Transplantation versus resection for patients with combined hepatocellular carcinoma-cholangiocarcinoma.

Although transplantation has demonstrated survival benefit for patients with hepatocellular carcinoma (HCC), there is limited data to support or refute transplantation for combined hepatocellular-cholangiocarcinoma (cHCC-CC). We hypothesized that cHCC-CC patients had poorer overall survival (OS) than HCC patients after liver transplantation. Patients with localized HCC and cHCC-CC treated with surgical resection or transplant were identified using the Surveillance, Epidemiology, and End Results (SEER) Database (1973-2007). Cox proportional hazards models were used to examine survival. We identified 3,378 (1,447 [43%] transplant, 1,931 [57%] resection) patients with HCC, and 54 (19 [35%] transplant, 35 [65%] resection) patients with cHCC-CC. Patients undergoing resection of HCC and cHCC-CC had similar 3-year OS (55% vs. 46%, P = 0.4). Three-year OS of patients undergoing transplant was significantly greater for HCC (78%) than for cHCC-CC (48%, P = 0.01). In adjusted models, patients transplanted for cHCC-CC had higher hazard of death compared to HCC patients (HR 2.5, 95% CI: 1.2-5.1, P = 0.01). Transplantation for localized cHCC-CC confers a survival benefit similar to liver resection for cHCC-CC, but inferior to transplantation for HCC. With survival data that mimics historic reports of transplant for intrahepatic cholangiocarcinoma, this study questions the benefit of transplantation for patients with cHCC-CC.

Groeschl RT ，Turaga KK ，Gamblin TC 《-》

Combined hepatocellular-cholangiocarcinoma: a population-level analysis of an uncommon primary liver tumor.

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare primary liver cancer. Our aims were to analyze the demographic, clinical, and pathological characteristics of cHCC-CC at a population level and to investigate the effects of these features as well as different management strategies on the prognosis. The Surveillance, Epidemiology, and End Results (SEER) database was analyzed for 1988-2009. Data analyses were performed with chi-square tests, analyses of variance, Kaplan-Meier curves, and Cox proportional hazards regression. Four hundred sixty-five patients with cHCC-CC, 52,825 patients with hepatocellular carcinoma (HCC), and 7181 patients with cholangiocarcinoma (CC) were identified. cHCC-CC was more common in patients who were white, male, and older than 65 years. Treatment was more frequently nonsurgical/interventional. Patients with cHCC-CC, HCC, and CC had 5-year overall survival (OS) and disease-specific survival rates of 10.5%, 11.7%, and 5.7% (P < 0.001) and 17.8%, 21.0%, and 11.9% (P < 0.001), respectively. For cHCC-CC patients, an increasing invasiveness of the therapeutic approach was significantly associated with prolonged survival (P < 0.001). In a multivariate model, black race, a distant SEER stage, and a tumor size of 5.0 to 10.0 cm were independently associated with lower survival for cHCC-CC patients; a year of diagnosis after 1995 and surgical treatment with minor hepatectomy, major hepatectomy (MJH), or liver transplantation (LT) were independently associated with better survival for cHCC-CC patients. Patients diagnosed with cHCC-CC, HCC, and CC and treated with LT had 5-year OS rates of 41.1%, 67.0%, and 29.0%, respectively (P < 0.001). In conclusion, cHCC-CC patients appear to have intermediate demographic, clinical, and survival characteristics in comparison with HCC and CC patients. cHCC-CC patients undergoing LT showed inferior survival in comparison with HCC patients, and the role and indications for LT in cHCC-CC have yet to be defined. At this time, MJH may be considered the best therapeutic approach for such patients.

Garancini M ，Goffredo P ，Pagni F ，Romano F ，Roman S ，Sosa JA ，Giardini V ... -  《-》

Combined hepatocellular carcinoma and cholangiocarcinoma: clinical features, treatment modalities, and prognosis.

Yin X ，Zhang BH ，Qiu SJ ，Ren ZG ，Zhou J ，Chen XH ，Zhou Y ，Fan J ... -  《-》

Multi-Center Analysis of Liver Transplantation for Combined Hepatocellular Carcinoma-Cholangiocarcinoma Liver Tumors.

