High-Frequency Irreversible Electroporation: Safety and Efficacy of Next-Generation Irreversible Electroporation Adjacent to Critical Hepatic Structures

Siddiqui, Imran; Kirks, Russell C.; Latouche, Eduardo L.; DeWitt, Matthew R.; Swet, Jacob H.; Baker, E.; Vrochides, Dionisios; Iannitti, David A.; Davalos, Rafael V.; McKillop, Iain H.

doi:10.1177/1553350617692202

Cited by 25 publications

(18 citation statements)

References 37 publications

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“…2 H-FIRE consists of the delivery of bursts of short bipolar pulses (1-5 ls pulse length) instead of the 70-100 ls monopolar pulses typically used in IRE, and has been successfully applied to treat solid tumors with minimal muscle contractions. 29,35,42,43,51 The electric fields required to kill cells with H-FIRE are significantly higher than in conventional IRE protocols, 38,39 but when moving from monopolar IRE waveforms to bipolar H-FIRE bursts, the excitation thresholds of peripheral nerves increase even more significantly than the thresholds for cell death. 26 Thus, it is possible to minimize muscle contractions while maintaining treatment efficacy with H-FIRE.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of Cell Death After Conventional IRE and H-FIRE Treatments

et al. 2020

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High-frequency irreversible electroporation (H-FIRE) has emerged as an alternative to conventional irreversible electroporation (IRE) to overcome the issues associated with neuromuscular electrical stimulation that appear in IRE treatments. In H-FIRE, the monopolar pulses typically used in IRE are replaced with bursts of short bipolar pulses. Currently, very little is known regarding how the use of a different waveform affects the cell death dynamics and mechanisms. In this study, human pancreatic adenocarcinoma cells were treated with a typical IRE protocol and various H-FIRE schemes with the same energized time. Cell viability, membrane integrity and Caspase 3/7 activity were assessed at different times after the treatment. In both treatments, we identified two different death dynamics (immediate and delayed) and we quantified the electric field ranges that lead to each of them. While in the typical IRE protocol, the electric field range leading to a delayed cell death is very narrow, this range is wider in H-FIRE and can be increased by reducing the pulse length. Membrane integrity in cells suffering a delayed cell death shows a similar time evolution in all treatments, however, Caspase 3/7 expression was only observed in cells treated with H-FIRE.

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Section: Introductionmentioning

confidence: 99%

Dynamics of Cell Death After Conventional IRE and H-FIRE Treatments

et al. 2020

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“…For example, muscle contractions with HF-IRE pulses were much less noticeable than with 100 μs long monopolar pulses in experiments on rabbit liver 33 ,57 ,58. Even in the absence of cardiac synchronization and paralytics, only minor muscle twitch was recorded in one out of 24 cases59 ,60 when treating porcine liver. Sano et al observed that HF-IRE waveforms reduced the intensity of muscle contractions in comparison with traditional IRE pulses on ex-vivo porcine model34 and in in vivo murine tumor 46.…”

Section: Discussionmentioning

confidence: 96%

“…In a first human study on high-frequency irreversible electroporation of prostate cancer, only a small amount of muscle relaxant was needed, and there were no visible muscle contractions during the pulse delivery process 36. Additionally, the histological analysis in in vivo porcine experiments indicates that with HF-IRE rapid and reproducible ablation in the liver can be achieved, while preserving gross vascular/biliary architecture 60. The mechanism for decreased muscle contractions is still unknown.…”

Section: Discussionmentioning

confidence: 99%

The use of high-frequency short bipolar pulses in cisplatin electrochemotherapy in vitro

