Primary Sclerosing Cholangitis
There is a high incidence of cholangiocarcinoma in patients (Figure 7) with ulcerative colitis (1 in 256) and primary sclerosing cholangitis (4–20%). The cumulative risk for cholangiocarcinoma is 11.2% at 10 years after diagnosis.

Figure 7. A, Klatskin’s tumor (tumor located in the hepatic duct bifurcation) in a patient with primary sclerosing cholangitis; B, corresponding cholangiogram (ERCP image).

Liver Flukes
Cholangiocarcinoma is more common in areas endemic to liver fluke infection (Hong Kong, Thailand). Liver flukes, such as Clonorchis sinensis or Opisthorchis viverrini, usually enter human’s gastrointestinal tract after ingestion of raw fish. Parasites travel via the duodenum into the host’s intrahepatic or extrahepatic biliary ducts. Liver flukes cause bile stasis, inflammation, periductal fibrosis and hyperplasia, with the subsequent development of cholangiocarcinoma (Figure 8).

Figure 8. A, Liver flukes; B, micrograph of liver fluke eggs in the liver (reused with permission: Sun et al., Ann. Clin. Lab. Sci., 1984).

Gallstones
Gallstones vary in size, shape and number, and may be found throughout the biliary tract. The link between cholangiocarcinoma and gallstones is unclear. Intrahepatic gallstones may cause chronic obstruction to bile flow, promote micro injury of the bile ducts, and are associated with a 2–10% risk of the development of cholangiocarcinoma (Figure 9). Congenital cystic dilation of intrahepatic biliary ducts (Caroli’s disease), and choledochus cysts have also been closely associated with development of cholangiocarcinoma.

Figure 9. Intrahepatic biliary gallstones resulting in ductal dilation.

Thorotrast
The radiocontrast agent, Thorotrast, was in use from the late 1920s through the 1950s. There are many reports of development of cholangiocarcinoma 30–35 years after exposure to this contrast material.