Small-bowel capsule endoscopy: A ten-point contemporary review

Table 3 Available meta-analyses and systematic reviews in the field of small-bowel capsule endoscopy

Ref.	Title	Search (start - end date)	Type	Subject	Data extractors	Total titles found	Titles entered meta-analysis	Individuals included	Outcome/conclusion
Liao et al[13]	Indications, detection, completion, and retention rates of SBCE: A systematic review	2000 - Jan 2009	Systematic review of evidence base	Indications, DR, CR and RR of SBCE	2	227	227	22753 Pts; 22840 CE	►Most common indications: OGIB (66.0%); investigation of clinical symptoms (10.6%); definite/suspected CD (10.4%);
									►Pooled DRs for overall, OGIB, CD, neoplasia: 59.4%, 60.5%, 55.3%, 55.9%, respectively;
									►Commonest cause for OGIB: angiodysplasia (50.0%);
									►Pooled CRs (overall): 83.5%; breakdown 83.6% (OGIB), 85.4% (clinical symptoms), 84.2% (CD);
									►Pooled RRs (overall): 1.4%; breakdown 1.2% (OGIB), 2.6% (clinical symptoms), 2.1% (CD);
									►Hence, most common indication for SBCE is OGIB, with high DR and low RR;
									►A relatively high RR is associated with definite/suspected CD and neoplasms
Marmo et al[17]	Meta-analysis: Capsule enteroscopy vs conventional modalities in diagnosis of SB diseases	Jan 1966 - Mar 2005	Meta-analysis of diagnostic test accuracy	DY/safety of SBCE vs alternative modalities (PE, SBBaR or enteroclysis) in SB disease	2	187	17	526 pts (289 OGIB and 237 CD)	►17 studies (526 patients) met inclusion criteria;
									►Overall, the rate difference for SB disease (i.e., the absolute pooled difference in the rate of positive findings) of SBCE vs alternative modalities was 41% (95%CI: 35.6-45.9);
									►For OGIB, 37% (95%CI: 29.6-44.1) for Crohn's disease 45% (95%CI: 30.9-58.0);
									►Incomplete SBCE occurred in 13%, more often in OGIB (17%) than in pts with CD (8%) (P < 0.006);
									►Adverse events: 29 pts (6%);
									►Capsule retention more frequent in pts with CD (3% vs 1%, OR 4.37)
Triester et al[18]	A meta-analysis of the yield of CE compared to other diagnostic modalities in patients with OGIB	N/A - April 2005	Meta-analysis of diagnostic test accuracy	IY (yield of CE-yield of comparative modality) and 95%CI of CE over comparative modalities	2	80	14	396 CE-PE; 88 CE-SBBaR	►14 studies (n = 396) compared DY CE vs PE in OGIB, 63% vs 28%, respectively (IY = 35%, P < 0.00001, 95%CI: 26%-43%);
									►For clinically significant findings (n = 376) DY was 56% (CE) vs 26% (PE), IY = 30%, P < 0.00001, 95%CI: 21%-38%;
									►3 studies (n = 88) compared DY of CE vs SBBaR, 67% vs 8%, respectively (IY = 59%, P < 0.00001, 95%CI: 48%-70%);
									►For clinically significant findings DY was 42% (CE) vs 6% (SBBaR); IY = 36%, P < 0.00001, 95%CI: 25%-48%;
									►NNT to yield one additional clinically significant finding with CE over either modality: 3 (95%CI: 2-4);
									►1 study compared DY (significant findings) of CE vs intraoperative enteroscopy (n = 42, IY = 0%, P = 1.0, 95%CI: -16%-16%);
									►1 study compared DY (significant findings) of CE vs CT enteroclysis (n = 8, IY = 38%, P = 0.08, 95%CI: -4%-79%);
									►1 study compared DY (significant findings) of CE vs mesenteric angiogram (n = 17, IY = -6%, P = 0.73, 95%CI: -39%-28%);
									►1 study compared DY (significant findings) of CE vs SB MRI (n = 14, IY = 36%, P = 0.007, 95%CI: 10%-62%);
									►CE-DY vs PE (vascular lesions): 36% vs 20% (IY = 16%, P < 0.00001, 95%CI: 9%-23%);
									►CE-DY vs PE (inflammatory lesions): 11% vs 2% (IY = 9%, P = 0.0001, 95%CI: 5%-13%);
									►CE-DY vs PE (tumours or "other" findings): no difference
