2015OngSLMD.pdf (70.07 MB)
Pilot study of hepatic microwave ablation using an extracorporeally perfused porcine liver model
thesis
posted on 2015-12-14, 10:45 authored by Seok Ling OngIntroduction:
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.
History
Supervisor(s)
Dennison, AshleyDate of award
2015-11-20Author affiliation
Department of Cancer Studies & Molecular MedicineAwarding institution
University of LeicesterQualification level
- Doctoral
Qualification name
- MD