Cardiac synchronization and arrhythmia during irreversible electroporation.

BACKGROUND AND OBJECTIVES: Irreversible electroporation (IRE) is a nonthermal electrical tumor ablative strategy for unresectable tumors. IRE is relatively safe around critical structures but may induce cardiac arrhythmia when its delivery is not synchronized to the cardiac cycle. We performed a systematic literature review to determine rates of arrhythmia when IRE was utilized with or without cardiac synchronization. METHODS: An online literature search was conducted with additional hand selection of articles. Data were extracted and pooled analyses were performed. RESULTS: Twelve articles were included in analysis. IRE was performed for 481 patients; 46% hepatic tumors (n = 223), 36% pancreatic lesions (n = 168), and multiple other locations including prostate. Synchronization was performed on 422 patients. Arrhythmias were noted in 3.7% of cases (n = 18/481); cardiac synchronization: 1.2% (n = 5/422) vs unsynchronized: 22.0% (n = 13/59), P < .0001. These events occurred in every organ except the prostate. CONCLUSIONS: IRE remains a potent technology for unresectable tumors, but arrhythmia is a clinical concern. This literature review confirms that cardiac gating should be used in all cases outside of prostate to prevent this potentially serious adverse event.

Health-related quality of life in dogs treated with electrochemotherapy and/or interleukin-12 gene electrotransfer.

The aim of this study was to evaluate the owners' perception of health-related quality of life (HRQoL) of dogs after treatment with electrochemotherapy (ECT) alone or combined with interleukin-12 gene electrotransfer (IL-12 GET) and/or surgery. The owners of 44 dogs with histologically different tumours were offered the ¼Cancer Treatment Form« at least one month after treatment. The owners assessed their dogs' quality of life (QoL) after treatment as good (mean 7.4) (from 1-very poor to 10-excellent) and the general health compared with the initial diagnosis of cancer as improving (mean 3.9) (from 1-worse to 5-better). The assessment of the current QoL was better within the group of dogs treated with non-invasive treatment (ECT and/or IL-12 GET only), compared with those that received invasive treatment, where, in addition to ECT and/or IL-12 GET, surgery was performed (p < .05). The owners of dogs that achieved an objective response (OR) to the treatment assessed the QoL as significantly better compared with those whose dogs did not respond to the treatment (p < .05). The majority of the owners (86.4%) would opt for the therapy again, regardless of the financial costs. In conclusion, the results of this study demonstrate that the majority of the owners of dogs assessed their dogs' QoL as good and felt that it improved after the treatment, especially in dogs, treated with non-invasive treatment and in those that responded to the treatment. This supports further use of ECT and IL-12 GET as suitable methods for the treatment of selected tumours in veterinary medicine.

Similar complication rates for irreversible electroporation and thermal ablation in patients with hepatocellular tumors.

Background To compare the frequency of adverse events of thermal microwave (MWA) and radiofrequency ablation (RFA) with non-thermal irreversible electroporation (IRE) in percutaneous ablation of hepatocellular carcinoma (HCC). Patients and methods We retrospectively analyzed 117 MWA/RFA and 47 IRE procedures (one tumor treated per procedure; 144 men and 20 women; median age, 66 years) regarding adverse events, duration of hospital and intensive care unit (ICU) stays and occurrence of a post-ablation syndrome. Complications were classified according to the Clavien & Dindo classification system. Results 70.1% of the RFA/MWA and 63.8% of the IRE procedures were performed without complications. Grade I and II complications (any deviation from the normal postinterventional course, e.g., analgesics) occurred in 26.5% (31/117) of MWA/RFA and 34.0% (16/47) of IRE procedures. Grade III and IV (major) complications occurred in 2.6% (3/117) of MWA/RFA and 2.1% (1/47) of IRE procedures. There was no significant difference in the frequency of complications (p = 0.864), duration of hospital and ICU stay and the occurrence of a post-ablation syndrome between the two groups. Conclusions Our results suggest that thermal (MWA and RFA) and non-thermal IRE ablation of malignant liver tumors have comparable complication rates despite the higher number of punctures and the lack of track cauterization in IRE.

Effect of Differing Parameters on Irreversible Electroporation in a Porcine Model.

