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

Background and Aim: Gallstones have been reported to be positively associated with hepatobiliary cancers. However, risks of these cancers by cholecystectomy or in patients with complicated gallstones are controversial. We studied the effect of cholecystectomy on the risk of cholangiocarcinoma (CCA) or hepatocellular carcinoma (HCC) in patients with gallstones and subgroup of complicated gallstones. Methods: Patients with gallstone disease (n = 958 677) and age-matched and sex-matched controls (n = 9 586 770) were identified using the Korean National Health Insurance database. Complicated gallstones were defined as gallstones associated with acute cholecystitis or acute cholangitis. Adjusted hazard ratios (adjusted hazard ratios, 95% confidence interval) of CCA and HCC incidences were evaluated in patients with gallstones who received cholecystectomy compared to the controls. We also analyzed these effects in patients with complicated gallstones. Results: Patients with gallstones showed increased risks of CCA (1.80, 1.67–1.93) and HCC (1.03, 1.00–1.07) compared with controls. Cholecystectomy had minimal effects on the risks of CCA (1.94, 1.76–2.14) and HCC (0.93, 0.87–0.99) compared with those without cholecystectomy. However, patients with complicated gallstones showed highly increased CCA risk (5.62, 4.89–6.46) and a 30% risk reduction after cholecystectomy (3.91, 3.43–4.46). Risk reduction by cholecystectomy was greater for extrahepatic CCA than for intrahepatic CCA or ampulla of Vater cancer. However, the risk of HCC was not different in patients with complicated gallstones and those who underwent cholecystectomy compared to controls. Conclusion: The risk of CCA was markedly increased in patients with complicated gallstones and was partially reduced by cholecystectomy. The risk change of HCC was minimal with gallstones or cholecystectomy.