Scuderi

Reberšek

Miklavčič

et al. 2019

Radiology and Oncology

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Background In electrochemotherapy (ECT), chemotherapeutics are first administered, followed by short 100 μs monopolar pulses. However, these pulses cause pain and muscle contractions. It is thus necessary to administer muscle relaxants, general anesthesia and synchronize pulses with the heart rhythm of the patient, which makes the treatment more complex. It was suggested in ablation with irreversible electroporation, that bursts of short high-frequency bipolar pulses could alleviate these problems. Therefore, we designed our study to verify if it is possible to use high-frequency bipolar pulses (HF-EP pulses) in electrochemotherapy. Materials and methods We performed in vitro experiments on mouse skin melanoma (B16-F1) cells by adding 1–330 μM cisplatin and delivering either (a) eight 100 μs long monopolar pulses, 0.4–1.2 kV/cm, 1 Hz (ECT pulses) or (b) eight bursts at 1 Hz, consisting of 50 bipolar pulses. One bipolar pulse consisted of a series of 1 μs long positive and 1 μs long negative pulse (0.5–5 kV/cm) with a 1 μs delay in-between. Results With both types of pulses, the combination of electric pulses and cisplatin was more efficient in killing cells than cisplatin or electric pulses only. However, we needed to apply a higher electric field in HF-EP (3 kV/cm) than in ECT (1.2 kV/cm) to obtain comparable cytotoxicity. Conclusions It is possible to use HF-EP in electrochemotherapy; however, at the expense of applying higher electric fields than in classical ECT. The results obtained, nevertheless, offer an evidence that HF-EP could be used in electrochemotherapy with potentially alleviated muscle contractions and pain.

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“… 31 , 32 Recently, high-frequency IRE has also been shown to be effective for hepatic ablation in a porcine model. 33 , 34 The first clinical trial using IRE was performed on tumors in the kidney, 35 and several studies have followed describing treatment of tumors in internal organs such as liver, lung, and pancreas as a treatment that seems safe and feasible. 36 – 38 Irreversible electroporation has been shown to be used for tissue destruction, and normal tissue seems to also be affected.…”

Section: Irreversible Electroporationmentioning

confidence: 99%

A Review on Differences in Effects on Normal and Malignant Cells and Tissues to Electroporation-Based Therapies: A Focus on Calcium Electroporation

Frandsen

Gehl

2018

Technol Cancer Res Treat

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Calcium electroporation is a potential novel anticancer treatment, where high concentrations of calcium are introduced into the cell cytosol by electroporation. This is a method where short, high-voltage pulses induce a transient permeabilization of the cell membrane and thereby allow influx and efflux of ions and molecules. Electroporation is used in combination with chemotherapeutic drugs (electrochemotherapy) as a standard treatment for cutaneous metastases, and electroporation using a higher electric field and number of pulses (irreversible electroporation) is increasingly being used as an anticancer treatment. In this review, calcium electroporation is described with emphasis on the investigations of differences in the effect on normal and malignant cells and tissues in vitro and in vivo. Calcium electroporation has been shown to induce cell death in vitro and tumor necrosis in vivo with a difference in sensitivity between different tumor types. Normal cells treated in vitro are significantly less affected than cancer cells, and a similar trend is shown in vivo where muscle and skin tissue surrounding a treated tumor as well as muscle and skin directly treated with calcium electroporation were less affected than tumors. The mechanism behind this difference in sensitivity is not fully understood but might be affected by differences in electric impedance, membrane repair, and expression of plasma membrane calcium ATPases in normal and malignant cells. The research on calcium electroporation shows a potential novel anticancer treatment with significant effect on cancer cells and tissues while normal cells and tissues are clearly less affected.

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High-Frequency Irreversible Electroporation: Safety and Efficacy of Next-Generation Irreversible Electroporation Adjacent to Critical Hepatic Structures

Cited by 25 publications

References 37 publications

Dynamics of Cell Death After Conventional IRE and H-FIRE Treatments

Dynamics of Cell Death After Conventional IRE and H-FIRE Treatments

The use of high-frequency short bipolar pulses in cisplatin electrochemotherapy in vitro

A Review on Differences in Effects on Normal and Malignant Cells and Tissues to Electroporation-Based Therapies: A Focus on Calcium Electroporation

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