INTRODUCTION AND OBJECTIVE: Irreversible electroporation (IRE) is a new ablative technology to treat small renal masses. We evaluated differed ablation settings on lesion size and temperature changes in a porcine model. MATERIALS AND METHODS: After Institutional Animal Care and Use Committee approval, 36 laparoscopy-guided and 16 open ablations were performed on 13 domestic female pigs. Ablation parameters studied were voltage (1000 V/cm, 1500 V/cm, or 2000 V/cm), probe exposure (1.0 or 1.5 cm), and lesion size over time (survival) (0-, 7-, or 14 day). Temperature changes were monitored during open ablations with differed settings. Gross lesion size was measured, and histologic analysis with hematoxylin and eosin and nicotinamide adenine dinucleotide staining was performed. RESULTS: The 1000 V/cm ablations had no gross or histologic lesions. A factorial analysis of variance demonstrated that day (p = 0.56), exposure (p = 0.33), and voltage (p = 0.06) did not demonstrate statistical significance for affecting lesion size. For 1.0 cm probe exposure, 2000 V/cm did more closely approximate expected lesion size (p = 0.02) compared with 1500 V/cm. While significance was not seen for 1.5 cm probe exposure, 2000 V/cm often exceeded expected lesion volume. Only 1 of 4 temperature sensors, located adjacent to one of the IRE probes, noted a significant increase with increased voltage. However, all maximum temperatures remained less than 70°C. CONCLUSIONS: Variation in lesion volume was seen with different ablation settings in this porcine model. Maximal energy and probe exposure settings should be utilized to ensure full coverage of target volume/mass, potentially without concern for thermal injury to renal collecting system or nearby structures.

Intradermal electroporation of naked replicon RNA elicits strong immune responses.

RNA-based vaccines represent an interesting immunization modality, but suffer from poor stability and a lack of efficient and clinically feasible delivery technologies. This study evaluates the immunogenic potential of naked in vitro transcribed Semliki Forest virus replicon RNA (RREP) delivered intradermally in combination with electroporation. Replicon-immunized mice showed a strong cellular and humoral response, contrary to mice immunized with regular mRNA. RREP-elicited induction of interferon-γ secreting CD8+ T cells and antibody responses were significantly increased by electroporation. CD8+ T cell responses remained substantial five weeks post vaccination, and antigen-specific CD8+ T cells with phenotypic characteristics of both effector and central memory cells were identified. The immune response during the contraction phase was further increased by a booster immunization, and the proportion of effector memory cells increased significantly. These results demonstrate that naked RREP delivered via intradermal electroporation constitute an immunogenic, safe and attractive alternative immunization strategy to DNA-based vaccines.

Self-powered electroporation using a singularity-induced nano-electroporation configuration.

This study demonstrates the feasibility of creating a self-powered (galvanic) electroporation device using the singularity-induced nano-electroporation configuration. Using this configuration, the electric field in a galvanic electrochemical cell can be amplified and used for electroporation. A secondary current distribution model of a self-powered electroporation device shows that the device can create both reversible and irreversible electroporation-inducing electric field magnitudes, and generate a small amount of power.

Transdermoterapia por electroporación en la lipólisis abdominal / Transdermotherapy by electroporation in abdominal lipolysis

Este estudio presenta los efectos conseguidos por la electroporación en la lipólisis abdominal utilizando la vehiculación de la fosfatidilcolina (fosfolípido que facilita la absorción de las grasas). Se llevó a cabo en 10 mujeres voluntarias, nulíparas, sedentarias, con una edad media de 25,10 años e índice de masa corporal entre 18,5 y 25 kg/m2. Recibieron 15 sesiones de tratamiento fisioterápico, constando esta de una aplicación tópica de fosfatidilcolina al 10% liposomada en el abdomen con electroporación. La técnica consistió en colocar el transductor del equipo en la pared abdominal emitiendo ondas electromagnéticas con un voltaje de 500 mV y una frecuencia de 50 Hz durante 30 minutos. Este tratamiento alcanzó una reducción del tejido adiposo subcutáneo de la pared abdominal, comprobada por medida perimétrica del abdomen, medida del pliegue cutáneo infraumbilical y por ultrasonografía. En la perimetría, la reducción media fue de 4,75 cm, en la plicometría de 2,43 mm y la ultrasonografía demostró una disminución del grosor del tejido adiposo que pasó de una media de 2,21 cm a 1,65 cm. Sin embargo, no se halló ninguna reducción ponderal significativa, aunque la disminución presentada en los tres métodos de evaluación sugiere que la utilización de la fosfatidilcolina con la electroporación puede desencadenar efectos lipolíticos(AU)

