2015OngSLMD.pdf (70.07 MB)
Pilot study of hepatic microwave ablation using an extracorporeally perfused porcine liver model
thesisposted on 2015-12-14, 10:45 authored by Seok Ling Ong
Introduction: Preclinical research into many aspects of microwave hepatic ablation has been traditionally conducted in in vivo studies. These are costly, can only be performed in laboratories with animal facilities and are associated with significant ethical issues. The main aim of this project was to study microwave ablation using an extracorporeally perfused porcine liver model to confirm that it accurately mimicked an in vivo model and could be used to investigate ablative techniques. Methods: Seventeen livers harvested from domestic pigs were subjected to extracorporeal normothermic autologous haemoperfusion followed by dissection of the hepatic artery and its branches to establish an effective procedure of liver procurement for subsequent experiments. A further seventeen livers in three experimental groups (control, microwave and Pringle groups) were perfused for six hours with tissue and blood samples collected at various time points for histological, biochemical and cytokine analyses. Seven livers in the control group did not undergo any ablation. Five livers in the microwave group underwent microwave ablations at three power settings after the first hour of perfusion for a fixed duration of two minutes per ablation. Five livers in the Pringle group underwent microwave ablation at the same power settings and for the same duration as the microwave group but the ablations were carried out with temporary cessation of blood flow to the liver. Results: Dissection of the hepatic artery and its bifurcation identified all the common variants and understanding these is crucial for successful liver perfusion. The livers were perfused at flows and pressures mimicking physiological levels with biochemical and blood gas analyses indicating normal function across all three experimental groups. The volume of the lesions increased with power of ablation in both the microwave and Pringle groups (p<0.001 and p=0.003 respectively), with no significant differences in overall volume between the groups (p=0.275) but a greater transition zone volume in the microwave group (p=0.012). Apoptotic activities in the transition zone lessened towards the periphery of the ablation in both microwave and Pringle groups (p<0.001 for both groups). There were significant elevations in the levels of circulating interleukin-6 and interleukin-8 over time with or without microwave ablation (p<0.001 for both cytokines in both groups). Conclusion: An extracorporeally perfused porcine liver model has a role in the preclinical study of microwave ablation. The model can be reliably used to study the histological and physical profile of microwave lesions. It also permits the study of the heat sink effect of ablation. Overall, it has a considerable potential to reduce the number of in vivo preclinical studies required. However, the ability of this isolated organ (which has a relatively short perfusion lifespan) to study the systemic effect of a microwave ablation is limited. Further experiments involving other hepatic ablative techniques should be conducted using this model to fully establish its role as a preclinical liver ablation research tool.
Date of award2015-11-20
Author affiliationDepartment of Cancer Studies & Molecular Medicine
Awarding institutionUniversity of Leicester