Liver transplantation for combined hepatocellular-cholangiocarcinoma: Outcomes and prognostic factors for mortality. A multicenter analysis.

INTRODUCTION: Combined hepatocellular-cholangiocarcinoma is rare and comprises features of hepatocellular carcinoma and cholangiocarcinoma. The treatment of choice has not yet been defined. The aim of the study was to analyze outcomes of patients with combined hepatocellular-cholangiocarcinoma, who underwent liver transplantation. MATERIAL AND METHODS: All patients with combined hepatocellular-cholangiocarcinoma, who underwent liver transplantation, from January 2001 to August 2018 were identified. Pre-, intra- and postoperative data were retrospectively assessed. A univariate analysis was performed to identify prognostic factors. RESULTS: A total number of 19 patients were included to this study. Perioperative death was seen in two patients (10.5%). Recurrent disease was reported in 11 patients (64.7%) within the median time of 4 months. One and three years survival rates were 57.1% (CI 0.301-1) and 38.1% (CI 0.137-1). Factors associated mortality were tumor size >3 cm, presence of lymphatic invasion, and prolonged ICU stay. Patients with mixed HCC-CC lesions have significantly better survival compared to patients with separate lesions of HCC and CCC in one liver (p = .025). CONCLUSION: Although overall survival rates are clearly decreased compared to HCC patients, liver transplantation should be taken under consideration for selected patients with early stage and real mixed HCC-CC, who are likely to benefit from liver transplantation.

Comparison of the sixth and the seventh editions of the UICC classification for intrahepatic cholangiocarcinoma.

BACKGROUND: The current seventh edition of the TNM classification for intrahepatic cholangiocarcinoma (ICC) includes tumor number, vascular invasion, lymph node involvement but no longer the tumor size as compared to the sixth edition. The impact of the seventh edition on stage-based prognostic prediction for patients with ICC was evaluated. METHODS: Between 03/2001 and 02/2013, 98 patients with the diagnosis of an ICC were surgically treated at our center. Median survival times were calculated for these patients after separate classification by both sixth and seventh editions. RESULTS: Median overall survival was increased in patients classified to the lower tumor stages I and II using the seventh as compared to the sixth edition: stage I (54.9 vs. 47.3 months), stage II (19.9 vs. 18.9 months), stage III (17.2 vs. 19.9 months), and stage IV (23.2 vs. 15.3 months), respectively. The seventh edition definition of the T category resulted in an increased median survival regarding the T1 (50.4 vs. 47.3 months) as well as the T2 category (19.9 vs. 15.6 months) and revealed a reduced median survival of patients within the T3 (21.6 vs. 24.8 months) as well as the T4 category (19.9 vs. 27.0 months). CONCLUSIONS: The UICC seventh edition TNM classification for ICC improves separation of patients with intermediate stage tumors as compared to the sixth edition. The prognostic value of the UICC staging system has been improved by the seventh edition. Trial registration The data for this study have been retrospectively registered and the study has been approved by the ethic committee of the medical faculty of the University Hospital of Essen, Germany (license number 15-6353-BO).

Polo-like kinase 3 is associated with improved overall survival in cholangiocarcinoma.

BACKGROUND & AIMS: Cholangiocarcinomas (CCA) paradoxically express the death ligand TRAIL and thus, are dependent on effective survival signals to circumvent apoptosis. Hedgehog signalling exerts major survival signals in CCA by regulating serine/threonine kinase polo-like kinase (PLK)2. We here aimed to examine the role of PLK1/2/3 expression for CCA tumour biology. METHODS: We employed CCA samples from 73 patients and human HUCCT-1/Mz-CHA1/KMCH-1 CCA cells. Immunohistochemistry for PLK1/2/3 was performed using tissue microarrays from representative tumour areas. RESULTS: PLK1/2/3-immunoreactive cancer cells were present in most of the CCA samples. However, only PLK1 and especially PLK3 were expressed in higher amounts within CCA cells as compared to normal liver. Given that fibroblast growth factor (FGF) can induce PLK3 expression and also is present in CCA, we examined the effect of FGF on PLK3 in vitro. Indeed, rhFGF rapidly increased PLK3 mRNA expression all three CCA cell lines giving an explanation for the abundant PLK3 presence in the tissue samples. Clinicopathologically, PLK3 expression was associated with decreased tumour cell migration and lymph/blood vessel infiltration whereas higher levels of PLK1 were correlated with larger tumour sizes. Moreover, strong PLK3 expression was associated with prolonged overall survival. CONCLUSIONS: The results suggest that PLK3 predominantly is expressed in CCA cells and that high PLK3 expression correlates with prolonged overall survival. These observations might have implications for prognosis prediction of human CCA as well as the potential therapeutic use of polo-like kinase inhibitors (i.e., PLK1/2 specifity).