IRE has the potential to damage nerves and may result in axonal swelling, fragmentation, and distal Wallerian degeneration. However, preservation of endoneurium architecture and proliferation of Schwann cells may suggest the potential for axonal regeneration. In contrast, RFA leads to thermal nerve damage, causing protein denaturation, and suggests a much lower potential for regeneration.

After IRE-ablation of nerves, the preservation of the architecture of the endoneurium and the proliferation of Schwann cells may enable axonal regeneration as demonstrated after 2 months in this study.

BACKGROUND Reversible electroporation has long been used to transfer macromolecules into target cells in the laboratory by using an electric field to induce transient membrane permeability. Recently, the electric field has been modulated to produce permanent membrane permeability and cell death. This novel technique, irreversible electroporation (IRE), is being developed for nonthermal cancer ablation. We hypothesize that outside the central zone of IRE exists a peripheral zone of reversible electroporation where gene transfer may occur. METHODS IRE of the liver was performed in a Yorkshire pig model with administration of a plasmid expressing the marker gene green fluorescent protein (GFP) by bolus or primed infusion through the hepatic artery or portal vein. After six hours, the livers were harvested for fluorescent microscopy and histologic examination. RESULTS 31 out of 36 liver specimens treated with IRE and the GFP plasmid demonstrated strong green fluorescence. Liver ablation by IRE was clearly demarcated on histology. CONCLUSION IRE is a promising technique not only for surgical tissue ablation but also for gene therapy. As IRE ablation may leave behind intact tumor antigens, these findings encourage clinical studies of tumor ablation with delivery of immunostimulatory plasmids for combined local eradication and systemic immunotherapy.

No abstract