Clinicopathological characteristics and prognostic factors analysis of combined hepatocellular-cholangiocarcinoma

Abstract

Objective To analyze the clinicopathological characteristics and prognostic factors of combined hepatocellular-cholangiocarcinoma (cHCC-CC). Methods The retrospective cohort study was conducted. The clinicopathological data of 72 patients with primary hepatocellular carcinoma (HCC) who were admitted to the Xiangya Hospital of Central South University between January 2005 and December 2014 were collected. Thirty-two patients who were diagnosed with cHCC-CC by postoperative pathological examination were allocated into the cHCC-CC group and 40 patients who were diagnosed with HCC by postoperative pathological examination were allocated into the HCC group. Observation indicators: (1) clinicopathological characteristics: male, age>60 years, positive hepatitis B surface antigen (HBsAg), positive alpha-fetoprotein (AFP), positive CA19-9, positive carcinoembryonic antigen (CEA), liver cirrhosis, Child-Pugh grade A, tumor diameter>5 cm, tumor with capsule, solitary tumor, portal vein tumor thrombus (PVTT), cancer thrombus of the bile duct, positive lymph node metastasis, stage Ⅰ-Ⅱ of TNM stage, Edmondson-Steiner stageⅠ-Ⅱ; (2) pathological features of surgical incision specimens; (3) follow-up situations: median survival time, 1-, 3-, 5-year survival rates and tumor-free survival rate; (4) prognostic factors analysis of patients with cHCC-CC: AFP, CA19-9, liver cirrhosis, tumor diameter, tumor capsule, number of tumor, PVTT, cancer thrombus of the bile duct, lymph node metastasis, Edmondson-Steiner stage, volume of intraoperative blood loss, intraoperative blood transfusion, distant from surgical margin. Follow-up using outpatient examination and telephone interview was performed to detect survival of patients and tumor recurrence or metastasis up to October 2015. Comparison of count data was analyzed using the chi-square test. The survival curve was drawn by the Kaplan-Meier method, and the survival analysis was done using the Log-rank test. The prognostic analysis was done using the COX regression model. Results (1) Clinicopathological characteristics: positive CA19-9, tumor with capsule, cancer thrombus of the bile duct and positive lymph node metastasis were detected in 16, 4, 12, 6 patients in the cHCC-CC group and 5, 17, 1, 1 patients in the HCC group, respectively, with statistically significant differences between the 2 groups (χ2=10.471, 9.723, 13.005, 4.009, P<0.05). (2) Pathological features of surgical incision specimens: pathological results showed that surgical incision specimens in the cHCC-CC group had characteristics of HCC tissues and cholangiocarcinoma tissues. The antigenic activity of hepatic cells in paraffin sections, Cytokeratin 7, Cytokeratin 19 and progenitor cell markers were positive by immunohistochemical staining detection. Patients in the HCC group had characteristics of HCC tissues, with positive AFP using immunohistochemical staining detection. (3) Follow-up situations: all the 72 patients were followed up for 5.0-74.0 months with a median time of 41.0 months. The median survival time, 1-, 3-, 5-year survival rates, 1-, 3-, 5-year tumor-free survival rates were 14.5 months, 62.3%, 38.9%, 19.1%, 50.0%, 23.9%, 4.0% in the cHCC-CC group and 46.8 months, 82.3%, 57.4%, 38.6%, 72.9%, 35.6%, 17.6% in the HCC group, respectively, with statistically significant differences in overall survival and tumor-free survival between the 2 groups (χ2=4.231, 3.881, P<0.05). (4) Prognostic factors analysis of patients with cHCC-CC: results of univariate analysis showed that CA19-9, tumor capsule, number of tumor, cancer thrombus of the bile duct, lymph node metastasis and Edmondson-Steiner stage were related factors affecting prognosis of patients with cHCC-CC [HR=1.824, 0.227, 0.441, 1.421, 1.887, 2.745, 95% confidence interval (CI): 1.126-2.172, 0.118-0.654, 0.318- 0.764, 1.071-4.231, 1.017-5.643, 1.223-6.421, P<0.05]. Results of multivariate analysis showed that lymph node metastasis and stage Ⅲ-Ⅳ of Edmondson-Steiner stage were independent risk factors affecting prognosis of patients with cHCC-CC (RR=1.658, 2.912, 95% CI: 1.027-7.542, 1.143 - 6.582, P<0.05). Conclusions The positive CA19-9, tumor without capsule, cancer thrombus of the bile duct and positive lymph node metastasis can partly predict cHCC-CC. The prognosis of patients with cHCC-CC is worse than that with HCC. The positive lymph node metastasis and stage Ⅲ-Ⅳof Edmondson-Steiner stage are independent risk factors affecting prognosis of patients with cHCC-CC. Key words: Hepatic neoplasms; Biliary neoplasms; Mixed type; Hepatectomy; Prognosis