Mixed hepatocellular and cholangiocarcinoma: a rare tumor with a mix of parent phenotypic characteristics.

Intrahepatic lesions of mixed hepatocellular (HCC) and intrahepatic cholangiocellular carcinoma (ICC) histology are rare. The aim was to describe the natural history of these tumors relative to monomorphic ICC or HCC utilizing the National Cancer Data Base (NCDB). Patients with ICC, HCC, and mixed histology (cHCC-CCA) were identified in the NCDB (2004-2012). Inter-group comparisons were made. Kaplan-Meier and multivariable Cox Proportional Hazards analyzed overall survival. The query identified 90,499 patients with HCC; 14,463 with ICC; and 1141 with cHCC-CCA histology. Patients with cHCC-CCA histology were relatively young (61 vs. 62 (HCC, p = 0.877) and 67 (ICC, p < 0.001) years) and more likely to have poorly differentiated tumor (29.2% vs. 10.3% (HCC) and 17.2% (ICC) p < 0.001). Median overall survival for cHCC-CCA was 7.9 months vs. 10.8 (HCC) and 8.2 (ICC, all p < 0.001). Stage-specific survival for mixed histology tumors was most similar to that of HCC for all stages. cHCC-CCA were transplanted at a relatively high rate, and transplant outcomes for mixed tumors were substantially worse than for HCC lesions. cHCC-CCA demonstrate stage-specific survival similar to HCC, but post-surgical survival more consistent with ICC. Patients with a pre-operative diagnosis of cHCC-CCA should undergo resection when appropriate.

Bergquist JR ，Groeschl RT ，Ivanics T ，Shubert CR ，Habermann EB ，Kendrick ML ，Farnell MB ，Nagorney DM ，Truty MJ ，Smoot RL ... -  《-》

The clinical characteristics and prognostic factors of combined Hepatocellular Carcinoma and Cholangiocarcinoma, Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma after Surgical Resection: A propensity score matching analysis.

Background: Clinical characteristics and prognosis among combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (cHCC-CC) with HCC and intrahepatic cholangiocarcinoma (ICC) were inconsistent in previous studies. The aim of this study was to compare postoperative prognosis among cHCC-CC, HCC and ICC, and investigated the prognostic risk factor of cHCC-CC after surgical resection. Methods: A total of 1041 eligible patients with pathological diagnosis of cHCC-CC (n=135), HCC (n=698) and ICC (n=208) were enrolled in this study. Univariate and multivariate Cox analysis were applied for assessing important risk factors. cHCC-CC were further 1:1 matched with HCC and ICC on important clinical risk factors. Survival curves of matched and unmatched cohorts were depicted by Kaplan-Meier method with log-rank test. Results: Patients with cHCC-CC had similar rate of sex, age and cirrhosis with HCC (p<0.05) and comparable incidence of hepatitis B or C with ICC (p=0.197). Patients of cHCC-CC had intermediate prognosis between HCC and ICC, with median overall survival (OS) time of cHCC-CC, HCC and ICC of 20.5 months, 35.7 months and 11.6 months (p<0.001). In matched cohorts, the OS of cHCC-CC were worse than HCC (p<0.001) but comparable with ICC (p=0.06), while the disease-free survival (DFS) of cHCC-CC was worse than HCC but better than ICC (p<0.05). And lymph node infiltration and postoperative transarterial chemoembolization (TACE) were independent risk factors of cHCC-CC associated with prognosis. Conclusion: The long term survival of cHCC-CC was worse than HCC but comparable with ICC when matched on albumin level, tumor size, lymph node infiltration, tumor stage and margin. Presence of lymph node infiltration and no postoperative TACE were associated with poor prognosis of cHCC-CC.

