DOI: 10.1097/MPA.0000000000000502

Online link: https://sci-hub.se/10.1097/MPA.0000000000000502

Systematic Review and Meta-Analysis

To investigate the potential roles of gallstones and cholecystectomy in pancreatic carcinogenesis, we performed the first meta-analysis of all currently published studies by pooling relative risks (RRs) with 95% confidence intervals (95% CIs). Stratified analysis by ethnicity, study design, and common adjusted factors were also conducted. Individuals with a history of gallstones and cholecystectomy were at increased risk of pancreatic cancer (RR,1.39; 95% CI, 1.28–1.52; P < 0.001). Gallstones and cholecystectomy were also associated with an elevated risk of pancreatic cancer, respectively (for gallstones: RR,1.70; 95% CI, 1.30–2.21; P < 0.001; for cholecystectomy: RR,1.31; 95% CI, 1.19–1.43; P < 0.001). The positive association is observed among not only the Asian population but also whites. The pooled findings were further confirmed by sensitivity analysis and stratified analyses in case-control and cohort studies. Stratified analyses by different adjusted factors further showed that the increased risk of pancreatic cancer was independent of confounders including diabetes, obesity, smoking, and follow-up years of postcholecystectomy. A history of gallstones and cholecystectomy is a robust risk factor for pancreatic cancer. Gallstone disease or cholecystectomy

–          Cholecystectomy is a major treatment for uncomplicated gallstone disease. The degradation of bile salts to secondary bile acids is enhanced after cholecystectomy. It has been implicated that secondary bile acids or metabolites may have carcinogenic effects on the colon, liver, and pancreas.

–          22 studies were included in this meta-analysis, with the earlies one published in 1973 and the latest in 2014.

–          Data from all these studies suggested that there is an association of gallbladder stones and/or cholecystectomy, with pancreatic cancer, especially in white and Asian population.

–          The association with pancreatic cancer was higher when patient with a history of gallbladder stones or cholecystectomy also had diabetes which had a synergistic effect in pancreatic carcinogenesis.

–          Having chronic gallstones was associated with higher rates of pancreatic cancer when compared to cholecystectomy.

–          One of the studies included in this meta-analysis reported that “During the period of observation, 1053 cases of pancreatic cancer were found, among which 231 (22%) occurred within 12 months after operation (cholecystectomy)”

–          Diabetes, obesity, and smoking could increase the risk of pancreatic cancer even more in patients after cholecystectomy.

–          In conclusion, the current meta-analysis strongly supports that individuals with a history of gallstones and cholecystectomy are at a significantly increased risk of pancreatic cancer.