Combined hepatocellular and cholangiocarcinoma: clinical features and prognostic study in a Thai population

Combined hepatocellular and cholangiocarcinoma (HCC-CC) is an uncommon subtype of primary liver cancer, the clinicopathological features of which have rarely been reported in detail. Some authors believe that HCC-CC behaves like HCC, but biliary differentiation may be associated with poorer prognosis. Moreover, CC has more frequent lymph node metastases. In this study, we aimed to determine the clinical course and survival outcome of HCC-CC patients in a Thai population by comparing them with patients with ordinary HCC.

The clinicopathological features of patients who were diagnosed with HCC-CC at Ramathibodi Hospital during 2000-2004 were retrospectively studied by comparing them with the features of patients suffering from ordinary HCC. Twenty-five patients who were diagnosed with HCC-CC were included in this study, and subsequently 50 patients with HCC who had tissues taken during the same period were selected randomly from among 148 HCC patients. Statistical analysis was done by using SPSS version 10.0. The Kaplan-Meier method was used to assess the survival rate. Multiple logistic regression analysis was performed to assess correlations. A value of P < 0.05 was considered statistically significant.

There were no significant differences in etiologic risk factors between HCC-CC and HCC patients: cirrhosis (50% vs 44%), chronic alcohol abuse (36% vs 43%), presence of hepatitis B surface antigen (HBsAg; 66% vs 78%) and presence of hepatitis C virus (HCV) antibody (13% vs 3%). The serum alpha-fetoprotein (AFP) value in the HCC-CC group was lower than that in the HCC group (5.87 vs 41.46 ng/ml). No differences in tumor characteristics or liver status (tumor size, presence of multinodular lesions, portal vein thrombosis, intrahepatic bile duct dilatation, intraabdominal lymphadenopathy, extrahepatic metastasis, liver cirrhosis, portal hypertension, and ascites) between these two groups were found. The overall median survival of HCC-CC patients was 38 weeks while that of HCC patients was 54 weeks. Multivariate analysis showed that elevated carbohydrate antigen (CA)19-9 (>/=80 U/ml) and the presence of intrahepatic bile duct dilatation were independent risk factors for worse survival.

The demographic and clinical features of patients with combined HCC-CC were similar to those of patients with HCC. The presence of cholangiocellular differentiation appeared to worsen the prognosis when compared with pure HCC, although this difference did not reach statistical significance. An increased CA19-9 level and intrahepatic bile duct dilatation in patients with HCC-CC were considered to be independent factors that suggested poor prognosis.