Leighton et al[19]	Capsule endoscopy: A meta-analysis for use with OGIB and CD	N/A - April 2005	Meta-analysis of diagnostic test accuracy	DY and safety of SBCE vs alternative modalities (PE, SBBaR or enteroclysis) in SB disease	2	80	20	537 pts	►CE superior to PE/SB radiography for diagnosing SB pathology in pts with OGIB (yield comparable to intraoperative endoscopy);
									►Incremental yield of CE over PE/SB radiography is > 30% for clinically significant findings, due to visualization of additional vascular, inflammatory lesions by CE;
									►CE was also superior to SB radiography, C + IL, CT enterography, PE for diagnosing non-stricturing SBCD;
									►Marked improvement in yield with the use of CE over all other methods in pts who had established CD and were evaluated for SB recurrence;
									►Unknown whether these results will translate into improved pt outcomes with the use of CE vs alternate methods
Leighton et al[19]	Capsule endoscopy: A meta-analysis for use with OGIB and CD	N/A - April 2005	Meta-analysis of diagnostic test accuracy	DY and safety of SBCE vs alternative modalities (PE, SBBaR or enteroclysis) in SB disease	2	80	20	537 pts	►CE superior to PE/SB radiography for diagnosing SB pathology in pts with OGIB (yield comparable to intraoperative endoscopy);
									►Incremental yield of CE over PE/SB radiography is > 30% for clinically significant findings, due to visualization of additional vascular, inflammatory lesions by CE;
									►CE was also superior to SB radiography, C + IL, CT enterography, PE for diagnosing non-stricturing SBCD;
									►Marked improvement in yield with the use of CE over all other methods in pts who had established CD and were evaluated for SB recurrence;
									►Unknown whether these results will translate into improved pt outcomes with the use of CE vs alternate methods
Triester et al[20]	A meta-analysis of the yield of CE compared to other diagnostic modalities in patients with non-stricturing SB Crohn’s disease	N/A - Aug 2005	Meta-analysis of diagnostic test accuracy		2	82	9	250 pts	►9 studies (n = 250) compared DY CE vs SBBaR in CD: 63% vs 23%, respectively (IY = 40%, P < 0.001, 95%CI: 28%-51%);
									►4 studies (n = 114) compared DY CE vs C + IL in CD: 61% vs 46%, respectively (IY = 15%, P = 0.02, 95%CI: 2%-27%);
									►3 studies (n = 93) compared DY CE vs CT enterography/enteroclysis: 69% vs 30%, respectively (IY = 38%, P = 0.001, 95%CI: 15%-60%);
									►2 studies compared DY CE vs PE: (IY = 38%, P < 0.001, 95%CI: 26%-50%);
									►1 study compared DY CE vs SBMRI (IY = 22%, P = 0.16, 95%CI: -9%-53%);
									Sub-analysis (pts with suspected CD): no difference in DY CE vs SBBaR (P = 0.09), C + IL (P = 0.48), CT enterography (P = 0.07) or PE (P = 0.51);
									Sub-analysis (pts with established CD): difference in DY CE vs SBBaR (P < 0.001 C + IL (P = 0.002), CT enterography (P < 0.001) and PE (P < 0.001)
Pasha et al[21]	DBE and CE have comparable DY in SB disease: A meta-analysis	N/A - Dec 2006	Meta-analysis of diagnostic test accuracy	Comparison of DY of CE vs DBE	2	113	11	397 pts	►Pooled DY CE vs DBE: 60% vs 57% (IYW = 3%, 95%CI: -4%-10%, P = 0.42, FEM);
									►Pooled DY CE vs DBE (vascular findings, 10 studies): 24% vs 24% (IYW = 0%, 95%CI: -5%-6%, P = 0.88, REM);
									►Pooled DY CE vs DBE (inflammatory findings, 9 studies): 18% vs 16% (IYW = 0%, 95%CI: -5%-6%, P = 0.89, FEM);
									►Pooled DY CE vs DBE (polyps/tumours, 9 studies): 11% vs 11% (IYW = -1%, 95%CI: -5%-4%, P = 0.76, FEM);
									►SB disease: CE vs DBE have comparable DY, including OGIB, CE should be the initial diagnostic test for determining the insertion route of DBE
Niv[22]	Efficiency of bowel preparation for capsule endoscopy examination: A meta-analysis	N/A - July 2007	Meta-analysis of RCTs and cohort studies	Purgative use vs fasting alone for SBCE	1	6	8	130 bowel prep; 107 fasting	►237 pts, 130 with and 107 without preparation;
