The outcomes and bioactivities of microbubble-enhanced ultrasound combined with prothrombin on microwave ablation in rabbit VX2 liver tumors

Abstract

Objective To investigate the sequential biological effects and outcomes of microbubble-enhanced ultrasound (MEUS) combined with prothrombin on microwave ablation (MWA) in rabbit VX2 liver tumors using examination of transmission electron microscopy, histopathology and contrast-enhanced ultrasound(CEUS). Methods Eighty New Zealand rabbits with VX2 liver tumors were randomly divided into 4 groups(20 per group), including physiological saline group, prothrombin group, cavitation of microbubbles group (cavitation group) and cavitation of microbubbles combined prothrombin group (combined group). After treatment, the targeted liver tumors in all groups were ablated with MWA. On the 0, 3, 7 and 14 d, the volumes of coagulated areas of 5 rabbits of each group randomly were measured using CEUS. Tissues in ablated areas, transition areas and surrounding areas were examined under light microscopy with histopathology and transmission electron microscopy to observe the differences among 4 groups. Tumor metastasis was graded using visual method. Results On the 0, 3, 7 and 14 d, the coagulated volumes in combined group were larger than those in remaining 3 groups (all P<0.001). Under light microscopy with HE stain, in transition area, the fibra band in combined group was wider than those in remaining 3 groups on the 7 and 14 d (all P<0.05). The observations under transmission electron microscopy showed that the cellular ultrastructure disorder in ablated area on the 0 d and mitochondrial injury in transition area on the 7 d were more severe in combined group than those in remaining 3 groups. Compared with the remaining 3 groups, the degree of tumor metastasis in combined group was less, and the time of ocurrence was later. Conclusions MEUS combined with prothrombin can significantly expand ablation volume, enhance the necrosis of ablated tissues, and inhibit tumor metastasis on rabbit VX2 liver tumors. The fibra bands in the transition areas can promote the organization and repair the surrounding tissue in the ablation areas. Key words: Cavitation; Microwave ablation; Prothrombin; VX2 liver tumors