Gallstones, Cholecystectomy and the Risk of Hepatobiliary and Pancreatic Cancer: A Nationwide Population-based Cohort Study in Korea

Abstract

Several epidemiological studies suggest a potential association between gallstones or cholecystectomy and hepatobiliary and pancreatic cancers (HBPCs). The aim of this study was to evaluate the risk of HBPCs in patients with gallstones or patients who underwent cholecystectomy in the Korean population. A retrospective cohort was constructed using the National Health Insurance Service-National Sample Cohort (NHIS-NSC). Gallstones and cholecystectomy were defined by diagnosis and procedure codes and treated as time-varying covariates. Hazard ratios (HRs) in relation to the risk of HBPCs were estimated by Cox proportional hazard models. Among the 704,437 individuals who were included in the final analysis, the gallstone prevalence was 2.4%, and 1.4% of individuals underwent cholecystectomy. Between 2002 and 2015, 487 and 189 individuals developed HBPCs in the gallstone and cholecystectomy groups, respectively. A significant association was observed between gallstones and all HBPCs (HR 2.16; 95% CI 1.92-2.42) and cholecystectomy and all HBPCs (HR 2.03; 95% CI 1.72-2.39). However, when 1-, 3-, and 5-year lag periods were applied, the HBPC and subsites risk approached zero. A significant association was observed between cholecystectomy and intrahepatic bile duct cancer (IBDC) (HR 2.68; 95% CI 1.63-4.40). When 1-, 3- and 5-year lag periods were applied, the IBDC risk after cholecystectomy was 2.86-fold (95% CI 1.68-4.85), 2.92-fold (95% CI 1.51-5.64), and 4.08-fold (95% CI 1.94-8.61) higher, respectively, than that in the comparison group. In conclusion, gallstone diagnosis and cholecystectomy seem to correlate with HBPCs, especially cholecystectomy and IBDC.

Keywords: Biliary tract neoplasms; Cholecystectomy; Gallstones; Liver neoplasms; Pancreatic neoplasms.

Figure 1. HR of hepatobiliary and pancreatic cancer in the gallstone group.

(A) Hepatobiliary and pancreatic cancer. (B) Hepatobiliary and pancreatic cancer subsite. HR, hazard ratio; HBPC, hepatobiliary and pancreatic cancer; BTC, biliary tract cancer; PC, pancreatic cancer; IBDC, intrahepatic bile duct caner; EBDC, extrahepatic bile duct cancer; GBC, gallbladder cancer; AOVC, ampulla of Vater cancer.

Figure 2. HR of hepatobiliary and pancreatic cancer in the cholecystectomy group.

(A) Hepatobiliary and pancreatic cancer. (B) Hepatobiliary and pancreatic cancer subsite. HR, hazard ratio; HBPC, hepatobiliary and pancreatic cancer; BTC, biliary tract cancer; PC, pancreatic cancer; IBDC, intrahepatic bile duct caner; EBDC, extrahepatic bile duct cancer; GBC, gallbladder cancer; AOVC, ampulla of Vater cancer. aAOVC female HR’s 95% CI shown in figure because too wide due to cannot shown in the figure.