A total of 627 biliary cancer patients (368 gallbladder, 191 bile duct, and 68 ampulla of Vater), 1037 stone patients (774 gallbladder and 263 bile duct), and 959 healthy controls were included. Most cancers were diagnosed at an advanced stage: 70, 61, and 44 of gallbladder, bile duct, and ampulla of Vater cancers, respectively, were diagnosed at stage III or IV. Of the tumours with histopathological information, over 90% were adenocarcinomas. Cancers diagnosed incidentally during surgery for gallstones accounted for 26.1, 14.1, and 8.8% of the patients with gallbladder, bile duct, and ampulla of Vater cancers, respectively. Of the 191 extrahepatic bile duct cancers, over half (60%) were in the upper third (including the cystic duct), 6% in the middle third, 10% in bile duct not otherwise specified, 18% in the lower third, and 6% in other or multiple parts. Among gallstone patients, 8.1% had intestinal metaplasia while 5.3% had dysplasia/carcinoma in situ.
shows selected characteristics of cases and controls with age (due to matching) similar in cancer cases and controls. Those with biliary stones and no cancer tended to be younger than cancer cases. Gallbladder cancer was more common in women than men, while slightly more men had cancers of extrahepatic bile ducts and ampulla of Vater. Relative to controls, gallbladder cancer patients had a lower education level, were less likely to smoke or drink alcohol, more likely to have a history of diabetes, and had a higher BMI.
Selected characteristics of cases and controls
shows ORs for biliary tract cancer in relation to gallstones. The overall prevalence of gallstones in the 959 controls was 23.4%, with 5.9% reporting a history of cholecystectomy, 11.3% of gallstones, and 6.2% having silent gallstones detected through ultrasound. The 5.5% of controls with biliary sludge or cholesterol crystals detected on abdominal ultrasound were not classified as having gallstones. In contrast, a history of gallstones were found for 83.7, 66.5, and 53% of gallbladder, bile duct, and ampulla of Vater cancer, respectively. The ORs associated with stones were 23.8 (95% CI, 17.0–33.4), 8.0 (95% CI 5.6–11.4), and 4.2 (95% CI 2.5–7.0) for cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, respectively. Further adjustment for smoking, drinking, BMI, tea drinking, aspirin use, and diabetes did not materially change the results. Location of gallstones was recorded for over 73% of the cancer patients with gallstones. For those with gallbladder cancer, 77% of the stones were in the gallbladder, 10% in the gallbladder neck, 9% in both the gallbladder and bile ducts, and 4% in bile ducts alone. The corresponding percentages for bile duct cancer were 68, 7, 11, and 13%, and for ampullary cancer 57, 0, 14, and 28%. The average age for biliary tract cancer cases with gallstones was about 5 years older than that for cases without gallstones (65 vs 60, P=0.0005).
Odds ratiosa and 95% confidence intervals for biliary tract cancer in relation to gallstones, Shanghai, China
As shown in , overall, younger age at gallstone diagnosis or longer duration of stones alone did not modify the 23-fold risk associated with gallstones. The very high ORs for bile duct and ampulla of Vater cancers related to having gallstones for 1 year or less were due to the frequency of incidental tumours shortly after or at the time of stone diagnosis. Similar risk patterns were observed for both men and women (data not shown).
Odds ratiosa and 95% confidence intervals for biliary tract cancer in relation to age at gallstone diagnosis and duration of stones, Shanghai, China
shows the combined effects of gallstones and related factors, including chronic cholecystitis, pancreatitis, diabetes, and high BMI, on biliary cancer risk. Since gallstones and cholecystitis may be detected concomitantly with biliary tract cancer, and gallstones may induce cholecystitis/pancreatitis, subjects with cholecystitis or pancreatitis diagnosed prior to 2 years of cancer diagnosis (mostly incidental tumours) or interview were excluded from the analysis. Subjects with both gallstones and (self-reported) chronic cholecystitis had a markedly increased risk of biliary cancer, especially of the gallbladder (OR=34.3; 95% CI 19.9–59.2), although the interaction between gallstones and the cholecystitis was not statistically significant. Similarly, subjects with both gallstones and diabetes had a higher risk of gallbladder cancer (OR=30.7, 95% CI 16.7–56.5). BMI and pancreatitis did not appear to modify the effect, and even among those with a low BMI (<23
); gallstones were a significant risk factor for all three subsites.
Odds ratiosa and 95% confidence intervals for biliary tract cancer in relation to gallstones and other factors, Shanghai, China
(see website) shows the morphological characteristics of gallstones for 249 biliary cancer patients (196 gallbladder, 53 bile duct) and 892 stone patients (668 gallbladder, 224 bile duct) as well as the biochemical composition of gallstones in 530 subjects with stones alone (358 gallbladder, 162 bile duct), 41 with gallbladder cancer, and 10 with bile duct cancer. Significant differences by subsite were seen in type, number, and weight, with pigment stones being more common in the bile duct patients or with bile duct cancer, and cholesterol stones in gallbladders patients or with gallbladder cancer. Compared with bile duct cancer, gallbladder cancer patients were more likely to have multiple (72 vs
=0.08), larger, and heavier stones. Their stones were also heavier (4.9 vs
=0.006) than those of gallstone patients, but no significant differences were seen in the size or number of stones. Patients with bile duct stones or extrahepatic bile duct cancer had higher levels of bile acids and bilirubin in their stones than patients with gallbladder stones or cancer (P