Neoplastic cascade towards cholangiocarcinoma in primary sclerosing cholangitis

PSC patients have an increased risk for the development of CCA. Since the tumor is often detected at a stage precluding curative treatment, the prognosis is devastating. Surveillance is hampered by a low diagnostic accuracy of current tumor markers, the difficulties of imaging techniques for the differentiation between benign and malignant biliary strictures, and the need for invasive procedures. This thesis aimed to expand the knowledge regarding the molecular processes during the development of PSC-CCA. Gaining a better insight into the pathophysiology of PSC-CCA may allow for improving diagnostic strategies and developing more effective therapeutic agents.
In this thesis, we identified genetic alterations in biliary biopsies and resections specimens during the neoplastic cascade of PSC-CCA, concluded that mutations can be reliable determined in biliary brush samples of PSC-CCA, and demonstrated the presence of subclonal cell populations. In addition, we
have investigated the influence of pro-inflammatory cytokines on the proliferation rate and growth of CCA organoids.