Irreversible Electroporation Ablation Research Articles

Modulating the immunotolerant tumor microenvironment to enhance irreversible electroporation ablation therapy

Modulating the immunotolerant tumor microenvironment to enhance irreversible electroporation ablation therapy

Chinese Expert Consensus on Open Irreversible Electroporation Ablation for Locally Advanced Pancreatic Cancer (Version 2023)

Pancreatic cancer is one of the most lethal malignancies, with increasing morbidity and mortality. Only 20% of all cases are candidates for surgical resection. Most locally advanced pancreatic cancer (LAPC) is deemed to be an unresectable disease because of the invasion of major vessels. Irreversible electroporation (IRE) is now increasingly applicable to treat LAPC. For the establishment of precise eligibility and the standardization of the IRE technique, a guideline is expected, aiming to improve safety, lead to reproducible outcomes, and facilitate further research into IRE. This article aimed to provide a set of technical recommendations for the treatment of LAPC by open IRE.

Impact of tissue-electrode contact force on irreversible electroporation for atrial fibrillation in potato models

Background: Irreversible electroporation (IRE) is an emerging tissue ablation technique that offers advantages over traditional catheter ablation, such as minimal thermal damage and reduced treatment time. However, as this technique also involves delivering energy through a catheter to target tissue, there are still challenges regarding the contact between the catheter and the targeted tissue, and there is a lack of relevant studies. In this study, we examined this issue using potato models with three groups of experiments. Methods: First, the relationship between the effect of biphasic and monophasic output modes and contact force (CF) was studied. Next, the effect of different voltages on biphasic output mode was examined. Finally, impedance analysis was conducted to test the contact impedance under different CFs. Results: The IRE ablation efficacy increased with the increase of CF in both monophasic and biphasic output modes, and there was a strong correlation between the ablation efficacy and the CF. In addition, at three voltage levels, the IRE ablation efficacy increased with increasing CF, and there was a strong correlation between the ablation efficacy and the CF. Conclusion: The results indicate that, under common IRE electrical parameter configuration, the effect of IRE on the tissue has a positive response to the CF of the electrode in the potato model. This finding has important implications for the design of electrodes used in IRE for the treatment of atrial fibrillation.

New Developments in Image-Guided Percutaneous Irreversible Electroporation of Solid Tumors.

This review will describe the various applications, benefits, risks, and approaches of conventional irreversible electroporation (IRE), as well as highlight the new technological developments of this procedure along with their clinical applications. Minimally invasive image-guided percutaneous IRE ablation has emerged as a newer, non-thermal ablation technique for tumors in the solid organs, particularly within the liver, pancreas, kidney, and prostate. IRE allows for ablation near heat-sensitive structures, including major blood vessels and nerves, and is not susceptible to the heat sink effect. However, it is limited by certain requirements, such as the need for precise parallel placement of at least two probes with a maximum inter-probe distance of 2.5 cm to reduce the risk of arching phenomenon, the requirement for general anesthesia with muscle relaxant, and the need for cardiac synchronization. However, new technological advancements in the ablation system and image guidance tools have been introduced to improve the efficiency and efficacy of IRE. IRE is a safe and effective treatment option for solid tumor ablation within the liver, pancreas, kidney, and prostate. Compared with other ablation techniques, IRE has several advantages, such as the absence of heat sink effect and minimal injury to blood vessels and bile ducts while activating the immune system. Novel techniques such as H-FIRE, needle placement systems, and robotics have enhanced the accuracy and performance in placement of IRE probes. IRE can be especially beneficial when combined with chemotherapy, immunomodulation, and immunotherapy.

Interventional hydrogel microsphere vaccine as an immune amplifier for activated antitumour immunity after ablation therapy

The response rate of pancreatic cancer to chemotherapy or immunotherapy pancreatic cancer is low. Although minimally invasive irreversible electroporation (IRE) ablation is a promising option for irresectable pancreatic cancers, the immunosuppressive tumour microenvironment that characterizes this tumour type enables tumour recurrence. Thus, strengthening endogenous adaptive antitumour immunity is critical for improving the outcome of ablation therapy and post-ablation immune therapy. Here we present a hydrogel microsphere vaccine that amplifies post-ablation anti-cancer immune response via releasing its cargo of FLT3L and CD40L at the relatively lower pH of the tumour bed. The vaccine facilitates migration of the tumour-resident type 1 conventional dendritic cells (cDC1) to the tumour-draining lymph nodes (TdLN), thus initiating the cDC1-mediated antigen cross-presentation cascade, resulting in enhanced endogenous CD8+ T cell response. We show in an orthotopic pancreatic cancer model in male mice that the hydrogel microsphere vaccine transforms the immunologically cold tumour microenvironment into hot in a safe and efficient manner, thus significantly increasing survival and inhibiting the growth of distant metastases.

