To our knowledge, this is the first meta-analysis to report pooled rates of each VCE adverse event, assess the predictors and provide time-trend analysis over the past two decades. The results demonstrated that VCE is a safe procedure worldwide with low rate of adverse events. The risk for retention should be assumed in patients with known IBD, which is a contraindication unless intestinal patency is proven, best by the passage of an intact PCE. Elder age is the risk or protect factor for small bowel incomplete examination or swallow disorder. In addition, the rate of retention and small bowel incomplete examination were declined over the years.
Retention is the most focused adverse event since retained capsules may cause partial or complete gastrointestinal obstruction, which limits wider utilization of VCE. Compared with previous study [18], we detected a lower pooled retention rate of 0.73%. This could be attributed to the usage of PCE, which predicts small bowel strictures in high-retention risk patients [36, 37]. As showed in the results, retention rate of after PCE group was 0.09% in subgroup analysis, and PCE significantly decreased retention rate by 5.04% in multivariable meta-regression. These findings confirm that performing an initial PCE before VCE is useful to avoid retention. The known IBD is the predictor increase retention rate by 4.29%, which may due to the presence of associated underlying inflammatory strictures [38]. Surgery is frequently performed for retained capsules in the early years [39]; however, for asymptomatic patients or with slight abdominal pain, later studies reported more favorable clinical outcomes using endoscopic methods or medical treatment [40, 41]. Our time-trend meta-regressions also showed decreasing trend for surgery and increasing trends for non-surgical management.
As VCE is usually swallowed in standing position, the esophageal transit time is very short due to gravity function, resulting in few images taken and causing esophagus incomplete examination. Right supine position [27], acquired image from both ends of VCE [42], increased frame rate [43], and stringed VCE [44, 45] were studied to overcome gravity effect and improved Z-line visualization. The invention of MCE provided a more viable approach for gastric examinations [6]. Since MCE cannot perform flushing and suctioning, visualization may be impaired by the presence of bubbles and mucus. The investigators have used detergents in gastric preparation, while the fundus still poor visualized [46, 47]. Because battery life is limited, incomplete examination of small bowel and colon could easily occur (12.08% and 19.19%, respectively). In this meta-analysis, age was an independent predictor affected small bowel incomplete examination rate, which is similar with the previous study of Girelli et al [48]. Small bowel incomplete examination rate declined over the past two decades, which may contributed by various investigations, such as prolonged battery life span in newer capsule generation [49, 50] or reduced gastric transit time (GTT). CCE was introduced with prolonged battery life, and we confirmed a significant relationship between CCE and lower small bowel incomplete examination rate. The methods included real-time viewer [51], administered prokinetic agents (such as metoclopramide[52, 53], mosapride[54], and erythromycin[55]), endoscopically placement [56, 57], and magnetic steering [58] can be used to improve the likelihood of a complete small bowel examination in routine clinical practice.
Since the VCE was introduced, it has been proven useful for many indications across a wide age range, the youngest child used VCE was only 8 months of age [59]. However, young age was an independent predictor significantly associated with higher swallow disorder rate. In one series, 63 of 83 children < 8 years old required AdvanCE™ placement device to deliver the VCE into the duodenum [60]. In this study, 0.75% patients were unable to swallow the capsule. It’s notable that, the capsule aspiration is an adverse event relating to swallowing disorder. Although very rare (5/23,449), case reports described it may cause life threatening acute respiration distress, and over half of patients required bronchoscopy intervention after capsule aspiration [24, 61, 62]. Aging, neurological or swallowing disorder and patients with a weak or absent cough are high risk for VCE aspiration [63]. Fortunately, the patients included in this meta-analysis had no respiratory distress, and the problem can resolved quickly by spontaneously coughing [23, 25, 48, 64].
The overall technical failures rate is significantly lower than previous study by Rondonotti et al (0.67% vs 8.59%) [25], this reflects the immature of early capsule and software prototypes. During VCE examination, male and ECE were significantly increased procedural adverse events rate. In esophagus examination, the use of string attachment could be able to prevent VCE rapid and unpredictable transmission, allowing controllable movement and real-time visualization. However, the retrieval of the capsule caused discomfort, usually lead to nausea and vomiting [3]. The detachable technique in string VCE avoid this problem, and comfort assessment was better than previous reports [45].
To date, this work is the largest overview including over 100,000 VCE procedures from 402 literatures. Our study has several strengths. First, compared with previous studies, this is the first systematic review and meta-analysis comprehensively summarized the full spectrum of VCE adverse events, ranging from retention, swallow disorder, aspiration, technique failure, procedural adverse events, and incomplete examination, demonstrating low adverse event rates and safe clinical application over its two decades of use. Second, we performed meta-regression to determine the predictors of each adverse event, and identified new risk or protective factor (age) for small bowel incomplete examination or swallow disorder. Third, this is the first study providing temporal changes of VCE adverse event rates. The retention and small bowel incomplete examination rates in this study were lower than previous systematic review [18] (0.73% vs 1.4%, and 12.08% vs 16.5%, respectively), and our time-trend analysis indicated rates of those adverse events declined over the past two decades, encouraging continued efforts to achieve and maintain safety targets in VCE practice.
There are several limitations. First, there were obvious heterogeneity in most VCE adverse event rates, and Egger test indicated potential publication bias for stomach incomplete examination rate, swallow disorder rate, aspiration rate, technical failure rate, and procedural adverse events rate, which may have compromised the precision of our study. Second, exclusion of studies with fewer than 50 patients may introduced selection bias to this analysis, the rate of rare VCE adverse events such as capsule aspiration may underestimated. Last, meta-regression analysis was conducted on the level of the studies, and the characteristics of studies, individual patients, and VCE could not be retrieved to identify other risk factors.
In conclusion, this systematic review and meta-analysis comprehensively summarized the full spectrum of VCE adverse events, demonstrating low adverse event rates and safe clinical application. Retention and small bowel incomplete examination rates declined over the past two decades. Patients with known inflammatory bowel disease or elder should be alerted to high risk of retention or small bowel incomplete examination. Future clinical practice and research will benefit from this knowledge and potential adverse events would be prevented.