italy,24,25 the United Kingdom,9,26 and Israel,27,28 and 1 study from each of the following countries: New Zealand,29 Germany,14 Korea,30 Norway,8 Spain,15 and Canada.31 Fifteen studies were retrospectively designed, whereas 6 other studies were prospective. Seventeen studies reported the manufacturer of the capsule, 15 of which were from Given Imaging Ltd and 2 from Jinshan Group (Chongqing, China).
Quality of studies The quality of each selected study was evaluated by using the QUADAS tool (Table 2). Collectively, 1 study8 www.giejournal.org
achieved 3 of the 5 quality items, and the remaining 20 studies achieved 4 or 5, suggesting a moderate-togood quality of most studies. The cohort of patients in one of the studies14 could not represent the patients receiving SBCE in practice, so item 1 was marked with “no.” Item 13 was labeled as “no” because the study8 neither reported the intermediate suspicious diagnostic yield (based on suspicious/inconclusive findings) nor detailed categories of the positive findings. Three studies9,15,28 did not report any incomplete examinations, and 5 studies8,17,21,24,25 reported incomplete cases without any explanation.
Diagnostic yield of SBCE There was a statistically significant heterogeneity among the 21 included studies (I2 Z 80.0%; P ! .001). The pooled diagnostic yield of SBCE was 20.9% (95% CI, 15.9%-25.9%) in study participants by a random-effect evaluation model (Fig. 2). By using a multivariable metaregression model, we found that the design of the study (P Z .981), capsule type (P Z .692), the number of centers (P Z .171), and sample size (P Z .893) were not the source of heterogeneity. The Begg funnel plot of diagnostic yield versus standard error showed symmetry (P for bias Z .274), indicating that there was no significant publication bias in this meta-analysis (Fig. 3). Fifteen articles9,11,13,15,17,18,20-22,25-28,30,31 reported clear categorizations of the significant findings by SBCE. Among the 1223 patients in those 15 studies, 23.7% (290 of 1223) had definitive pathologic findings, including inflammatory lesions (78.3%, 227 of 290; eg, erosion, Crohn’s disease, nonsteroidal anti-inflammatory drug/ radiation–induced enteritis), tumor/mass lesions (9.0%, Volume
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TABLE 1. Characteristics of selected studies
Study
No. of Sex, No. of Capsule patients male/ centers manufacturer with AP female
Age, mean (range)
Diagnostic yield, no.
N/A
N/A
2
62
27/35
43 (20-78)
9
N/A
72
N/A
45.3 (14-81)
30
Design
Consecutive
Country
Retrospective
Yes
New Zealand
Single
Giveny
10
Retrospective
Yes
China
Single
OMOMz
Katsinelos11
Prospective
Yes
Greece
Multiple
Rondonotti24
Khan29 21
Zhang
Retrospective
Yes
Italy
Multiple
Giveny
155
N/A
N/A
23
22
Retrospective
Yes
China
Multiple
OMOMz
642
N/A
49 (9-91)*
137
FritscherRavens26
Prospective
Yes
United Kingdom
Multiple
Giveny
12
N/A
6.3 (4.5-7.9)
4
Retrospective
Yes
USA
Single
Giveny
30
N/A
55.7 (18-91)*
7
Buscaglia
Retrospective
Yes
USA
Multiple
Giveny
54
N/A
51.8*
23
14
May
Prospective
Yes
Germany
Multiple
Giveny
50
16/34
41 (18-72)
18
Shamir27
Prospective
Yes
Israel
Single
Giveny
10
5/5
13 (10-17.5)
2
Spada25
Prospective
Yes
Italy
Single
Giveny
16
6/10
42.7 (18-75)
1
Retrospective
Yes
Korea
Multiple
N/A
110
70/40
50.8
18
Retrospective
Yes
United Kingdom
Single
N/A
16
N/A
39.5 (7-86)*
7
Retrospective
Yes
USA
Single
Giveny
50
22/28
42 (20-83)
4
Liao
Toy17 18
30
Shim
9
Makins Fry13
8
Prospective
Yes
Norway
Single
N/A
25
N/A
58 (14-90)*
1
19
Tatar
Retrospective
Yes
USA
Single
Giveny
41
N/A
61.5*
5
Carlo20
Retrospective
Yes
USA
Single
Giveny
81
N/A
N/A
33
Kalantzis23
Retrospective
Yes
Greece
Single
Giveny
16
N/A
N/A
1
15
Retrospective
Yes
Spain
Single
Giveny
29
16/13
47.2
7
Retrospective
Yes
Canada
Single
Giveny
19
N/A
N/A
3
Retrospective
Yes
Israel
Single
Giveny
20
8/12
34.5 (21-70)
5
Qvigstad
Caunedo 31
Enns
28
Bardan
AP, Abdominal pain; N/A, not applicable. *Age of patients with abdominal pain was not recorded separately in these studies; presented here is the average age (age range) of patients, including those with indications other than abdominal pain. yPillCam, Given Imaging, Yoqneam, Israel. zOMOM capsule endoscopy system, Jinshan Science and Technology Company, Chongqing, China.
