Reduction of Muscle Contractions during Irreversible Electroporation Therapy Using High-Frequency Bursts of Alternating Polarity Pulses: A Laboratory Investigation in an Ex Vivo Swine Model

Sano, Michael B.; Fan, Richard E.; Cheng, Kai; Sáenz, Yamil; Sonn, Geoffrey A.; Hwang, Gloria L.; Li, Xing

doi:10.1016/j.jvir.2017.12.019

Cited by 51 publications

(48 citation statements)

References 21 publications

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“…However, the requirement of intraoperative paralytic agents and cardiac synchronization for all IRE procedures can be an impediment, adding more complexity to the modality (7,8). HFIRE therapy, a next-generation IRE therapy, can be safely applied in the absence of intraoperative paralytic agents and cardiac synchronization required during traditional IRE (12,23). Additionally, IRE and HFIRE therapies alike can, at times, benefit from multiple-electrode (!…”

Section: Discussionmentioning

confidence: 99%

“…High-frequency IRE (HFIRE) could be used to capitalize on these proinflammatory conditions after therapy and minimize the difficulties associated with typical IRE procedures. This next generation of IRE negates the need for cardiac synchronization and paralytic agents by using rapid bipolar pulses that minimize nerve and muscle excitation (9)(10)(11)(12). Further, HFIRE therapy has been shown to preferentially target malignant cells in vitro (13,14).…”

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confidence: 99%

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High-Frequency Irreversible Electroporation for Treatment of Primary Liver Cancer: A Proof-of-Principle Study in Canine Hepatocellular Carcinoma

Partridge

O’Brien

Lorenzo

et al. 2020

Journal of Vascular and Interventional Radiology

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Purpose: To determine the safety and feasibility of percutaneous high-frequency irreversible electroporation (HFIRE) for primary liver cancer and evaluate the HFIRE-induced local immune response. Materials and Methods: HFIRE therapy was delivered percutaneously in 3 canine patients with resectable hepatocellular carcinoma (HCC) in the absence of intraoperative paralytic agents or cardiac synchronization. Pre-and post-HFIRE biopsy samples were processed with histopathology and immunohistochemistry for CD3, CD4, CD8, and CD79a. Blood was collected on days 0, 2, and 4 for complete blood count and chemistry. Numeric models were developed to determine the treatment-specific lethal thresholds for malignant canine liver tissue and healthy porcine liver tissue. Results: HFIRE resulted in predictable ablation volumes as assessed by posttreatment CT. No detectable cardiac interference and minimal muscle contraction occurred during HFIRE. No clinically significant adverse events occurred secondary to HFIRE. Microscopically, a well-defined ablation zone surrounded by a reactive zone was evident in the majority of samples. This zone was composed primarily of maturing collagen interspersed with CD3 þ /CD4 À /CD8 À lymphocytes in a proinflammatory microenvironment. The average ablation volumes for the canine HCC patients and the healthy porcine tissue were 3.89 cm 3 ± 0.74 and 1.56 cm 3 ± 0.16, respectively (P ¼ .03), and the respective average lethal thresholds were 710 V/cm ± 28.2 and 957 V/cm ± 24.4 V/cm (P ¼ .0004). Conclusions: HFIRE can safely and effectively be delivered percutaneously, results in a predictable ablation volume, and is associated with lymphocytic tumor infiltration. This is the first step toward the use of HFIRE for treatment of unresectable liver tumors.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

High-Frequency Irreversible Electroporation for Treatment of Primary Liver Cancer: A Proof-of-Principle Study in Canine Hepatocellular Carcinoma

Partridge

O’Brien

Lorenzo

et al. 2020

Journal of Vascular and Interventional Radiology

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“…Building upon the advantages of IRE, a novel technology termed high-frequency irreversible electroporation (H-FIRE) utilizes 1-10 µs bipolar bursts applied in a pattern with interpulse delay when switching poles. These parameters are highly effective in non-thermally ablating tissues without causing the muscle contractions and heart dysrhythmia associated with the longduration monophasic pulses of IRE (8,(109)(110)(111)(112). Its use in pre-clinical models has progressed without the need for cardiac synchronization as well (112).…”

Section: High-frequency Irreversible Electroporation (H-fire)mentioning

confidence: 99%

Starting a Fire Without Flame: The Induction of Cell Death and Inflammation in Electroporation-Based Tumor Ablation Strategies

et al. 2020

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New therapeutic strategies and paradigms are direly needed for the treatment of cancer. While the surgical removal of tumors is favored in most cancer treatment plans, resection options are often limited based on tumor localization. Over the last two decades, multiple tumor ablation strategies have emerged as promising stand-alone or combination therapeutic options for patients. These strategies are often employed to treat tumors in areas where surgical resection is not possible or where chemotherapeutics have proven ineffective. The type of cell death induced by the ablation modality is a critical aspect of therapeutic success that can impact the efficacy of the treatment and systemic anti-tumor immune system responses. Electroporation-based ablation technologies include electrochemotherapy, irreversible electroporation, and other modalities that rely on pulsed electric fields to create pores in cell membranes. These pores can either be reversible or irreversible depending on the electric field parameters and can induce cell death either alone or in combination with a therapeutic agent. However, there have been many controversial findings among these technologies as to the cell death type initiated, from apoptosis to pyroptosis. As cell death mechanisms can impact treatment side effects and efficacy, we review the main types of cell death induced by electroporation-based treatments and summarize the impact of these mechanisms on treatment response. We also discuss potential reasons behind the variability of findings such as the similarities between cell death pathways, differences between cell-types, and the variation in electric field strength across the treatment area.

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“…Electrochemotherapy (ECT) and gene electrotransfer (GET) utilize RE while IRE is mostly used as a non-thermal tumor ablation modality (Golberg and Yarmush, 2013;Haberl et al, 2013;Yarmush et al, 2013). Recently, another improved type of IRE termed high-frequency IRE (HFIRE) (Arena et al, 2011;Sano et al, 2015Sano et al, , 2018 was proved to ablate tumors with a benefit of mitigating muscle contraction and showed some promising results (Dong et al, 2018;DeWitt et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Development of a Multi-Pulse Conductivity Model for Liver Tissue Treated With Pulsed Electric Fields

Zhao

Zheng

Beitel-White

et al. 2020

Front. Bioeng. Biotechnol.

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Reduction of Muscle Contractions during Irreversible Electroporation Therapy Using High-Frequency Bursts of Alternating Polarity Pulses: A Laboratory Investigation in an Ex Vivo Swine Model

Cited by 51 publications

References 21 publications

High-Frequency Irreversible Electroporation for Treatment of Primary Liver Cancer: A Proof-of-Principle Study in Canine Hepatocellular Carcinoma

High-Frequency Irreversible Electroporation for Treatment of Primary Liver Cancer: A Proof-of-Principle Study in Canine Hepatocellular Carcinoma

Starting a Fire Without Flame: The Induction of Cell Death and Inflammation in Electroporation-Based Tumor Ablation Strategies

Development of a Multi-Pulse Conductivity Model for Liver Tissue Treated With Pulsed Electric Fields

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