Utilizing ultra short pulsed but very strong electrical fields, micropores and nanopores are induced in the phospholipid bilayers which form the outer cell membranes. Two kinds of damage can occur: # Reversible<unk>  (RE): Temporary and limited pathways for molecular transport via nanopores are formed, but after the end of the electric pulse, the transport ceases and the cells remain viable. Medical applications are, for example, local introduction of intracellular cytotoxic pharmaceuticals such as bleomycin<unk>  and electrochemotherapy). #<unk>  <unk> : After a certain degree of damage to the cell membranes by<unk> , the leakage of intracellular contents is too severe or the resealing of the cellular membrane is too slow, leaving healthy and/or cancerous cells<unk>  damaged. They die by either apoptosis or via cell-internally induced necrotic pathways, which is unique to this ablation technique. It should be stated that even though the ablation method is generally accepted to be apoptosis, some findings seem to contradict a pure apoptotic cell death, making the exact process by which<unk>  causes cell death unclear. In any case, all studies gree that the cell death is an induced one with the cells dying over a varying time period of hours to days and does not rely on local extreme heating and melting of tissue via high energy deposition like most ablation technologies (see radiofrequency ablation, microwave ablation, High-intensity focused ultrasound). When an electrical field of more than 0.5 V/nm is applied to the resting trans-membrane potential, it is proposed that water enters the cell during this dielectric breakdown. Hydrophilic pores are formed. A molecular dynamics simulation by Tarek illustrates this proposed pore formation in two steps: # After the application of an electrical field, water molecules line up in single file and penetrate the hydrophobic center of the bilayer lipid membrane. # These water channels continue to grow in length and diameter and expand into water-filled pores, at which point they are stabilized by the lipid head groups that move from the membrane-water interface to the middle of the bilayer. It is proposed that as the applied electrical field increases, the greater is the perturbation of the phospholipid head groups, which in turn increases the number of water filled pores. This entire process can occur within a few nanoseconds. Average sizes of nanopores are likely cell-type specific. In swine livers, they average around 340-360 nm, as found using SEM. A secondary described mode of cell death was described to be from a breakdown of the membrane due to transmembrane transfer of electrolytes and adenosine triphosphate. Other effects like heat or electrolysis were also shown to play a role in the currently clinically applied<unk>  pulse protocols.
Irreversible electroporation
Irradiation
Sonodynamic therapy
Carboxytherapy
Cytoluminescent therapy
Combination therapy
Dose fractionation
Neoadjuvant therapy