Tang Y ，Wang L ，Teng F ，Zhang T ，Zhao Y ，Chen Z ... -  《International Journal of Medical Sciences》

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 ... -  《-》

Radiological features and outcomes of combined hepatocellular-cholangiocarcinoma in patients undergoing surgical resection.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer. Preoperative diagnosis of cHCC-CCA is difficult, and outcome of cHCC-CCA is obscured. Our study aimed to investigate the clinicopathological and radiological features of cHCC-CCA and compare their outcomes with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). From August 2010 to December 2017, 891 patients undergoing liver tumor resection in Taipei Veterans General Hospital, including 30 patients with pathology-proven cHCC-CCA, 819 HCC, and 42 ICC were retrospectively reviewed. Radiological features of contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) in patients with cHCC-CCA were reevaluated by a radiologist. Factors association with disease-free survival (DFS) and overall survival (OS) were analyzed. The mean age of cHCC-CCA, HCC and ICC was similar. Hepatitis B virus infection was prevalent in patients with cHCC-CCA (22/30, 73.3%). Most (70%) of the cHCC-CCA had atypical radiological pattern of HCC and belonged to classic type in pathological features. cHCC-CCA and ICC had worse DFS, but the 5-year OS of cHCC-CCA was substantial adequate after surgery. Of the 891 patients, male gender, advanced T stage, multiple tumor number, alpha-fetoprotein (AFP) level >20 ng/ml, cHCC-CCA, and ICC were factors associated with poor DFS in multivariable analysis. Older age, T stage 3 or 4, presence of macrovascular invasion, AFP >20 ng/mL, cHCC-CCA, and ICC were factors significantly associated with OS. cHCC-CCA is associated with high risk of recurrence following surgical resection as compared with HCC. Closely post-operative monitoring is highly recommended.

Chi CT ，Chau GY ，Lee RC ，Chen YY ，Lei HJ ，Hou MC ，Chao Y ，Huang YH ... -  《JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION》

Propensity-Matched Analysis of Patients with Mixed Hepatocellular-Cholangiocarcinoma and Hepatocellular Carcinoma Undergoing Liver Transplantation.

Mixed hepatocellular-cholangiocarcinomas (HCC-CCAs) are rare tumors with both hepatocellular and biliary differentiation. While liver transplantation (LT) is the gold standard treatment for patients with unresectable hepatocellular carcinoma (HCC), it is contraindicated in known HCC-CCA because of concerns of poor prognosis. We sought to compare posttransplant oncologic outcomes for HCC-CCA and a matched cohort of HCC LT recipients. A retrospective, single-center analysis (1984-2015) identified 12 patients with mixed HCC-CCA who were matched 1:3 to patients with HCC on both pretransplant (radiologic diameter and alpha-fetoprotein) and explant (pathologic diameter, grade/differentiation, and vascular invasion) tumor characteristics. Compared with HCC patients matched on pretransplant characteristics (n = 36), HCC-CCA had higher explant tumor grade, more poorly differentiated tumors, but similar T stage and vascular invasion. HCC-CCA recipients trended toward inferior recurrence-free survival at 5 years (28% versus 61%; P = 0.12) and greater recurrence (HCC-CCA: 50%, median time to recurrence 297 days versus HCC: 22%, median time to recurrence 347 days; P = 0.07). However, when matched to a separate HCC cohort with similar explant pathology, HCC-CCA had similar 5-year recurrence-free survival (42% versus 44%; P = 0.45) and posttransplant recurrence (50% versus 27%; P = 0.13). All 6 HCC-CCA recurrences occurred with poorly differentiated tumors (median survival 21.3 months), without a single recurrence in 5 of the 12 HCC-CCA patients with well-moderately differentiated tumors (median survival 60.2 months). Mixed HCC-CCA tumors are more likely poorly differentiated tumors compared with HCC with similar pretransplant characteristics. However, compared with HCC with similar pathologic characteristics, they display similar recurrence-free survival and are not inherently more aggressive tumors. Low-grade, well-moderately differentiated HCC-CCAs have excellent survival with a low risk for post-LT recurrence, and they should not be excluded from LT. Improved pretransplant identification of pathologic characteristics in HCC-CCA may allow for successful utilization of LT in this subset of patients.

Lunsford KE ，Court C ，Seok Lee Y ，Lu DS ，Naini BV ，Harlander-Locke MP ，Busuttil RW ，Agopian VG ... -  《-》