Analysis of safety and efficacy of irreversible electroporation hepatic ablation with high-frequency bipolar pulse in swine

Abstract

Objective To investigate the safety and efficacy of irreversible electroporation (IRE) hepatic ablation with high-frequency bipolar pulse in swine. Methods The experimental study was conducted. A total of 18 swines of either gender, aged (6.8+ 0.8)months with a range of 5.5-8.0 months, were collected from Animal Laboratory Center of Army Medical University. were randomly divided into 15 in experimental group and 3 in control group. The swines in experimental group underwent IRE hepatic ablation with high-frequency bipolar pulse, and 3 swines were chose randomly and underwent enhanced CT examination immediately after ablation, and at 3, 7, 14, and 28 days after ablation. The liver tissues were taken for histopathological examination. The swines in the control group underwent IRE hepatic ablation with high-frequency monopolar burst, and was performed enhanced CT examination at 3 days after ablation. Liver tissues were taken for histopathological examination. Observation indicators: (1) comparison of muscle contraction of siwnes between two groups; (2) imaging performance on enhanced CT after IRE ablation in the experimental group; (3) hepatic histopathological findings after IRE ablation in the experimental group; (4) comparison of apoptotic index in the ablation zone between two groups. The measurement data with normal distribution were expressed as Mean±SD, and comparison between groups was performed by the independent sample t test. Results (1) Comparison of muscle contraction between two groups: swines in both groups underwent ablation successfully. The degree of muscle contraction was (9.8±0.4)m/s2 and (48.6±0.5)m/s2 in the experimental group and in the control group, respectively, showing statistically significant difference between the two groups (t=-163.50, P<0.05). (2) Imaging performance on enhanced CT after IRE ablation in the experimental group: the enhanced CT examination of swines immediately after IRE ablation showed a low-density shadow and clear boundary in the ablation zone. There was no obvious abnormality in the ablation zone and its adjacent large vessels. No serious complications occurred after the ablation. The boundary between the ablation zone and the normal liver tissue of the experimental group gradually became blurred over time, and the ablation zone was gradually replaced by normal liver tissue. The ablation zone at the 28 days after ablation was significantly reduced or even disappeared on imaging of enhanced CT examination.The maximum diameter of the ablation zone was (1.81±0.17)cm immediately after ablation, (1.75±0.19)cm at the 3 days after ablation, (1.32±0.22)cm at the 7 days after ablation, (0.65±0.14)cm at the 14 days after ablation, (0.28±0.10)cm at the 28 days after ablation, respectively. (3) Hepatic histopathological findings after IRE ablation in the experimental group: the HE staining of ablated tissue immediately after ablation showed that the cells in the ablation zone were swollen, arranged disorderly, and bleeding was observed around some of the needles.The bile ducts and blood vessels were intact in the ablation zone, and a large number of deeply stained nuclei were seen at 3 days after ablation, some of the nucleus and apoptotic bodies were partially dissolved or cleaved. A large number of inflammatory cell were infiltrated around the ablation zone. Intact vascular and biliary endothelial cells were observed by von Willebrand factor staining, a larger number of apoptotic cells with deeply stained nuclei in the ablation zone were observed by terminal-deoxynucleoitidyl transferase mediated nick end labeling staining, and partial deposited dark brown calcium salt was seen by Von Kossa staining. More newborn hepatocytes were observed growing from the periphery of the ablation zone to the center at the 7, 14, 28 days after ablation. Smooth muscle cell proliferation was observed at 14 and 28 days after ablation. The ablation zone was replaced by new cells on 28 days after ablation. (4) Comparison of apoptotic index in the ablation zone between two groups: the apoptotic index of the ablation zone was significantly higher in the experimental group than in the control group on the 3 days after operation (76.67%±0.04% vs. 64.03%±0.05%, t=4.79, P<0.05). Conclusion IRE hepatic ablation of swine using high-frequency bipolar pulse is safe and reliable, and it has more apoptotic cells than IRE ablation with high-frequency monopolar burst. Key words: Ablation; Swine; Hepatic issues; High-frequency bipolar pulse; Irreversible electroporation