The literature search resulted in 13,168 citations, 811 potentially relevant studies met the eligibility criteria were reviewed in full. After excluding ineligible reports, 402 studies were selected for systematic review and meta-analysis (Figure 1).
Study Characteristics
The baseline characteristics of the included studies were summarized in Table 1. The final analysis included 108,079 VCE procedures, the SBCE usage rate was predominated (303 studies [75.37%], 91,872 SBCE [85.00%] out of 91,069 patients [84.89%]). As time went on, ECE (study period midpoint, 2008 [range, 2005-2012]), CCE (study period midpoint, 2012 [range, 2006-2017]), and GCE (study period midpoint, 2014 [range, 2004-2017]) had been invented in succession. Most studies were observational designed (360 [89.55%]; including 156 prospective and 204 retrospective studies), forty-two (10.45%) studies were RCT. The studies were conducted mainly in the Europe (n = 172 [42.79%]) and Asia (n = 136 [33.83%]), followed by North America (n = 79 [19.65%]). Fewer studies were conducted in Oceania (n = 8 [1.99%]), multiple continents (n = 3, 0.75%), Latin America (n = 3 [0.75%]), and Africa (n = 1 [0.25%]). The mean age of patients was 52.56 years (range 9.92 to 73.3 years) and approximately equal sex distribution (mean prevalence of males, 52.51%).
Overall VCE adverse event rate and Publication Bias
The pooled rate of retention, swallow disorder, aspiration, technical failure, and procedural adverse events were 0.73% (1096/86742; 95% confidence interval [CI], 0.59%-0.89%; 289 studies), 0.75% (426/37270; 95% CI, 0.43%-1.13%; 155 studies), 0.00% (5/23449; 95% CI, 0.00%-0.00%; 86 studies), 0.94% (396/37297; 95% CI, 0.65%-1.28%; 146 studies), 0.67% (198/18317; 95% CI, 0.32%-1.10%; 108 studies), respectively; the esophagus, stomach, small bowel, and colon incomplete examination pooled rate were 9.05% (112/924; 95% CI, 3.14%-17.33%; 12 studies), 7.69% (103/4027; 95% CI, 2.45%-15.21%; 12 studies), 12.08% (9902/68091; 95% CI, 10.89%-13.32%; 278 studies), and 19.19% (874/4483; 95% CI, 14.06%-24.88%; 37 studies), respectively (Table 2 and Supplementary Figure 1 to 6). The characteristics of VCE technical failures were summarized in Supplementary Table 1.
The Egger’s test did not indicate the existence of obvious publication bias for retention rate (P = .6063), incomplete examination rate of esophagus (P = .7632), small bowel (P = .1315), and colon (P = .1393), while for the rate of stomach incomplete examination (P = .0017), swallow disorder (P < .0001), aspiration (P < .0001), technical failure (P < .0001), and procedural adverse events (P < .0001) showed significant asymmetry (Table 2). The effect estimated from the sensitivity analysis showed little change (Supplementary Figure 7).
Subgroup analysis and Meta-regression analysis
Factors and Predictors associated with retention rate
Subgroup analysis according to VCE type indicated SBCE associated with higher retention rate (1017/74115; 0.93%, 95% CI 0.75%-1.12%). Univariate meta-regression analysis suggested that study period midpoint, patient groups, and VCE type were eligible for inclusion in multivariate analysis. The after PCE (coefficient = -5.04%, 95% CI -8.75% to -1.33%, P = .0077) and known IBD (coefficient = 4.29%, 95% CI 1.46% to 7.12%, P = .0029), remained significant (Table 3).
Factors and Predictors associated with small bowel incomplete examination rate
Subgroup analysis of VCE type showed small bowel incomplete examination rate was markedly lower in CCE and after PCE group (136/3004, 3.99% [95%CI, 2.51%-5.75%] and 85/1268, 3.79% [95%CI, 0.12%-11.08%], respectively; P < .0001). Univariate meta-regression analysis showed that study area, patient groups, mean age, and VCE type were significant predictors, and multivariate meta-regression showed that multiple continents (coefficient = -19.57%, 95% CI -38.64% to -0.49%, P = .0444), mean age (coefficient = 0.30%, 95% CI 0.10% to 0.49%, P = .0031), and CCE (coefficient = -10.76%, 95% CI -19.50% to -2.02%, P = .0158) had a significant effect on small bowel incomplete examination rate (Supplementary Table 2).
Factors and Predictors associated with swallow disorder rate
In VCE subgroup analysis, swallow disorder rate was highest in after PCE group (37/630, 7.80%, 95% CI 0.00%-26.93%). In univariate meta-regression analysis, retrospective design, study region, known IBD group, mean age, and after PCE were predictor of swallow disorder rate. Multivariate meta-regression showed that Europe (coefficient = 4.01%, 95% CI 0.02% to 8.00%, P = .0486), North America (coefficient = 7.51%, 95% CI 2.26% to 12.76%, P = .0051), Oceania (coefficient = 20.80%, 95% CI 8.01% to 33.58%, P = .0014), known IBD (coefficient = -16.49%, 95% CI -24.68% to -8.30%, P < .0001), and mean age (coefficient = -0.72%, 95% CI -0.89% to -0.56%, P < .0001) significantly associated with swallow disorder rate (Supplementary Table 3).
Factors and Predictors associated with procedural adverse events rate
The procedural adverse events rate in ECE was significantly higher than other VCE types (133/1695, 6.48%, 95%CI 2.65%-11.65%, P < .0001) according to VCE subgroup analysis. Univariate meta-regression analysis showed that prospective designed, North America, OGIB group, male, and VCE type were significantly affected procedural adverse events rate. The multivariate analysis showed North America (coefficient = 5.85%, 95% CI 0.34% to 11.36%, P = .0373), male (coefficient = 23.90%, 95% CI 7.56% to 40.24%, P = .0041), and ECE (coefficient = 11.38%, 95% CI 4.37% to 18.40%, P = .0015) were the significant predictors of procedural adverse events rate (Supplementary Table 4).
Reasons and interventions of retention and Time-trends of each VCE adverse event rate
The definite reasons for retention were reported in 610 VCEs according to 119 studies (Supplementary Figure 8). Crohn’s disease was the most common retention reason (n = 216, 35.41%). Among the 766 retained capsules, surgery was the most frequently used intervention (n = 352, 45.95%), followed by endoscopically management (n = 199, 25.98%), no intervention (n = 176, 22.98%) and medical therapy (n = 39, 5.09%). Although there was no significant change in time-trend analysis of retention interventions, surgery had a downward trend and other interventions had upward trends (Supplementary Figure 9).
The retention rate (coefficient = -0.34%, 95% CI -0.53% to -0.14%, P = .0006) and small bowel incomplete examination rate (coefficient = -1.44, 95% CI -1.92 to -0.97, P < .0001) decreased significantly over the years (Figure 2). The small bowel incomplete examination rate of SBCE significantly declined over time (P < .0001), while the rate of CCE unchanged (P = .6815) (Supplementary Figure 10). The stomach and esophagus incomplete examination rate were not analyzed because there was an insufficient number of studies.