The present study presents the effects achieved with electroporation in abdominallipolysis using vehiculization of phosphatidylcholine (phospholipide that facilitates fatabsorption). The study was conducted in 10 voluntary women, nulliparous, sedentary women, with a mean age of 25.10 years and body mass index between 18.5 and 25 kg/m2.They were administered 15 sessions of physiotherapy, this being made up of a topicalapplication of 10% liposomal phosphatidylcholine in the abdomen with electroporation.The technique consisted in placing the equipment transductor on the abdominal wall,emitting electromagnetic waves with a 500mV voltage and 50 Hz frequency for 30 minutes.This treatment achieved a reduction of the subcutaneous adipose tissue of the abdominalwall, verified by perimetric measurement of the abdomen, measurement of infraumbilicalskin fold and by ultrasound. In the perimetry, the mean reduction was 4.75 cm, in theplicometry 2.43mm and the ultrasonograph showed a decrease of adipose tissue thicknessthat went from a mean of 2.21 cm to 1.65 cm. However, no significant weight reduction wasfound, although the decrease found in the three evaluation methods suggests that the useof phosphatidylcholine with electroporation may precipitate lipolitic effects(AU)

Electrically modulated transdermal delivery of fentanyl.

PURPOSE: Test to determine if iontophoresis and electroporation, alone or in combination, can be used for rapid and modulated delivery of fentanyl. METHODS: Fentanyl citrate (5 mg/ml) dissolved in pH 4.0 citrate buffer was delivered in vitro across human epidermis. For iontophoresis. a current of 0.5 mA/cm2 was applied for 5 h, using silver/silver chloride electrodes. Electroporation protocol consisted of applying 15 exponential pulses of 500V (applied voltage) and 200 msec duration at the rate of 1 pulse per minute at time zero and, in some cases, repeating at 1.5 and 2.5 h. RESULTS: There was no measurable permeation of fentanyl through human epidermis under passive conditions. A significant flux (about 80 microg/cm2-hr) was achieved using iontophoresis and decreased once the current was turned off. A 4-fold higher flux and shorter lag time was observed with electroporation as compared to iontophoresis. The flux was found to recover quickly (within 1 h) following pulsing. Modulation of transdermal delivery of fentanyl was demonstrated by both iontophoresis and electroporation. CONCLUSIONS: Electrically assisted transdermal delivery of fentanyl significantly increased transport compared to passive delivery. Also, rapid and modulated delivery was shown to be feasible by programming the electrical parameters.

Improved energy model for membrane electroporation in biological cells subjected to electrical pulses.

A self-consistent model analysis of electroporation in biological cells has been carried out based on an improved energy model. The simple energy model used in the literature is somewhat incorrect and unphysical for a variety of reasons. Our model for the pore formation energy E(r) includes a dependence on pore population and density. It also allows for variable surface tension, incorporates the effects of finite conductivity on the electrostatic correction term, and is dynamic in nature. Self-consistent calculations, based on a coupled scheme involving the Smoluchowski equation and the improved energy model, are presented. It is shown that E(r) becomes self-adjusting with variations in its magnitude and profile, in response to pore population, and inhibits uncontrolled pore growth and expansion. This theory can be augmented to include pore-pore interactions to move beyond the independent pore picture.

In vivo assessment of skin electroporation using square wave pulses.

The application of short-duration high-voltage pulses to the skin has been shown to enhance transdermal drug delivery by several orders of magnitude and to transiently permeabilize cells in tissue. Both exponentially decaying (ED) pulses and square wave (SW) pulses have been applied. The latter have also been used for electrochemotherapy. To date, their effect on skin integrity has not been analyzed. The scope of this work was (i) to investigate the effect induced by SW pulses on the stratum corneum and the skin, (ii) to evaluate the safety issue associated with electroporation, (iii) to contribute to the understanding of drug transport. Biophysical techniques (transepidermal water loss, chromametry, impedance and laser Doppler velocimetry or imaging measurement) and histological methods were combined to provide a global picture of the effects. Ten SW pulses applied to the skin induced a mild impairment of the skin barrier function and a dramatic decrease in skin resistance. These changes were reversible. A transient decrease (<5 min) in blood flow was observed. Neither inflammation, nor necroses were observed. These studies confirm the tolerance of the skin to square wave pulses in vivo.