Use of single needle high frequency irreversible electroporation (sn-hfire) to create reproducible pancreatic ablations in a survival swine model

Abstract

Presenter: Patrick Salibi MD | Atrium Health Background: Irreversible electroporation (IRE) is an alternative to thermal ablation for treating unresectable pancreatic malignancies. However, IRE can be technically demanding due to the need to place multiple electrodes in an anatomically challenging environment, the risk of thermal damage to critical structures adjacent to the electrodes and extended intraoperative times (relative to thermal ablation). To address these limitations, we developed an experimental single needle-dual electrode high frequency IRE (SN-HFIRE) delivery system. The aim of this study was to evaluate the efficacy of SN-HFIRE in vivo by performing pancreatic ablations using different pulse delivery parameters designed to maintain ablation size while reducing the potential for thermal damage in a survival swine model. Methods: Under surgical anesthesia and ultrasound guidance, the SN-HFIRE device was placed in either the head or tail of the pancreas. Bipolar HFIRE pulses of 2,250 or 2,750V were delivered using a 2-5-2 pulse waveform (on-off-on time [μs]) as either a single contiguous series of pulse trains (CD; 2,250V, 1x100-bursts, 100μs on-time/burst), or four sets of 25 bursts (2,500V, 4x25-bursts, 60μs on-time/burst) with a 60sec delay between each set (DD). Intraoperative SN-HFIRE delivery was performed in the absence of paralytics or cardiac synchronization. Intraoperatively, tissue surface and electrode temperature were continuously measured along with physiological parameters (Chem-8), muscle movement, and cardiac output. Following SN-HFIRE delivery the laparotomy was closed and animals recovered and monitored for 3-days. At necropsy, tissue was collected and analyzed for ablation size, and ablation characteristics assessed histologically to identify areas of necrotic versus apoptotic cell death. Results: All animals (n=4) survived the procedures to experimental completion in the absence of detectable adverse events. Pancreatic SN-HFIRE device placement was achieved in less than 5mins and delivery of SN-HFIRE pulses was completed in 100secs (CD) versus 240sec (DD) (n=4 per group). No discernable muscle movement or cardiac events were detected during SN-HFIRE delivery for either CD or DD settings. Electrode surface temperature was significantly higher in CD versus DD (16.3+/-1.00C versus 6.5+/-0.60C) and translated to changes in measurement of tissue surface temperature (5.6+/-1.3 (CD) versus 0.3+/-0.50C [DD]). At necropsy, there were no abnormalities in the physiological parameters measured (Chem-8), and sites of ablation were readily identifiable prior to sectioning/staining. Following tissue staining (tetrazolium chloride) ablated regions demonstrated clearly defined boundaries of live-dead tissue from which measurements were used to calculate ablation volume. Using the CD approach mean ablation volume was 938+/-181mm3 versus 1044+/-208cm3 (DD). Histologically, H&E staining confirmed clear demarcation between ablated and healthy tissue, with a notable absence of infiltrating immune cells in both the CD and DD groups. Conclusion: SN-HFIRE allows the ability to rapidly create reproducible pancreatic ablations in vivo using a single-needle delivery device. The use of SN-HFIRE further simplifies intraoperative procedures and reduces pulse delivery time as it obviates the need for cardiac synchronization or intraoperative paralytics. Refining the pulse characteristics to include a delay between pulse train delivery significantly reduces the potential for thermal damage adjacent to the electrodes without compromising the ablation size that can be achieved.