Irreversible electroporation or IRE is a soft tissue ablation technique using short but strong electrical fields to create permanent and hence lethal nanopores in the cell membrane, to disrupt cellular homeostasis.
[1][2][3][4] The main use of IRE lies in tumor ablation in regions where precision and conservation of the extracellular matrix, blood flow and nerves are of importance.
The first generation of IRE for clinical use, in the form of the NanoKnife System, became commercially available for research purposes in 2009, solely for the surgical ablation of soft tissue tumors.
In the following decade, the combination of high-voltage pulsed electric fields with the chemotherapeutic drug bleomycin and with DNA yielded novel clinical applications: electrochemotherapy and gene electrotransfer, respectively.
[17] Utilizing ultra short pulsed but very strong electrical fields, micropores and nanopores are induced in the phospholipid bilayers which form the outer cell membranes.
[citation needed] When an electrical field of more than 0.5 V/nm[19] is applied to the resting trans-membrane potential, it is proposed that water enters the cell during this dielectric breakdown.
[41] In 2013, the UK National Institute for Health and Clinical Excellence issued a guidance that the safety and efficacy of the use of irreversible electroporation of the treatment of various types of cancer has not yet been established.
[27][43][44] Potential organ systems, where IRE might have a significant impact due to its properties include the pancreas, liver, prostate and the kidneys, which were the main focus of the studies listed in Table 1-3 (state: June 2020).
[90] Using IRE, the urethra, bladder, rectum and neurovascular bundle and lower urinary sphincter can potentially be included in the treatment field without creating (permanent) damage.
[citation needed] IRE has been in use against prostate cancer since 2011, partly in form of clinical trials, compassionate care or individualized treatment approach.
The largest cohort presented by Guenther et al.[85] with up to 6-year follow-up is limited as a heterogeneous retrospective analysis and no prospective clinical trial.
While nephron-sparing surgery is the gold standard treatment for small, malignant renal masses, ablative therapies are considered a viable option in patients who are poor surgical candidates.
In accordance with the prospective protocol designed by the authors, the treated patients will subsequently undergo radical nephrectomy to assess IRE ablation success.
[93] Later phase 2 prospective trials showed good results in terms of safety and feasibility [94][95] for small renal masses but the cohort was limited in numbers (7 and 10 patients respectively), hence efficacy is not yet sufficiently determined.
Complications included pneumothoraces (11 of 23 patients), alveolar hemorrhage not resulting in significant hemoptysis, and needle tract seeding was found in 3 cases (13%).
[97][98] A major obstacle of IRE in the lung is the difficulty in positioning the electrodes; placing the probes in parallel alignment is made challenging by the interposition of ribs.
[99] Maor et el have demonstrated the safety and efficiency of IRE as an ablation modality for smooth muscle cells in the walls of large vessels in rat model.
[citation needed] Numerous studies in animals have demonstrated the safety and efficiency of IRE as a non-thermal ablation modality for pulmonary veins in the context of atrial fibrillation treatment.
[104] Successful ablations in animal tumor models have been conducted for lung,[105][106] brain,[107][108] heart,[109] skin,[110][111] bone,[112][113] head and neck cancer,[114] and blood vessels.