A system for treating a tissue site. At least first and second mono-polar electrodes are configured to be introduced at or near a tissue site of the patient. A voltage pulse generator is coupled to the first and second mono-polar electrodes. The voltage pulse generator is configured to apply sufficient electrical pulses between the first and second mono-polar electrodes to induce electroporation of cells in the tissue site, to create necrosis of cells of the tissue site, but insufficient to create a thermal damaging effect to a majority of the tissue site.