Focused transhepatic electroporation mediated by hypersaline infusion through the portal vein in rat model. Preliminary results on differential conductivity

Abstract

BackgroundSpread hepatic tumours are not suitable for treatment either by surgery or conventional ablation methods. The aim of this study was to evaluate feasibility and safety of selectively increasing the healthy hepatic conductivity by the hypersaline infusion (HI) through the portal vein. We hypothesize this will allow simultaneous safe treatment of all nodules by irreversible electroporation (IRE) when applied in a transhepatic fashion.Material and methodsSprague Dawley (Group A, n = 10) and Athymic rats with implanted hepatic tumour (Group B, n = 8) were employed. HI was performed (NaCl 20%, 3.8 mL/Kg) by trans-splenic puncture. Deionized serum (40 mL/Kg) and furosemide (2 mL/Kg) were simultaneously infused through the jugular vein to compensate hypernatremia. Changes in conductivity were monitored in the hepatic and tumour tissue. The period in which hepatic conductivity was higher than tumour conductivity was defined as the therapeutic window (TW). Animals were monitored during 1-month follow-up. The animals were sacrificed and selective samples were used for histological analysis.ResultsThe overall survival rate was 82.4% after the HI protocol. The mean maximum hepatic conductivity after HI was 2.7 and 3.5 times higher than the baseline value, in group A and B, respectively. The mean maximum hepatic conductivity after HI was 1.4 times higher than tumour tissue in group B creating a TW to implement selective IRE.ConclusionsHI through the portal vein is safe when the hypersaline overload is compensated with deionized serum and it may provide a TW for focused IRE treatment on tumour nodules.

Glucose Solution Through the Hepatic Artery May Focus Irreversible Electroporation Into the Tumor. A Preliminary Safety and Efficacy Evaluation

“…Thus, it would be possible to cause electroporation in tumor cells and avoid this phenomenon in healthy liver tissue 26 . HI concentrates the electric eld in tumor tissue, as we were able to observe conductivity changes of the liver up 1.4 folds higher than tumor tissue 22 , which could focus the treatment on tumor tissue and reduce unwanted damages in the healthy tissue 26 . These results proved that selective electroporation would be available while the electrical eld is modi ed by conductive uids such as HI through the portal vein 22 .…”

“…The tissue's physical properties, like impedance, could be a suitable material to reduce the electrical eld throughout the tissues and decrease the damage of the healthy tissues besides the tumor 29 . Following our previous studies on changes in the liver tissue conductivity and its safety, we started exploring various biocompatible materials with low toxicity and capable of manipulating tissue impedance to observe the results in the electrical impedance of the tissue 22,26,30 . Finally, GS5% was selected for model 31 .…”

“…However, it is a non-thermal technique to spare the extracellular matrix but induces apoptosis in healthy and tumor tissue where the electric eld applies 20,21 . Achieving perfect irreversible electroporation requires precision and improving the selectivity of the process 22 to raise the concentration of the ablation on tumor cells.…”

Multi-Electrode Architecture Modeling and Optimization for Homogeneous Electroporation of Large Volumes of Tissue

“…Also, this type of electrode normally requires several repositioning/application processes to treat large volumes [10,15]. For this reason, this paper is focused on the study of parallel-plate electrodes [3,[16][17][18] to achieve adequate electric field distribution [19,20], as can be seen in Figure 2fh Currently, the most commonly used electrodes are parallel-needle electrodes [10][11][12], as they normally allow quick and easy placement. The main limitation of needle-based electrodes is that they create an irregular electric field [13], which is concentrated in several points producing undesired thermal effects [14].…”

“…Also, this type of electrode normally requires several repositioning/application processes to treat large volumes [10,15]. For this reason, this paper is focused on the study of parallel-plate electrodes [3,[16][17][18] to achieve adequate electric field distribution [19,20], as can be seen in Figure 2f-h.…”