Irreversible Electroporation Improves Tendon Healing in a Rat Model of Collagenase-Induced Achilles Tendinopathy

Background: Treatment of painful chronic tendinopathy is challenging, and there is an urgent need to develop new regenerative methods. Irreversible electroporation (IRE) can lead to localized cell ablation by electrical pulses and induce new cell and tissue growth. Previously, the authors’ group reported that electroporation-ablated tendons fully regenerated. Purpose: To assess the efficiency of IRE in improving tendon healing using a collagenase-induced Achilles tendinopathy rat model. Study Design: Controlled laboratory study. Methods: After screening for the IRE ablation parameters, a collagenase-induced Achilles tendinopathy rat model was used to assess the efficacy of IRE in improving tendon healing via biomechanical, behavioral, histological, and immunofluorescence assessments. Results: The experiments showed that the parameter of 875 V/cm 180 pulses could ablate most tenocytes, and apoptosis was the main type of death in vitro. In vivo, IRE promoted the healing process of chronic tendinopathy in the Achilles tendon of rats, based on biomechanical, behavioral, and histological assessments. Finally, immunofluorescence results revealed that IRE improved blood supply in the early stages of tendon repair and could potentially reduce neuropathic pain. Conclusion: IRE enhanced tendon tissue healing in a rat model of collagenase-induced Achilles tendinopathy. Clinical Relevance: IRE may as a potential alternative treatment for tendinopathy in clinical usage.

Abstract 4917: High-frequency irreversible electroporation ablation of glioma alters extracellular vesicles and disrupts the blood-brain barrier endothelium

Abstract High-frequency irreversible electroporation (H-FIRE) is a nonthermal tumor ablation technology that kills cancer cells via pulsed electric fields. H-FIRE has been shown to precisely and nonthermally ablate brain tumors while transiently disrupting the peritumoral blood-brain barrier (BBB). The enhanced BBB permeability post-tumor ablation can be exploited to enhance therapeutic delivery to invasive tumor margins, but the mechanisms of H-FIRE-induced BBB disruption remain incompletely characterized. We hypothesize that bystander effects of H-FIRE tumor cell ablation, specifically the release of tumor-derived extracellular vesicles (TDEVs), mediate peritumoral BBB endothelium disruption. F98 glioma and bEnd.3 cerebral endothelial cell lines modelled primary brain cancer and the BBB endothelium, respectively. F98 glioma cells were treated in vitro with sham treatment, a sub-ablative (1,500 V/cm), or an ablative (3,000 V/cm) electric field dose of H-FIRE, and TDEVs were isolated from the supernatants via filtration and ultracentrifugation. Post-H-FIRE TDEVs were characterized via nanoparticle tracking analysis and transmission electron microscopy, with ablative doses of H-FIRE resulting in decreased release of TDEVs compared to sub-ablative H-FIRE and sham treatment. Post-H-FIRE TDEVs were then applied to Transwell models of the BBB endothelium to evaluate the effect of H-FIRE-induced TDEVs on BBB endothelium permeability. TDEVs released after the ablative H-FIRE dose (3,000 V/cm) significantly increased permeability of the BBB endothelium in vitro compared to TDEVs released after sub-ablative and sham H-FIRE treatment. TDEVs were then fluorescently labelled with CFSE, and confocal microscopy was used to characterize internalization of post-H-FIRE TDEVs by cerebral endothelial cells. The TDEVs released after ablative doses of H-FIRE were significantly internalized by bEnd.3 cerebral endothelial cells, while TDEVs released after sub-ablative and sham treatment were not internalized. The proteomic payloads of the post-H-FIRE TDEVs were characterized using mass spectrometry, and clustering analysis demonstrated that the in vitro BBB-modulatory TDEVs released after 3,000 V/cm H-FIRE had distinct proteomic payloads compared to the non-BBB-modulatory TDEV populations released after sham and 1,500 V/cm H-FIRE treatment. Proteins associated with proteasomal degradation, cellular adhesion, and modulation of junctional integrity were increased in the BBB-modulatory group of TDEVs. Taken together, our results suggest that H-FIRE ablation of glioma significantly alters the proteomic cargo of TDEVs to increase internalization of TDEVs by cerebral endothelial cells and increase permeability of the BBB endothelium. Citation Format: Kelsey Murphy, Kenneth Aycock, Spencer Marsh, Alayna Hay, Christine Chang, Shay Bracha, Robert Gourdie, Rafael Davalos, John H. Rossmeisl, Nikolaos Dervisis. High-frequency irreversible electroporation ablation of glioma alters extracellular vesicles and disrupts the blood-brain barrier endothelium. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4917.

