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

Abstract

Cholelithiasis is a disease that manifests frequently in adults, and the prevalence rate of gallstones is 10% to 15% in western countries and 3% to 10% in Asian countries [1,2]. In Korea, the prevalence rate of gallstones ranges from 2% to 5%, and there is a trending increase in the number of patients diagnosed with gallstones annually [1]. The reasons for this increase include the aging population, changes in the dietary habits of people in the modern era, such as consumption of high cholesterol foods, and ease of detecting the disorder through examinations, such as ultrasonography, due to the advancement of diagnostic technologies. Gallstones induce complications, including acute cholangitis, hepatocirrhosis and acute pancreatitis, and it has been suggested that gallstones may increase the risk of gallbladder and biliary tract cancers [3,4]. Gallstones occur in approximately 75% to 90% of patients with gallbladder cancer, and the rate of gallbladder cancer is high in regions with frequent detection of gallstones [5-7]. According to previous studies, gallstones are considered to damage various tissues due to repetitive inflammatory exposure or changes in bile due to gallstones rather than gallstones themselves and cause the development of relevant cancers by depleting detoxification and carcinogenic suppressing substances. Several studies have demonstrated a correlation between gallstones and liver, biliary duct and pancreatic cancer when considering gallstones overall. How

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

“…6,19 Risk reduction by cholecystectomy increased gradually, and after lag time, the risk of gallstones was no longer seen. 6,32,33 In other studies, cholecystectomy had a negligible effect on CCC risk. [23][24][25] Although controversies exist between studies, the risk change of CCA following cholecystectomy was minimal.…”

“…However, several studies reported that risk of CCA was reduced after cholecystectomy 6,19 . Risk reduction by cholecystectomy increased gradually, and after lag time, the risk of gallstones was no longer seen 6,32,33 . In other studies, cholecystectomy had a negligible effect on CCC risk 23–25 .…”

“…33 They presumed that the increased CCA risk in patients with gallstones or cholecystectomy is not causal correlation but by high detection rate or development of symptoms by corresponding cancers. 33 To eliminate this bias, we excluded the cases of CCA diagnosed within 1 year after cholecystectomy. In addition, cumulative incidences of HCC or CCA were followed up for 15 years revealing persistent increase of them in this study.…”

“…Acute cholangitis can be developed by malignant biliary obstruction and CCA could be manifested as acute cholangitis. A recent study in Korea reported that the increased risks of ECC and AVC in patients with gallstones who underwent cholecystectomy disappeared after 1 year of lag 33 . They presumed that the increased CCA risk in patients with gallstones or cholecystectomy is not causal correlation but by high detection rate or development of symptoms by corresponding cancers 33 .…”

Pathophysiology of Gallstones

“…Gallstones can cause biliary colic, cholecystitis, pancreatitis, empyema Gallbladder, perforation of gallbladder, cholangitis, bile duct obstruction [3], and cancers (gallbladder [4], colorectal [5,6], pancreatic [7]). In 85% of patients with gallbladder cancer, gall stones are present [8].…”