									►Seven out of 8 studies included a comparison of GTT, SBTT and CR;
									►SBCE CR: 76% in pts with preparation vs 68% without prep (difference did not reach statistical significance);
									►No statistically significant difference between CEs performed with or without preparation in GTT (pooled effect size, -0.054; 95%CI: -0.418-0.308) or SBTT (pooled effect size, -0.327; 95%CI: -1.419 - -0.765)
El-Matary et al[23]	Diagnostic characteristics of given video capsule endoscopy in diagnosis of celiac disease: A meta-analysis		Meta-analysis of diagnostic test accuracy	Coeliac and CE	2	N/A	3	107 pts	►3 studies (n = 107, 63 pts with CD/44 without) met inclusion criteria;
									►Pooled SBCE (overall) Sens and Spec: 83% (95%CI: 71%-90%) and 98% (95%CI: 88%-99.6%), respectively;
									►No major complications reported;
									►Costs mentioned only in 1 study. Overall, diagnostic characteristics of SBCE, could not justify the routine use of SBCE as alternative to biopsy
Chen et al[24]	A meta-analysis of the yield of CE compared to DBE in pts with SB diseases	N/A - Feb 2007	Meta-analysis of diagnostic test accuracy	Comparison of DY of CE vs DBE	2	163	8	277 pts	►8 studies (n = 277 pts) prospectively compared the yield of CE and DBE were included;
									►No difference between the yield of CE and DBE (170/277 vs 156/277, OR 1.21, 95%CI: 0.64-2.29);
									►Sub analysis: yield of CE significantly higher than that of DBE without combination of oral+anal insertion approaches (137/219 vs 110/219, OR 1.67, 95%CI: 1.14-2.44, P < 0.01), but not superior to the yield of DBE with combination of the two insertion approaches (26/48 vs 37/48, OR 0.33, 95%CI: 0.05-2.21, P < 0.05);
									►Focused meta-analysis of the fully published articles concerning OGIB showed similar results wherein the yield of CE was significantly higher than that of DBE without combination of oral + anal insertion approaches (118/191 vs 96/191, fixed model: OR 1.61, 95%CI: 1.07-2.43, P < 0.05) and the yield of CE was significantly lower than that of DBE by oral+ anal combinatory approaches (11/24 vs 21/24, fixed model: OR 0.12, 95%CI: 0.03-0.52, P < 0.01)
Rokkas et al[25]	Does purgative preparation influence the diagnostic yield of small bowel video capsule endoscopy? A meta-analysis	N/A - Feb 2008	Meta-analysis of RCTs and cohort studies	Purgative use vs fasting alone for SBCE	2	194	12	718 pts purgative; 444 controls	►12 eligible studies (6 prospective/6 retrospective), including 16 sets of data;
									►Significant difference in DY between pts prepared with purgatives (n = 263) vs pts prepared with clear liquids (n = 213): OR = 1.813 (95%CI: 1.251-2.628, P = 0.002);
									►Significant difference in SBVQ between pts prepared with purgatives (n = 404) vs pts prepared with clear liquids (n = 249): OR = 2.113 (95%CI: 1.252-3.566, P = 0.005); There was no statistically significant difference regarding CR rate. Purgatives did not affect VCE GTT or VCE SBTT
Dionisio et al[26]	CE has a significantly higher DY in patients with suspected and established small-bowel CD: A meta-analysis	2000 - May 2009	Meta-analysis of diagnostic test accuracy	DY of CE vs modalities in patients with suspected/ established CD	2	291	12	428 pts	►8 studies (n = 236 pts) compared CE vs C + IL, 4 (n = 119 pts) CE vs CTE, 2 (n = 102 pts) vs PE, 4 (n = 123 pts) vs MRE;
									►For suspected CD, several comparisons met statistical significance; Yields in this subgroup were: CE vs SBR: 52% vs 16% (IYw = 32%, P < 0.0001, 95%CI: 16%-48%), CE vs CTE: 68% vs 21% (IYw = 47%, P < 0.00001, 95%CI: 31%-63%), CE vs C + IL: 47% vs 25% (IYw = 22%, P = 0.009, 95%CI: 5%-39%);