V10-08 THE USE OF FOCAL IRREVERSIBLE ELECTROPORATION FOR PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023V10-08 THE USE OF FOCAL IRREVERSIBLE ELECTROPORATION FOR PROSTATE CANCER John Torosyan, Amy Cherry, Hasan Abbas, Shima Tayebi, and Abhinav Sidana John TorosyanJohn Torosyan More articles by this author , Amy CherryAmy Cherry More articles by this author , Hasan AbbasHasan Abbas More articles by this author , Shima TayebiShima Tayebi More articles by this author , and Abhinav SidanaAbhinav Sidana More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003328.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Focal therapy of prostate cancer is a treatment strategy that aims to destroy the cancer-containing parts of the prostate while preserving uninvolved prostatic tissue in an attempt to preserve genitourinary function. Irreversible Electroporation (IRE) is a novel ablative modality which utilizes electrical pulses to induce cell apoptosis and can be applied to various malignancies, including prostate cancer. The objective of this video is to discuss the mechanism of action of IRE and describe the components, setup, and operative technique for performing IRE for the focal treatment of prostate cancer. METHODS: IRE is performed under general anesthesia with the patient placed in lithotomy position. Monopolar electrodes are inserted into the prostate under ultrasound guidance and using a brachytherapy grid. The probes are placed 1.5 to 2cm away from one another, and 3-5mm away from the prostatic capsule using cognitive fusion to cover the lesion and 5-10mm margin. After initially estimating voltage configurations, ten test impulses are fired between each probe pair to assess resulting currents. Using test results, final voltages are assigned, and the remaining 80 impulses are fired between each probe pair. RESULTS: This case involves a 74-year-old male with a history of hypertension and hyperlipidemia who presented with an elevated Prostate-Specific Antigen (PSA) of 6.35 and was found to have Gleason 3+4 cancer in the Prostate Imaging Reporting & Data System (PI-RADS) 4 lesion localized in the right mid gland to apex. The patient had a pre-treatment International Prostate Symptom Score (IPSS) of 4-1 and a Sexual Health Inventory for Men (SHIM) of 18 without the use of erectile dysfunction medication. The patient underwent a successful IRE ablation of the lesion along with the margin. The procedure was tolerated well, and the patient was discharged later that day. At his 6-week follow-up, PSA declined to 0.66 and he had an unchanged IPSS/SHIM. CONCLUSIONS: The use of focal therapy in prostate cancer is promising because of its effectiveness paired with minimal procedural side effects. Focal IRE provides a safe and effective way to achieve focal therapy of prostate cancer. Source of Funding: None. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e928 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Torosyan More articles by this author Amy Cherry More articles by this author Hasan Abbas More articles by this author Shima Tayebi More articles by this author Abhinav Sidana More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract No. 51 Differentiation of Irreversible Electroporation Regions in Normal and Tumor Tissues Using MRI Textures

