Abstract: A total of 16 studies were included. All studies reported on TAUS and EUS as separate tests and not as a combination of tests. All studies were at high or unclear risk of bias, ten studies had high applicability concerns in participant selection (because of inappropriate participant exclusions) or reference standards (because of lack of follow-up for non-operated polyps), and three studies had unclear applicability concerns in participant selection (because of high prevalence of gallbladder polyps) or index tests (because of lack of details on ultrasound equipment and performance). A meta-analysis directly comparing results of TAUS and EUS in the same population could not be performed because only limited studies executed both tests in the same participants. Therefore, the results below were obtained only from indirect test comparisons. There was significant heterogeneity amongst all comparisons (target conditions) on TAUS and amongst studies on EUS for differentiating true and pseudo polyps. Detection of gallbladder polyps: Six studies (16,260 participants) used TAUS. We found no studies on EUS. The summary sensitivity and specificity of TAUS for the detection of gallbladder polyps was 0.84 (95% CI 0.59 to 0.95) and 0.96 (95% CI 0.92 to 0.98), respectively. In a cohort of 1000 people, with a 6.4% prevalence of gallbladder polyps, this would result in 37 overdiagnosed and seven missed gallbladder polyps. Differentiation between true polyp and pseudo gallbladder polyp: Six studies (1078 participants) used TAUS; the summary sensitivity was 0.68 (95% CI 0.44 to 0.85) and the summary specificity was 0.79 (95% CI 0.57 to 0.91). Three studies (209 participants) used EUS; the summary sensitivity was 0.85 (95% CI 0.46 to 0.97) and the summary specificity was 0.90 (95% CI 0.78 to 0.96). In a cohort of 1000 participants with gallbladder polyps, with 10% having true polyps, this would result in 189 overdiagnosed and 32 missed true polyps by TAUS, and 90 overdiagnosed and 15 missed true polyps by EUS. There was no evidence of a difference between the diagnostic accuracy of TAUS and EUS (relative sensitivity 1.06, P = 0.70, relative specificity 1.15, P = 0.12). Differentiation between dysplastic polyps/carcinomas and adenomas/pseudo polyps of the gallbladder: Four studies (1,009 participants) used TAUS; the summary sensitivity was 0.79 (95% CI 0.62 to 0.90) and the summary specificity was 0.89 (95% CI 0.68 to 0.97). Three studies (351 participants) used EUS; the summary sensitivity was 0.86 (95% CI 0.76 to 0.92) and the summary specificity was 0.92 (95% CI 0.85 to 0.95). In a cohort of 1000 participants with gallbladder polyps, with 5% having a dysplastic polyp/carcinoma, this would result in 105 overdiagnosed and 11 missed dysplastic polyps/carcinomas by TAUS and 76 overdiagnosed and seven missed dysplastic polyps/carcinomas by EUS. There was no evidence of a difference between the diagnostic accuracy of TAUS and EUS (log likelihood test P = 0.74). Although TAUS seems quite good at discriminating between gallbladder polyps and no polyps, it is less accurate in detecting whether the polyp is a true or pseudo polyp and dysplastic polyp/carcinoma or adenoma/pseudo polyp. In practice, this would lead to both unnecessary surgeries for pseudo polyps and missed cases of true polyps, dysplastic polyps, and carcinomas. There was insufficient evidence that EUS is better compared to TAUS in differentiating between true and pseudo polyps and between dysplastic polyps/carcinomas and adenomas/pseudo polyps. The conclusions are based on heterogeneous studies with unclear criteria for diagnosis of the target conditions and studies at high or unclear risk of bias. Therefore, results should be interpreted with caution. Further studies of high methodological quality, with clearly stated criteria for diagnosis of gallbladder polyps, true polyps, and dysplastic polyps/carcinomas are needed to accurately determine diagnostic accuracy of EUS and TAUS.

Plain-language summary: A total of 16 studies were included. All studies reported on TAUS and EUS as separate tests and did not use a combination of TAUS and EUS. Six studies (16,260 participants) used TAUS for diagnosis of gallbladder polyps. No studies on the diagnosis of gallbladder polyps by EUS were found. Six studies (1,078 participants) used TAUS and three studies (209 participants) used EUS for differentiating between true and pseudo polyps. Four studies (1,009 participants) used TAUS and three studies (351 participants) used EUS for differentiating between (pre)cancerous and benign polyps. In a general population of 1000 people (in which 6.4% have a gallbladder polyp), TAUS will overdiagnose 37 people without a polyp as having a polyp, and in 7 people with a polyp, the polyp will be missed. In a population of 1000 people with a gallbladder polyp, of which 10% have a true polyp, 189 people with a pseudo polyp will be indicated as having a true polyp by TAUS, and 90 people by EUS. These people may be treated, which is not necessary. In 32 people, the true polyp will be misclassified as a pseudo polyp by TAUS and in 15 people by EUS. These people would not be treated, while they may need treatment. In a population of 1000 people with a gallbladder polyp, of which 5% have a (pre)cancerous polyp, 105 people with a benign polyp will be indicated as having a (pre)cancerous polyp by TAUS, and 75 people by EUS. These people may be overtreated for a (precursor of) cancer, which is not there. In 11 people, the (pre)cancerous polyp will be misclassified as a benign polyp by TAUS, and in 7 people by EUS. These participants may not receive proper treatment for their (precursor of) cancer. TAUS will correctly diagnose 956 out of 1000 people regarding the presence or absence of gallbladder polyps. For differentiating between polyp types, fewer people will be correctly diagnosed by TAUS, leading to unnecessary treatment for pseudo polyps and neglect of (pre)cancerous polyps. There was insufficient evidence that EUS is better than TAUS in differentiating between true and pseudo polyps and between (pre)cancerous and benign polyps. All studies were either at high or unclear risk of bias and 13 studies had either high or unclear applicability concerns. This may undermine the validity of the studies. Further studies of high methodological quality and with clearly reported criteria for diagnosis of gallbladder polyps, true polyps, and (pre)cancerous polyps are necessary.