Dr. Yee and his colleagues have offered a comprehensive overview of the epidemiology, diagnosis, and therapy of both gallbladder carcinoma and cholangiocarcinoma. They correctly note the infrequency of these two neoplasms, with approximately 7,500 cases diagnosed in the United States each year, two-thirds of which are gallbladder cancer. Unfortunately, neither the incidence rate nor prognosis of these neoplasms has changed substantially since biliary tumors were last reviewed in this journal; the median 5-year survival rate has remained at 5%. Some progress has been made, however, in our understanding of the etiology of cancers of the biliary tract, and a body of literature continues to emerge exploring the question of how best to approach screening and prophylaxis in high-risk populations.
Risk Factors for Gallbladder Cancer
As Yee et al discuss, while its pathogenesis has yet to be fully delineated, some risk factors for biliary tract carcinoma have been identified. Cholelithiasis has been widely recognized as a factor that predisposes toward its development, especially if the gallstones are symptomatic and large. "Porcelain gallbladder" or calcification of the gallbladder wall predicts a high risk of concurrent or future gallbladder cancer. An anomalous pancreaticobiliary ductal junction, a congenital defect most common among Asians, is closely connected with gallbladder cancer; 15% to 40% of patients with this anomaly go on to develop the malignancy.
Other links have been made between gallbladder cancer and bacterial infections of the biliary tract, most notably Salmonella typhi and, intriguingly, bile-resistant Helicobacter spp. Some investigators have attempted to identify biochemical changes in the composition of bile that may predispose to metaplasia. Although early data suggested that patients with gallstones and gallbladder cancer possess a higher biliary concentration of lithocholatea known carcinogenthan do patients with gallstones but no concomitant malignancy, subsequent data have failed to confirm this.
Whether one or more of these factors contributes to the striking geographic and ethnic differences identified by Yee et al in gallbladder cancer incidence rates is unclear, but the suggestions posited by preliminary data merit further investigation. Less clear are the potential roles of estrogens(Drug information on estrogens) and tobacco in the etiology of gallbladder cancer. Some case-control and observational series have identified them as risk factors, but the incidence of gallbladder cancer is not higher than predicted among patients who have developed other more clearly defined tobacco- and estrogen-associated tumors.
Risk Factors for Cholangiocarcinoma
High-risk populations for cholangiocarcinoma have been identified as well. Patients with gallstones are also at increased risk for cholangiocarconoma, although less so than for gallbladder cancer. However, other patient populations are at far greater risk. Notably, patients with primary sclerosing cholangitis have a lifetime risk of at least 10% (some have reported this risk to exceed 30%). Patients with ulcerative colitis in the absence of primary sclerosing cholangitis are at increased risk of developing cholangiocarcinoma as well, as are those with rarer conditions, including Caroli’s disease, multiple biliary papillomatosis, exposure to thorium dioxide (Thorotrast), and, in endemic regions, infestation with the trematodes Clonorchis sinensis or Opisthorchis viverrini.