Irreversible electroporation (IRE) is a promising tissue ablation technique for liver cancer patients unsuitable for surgical resection or liver transplantation. The main clinical challenge in IRE ablation is differentiating IRE ablation zones for immediate assessment. Here, we investigated the reproducibility of radiomic analysis of conventional T1w MRI data acquired from liver tumors and normal liver tissues for assessment of IRE outcomes. IRE ablation was performed on twenty-six rabbits' normal liver or tumors. Anatomical and perfusion MRI data were acquired immediately after the completion of the procedure. IRE and RE zones were outlined on perfusion MRI data with histology validation and mask images were translated to T1w images. T1w MRI data were normalized using three levels to examine the effects of different image specificity (8, 16, and 32) while determining the characteristic patterns related to IRE ablation. At each specificity level, quantitative imaging features were computed by analyzing intensity distribution and textural patterns. The relevant variables were identified by following a multi-step feature selection framework that integrates pairwise likelihood, analysis, and LASSO. Multiple classification models were generated using logistic regression, nonlinear support vector machines, and random forest (RF) with a five-fold cross-validation approach. The accuracy, sensitivity, specificity, and receiver operating characteristic (ROC) curves were employed for the evaluation of the developed classification methods. Random forest classification models outperformed logistic regression and support vector machine models. In terms of image specificity levels, the images sampled with sixteen intensity levels facilitated the most accurate and robust performance compared with images with lower and higher details. The random forest classifier equipped with features computed from images with sixteen levels obtained a training accuracy of 90.86% and a validation accuracy of 81.09% for T1w images. The model sensitivity was 92.33% and 81.33%, and specificity was 89.33% and 80.67% for training and validation sets, respectively. Moreover, we recorded the area under the ROC curve as 97.86% for training and 89.47% for the validation cohort. T1w MRI radiomic features reveal IRE ablation-related effects performed on normal liver and tumor tissues, which demonstrates the potential benefit of quantitative analysis of conventional MRI data for immediate assessment of IRE ablation zones in other solid cancers.

Abstract No. 180 Quantitative MRI Texture Analysis for Evaluating Treatment Response Following Irreversible Electroporation Ablation in Hepatocellular Carcinoma

Abstract No. 180 Quantitative MRI Texture Analysis for Evaluating Treatment Response Following Irreversible Electroporation Ablation in Hepatocellular Carcinoma

Abstract No. 158 Characterizing the Anti-Tumor Immune Response to IRE vs Thermal Ablation Therapy in an Immunocompetent Oncopig Model of Hepatocellular Carcinoma

Immunotherapies for cancer treatment are designed to mobilize a patient’s own immune system against their malignancy locally and systemically. Percutaneous ablation techniques have the potential to work in conjunction with modern immunotherapies by priming the patient’s own lymphocytes to attack previously untreated cancer cells. This phenomenon, known as the abscopal effect, has garnered interest because of the potential for locoregional therapies to induce local and systemic anti-tumor effects and shrinkage of distant tumors (Fionda, 2020). The goal of this study is to evaluate the anti-tumor immune response to irreversible electroporation (IRE) compared with microwave (MWA) and cryoablation in an immunocompetent Oncopig liver tumor model of hepatocellular carcinoma. In-situ liver tumors were induced in a transgenic immunocompetent porcine liver model (2-4 tumors in each liver) with Cre-recombinase induced TP53 and KRAS mutations (Oncopig). Oncopigs were separated into three treatment groups (n = 2), each undergoing either MWA, cryoablation or IRE treatment of a single liver tumor under US or CT guidance. Pre-, immediate post- and 1-week post ablation imaging was performed to evaluate treated and non-treated tumor growth. At each time point, venous blood was also drawn and assayed for critical cytokines related to anti- or pro-tumor immune response. Systemic cytokine levels were correlated to targeted and off-targeted tumor volumes after each time point. Liver tumors were induced at an 83.3% (20/24) success rate. Treated tumors decreased by an average 7% in volume across all treatment modalities on 1-week follow-up imaging. Off-target tumors increased by volume by 71.7% with IRE, 13.6% with MWA and 1.4% with cryoablation. On 1-week blood samples, IRE treated pigs demonstrated lower circulating concentrations of pro-inflammatory IL-2 cytokines when compared with cryoablation (10.9 vs 40.7 pg/mL; P = 0.051). There was no difference in IL-2 levels between MWA and cryoablation-treated pigs (40.7 vs 42.4 pg/mL; P = 0.97). The pro- and anti-tumor immune response is dependent on the type of ablation modality. IRE had the lowest levels of inflammatory marker IL-2 and the lowest degree of tumor control in off target tumors at the one-week time point. Modulating inflammatory pathways via these cytokines after IRE may potentially play a role in amplifying the abscopal effect in liver tumors.

