Epidemiology, risk factors, and pathogenesis of cholangiocarcinoma

Abstract

Cholangiocarcinoma (CCA) is a fatal cancer of the biliary epithelium, arising either within the liver (intrahepatic, ICC) or in the extrahepatic bile ducts (extrahepatic ECC). Globally, CCA is the second most common primary hepatic malignancy. Several recent epidemiological studies have shown that the incidence and mortality rates of ICC are increasing. This review of the literature on the international epidemiological rates of CCA, both intra- and extrahepatic, explores possible explanations for the trends found. The possible role of epidemiological artifact in the findings is discussed and the known risk factors for CCA are summarized. These include primary sclerosing cholangitis, liver fluke infestation, congenital fibropolycystic liver, bile duct adenomas, and biliary papillomatosis, hepatolithiasis, chemical carcinogens such as nitrosamines, Thorotrast, chronic viral hepatitis, cirrhosis, chronic non-alcoholic liver disease and obesity. Potential pathways involved in the molecular pathogenesis of CCA are also summarized.

Keywords: Cholangiocarcinoma.

Figure 1.

Mortality trends in men from 1979 onwards for: (a) ICD-9 155.0 (primary hepatic parenchymal cancer, including hepatocellular carcinoma, HCC), (b) 155.1 (ICC) and (c) 156 (tumors of the gallbladder and ECC). Source: Khan et al. J Hepatol 2002;37:806–13.

Figure 2.

Regional differences in the mean estimated annual percentage change in age-adjusted (1970 World Standard population) gender-specific mortality rates from intrahepatic biliary tract tumors (top) and gallbladder and extrahepatic biliary tract tumors (bottom). Source: Patel BMC Cancer 2002;2:10.