Association between gallstones and the risk of biliary tract cancer risk: a systematic review and meta-analysis.

Objectives: Biliary tract cancers (BTCs) are rare but highly fatal. Although the etiology of BTC is poorly understood, gallstones are proposed to be an imperative risk factor. We conducted a systematic review and meta-analysis to examine the associations between gallstone characteristics and the risk of BTC.

Methods: We searched the Medline, Embase, and Cochrane Central databases and systematically reviewed cohort and case-control studies published before April 9, 2018. All the included studies reported appropriate risk estimates and their confidence intervals (CIs) on the association between the presence, size, number, or duration of gallstones and the risk of BTC, including gallbladder cancer (GBC), extrahepatic bile duct cancer (EBDC), and ampulla of Vater cancer (AOVC). Summary odds ratios (ORs) and their 95% CIs were calculated using a random-effects model meta-analysis. Subgroup analyses were conducted to inspect the source of potential heterogeneity, and Egger's test was performed to assess publication bias.

Results: A total of seven cohort studies and 23 case-control studies in the Asian, European, and American populations were included. The presence of gallstones was associated with an increased risk of BTC (OR=4.38; 95% CI=3.23-5.93; I2 =91.2%), GBC (OR=7.26; 95% CI=4.33-12.18), EBDC (OR=3.17; 95% CI=2.24-4.50), and AOVC (OR=3.28; 95% CI=1.33-8.11). Gallstone size (>1 cm vs. <1 cm; OR=1.88, 95% CI=1.10-3.22) was significantly associated with the risk of GBC.

Conclusion: This systematic review and meta-analysis indicates that gallstone characteristics, such as presence, size, and number, are associated with an increased risk of BTC. However, the study has limitations that significantly high heterogeneities were present in the meta-analyses.