									►For established CD, statistically significant yields for CE vs an alternate diagnostic modality in patients were seen: CE vs PE: 66 vs 9% (IYw = 57%, P < 0.00001, 95%CI: 43-71%), CE vs SBR: 71 vs 36% (IYw = 38%, P < 0.00001, 95%CI: 22%-54%), CE vs CTE: 71 vs 39% (IYw = 32%, P ≤ 0.0001, 95%CI: 16%-47%)
Wu et al[27]	Systematic review and meta-analysis of RCTs of Simethicone for GI endoscopic visibility	N/A- Nov 2009	Meta-analysis of RCTs	Simethicone and CE	2	128	4	121 pts	►Adequate or excellent/good SB mucosa visualization in pts receiving Simethicone vs those who did not (66.1% vs 37.2%);
									►Pooled OR = 2.84 (95%CI: 1.74-4.65, P = 0.00); no significant heterogeneity (P = 0.16, I2 = 38.8%) or publication bias (P = 0.251);
									►Sens analysis: studies stratified by factors such as bowel preparation (purgative vs fasting): Significant results for bowel preparation + fasting (OR = 4.43, 95%CI: 1.82-10.76, P = 0.00) with P = 0.78, I2 = 0.0%, No significant results for bowel preparation + purgative (OR = 1.59, 95%CI: 0.78-3.27, P = 0.203) with P = 0.20, I2 = 38.9%
Rokkas et al[25]	Does purgative preparation influence the diagnostic yield of small bowel video capsule endoscopy? A meta-analysis	N/A - Feb 2008	Meta-analysis of RCTs and cohort studies	Purgative use vs fasting alone for SBCE	2	194	12	718 pts purgative; 444 controls	►12 eligible studies (6 prospective/6 retrospective), including 16 sets of data;
									►Significant difference in DY between pts prepared with purgatives (n = 263) vs pts prepared with clear liquids (n = 213): OR = 1.813 (95%CI: 1.251-2.628, P = 0.002);
									►Significant difference in SBVQ between pts prepared with purgatives (n = 404) vs pts prepared with clear liquids (n = 249): OR = 2.113 (95%CI: 1.252-3.566, P = 0.005); There was no statistically significant difference regarding CR rate. Purgatives did not affect VCE GTT or VCE SBTT
Dionisio et al[26]	CE has a significantly higher DY in patients with suspected and established small-bowel CD: A meta-analysis	2000 - May 2009	Meta-analysis of diagnostic test accuracy	DY of CE vs modalities in patients with suspected/ established CD	2	291	12	428 pts	►8 studies (n = 236 pts) compared CE vs C + IL, 4 (n = 119 pts) CE vs CTE, 2 (n = 102 pts) vs PE, 4 (n = 123 pts) vs MRE;
									►For suspected CD, several comparisons met statistical significance; Yields in this subgroup were: CE vs SBR: 52% vs 16% (IYw = 32%, P < 0.0001, 95%CI: 16%-48%), CE vs CTE: 68% vs 21% (IYw = 47%, P < 0.00001, 95%CI: 31%-63%), CE vs C + IL: 47% vs 25% (IYw = 22%, P = 0.009, 95%CI: 5%-39%);
									►For established CD, statistically significant yields for CE vs an alternate diagnostic modality in patients were seen: CE vs PE: 66 vs 9% (IYw = 57%, P < 0.00001, 95%CI: 43-71%), CE vs SBR: 71 vs 36% (IYw = 38%, P < 0.00001, 95%CI: 22%-54%), CE vs CTE: 71 vs 39% (IYw = 32%, P ≤ 0.0001, 95%CI: 16%-47%)
Wu et al[27]	Systematic review and meta-analysis of RCTs of Simethicone for GI endoscopic visibility	N/A - Nov 2009	Meta-analysis of RCTs	Simethicone and CE	2	128	4	121 pts	►Adequate or excellent/good SB mucosa visualization in pts receiving Simethicone vs those who did not (66.1% vs 37.2%);
									►Pooled OR = 2.84 (95%CI: 1.74-4.65, P = 0.00); no significant heterogeneity (P = 0.16, I2 = 38.8%) or publication bias (P = 0.251);
									►Sens analysis: studies stratified by factors such as bowel preparation (purgative vs fasting): Significant results for bowel preparation + fasting (OR = 4.43, 95%CI: 1.82-10.76, P = 0.00) with P = 0.78, I2 = 0.0%, No significant results for bowel preparation + purgative (OR = 1.59, 95%CI: 0.78-3.27, P = 0.203) with P = 0.20, I2 = 38.9%
