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Cholangiocarcinoma

Cholangiocarcinoma is a highly malignant neoplasm that carries a poor prognosis and lacks effective therapy. It is the second most common primary hepatic tumor, and it is increasing in incidence and carries a high mortality. The tumor arises from the ductular epithelium of the biliary tree, either within the liver (intrahepatic cholangiocarcinoma: ICC) or more commonly from the extrahepatic bile ducts (extrahepatic cholangiocarcinoma). Several studies have demonstrated mutations resulting in overexpression of K-ras and p53 genes. These genetic alterations are associated with a more aggressive phenotype in this cancer. Many reports have implicated overexpression of the tyrosine kinase proto-oncogenes c-erbB-2 (HER-2/neu) and c-Met, as well as cyclo-oxygenase-2 (COX-2) activity in intrahepatic cholangiocarcinoma.

Carcinogen

pisthorchis viverrini (infection with)
Radium-224 and its decay products *Chimney sweeping
*2,3,7,8-Tetrachlorodibenzo-para-dioxin

*Thorium-232 and its decay products, administered intravenously as a colloidal dispersion of thorium232 dioxide
*Tobacco smoking and tobacco smoke
*: Although this is a risk factor for liver cancer in general, the strength of association with different histological tumor types is not well understood.

Pathogen

Opisthorchis viverrini

Drug

Fluorouracil

Streptozocin

Gemcitabine

Leucovorin

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