Clinicopathologic characteristics and prognosis in multinodular and multicentric occurrence hepatocellular carcinoma / 中华普通外科杂志

ABSTRACT

Objective To analyze the clinicopathologic characteristics and prognosis in multinodular and multicentric occurrence of hepatocellular carcinoma (HCC). Methods Study group (multinodular HCCs) involved 42 multinodular HCCs patients with a total of 112 HCC nodules. 16 patients with single HCC nodule, and 4 patients with portal vein tumor embolus, 5 normal livers served as controls. MtDNA D-Loop sequences were compared among multinodular lesions in the study group, between inconsecutive tumor tissues and between tumor and embolus tissues in the study group with regard to their clinicopathologic characteristics. Results In study group, for the multinodular HCCs 20 cases were categorized as multicentric occurrence (MO) based on their variant mtDNA D-Loop sequences in each nodule from the same patient. 22 cases were characterized as intrahepatic metastasis (IM) based on the identical sequences found in each nodule from the same patient. In all 20 cases for the rest of the study group (16 patients with single HCC nodule and 4 patients with portal vein tumor embolus), the inconsecutive tumor tissues or the portal vein tumor embolus and original tumors shared identical sequences. HBeAg (P =0. 008), tumor size ( sizes of all nodules) ( P = 0. 029), position of nodules (P = 0. 040), cirrhosis ( P =0. 011 ), portal vein and microscopic tumor embolus ( P = 0. 023 ) and differentiation ( Edmondson grade) of the main nodule (P = 0. 027 ) were significantly different between the IM and MO HCCs, thus were considered to be the important factors in determinning the clonal origin of multinodular HCC. Positive HBeAg, cumulative diameter of all nodules ≤7 cm, nodules located in different lobes, cirrhosis, negative for portal vein or microscope tumor embolus and/or well/moderate differentiation of main nodular histopathology were found in high rate in MO. Tumor-free survival of the MO subjects was significantly longer than that of the IM subjects (21.6 ±4. 2) months vs. (8.7 ±2. 5) months, P =0. 031 ). Similarly, overall survival of the MO subjects was longer than that of the IM subjects (29. 6±4. 7) months vs. ( 14. 6 ±2. 9) months, P = 0. 034). Multivariate analysis revealed that the IM/MO characteristic was an independent factor influencing both tumor-free survival ( P = 0.012 ) and overall survival ( P = 0.011 ).Conclusions HBeAg, tumor size ( sizes of all nodules), position of nodules, cirrhosis, portal vein and microscopic tumor embolus and differentiation of the main nodule are important factors in differentiating IM and MO. Positive HBeAg, cumulative diameter of all nodules ≤ 7 cm, nodules located in different lobes, cirrhosis, negative for portal vein or microscopic tumor embolus and/or well/moderate differentiation of main nodular histopathology are frequent phenomena in MO. MO HCC patients might have a favorable outcome compared with IM patients.