Histopathologic analysis of mice to examine possible causes of death showed disease relapse with strong local tumor recurrence/intrahepatic metastases (Fig. 5C, left) accompanied by peritoneal carcinomatosis and small lung metastases (Fig. 5C, right lane). Since metastases could not be found in nonresected animals, the prolonged life span gained by resection obviously Idasanutlin concentration allows for the outgrowth of circulating

micrometastases. As an important hallmark of R0-resection, the resection margin should be absolutely tumor-free. In orthogonally sectioned samples of tumors following resection, in all samples we achieved a minimum distance of at least 9 mm between tumor tissue and resection margin (Fig. 5D, left). Since satellites were detectable with a maximum visible distance of around 700 μm to the tumor margin, the performed resections were actually R0 (Fig. 5D, right). It is common sense in clinical oncology that satellite formation with vascular invasion during tumor progression can be regarded as a strong indication for local tumor recurrence after resection.[32, 33] Concepts for adjuvant therapies are recommended and deserve more detailed investigations to

overcome life-limiting disease relapse.[34] Therefore, we tested in our model the therapeutic efficacy of adjuvant selleck inhibitor gemcitabine treatment as used in recent clinical cholangiocarcinoma trials.[22] At first, gemcitabine treatment as a palliative approach in sham-operated mice showed no survival benefit compared to the sham-operated control group (Fig. 6), whereas tumor resection itself resulted in prolonged survival compared Cytidine deaminase to both sham-operated groups. Compared to the resection

group, we observed a significant survival benefit by an adjuvant gemcitabine approach. Therefore, our data indicate a life-prolonging outcome if gemcitabine is used in the adjuvant setting after surgical R0-resection of ICC. Together, our results show that our established model reflects both genetic and clinical characteristics of human ICC and thus represents an excellent tool to investigate novel adjuvant ICC therapies in an animal model of highly predictive value. Intrahepatic cholangiocarcinoma is representative of tumor entities where resection of the primary tumor is the only option for cure, but frequent disease recurrence limits survival.[35] In general, clinical development of novel cancer therapies is expensive and time-consuming, since a large number of promising agents or strategies fail in late-stage clinical trials. Those disappointing results emphasize that preclinical animal models of reliable predictive value are urgently required, particularly for investigations of adjuvant systemic therapies. To meet these predictive requirements genetically engineered mouse models have been developed[36] and several new treatment strategies could be developed on the basis of these models.