The Effect Of Ablation By HIFU Combined With UCA On Different Range Of Normal Tissue Around VX2 Liver Tumor In Rabbit

Objective:This study was to determine the optimized range of the tissue around the VX2 liver tumor in rabbits ablated by HIFU combined with UCA. After the treatment, the general state of health, skin of the targeting area, pathology, the metastasis of the distant organs, hepatic function, volume of the tumor and the survival time after ablation were compared, and the optimized range was determined depend on the discrepant therapeutic effect. This study will provide theoretical and experimental evidence for clinical use.Methods:51 rabbits models of VX2 liver tumor were established and divided into three groups randomly: tumor ablation only (group A), ablation of the tumor and the normal tissue 2mm around the tumor (group B), and 4mm around the tumor (group C), there are 13 rabbits in each group. After the treatment , (1) the general state of the health, the skin of the targeting area and the healing of the wound were investigated;(2) the pathology of the targeting tissue was studied in a rabbit in each group at d1, d3, d7.(3)9 rabbits in each group were randomly used to measure the maximum and the minimum diameter of the tumor by B type ultrasound before and 2 weeks after treatment. The metastatic status of the liver, lungs and abdominal cavity were compared. (4) 5 left rabbits In each group were used to investigate the serum ALT levels,the survival time 2 month later.Result:The tumors were found in all the rabbit liver by ultrasound at d7. The diameter of the tumors were around 1.4-1.8cm at d17. In 24h after the treatment, the general state of health were bad and gradually improved after 24h and recovered 3 days later. Small area of skin of all rabbit were burned by HIFU generated heat. Skin lesion in 2 rabbit was not healed because of serious injury and infection. The necrotic regions in liver caused by HIFU were easy to identify by colo(rwhite versus red-brown),and there were no residual tumor tissue under microscope in 24h. 7 days later,the tumor tissue could be found in each rabbit in group A either by eye or microscope. It also happened in some rabbits in group B and group C. 2 weeks after therapy, the metastasis to distant organs occurred in each rabbit . Compared with group A, the metastasis rate of group B and group C were statistically lower, and there were no statistic difference between group B and group C . The serum ALT level were significantly elevated 17 days after tumor tissue transplanted into the liver (P<0.05), and there were no statistic difference among the three groups (P>0.05). After the treatment,the serum ALT level in each group increased and reached to the highest at d5. The serum ALT levels of group C were statistically higher than either group A or group B on 3d and 5d, and had no statistically difference between group B and group C 7 days later. On the 14d,the serum ALT level decreased to the normal range but the ALT level of group A was significantly higher(P<0.05). Two weeks after the treatment, only the volume of the tumor in group A was increased significantly than group B and group C. There was no significant difference between group B and group C. Compared with group A, the tumor growth rate was slower in group B and group C. The survival time both in group B and group C were significantly longer than group A, and there were no statistically different between group B and group C. The biopsy of the rabbits showed that the animals were mainly died from the tumor metastasis to the liver,lungs and the abdominal cavity.Conclusion:1. The transplanted VX2 tumor in rabbit liver is a solid tumor rich in hypervascular and grow rapidly. It could be a good model to illustrate the therapeutic effect and complications of liver tumor ablated by HIFU with UCA.2. The skin of the targeting regions can be burned by HIFU generated heat, and the influence of HIFU on liver function is evident, but it is reversible.3. Ablating different range of the tissue around the VX2 tumor in rabbit liver affect the tumor growth rate, metastasis to the distant organs, the survival time and the therapy effect. Comprised with group A,the group B and group C is statistic lower.4. The therapeutic effect of group B is similar to group C,and with less side effect. Ablating 2mm tissue around the VX2 tumor in rabbit liver may be the optimized range when using HIFU combined with UCA.