Percutaneous ethanol injection enhanced the efficacy of radiofrequency ablation in the treatment of HCC: an insight into the mechanism of ethanol action

Abstract

Purpose: To discuss the possible reasons why percutaneous intratumoral ethanol injection (PEI) combined with radiofrequency ablation (RFA) to treat hepatocellular carcinoma (HCC) reduced the recurrence and metastasis compared with RFA alone. Materials and methods: Forty VX2 tumor-bearing rabbits were randomly divided into four groups (n = 10): the PEI, RFA, PEI-RFA, and control groups. Five rabbits from each group were sacrificed on the 3rd and 7th days after ablation. The number of metastatic tumors in the lung was counted. The ablation volume was measured, and residual tumor specimens were prepared for hematoxylin and eosin staining and caspase-3, Ki-67, and VEGF immunohistochemical staining. Results: The volume of ablation in the PEI-RFA group was significantly larger than that in the RFA and PEI groups (p < 0.05). However, no significant differences in the number of lung metastases after ablation were observed among the groups (p > 0.05). The number of microthrombi in the PEI-RFA group was greater than that in the control and RFA groups (p < 0.001 and p < 0.05). The Ki-67 labeling index (LI) and H-score of VEGF in the PEI-RFA group were lower than those in the RFA group, while the H-score of caspase-3 was higher than that in the RFA group on the 7th day after ablation (p < 0.05). Conclusion: PEI occluded blood vessels by inducing microthrombi formation, and thereby reducing heat dissipation and increasing the effect of RFA. More importantly, in comparison with an incomplete RFA, PEI-RFA inhibited the increase in the Ki-67 and VEGF expression levels and the decrease in the caspase-3 expression level to happen at some extent and therefore improved the prognosis.