Combined hepatocellular-cholangiocarcinoma liver tumors (cHCC-CCA) with pathologic differentiation of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma within the same tumor are not traditionally considered for liver transplantation due to perceived poor outcomes. Published results are from small cohorts and single centers. Through a multicenter collaboration, we performed the largest analysis to date of the utility of liver transplantation for cHCC-CCA. Liver transplant and resection outcomes for HCC (n = 2,998) and cHCC-CCA (n = 208) were compared in a 12-center retrospective review (2009 to 2017). Pathology defined tumor type. Tumor burden was based on radiologic Milan criteria at time of diagnosis and applied to cHCC-CCA for uniform analysis. Kaplan-Meier survival curves and log-rank test were used to determine overall survival and disease-free survival. Cox regression was used for multivariate survival analysis. Liver transplantation for cHCC-CCA (n = 67) and HCC (n = 1,814) within Milan had no significant difference in overall survival (5-year cHCC-CCA 70.1%, HCC 73.4%, p = 0.806), despite higher cHCC-CCA recurrence rates (23.1% vs 11.5% 5 years, p < 0.001). Irrespective of tumor burden, cHCC-CCA tumor patient undergoing liver transplant had significantly superior overall survival (p = 0.047) and disease-free survival (p < 0.001) than those having resection. For cHCC-CCA within Milan, liver transplant was associated with improved disease-free survival over resection (70.3% vs 33.6% 5 years, p < 0.001). Regardless of tumor burden, outcomes after liver transplantation are superior to resection for patients with cHCC-CCA. Within Milan criteria, liver transplant for cHCC-CCA and HCC result in similar overall survival, justifying consideration of transplantation due to the higher chance of cure with liver transplantation in this traditionally excluded population.

Dageforde LA ，Vachharajani N ，Tabrizian P ，Agopian V ，Halazun K ，Maynard E ，Croome K ，Nagorney D ，Hong JC ，Lee D ，Ferrone C ，Baker E ，Jarnagin W ，Hemming A ，Schnickel G ，Kimura S ，Busuttil R ，Lindemann J ，Florman S ，Holzner ML ，Srouji R ，Najjar M ，Yohanathan L ，Cheng J ，Amin H ，Rickert CA ，Yang JD ，Kim J ，Pasko J ，Chapman WC ，Majella Doyle MB ... -  《-》

Long-term outcome of patients undergoing liver transplantation for mixed hepatocellular carcinoma and cholangiocarcinoma: an analysis of the UNOS database.

Mixed hepatocellular and cholangiocarcinoma (HCC-CC) have been associated with a poor prognosis after liver transplantation (LT). We aimed to evaluate long-term outcomes in patients undergoing LT for HCC-CC versus patients with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC). Retrospective analysis of the United Network for Organ Sharing (UNOS) database from 1994-2013. Overall survival (OS) in patients with HCC-CC, HCC, and CC, were compared. We identified 4049 patients transplanted for primary malignancy (94 HCC-CC; 3515 HCC; 440 CC). Mean age of patients with HCC-CC was 57 ± 10 years, and 77% were male. MELD score did not differ among the groups (p = 0.637). Hepatitis C virus was the most common secondary diagnosis within the HCC-CC (44%) and HCC (36%) cohorts, with primary sclerosing cholangitis in the CC (16%) cohort. OS rates at 1, 3 and 5 years for HCC-CC (82%, 47%, 40%) were similar to CC (79%, 58%, 47%), but significantly worse than HCC (86%, 72%, and 62% p = 0.002). Patients undergoing LT for HCC had significantly better survival compared to those transplanted for HCC-CC and CC. LT for mixed HCC-CC confers a survival rate similar to selected patients with CC. Efforts should be made to identify HCC-CC patients preoperatively.

Vilchez V ，Shah MB ，Daily MF ，Pena L ，Tzeng CW ，Davenport D ，Hosein PJ ，Gedaly R ，Maynard E ... -  《-》