Effect of Focal vs Extended Irreversible Electroporation for the Ablation of Localized Low- or Intermediate-Risk Prostate Cancer on Early Oncological Control

Focal ablative irreversible electroporation (IRE) is a therapy that treats only the area of the tumor with the aim of achieving oncological control while reducing treatment-related functional detriment. To evaluate the effect of focal vs extended IRE on early oncological control for patients with localized low- and intermediate-risk prostate cancer. In this randomized clinical trial conducted at 5 centers in Europe, men with localized low- to intermediate-risk prostate cancer were randomized to receive either focal or extended IRE ablation. Data were collected at baseline and at regular intervals after the procedure from June 2015 to January 2020, and data were analyzed from September 2021 to July 2022. Oncological outcome as indicated by presence of clinically significant prostate cancer (International Society of Urological Pathology grade ≥2) on transperineal template-mapping prostate biopsy at 6 months after IRE. Descriptive measures of results from that biopsy included the number and location of positive cores. A total of 51 and 55 patients underwent focal and extended IRE, respectively. Median (IQR) age was 64 years (58-67) in the focal ablation group and 64 years (57-68) in the extended ablation group. Median (IQR) follow-up time was 30 months (24-48). Clinically significant prostate cancer was detected in 9 patients (18.8%) in the focal ablation group and 7 patients (13.2%) in the extended ablation group. There was no significant difference in presence of clinically significant prostate cancer between the 2 groups. In the focal ablation group, 17 patients (35.4%) had positive cores outside of the treated area, 3 patients (6.3%) had positive cores in the treated area, and 5 patients (10.4%) had positive cores both in and outside of the treated area. In the extended group, 10 patients (18.9%) had positive cores outside of the treated area, 9 patients (17.0%) had positive cores in the treated area, and 2 patients (3.8%) had positive cores both in and outside of the treated area. Clinically significant cancer was found in the treated area in 5 of 48 patients (10.4%) in the focal ablation group and 5 of 53 patients (9.4%) in the extended ablation group. This study found that focal and extended IRE ablation achieved similar oncological outcomes in men with localized low- or intermediate-risk prostate cancer. Because some patients with intermediate-risk prostate cancer are still candidates for active surveillance, focal therapy may be a promising option for those patients with a high risk of cancer progression. ClinicalTrials.gov Identifier: NCT01835977.

Comparative Analysis of Temperature Rise between Convective Heat Transfer Method and Computational Fluid Dynamics Method in an Anatomy-Based Left Atrium Model during Pulsed Field Ablation: A Computational Study.

The non-thermal effects are considered one of the prominent advantages of pulsed field ablation (PFA). However, at higher PFA doses, the temperature rise in the tissue during PFA may exceed the thermal damage threshold, at which time intracardiac pulsatile blood flow plays a crucial role in suppressing this temperature rise. This study aims to compare the effect of heat dissipation of the different methods in simulating the pulsatile blood flow during PFA. This study first constructed an anatomy-based left atrium (LA) model and then applied the convective heat transfer (CHT) method and the computational fluid dynamics (CFD) method to the model, respectively, and the thermal convective coefficients used in the CHT method are 984 (W/m2*K) (blood-myocardium interface) and 4372 (W/m2*K) (blood-catheter interface), respectively. Then, it compared the effect of the above two methods on the maximum temperature of myocardium and blood, as well as the myocardial ablation volumes caused by irreversible electroporation (IRE) and hyperthermia under different PFA parameters. Compared with the CFD method, the CHT method underestimates the maximum temperature of myocardium and blood; the differences in the maximum temperature of myocardium and blood between the two methods at the end of the last pulse are significant (>1 °C), and the differences in the maximum temperature of blood at the end of the last pulse interval are significant (>1 °C) only at a pulse amplitude greater than 1000 V or pulse number greater than 10. Under the same pulse amplitude and different heat dissipation methods, the IRE ablation volumes are the same. Compared with the CFD method, the CHT method underestimates the hyperthermia ablation volume; the differences in the hyperthermia ablation volume are significant (>1 mm3) only at a pulse amplitude greater than 1000 V, a pulse interval of 250 ms, or a pulse number greater than 10. Additionally, the hyperthermia ablation isosurfaces are completely wrapped by the IRE ablation isosurfaces in the myocardium. Thus, during PFA, compared with the CFD method, the CHT method cannot accurately simulate the maximum myocardial temperature; however, except at the above PFA parameters, the CHT method can accurately simulate the maximum blood temperature and the myocardial ablation volume caused by IRE and hyperthermia. Additionally, within the range of the PFA parameters used in this study, the temperature rise during PFA may not lead to the appearance of additional hyperthermia ablation areas beyond the IRE ablation area in the myocardium.

