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

Abstract

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; I 2 =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. Conclusions: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 E p u b a h e a d o f p r i n t present in the meta-analyses.

Cholecystectomy reduces the risk of cholangiocarcinoma in patients with complicated gallstones, but has negligible effect on hepatocellular carcinoma

“…Gallstones have been reported as a risk factor of CCA. 8 Our study revealed a 1.80-fold increased risk of CCA in patients with gallstones. However, patients with complicated gallstones revealed a 5.62 (4.89-6.46)-fold risk of CCA.…”

“…A positive association between gallstones and cholangiocarcinoma (CCA) [6][7][8] or hepatocellular carcinoma (HCC) [9][10][11][12] has been reported with a 2.0-fold to 2.5-fold risks compared with the general population. However, the risks of hepatobiliary cancers may differ according to the presence of biliary tract inflammation.…”

Primary spindle cell sarcoma of gallbladder

“…[ 36 ] Gallbladder stones and/or infectious agents cause cancer as a result of recurrent trauma and chronic inflammation. [ 37 ] In our study, 59.6% of patients were diagnosed with cholecystolithiasis, but it remains unclear whether gallbladder stones and concomitant inflammation initiate the transformation of mesenchymal cells. Many studies have shown that sarcoma might originate from mesenchymal stem cells (MSCs), which show that rodent MSCs are prone to spontaneous sarcomagenesis upon prolonged in vitro culture, and that MSCs have been used to establish several crucial experimental sarcoma models.…”

Evolving Paradigms in the Systemic Treatment of Advanced Gallbladder Cancer: Updates in Year 2022

“…In more recent years, there has also been an increase in GBC incidence rates in the African American population [ 4 ]. Gallstones are found in 69–86% of all GBC patients and have been strongly associated with GBC [ 5 , 6 , 7 , 8 ]. However, the incidence of GBC in patients with gallstones was reported to be 0.5, and the majority of patients with gallstones will not develop gallbladder cancer in their lifetimes [ 9 ].…”