Ultrasonic Cavitation Ameliorates Antitumor Efficacy of Residual Cancer After Incomplete Radiofrequency Ablation in Rabbit VX2 Liver Tumor Model

Abstract

Residual cancer after incomplete ablation remains a major problem for radiofrequency ablation (RFA). We aimed to investigate the synergetic treatment efficacy of RFA combined with ultrasonic cavitation for liver tumor. Sixty rabbits with VX2 liver tumor were randomly divided into three groups. Group A was control group without any treatment. Combined ultrasonic cavitation with RFA was performed for group B1. Group B2 underwent RFA alone. The histopathological results were compared at the 5th, 11th, and 18th day of experiment, and the survival time and metastasis were assessed. The tumor volume growth rate, percentage of necrosis area, microvessel density, and apoptosis index showed significant differences among these groups at the 5th day, 11th day, and 18th day of experiment (P < .05). In contrast, the difference of metastatic score was not significant at the 5th and 11th day (P > .05). At the 18th day, the metastatic score of group A was significant higher than that of group B1 (P < .05), whereas the differences between group A and group B2, or group B1 and group B2 were not significant (P > .05). The median/range interquartile of survival time in groups A, B1, and B2 were 25/8 days, 50/19 days, and 48/20 days, respectively, and there was significant difference between groups A and B1 or B2 (P < .05). The difference between groups B1 and B2 was not significant (P > .05). Ultrasonic cavitation after incomplete RFA for liver tumor improved the antitumor effect, which could be considered as a potentially useful combined therapeutic strategy for liver malignancy.

Keywords: Liver neoplasms; Microbubbles; Radiofrequency ablation; Residual cancer; Ultrasound.

Figure 1

Schematic diagram of arrangement of RFA electrode for inducing residual tumor (A) and irradiated points for ultrasonic cavitation (B).

Figure 2

The findings of H&E staining (×100; figures A, D, G), MVD (×200; figures B, E, H) and apoptosis (×200; figures C, F, I) at the 18th day of experiment. Figures A-C were group A, D-F were group B1, and G-I were group B2. The asterisk in figure D and G showed the necrosis area. Large arrows in figure B, E, and H demonstrated the microvessel. Small arrows in figure F and I indicated the positive staining of apoptosis cells.

Figure 3

CEUS images at different time points (before RFA: A, E, J; immediately after RFA: F, K; the 5th day: B, G, L; the 11th day: C, H, M; the 18th day: D, I, N) for these three groups. Figures A-D were group A, E-I were group B1, and J-N were group B2. The viable tumor tissue appeared as hyperenhancement by CEUS (shown by the marker lines). The tumor size was gradually increasing in groups A and B2.

Figure 4

The changing curves of TVGR (A), percentage of necrosis area (B), MVD (C), and apoptosis index (D).

Figure 5

The survival curves of these three groups.