Expert recommendation on image-guided irreversible electroporation ablation treatment for renal carcinoma (2023 edition)

Irreversible electroporation ablation therapy can destroy tumor cells while retaining the integrity of the important surrounding physiological structures. It is suitable for patients with renal cell carcinoma who cannot be surgically resected or who do not want surgical resection, and can ensure the best postoperative renal function to the greatest extent, and has advantages that other thermal ablation treatments do not have. However, since irreversible electroporation therapy has high requirements for electrode needles and parameter settings, improper operation will directly affect the prognosis of patients. In order to improve the level of comprehensive treatment of renal cell cancer and standardize the operation technique of irreversible electroporation for renal cell carcinoma, the Committee of interventional minimally invasive therapy of the Chinese Medical Education Association took the lead in formulating the Expert Recommendation on image-guided irreversible electroporation ablation for Renal Cancer (2022 edition). The article introduces in detail the indications, contraindications, perioperative preparation, basic principles of operation, complications and related management and follow-up of irreversible electroporation for renal cell carcinoma, in order to provide reference for clinical practice.

New Surgical Approach to Treat Fibroids and Solid Tumors - Thermal and Nonthermal Ablation.

There is a trend toward more minimally invasive treatment for symptomatic uterine fibroids. They are image-guided ablation surgery with focused ultrasound, microwave, and radiofrequency ablations that are becoming tested and used in some medical centers or hospitals. Nevertheless, these image-guided ablation surgeries involve thermal ablation to the fibroids, which might lead to thermal injury to the surrounding tissues, for example, nerve injury, vessel injury, and skin burn due to heat diffusion. A new technology - irreversible electroporation (IRE) - is a new paradigm for treating solid tumors. This nonthermal ablation process does not induce high temperatures when treating cancers or solid tumors. The IRE treatment may soon be used for treating fibroids or other solid tumors. In a few clinical trials, IRE is currently used in experimental studies for treating gynecological cancers. This paper will present the minimally invasive thermal ablation treatments for fibroids, introduce this new nonthermal IRE ablation in treating gynecological cancer, and propose its future uses in uterine fibroids.

Assessment of Hepatic Lesions After non-Thermal Tumor Ablation by Irreversible Electroporation in a Pig Model.

Irreversible electroporation (IRE) is a non-thermal and minimal invasive modality to ablate pathologic lesions such as hepatic tumors. Histological analysis of the initial lesions after IRE can help predict ablation efficacy. We aimed to investigate the histological characteristics of early hepatic lesions after IRE application using animal models. IRE (1500 V/cm, a pulse length of 100 μs, 60 or 90 pulses) was applied to the liver of miniature pigs. H&E and TUNEL staining were performed and analyzed. Ablated zones of pig liver were discolored and separated from the normal zone after IRE. Histologic characteristics of ablation zones included preserved hepatic lobular architecture with a unique hexagonal-like structure. Apoptotic cells were detected, and sinusoidal dilatation and blood congestion were observed, but hepatic arteries and bile ducts were intact around the ablation zones. The early lesions obtained by delivering monophasic square wave pulses through needle electrodes reflected typical histological changes induced by IRE. Therefore, it was found that the histological assessment of the early hepatic lesion after IRE can be utilized to predict the IRE ablation effect.

Liver tissue remodeling following ablation with irreversible electroporation in a porcine model.

