Aetna considers the use of irreversible electroporation (IRE) including use of the NanoKnife for tissue ablation experimental and investigational due to insufficient evidence in the peer-reviewed literature.

The field of irreversible electroporation (IRE) in medicine has been growing in recent years as a tool in tissue ablation (Rubinsky, 2007).  The process of IRE occurs as a consequence of  certain electrical fields being applied across a cell permeabilizing the cell membrane and leading to cell death, primarily when the electrical fields cause permanent permeabilization and consequent loss of cell homeostasis.  In comparison with current physical ablation technologies, IRE does not result in any thermal effect (Breton and Mir, 2011).

The Nanoknife is a low-energy direct current (LEDC) thermal ablation system, which received Food and Drug Administration (FDA) 510K clearance on October 24, 2011 (FDA, 2011).  The NanoKnife System has received FDA clearance for the surgical ablation of soft tissue.  It has not received clearance for the therapy or treatment of any specific disease or condition (AngioDynamics, 2011).  The NanoKnife System transmits LEDC energy from the generator to electrode probes placed in a target area for the surgical ablation of soft tissue.

Ball et al (2010) conducted a clinical trial of IRE for tumor ablation therapy.  A pulsating direct current of 20 to 50 A and 500 to 3000 V was delivered into metastatic or primary tumors of the liver, kidney, or lung via needle electrodes inserted under computed tomography (CT) or ultrasound guidance with use of a relaxant general anesthetic.  Twenty-one patients were included.  The results showed that electrical discharge produced generalized upper body muscular contractions requiring neuromuscular blockade.  Two patients developed positional neuropraxia because of the extended arm position requested for CT scanning.  Some patients developed self-limiting ventricular tachycardias that are now minimized by using an electrocardiogram (ECG) synchronizer.  Three patients developed pneumothoraces as a result of the needle electrode insertion.  The authors concluded that relaxant general anesthesia is required for IRE of the liver, lung, and kidney and that an ECG synchronizer should be used to minimize the risk of arrhythmias.  The authors further  noted that attention to the position of the arms is required to maximize CT scan quality but minimize brachial plexus strain and that simple post-operative analgesia is all that is required in most patients.

Pech et al (2011) studied 6 patients scheduled for curative resection of renal cell carcinoma (RCC) to assess the feasibility and safety of ablating RCC tissue by IRE.  Irreversible electroporation was performed during anesthesia immediately before the resection with ECG synchronization.  Analysis of hematological, serum biochemical, and ECG variables, including ST waveforms and axis deviations, showed no relevant changes during the study period.  No changes in cardiac function after IRE therapy were found, but 1 case of supraventricular extrasystole was encountered.  Initial histopathologic examination did not identify any immediate adverse effects of IRE.  The authors concluded that “IRE seems to offer a feasible and safe technique by which to treat patients with kidney tumours and could offer some potential advantages over current thermal ablative techniques.”

Thomson et al (2011) conducted a single-center prospective non-randomized cohort study to investigate the safety of IRE for tumor ablation in humans.  Thirty-eight study subjects received IRE treatment under general anesthesia.  The study population included patients with advanced malignancy of the liver, kidney, or lung (69 separate tumors) which were unresponsive to alternative treatment.  Clinical examination, biochemistry, and CT scans of the treated organ were performed before, immediately after, and at 1 month and 3 post-procedure.  The authors reported no mortalities occurring by 30 days post-procedure and that transient ventricular arrhythmia occurred in 4 patients and that ECG synchronized delivery was used subsequently in the remaining 30 patients, with 2 further arrhythmias (supraventricular tachycardia and atrial fibrillation).  One patient developed obstruction of the upper ureter after IRE.  One adrenal gland was unintentionally directly electroporated, which produced transient severe hypertension.  There was no other evidence of adjacent organ damage related to the electroporation.  Two patients developed temporary neurapraxia as a result of arm extension during a prolonged period of anesthesia and biopsy in 3 patients showed coagulative necrosis in the regions treated by IRE.  The authors further noted that complete target tumor ablation verified by CT was achieved in 46 of the 69 tumors treated with IRE (66 %), while most treatment failures occurred in renal and lung tumors.   The authors concluded that IRE appears safe for human clinical use if ECG-synchronized delivery is utilized.  They recommended comparative  evaluation with alternative ablative technologies.