Cohen et al[28]	Use of CE in diagnosis and management of pediatric patients, based on meta-analysis	Jan 2001 - May 2010	Systematic review of evidence base	Systematic compilation of data on indications and outcomes of CE in paediatric patients	2	N/A	15	740 examinations; 723 pts	►Most common indication for CE (in pts < 18 yr): suspicion or evaluation of IBD (overall 54%), Breakdown: suspected CD (34%), known CD (16%), UC (1%), indeterminate colitis (3%)
									►CR and RR: 86.2% (95%CI: 81.5-90.3%) and 2.6% (95%CI: 1.5-4.0%), respectively;
									►CE RR (gastric and SB): 0.5% and 1.9%, respectively, similar to those of adults, by indication;
									►CE with positive findings: 65.4% (95%CI: 54.8%-75.2%);
									►CE resulting in new diagnosis: 69.4% (95%CI: 46.9%-87.9%); CE leading to change in therapy: 68.3% (95%CI: 43.6%-88.5%)
Teshima et al[29]	DBE and CE for OGIB: An updated meta-analysis	N/A - June 2010	Meta-analysis of diagnostic test accuracy	OGIB; CE or DBE	2	147	10	651 CE; 642 DBE	►Pooled DY for CE: 62% (95%CI: 47.3%-76.1%)
									►Pooled DY for DBE 56% (95%CI: 48.9%-62.1%); OR for CE vs DBE of 1.39 (95%CI: 0.88-2.20; P = 0.16);
									Subgroup analyses
									►DBE-DY after (+)ve CE: 75.0% (95%CI: 60.1%-90.0%)
									►DBE-DY after (-)ve CE: 27.5% (95%CI: 16.7%-37.8%)
									►DBE-OR (for successful diagnosis after (+)ve CE) compared with DBE: 1.79 (95%CI: 1.09-2.96, P = 0.02)
									►In OGIB CE and DBE have similar DY, DBE-DY significantly higher when performed in pts with prior positive CE
Belsey et al[30]	Meta-analysis: efficacy of SB preparation for SBCE	Jan 2000 - Dec 2010	Meta-analysis of RCTs	Purgative use vs fasting alone for SBCE	2	33	8	291 PEG; 133 NaP; 322 fasting	►8 studies, using PEG or NaP-based bowel cleansing regimens;
									►Any form of purgative significantly better visibility than fasting alone (OR = 2.31; 95%CI: 1.46-3.63, P < 0.0001);
									►Similar results on DY (OR = 1.88; 95%CI: 1.24-2.84; P = 0.023);
									Subgroup analyses (per cleansing regimen used):
									►PEG-based regimens showed benefit (OR = 3.11; 95%CI: 1.96-4.94, P < 0.0001);
									►NaP-based regimens no significant difference from fasting alone (OR = 1.32; 95%CI: 0.59-2.96, P < 0.0001);
									►Use of purgatives (alongside fasting) is recommended in SBCE; PEG-based regimens offer a clear advantage over NaP;
									►Lower volume PEG regimens as efficacious as higher volumes traditionally used for colonoscopy preparation
Rokkas et al[31]	The role of video CE in the diagnosis of coeliac disease: A meta-analysis	N/A - April 2011	Meta-analysis of diagnostic test accuracy	Coeliac and CE	2	461	6	166 pts	►Pooled CE Sens: 89% (95%CI: 82%-94%) and Spec: 95% (95%CI: 89%-98%), AuROC: 0.9584;
									►Although not as accurate as pathology, CE a reasonable alternative method of diagnosing coeliac disease
Koulaouzidis et al[32]	Diagnostic yield of SBCE in patients with IDA: A systematic review	Jan 2001 - Nov 2011	Systematic review of evidence base	IDA and CE	2	1225	24	1960 pts	►Pooled SBCE-DY in IDA: 47% (95%CI: 42%-52%), with significant heterogeneity among included studies (I2 = 78.8%, P < 0.0001);

CE: Capsule endoscopy; N/A: Not available or not applicable; Sens: Sensitivity; Spec: Specificity; AuROC: Area under Receiver operation characteristics curve; DBE: Double-balloon enteroscopy; OGIB: Obscure gastrointestinal bleeding; DY: Diagnostic Yield; pts: Patients; IY: Incremental yield; GTT: Gastric transit time; SBTT: Small bowel transit time; SBCE: Small-bowel capsule enteroscopy; OR: Odds ratio; RR: Relative risk; C + IL: Colonoscopy with ileoscopy; PE: Push enteroscopy; SBCD: Small bowel Crohn's disease; CT: Computed tomography; IDA: Iron deficiency anemia; FEM: Fixed effect model.