26 of 290), and other findings (12.8%, 37 of 290; eg, celiac disease, parasites, ischemic ileitis, stricture) (Table 3).
DISCUSSION Abdominal pain is a common symptom but becomes a diagnostic challenge in the primary care setting. Numerous disorders in the small intestine could cause abdominal pain. Patients with unexplained abdominal pain will generally undergo a series of examinations including US, radiography, gastroduodenoscopy, and colonoscopy. However, the diagnostic value of SBCE in 4 GASTROINTESTINAL ENDOSCOPY Volume
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those patients is controversial.7 SBCE is an effective tool in evaluating small-bowel pathology, with obscure GI bleeding as the primary indication. A systematic review showed that small-bowel lesions in nearly half of patients with iron deficiency anemia could be confirmed by SBCE to explain the anemia.32 National Institute of Clinical Excellence guidelines did not recommend SBCE as a routine examination for patients with abdominal pain,6 but several studies focusing on the application of SBCE revealed the existence of small-bowel tumors and indicated that judicious use of SBCE might result in the negligence of significant pathologic findings.9 Previous clinical studies have reported the efficacy of SBCE in patients www.giejournal.org
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TABLE 2. Quality of studies by using the QUADAS* tool Study
Item 1
Item 2
Items 3-11
Item 12
Item 13
Item 14
Khan29
Y
Y
N/A
Y
Y
Y
Zhang21
Y
Y
N/A
Y
Y
N
Katsinelos11
Y
Y
N/A
Y
Y
Y
Rondonotti24
Y
Y
N/A
Y
Y
N
Y
Y
N/A
Y
Y
Y
Y
Y
N/A
Y
Y
Y
Y
Y
N/A
Y
Y
N
Buscaglia
Y
Y
N/A
Y
Y
Y
14
N
Y
N/A
Y
Y
Y
Y
Y
N/A
Y
Y
Y
Y
Y
N/A
Y
Y
N
Y
Y
N/A
Y
Y
Y
Y
Y
N/A
Y
Y
U
Y
Y
N/A
Y
Y
Y
Qvigstad
Y
Y
N/A
Y
N
N
Tatar19
Y
Y
N/A
Y
Y
Y
Carlo20
Y
Y
N/A
Y
Y
Y
Kalantzis23
Y
Y
N/A
Y
Y
Y
15
Y
Y
N/A
Y
Y
U
Y
Y
N/A
Y
Y
Y
Y
Y
N/A
Y
Y
U
22
Liao
26
Fritscher-Ravens 17
Toy
18
May
27
Shamir
25
Spada
30
Shim
9
Makins 13
Fry
8
Caunedo 31
Enns
28
Bardan
Y, Yes; N/A, not applicable; N, no. *QUADAS, Quality Assessment of Diagnostic Accuracy Studies.
Item Item Item Item Item
1. Was the spectrum of patients representative of the patients who will receive the test in practice? 2. Were selection criteria clearly described? 12. Were the same clinical data available when test results were interpreted as would be available when the test is used in practice? 13. Were uninterpretable/intermediate test results reported? 14. Were withdrawals from the study explained?
with abdominal pain, but the results differ vastly among them. In the present study, we systematically reviewed the existing medical literature in evaluating the utility of SBCE in patients with unexplained abdominal pain. The pooled diagnostic yield is relatively low at 20.9% from 21 studies with a total of 1520 patients. Exclusion of suspicious and potentially relevant findings was partially responsible for the low diagnostic yield by SBCE. In addition, some of the patients with negative findings based on SBCE examinations actually might have functional symptoms or irritable bowel syndrome. Moreover, the relatively high heterogeneity (I2 Z 80.0%) across all studies reflected the variability in the reported diagnostic yield. www.giejournal.org
Several studies have reported that patients who had additional symptoms besides abdominal pain might have a higher positive diagnostic yield from SBCE examinations. Studies showed that SBCE could be more useful in patients with abdominal pain accompanied by weight loss.33 A Korean multicenter study found that abdominal pain accompanied by weight loss increased the diagnostic yield of SBCE by 17.6-fold.30 Delvaux et al34 revealed that the diagnostic yield of SBCE was significantly higher in patients with abdominal pain and alarm signs (weight loss, fever, or positive fecal occult blood test), compared with those with abdominal pain alone (41.7% vs 18%). However, such consistent results were not observed in a prospective multicenter trial, where patients with Volume
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Figure 2. Forrest plot of the diagnostic yield of small-bowel capsule endoscopy in patients with unexplained chronic abdominal pain. AP, abdominal pain; SBCE, small-bowel capsule endoscopy; DY, diagnostic yield; CI, confidence interval.