Irreversible electroporation (IRE) is a method of non-thermal focal tissue ablation characterized by irreversibly permeabilizing the cell membranes while preserving the extracellular matrix. This study aimed to investigate tissue remodeling after IRE in a porcine model, especially focusing on the extracellular matrix and hepatic stellate cells. IRE ablation was performed on 11 female pigs at 2,000 V/cm electric field strength using a versatile high-voltage generator and 3 cm diameter parallel-plate electrodes. The treated lobes were removed during surgery at 1, 3, 7, 14, and 21 days after IRE. Tissue remodeling and regeneration were assessed by histopathology and immunohistochemistry. Throughout the treated area, IRE led to extensive necrosis with intact collagenous structures evident until day 1. From then on, the necrosis progressively diminished while reparative tissue gradually increased. During this process, the reticulin framework and the septal fibrillar collagen remained in the necrotic foci until they were invaded by the reparative tissue. The reparative tissue was characterized by a massive proliferation of myofibroblast-like cells accompanied by a complete disorganization of the extracellular matrix with the disappearance of hepatic architecture. Hepatic stellate cell markers were associated with the proliferation of myofibroblast-like cells and the reorganization of the extracellular matrix. Between 2 and 3 weeks after IRE, the lobular architecture was almost completely regenerated. The events described in the present study show that IRE may be a valid model to study the mechanisms underlying liver regeneration after extensive acute injury.

Optimization of Transpedicular Electrode Insertion for Electroporation-Based Treatments of Vertebral Tumors.

Electroporation-based treatments such as electrochemotherapy and irreversible electroporation ablation have sparked interest with respect to their use in medicine. Treatment planning involves determining the best possible electrode positions and voltage amplitudes to ensure treatment of the entire clinical target volume (CTV). This process is mainly performed manually or with computationally intensive genetic algorithms. In this study, an algorithm was developed to optimize electrode positions for the electrochemotherapy of vertebral tumors without using computationally intensive methods. The algorithm considers the electric field distribution in the CTV, identifies undertreated areas, and uses this information to iteratively shift the electrodes from their initial positions to cover the entire CTV. The algorithm performs successfully for different spinal segments, tumor sizes, and positions within the vertebra. The average optimization time was 71 s with an average of 4.9 iterations performed. The algorithm significantly reduces the time and expertise required to create a treatment plan for vertebral tumors. This study serves as a proof of concept that electrode positions can be determined (semi-)automatically based on the spatial information of the electric field distribution in the target tissue. The algorithm is currently designed for the electrochemotherapy of vertebral tumors via a transpedicular approach but could be adapted for other anatomic sites in the future.

Novel irreversible electroporation ablation (Nano-knife) versus radiofrequency ablation for the treatment of solid liver tumors: a comparative, randomized, multicenter clinical study.

Irreversible electroporation (IRE) is a soft tissue ablation technique that uses short electrical fields which induce the death of target cells. To evaluate the safety and efficacy of an IRE-based device compared to regular radiofrequency ablation (RFA) of solid liver tumors, in this multicenter, randomized, parallel-arm, non-inferiority study, 152 patients with malignant liver tumors were randomized into IRE (n = 78) and RFA (n = 74) groups. The primary endpoint was the success rate of tumor ablation; the secondary endpoints included the tumor ablation time, complications, tumor recurrence rates and treatment-related adverse events (TRAE). The success rate of tumor ablation using IRE was 94.9% and was non-inferior to the RFA group (96.0%) (P = 0.761). For the secondary endpoints, the average ablation time was 34.29 ± 30.38 min for the IRE group, which was significantly longer than for the RFA group (19.91 ± 16.08 min) (P < 0.001). The incidences of postoperative complications after 1 week (P = 1.000), 1 month (P = 0.610) and 3 months (P = 0.490) were not significantly different between the 2 groups. The recurrence rates of liver tumor at 1, 3 and 6 months after ablation were 0 (0.0%), 10 (13.9%) and 10 (13.3%) in the IRE group and 2.9%, 7.3% and 19.7% in the RFA control group (all P > 0.05), respectively. For safety assessments, 51 patients experienced 191 AEs (65.4%) in the IRE group, which was not different from the RFA group (73.0%, 54/184) (P = 0.646). In 7 IRE patients, 8 TRAEs (7.9%) occurred, the most common being edema of the limbs (mild grade) and fever (severe grade), while no TRAEs occurred in the RFA group. This study proved that the excellent safety and efficacy of IRE was non-inferior to the regular radiofrequency device in ablation performance for the treatment of solid liver tumors. Clinical trial registration: Chinese Clinical Trial Registry: ChiCTR1800017516

Cause Analysis and Nursing Countermeasures of Hypertension during Irreversible Electroporation Ablation

Cause Analysis and Nursing Countermeasures of Hypertension during Irreversible Electroporation Ablation