Development of upper gastrointestinal cancer in patients with symptomatic gallstones, cholecystectomy, and sphincterotomy: A nationwide cohort study

Abstract

Background and objective: Exposures of gallstones and treatments thereof in relation to development of cancer have not been explored before in long-term follow-up studies. Our objective was to determine whether symptomatic gallstones, cholecystectomy, or sphincterotomy were associated with development of upper gastrointestinal cancers. Methods: This is a nationwide cohort study of persons born in Denmark 1930–1984 included from age 30 years with long-term follow-up (1977–2014). Exposures were hospital admissions with gallstones, cholecystectomy, and sphincterotomy. Time-varying covariates were included in analyses to allow the impact of exposures to change with time. Follow-up periods were 2–5 and > 5 years. Hazard ratios (HR) with 95% confidence intervals (CI) were reported. Results: A total of 4,465,962 persons were followed. We found positive associations between sphincterotomy and biliary (>5 years HR 4.34, CI [2.17–8.70]), gallbladder (2–5 years HR 20.7, CI [8.55–50.1]), and pancreatic cancer (2–5 years HR 3.68, CI [2.09–6.49]). Cholecystectomy was positively associated with duodenal (2–5 years HR 2.94, CI [1.31–6.58]) and small bowel cancer (2–5 years HR 2.75, CI [1.56–4.87]). Inverse associations were seen for cholecystectomy and biliary (>5 years HR 0.60, CI [0.41–0.87]), pancreatic (>5 years HR 0.45 CI [0.35–0.57]), esophageal (>5 years HR 0.57, CI [0.43–0.74]), and gastric cancer (>5 years HR 0.68, CI [0.55–0.86]) and for gallstones and pancreatic cancer (>5 years HR 0.66, CI [0.47–0.93]). Gallstones were positively associated with gallbladder (>5 years HR 3.51, CI [2.02–6.10]) and small bowel cancer (2–5 years HR 3.21, CI [1.60–6.45]). Conclusions: A positive association between sphincterotomy and biliary cancer was identified. Cholecystectomy seems to be inversely associated with biliary, pancreatic, esophageal, and gastric cancer. Associations should be explored in similar large cohorts.