abdominal pain as well as weight loss failed to benefit from SBCE.14 We reviewed studies that reported definite findings by SBCE and found that inflammatory lesions (78.3%) were the predominant reason for unexplained abdominal pain among 290 patients. Inflammation is the most common lesion in the small-intestinal tract, including small-bowel Crohn’s disease and nonsteroidal anti-inflammatory drug/ radiation–induced enteritis.35,36 Laboratory signs of inflammation will greatly increase the diagnostic yield of SBCE in evaluating unexplained abdominal pain. A 3-fold greater chance of a relevant finding was identified if there were signs of inflammation (elevated erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP] level, thrombocytosis, and leukocytosis).14 In addition, another study indicated that the diagnostic yield of SBCE was increased to 62.5% in patients with elevated CRP levels when compared with 18% in those with abdominal pain alone.34 Univariate analysis in one study showed that positive findings by SBCE were significantly associated with elevated ESR and CRP levels, with odds ratios of 11.5 and 5.0, respectively, whereas multivariate analysis failed to demonstrate a significant difference.30 Small-bowel tumors account for approximately 3% to 6% of all digestive tract neoplasms.37 Patients with smallbowel tumors typically remain asymptomatic for years or present only with nonspecific symptoms such as abdominal pain.38 A systematic review showed that the prevalence of small-bowel tumors in patients undergoing 6 GASTROINTESTINAL ENDOSCOPY Volume
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Figure 3. Funnel plot comparing diagnostic yield versus standard error of diagnostic yield (Begg asymmetry test). Open circles represent studies included. Two-pair studies have equal diagnostic yields and standard errors inside each pair, so the funnel presents only 19 circles. The symmetrical funnel indicates no significant publication bias (P for bias Z .274). DY, diagnostic yield; s.e., standard error.
SBCE is about 4.0%.39 Our results showed that 2.1% of the patients with unexplained abdominal pain were diagnosed with a small-bowel tumor/mass lesion by SBCE, accounting for 9.0% of all positive findings. In the study conducted by Shim et al,30 2 patients were diagnosed with tumors by SBCE and confirmed later by surgical resection of the intestinal lesion or biopsy of the lymph node. These studies suggest that its ability to detect malignancy may justify its use in certain situations, www.giejournal.org
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TABLE 3. Categorical diagnostic yield in studies with detailed findings reported Diagnostic yield categories No. of patients
No. of significant findings
No. of inflammatory lesions
No. of tumor/ mass lesions
No. of other significant lesions
62
9
4
3
2
Katsinelos
72
30
24
5
1
Liao22
642
137
121
4
12
Fritscher-Ravens26
12
4
3
0
1
Toy17
30
7
6
1
0
54
23
20
0
3
10
2
2
0
0
16
1
1
0
0
110
18
10
2
6
Makins
16
7
7
0
0
13
50
4
3
1
0
81
33
18
10
5
29
7
7
0
0
19
3
2
0
1
20
5
3
0
2
1223
290
227
26
37
23.7
18.6
2.1
3.0
Authors Zhang21 11
18
Buscaglia 27
Shamir
25
Spada
30
Shim
9
Fry
20
Carlo
15
Caunedo 31
Enns
28
Bardan
Total (no.) Total (%)
despite the overall low diagnostic yield of SBCE. Besides, the diagnostic yield would become higher in patients with abdominal pain accompanied by weight loss and signs of inflammation. These additional conditions might be the optimal indications when SBCE could exhibit a higher diagnostic yield. The present study has some limitations. First, we limited our analysis to those studies written in English. Second, the majority of the studies included were retrospectively designed. Therefore, errors associated with the retrospective retrieval of information from databases were inevitable. Third, the time for which the abdominal pain persists and the previous examinations before SBCE in each study were not well-documented. Fourth, this review included patients of all ages. Children usually are less tolerant of device-assisted enteroscopy,40 and the elderly usually are less tolerant of the anaesthetic agents41 during deviceassisted enteroscopy, thus SBCE examinations are more likely to be performed. Moreover, different age groups have different disease spectrums.42 Finally, analysis was restricted to lesions defined as clinically significant by authors. The criteria of significant or relevant might be variable among providers. These limitations likely explain www.giejournal.org
the high heterogeneity of the studies included. Further subgroup analysis and prospective, multicenter studies with appropriately selected patients, clear inclusion criteria, and follow-up are needed to confirm the value of SBCE in patients with unexplained abdominal pain. In conclusion, this review indicates that SBCE is of limited value in patients with unexplained chronic abdominal pain. The overall diagnostic yield was about 20.9%, and inflammatory lesions occurred most frequently among those positive findings.
REFERENCES 1. Hammond EC. Some preliminary findings on physical complaints from a prospective study of 1,064,004 men and women. Am J Public Health Nations Health 1964;54:11-23. 2. Fry LC, Vormbrock K, Olano C, et al. Small-bowel endoscopy. Endoscopy 2011;43:978-84. 3. Tennyson CA, Semrad CE. Advances in small bowel imaging. Curr Gastroenterol Rep 2011;13:408-17. 4. Appleyard M, Glukhovsky A, Swain P. Wireless-capsule diagnostic endoscopy for recurrent small-bowel bleeding. N Engl J Med 2001; 344:232-3.
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