An update on cholangiocarcinoma associated with primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is being diagnosed with increasing frequency. The most feared complication is the presence or development of cholangiocarcinoma (CCA). The present review summarizes recent data with regards to diagnosis, pathobiology and treatment.

Several investigations have focused on aspects of the molecular biology of CCA in general; such data should be explored now in the context of PSC-related CCA to yield new diagnostic markers and approaches for therapy.

CCA has to be suspected in any new PSC patient presenting with jaundice. Exploration should include carbohydrate antigen19-9 and two imaging techniques. Endoscopic cholangioscopy might become very rewarding. Important progress has been achieved in liver transplantation by the use of preoperative radio-chemotherapy. Molecular biology points to inflammation-induced cytokines with mutagenic action and to the relevance of extracellular matrix proteins for invasion but also for proliferation. Micro-RNAs prove to be very important in the control of cell proliferation, differentiation and apoptosis. Mutated p53, cyclins, wnt/beta-catenin signaling, proliferation indices, mucins, carbohydrate antigen19-9, CRP and aneuploidy appear to hold significant potential as predictors of outcome in CCA. It is expected that the further unraveling of these molecular processes will ultimately lead to development of tests allowing early diagnosis and to development of medical approaches to retard tumor formation or recurrence following surgical interventions.