Abstracts Poster Abstracts - Dr Falk

Etiology and pathogenesis of biliary cancerKonstantinos N. Lazaridis, MDAssistant Professor of Medicine, Mayo College of Medicine, Rochester, MN 55905,USACholangiocarcinoma (CCA) is the primary cancer of extra- and intra-hepatic bileducts. Although it is a rare neoplasm, its incidence has increased. CCA derives frommalignant transformation of the cholangiocyte - the cell that line the bile ducts.Extra-hepatic CCA arises in left and right hepatic ducts, common hepatic andcommon bile ducts. These tumors present usually with clinical and biochemicalfeatures of biliary obstruction. In contrast, intra-hepatic CCA develops insidiouslywithin the liver parenchyma and frequently presents with characteristic solid masslesions at an advanced stage. It is probable that the etiopathogenetic mechanism(s)of extra- vs. intra-hepatic CCA are discrete.To date, the etiology and pathogenesis of CCA are limited. A number of risk factorshave been identified although in most cases the cause remains elusive. Commonfeatures among several of the known risk factors include a mileu of chronic biliaryinflammation and cholestasis. This biliary environment results in production ofcytokines and reactive oxygen species resulting in cholangiocyte malignant transformationas indicated by sub-cellular and cellular changes of bile duct cells. Postulatedmolecular mechanisms leading to bile duct carcinogenesis include cholangiocyteself-sufficiency/proliferation, evasion of apoptosis and escape from senescence.Expression of proteins that induce CCA invasiveness and metastasis, preservation oftelomere shortening and promotion of angiogenesis are additional pathways involvedin CCA pathogenesis.In the past decade, we have begun to better understand the biology of CCA. Nevertheless,more studies are in high demand to further the current knowledge beforeearly detection and effective therapies for CCA become a reality.24