Irreversible Electroporation Treatment Research Articles

Effectiveness and safety of irreversible electroporation when used for the ablation of stage 3 pancreatic adenocarcinoma: A registry study (DIRECT).

e16301 Background: Outcomes for patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) remain poor with a mean overall survival (OS) of 11 months. Irreversible electroporation (IRE) is a method of local tumor ablation that causes cell death by disrupting homeostasis in the cell membrane. Previous research suggests IRE can be useful in the multi-disciplinary treatment of Stage 3 PDAC. The present study was designed to assess the effectiveness and safety of IRE for Stage 3 PDAC in a real-world setting after induction chemotherapy. Methods: Patients with Stage 3 PDAC treated with IRE were prospectively enrolled in a multicenter registry study. Enrollment required 3 months of active multi-agent chemotherapy, with no progression before IRE treatment. Endpoints were 30- and 90-day mortality from enrollment and the new onset of an adverse event (AE). Results: 87 patients were enrolled in the registry between May 2019 and May 2023. Mean age was 64.0 ± 8.4 years, 57.5% were female and mean tumor diameter was 2.2 ± 0.7 cm. Mean time from diagnosis to IRE treatment was 8.9 ± 4.9 months. All subjects underwent induction chemotherapy with the most common being FOLFIRINOX alone, gemcitabine with albumin-bound paclitaxel, or a combination of both in 47 (54.0%) patients. Thirty-seven (42.5%) patients had prior radiation therapy. All procedures were performed using an open approach with 50 (57.5%) for in-situ tumor ablation and 37 (42.5%) with the intent of margin accentuation in combination with resection. Major adjunctive procedures were performed for 70 (80.5%) patients. Common adjunctive surgeries were cholecystectomy (33.3%), Whipple procedure (28.7%) and either distal or subtotal pancreatectomy (11.4%). Mean IRE delivery time was 55.7 ± 54.5 minutes with an average of 3.1 probes (range 2 to 6) used per procedure. There was a mean of 1031.1 ± 882.1 pulses delivered per procedure. The 30- and 90-day mortality was 3/87 (3.4%) and 4/82 (4.9%) respectively. There were 21 (24.1%) patients who developed AEs related to IRE treatment during the 90-day post-procedure period (9 patients had AEs that were definitely related to IRE, 5 probably and 7 possibly). Of these related events, only three were Grade 4 or higher (arterial hemorrhage, cardiac arrest, and septic shock). Overall, gastrointestinal related AEs were the most common representing 16 of the 28 (57.1%) of all AEs associated with the IRE procedure. One patient died within 30 days of the procedure due to an intraperitoneal arterial hemorrhage that was deemed to be definitely related to the IRE treatment. Conclusions: The use of IRE for curative intent tumor ablation alone or in combination with resection following induction chemotherapy in patients with locally advanced Stage 3 PDAC has acceptable safety and is associated with acceptable morbidity and mortality rates in appropriately selected patients. Clinical trial information: NCT03899649 .

Irreversible electroporation promotes a pro-inflammatory tumor microenvironment and anti-tumor immunity in a mouse pancreatic cancer model.

Pancreatic cancer is a significant cause of cancer-related mortality and often presents with limited treatment options. Pancreatic tumors are also notorious for their immunosuppressive microenvironment. Irreversible electroporation (IRE) is a non-thermal tumor ablation modality that employs high-voltage microsecond pulses to transiently permeabilize cell membranes, ultimately inducing cell death. However, the understanding of IRE's impact beyond the initiation of focal cell death in tumor tissue remains limited. In this study, we demonstrate that IRE triggers a unique mix of cell death pathways and orchestrates a shift in the local tumor microenvironment driven, in part, by reducing the myeloid-derived suppressor cell (MDSC) and regulatory T cell populations and increasing cytotoxic T lymphocytes and neutrophils. We further show that IRE drives induce cell cycle arrest at the G0/G1 phase in vitro and promote inflammatory cell death pathways consistent with pyroptosis and programmed necrosis in vivo. IRE-treated mice exhibited a substantial extension in progression-free survival. However, within a span of 14 days, the tumor immune cell populations reverted to their pre-treatment composition, which resulted in an attenuation of the systemic immune response targeting contralateral tumors and ultimately resulting in tumor regrowth. Mechanistically, we show that IRE augments IFN-γ signaling, resulting in the up-regulation of the PD-L1 checkpoint in pancreatic cancer cells. Together, these findings shed light on potential mechanisms of tumor regrowth following IRE treatment and offer insights into co-therapeutic targets to improve treatment strategies.

The Induction of Combined Hyperthermal Ablation Effect of Irreversible Electroporation with Polydopamine Nanoparticle-Coated Electrodes.

Irreversible electroporation (IRE) is a prominent non-thermal ablation method widely employed in clinical settings for the focal ablation therapy of solid tumors. Utilizing high-voltage, short-duration electric pulses, IRE induces perforation defects in the cell membrane, leading to apoptotic cell death. Despite the promise of irreversible electroporation (IRE) in clinical applications, it faces challenges concerning the coverage of target tissues for ablation, particularly when compared to other thermal ablation therapies such as radiofrequency ablation, microwave ablation, and cryoablation. This study aims to investigate the induced hyperthermal effect of IRE by applying a polydopamine nanoparticle (Dopa NP) coating on the electrode. We hypothesize that the induced hyperthermal effect enhances the therapeutic efficacy of IRE for cancer ablation. First, we observed the hyperthermal effect of IRE using Dopa NP-coated electrodes in hydrogel phantom models and then moved to in vivo models. In particular, in in vivo animal studies, the IRE treatment of rabbit hepatic lobes with Dopa NP-coated electrodes exhibited a two-fold higher increase in temperature (ΔT) compared to non-coated electrodes. Through a comprehensive analysis, we found that IRE treatment with Dopa NP-coated electrodes displayed the typical histological signatures of hyperthermal ablation, including the disruption of the hepatic cord and lobular structure, as well as the infiltration of erythrocytes. These findings unequivocally highlight the combined efficacy of IRE with Dopa NPs for electroporation and the hyperthermal ablation of target cancer tissues.

Consensus Guidelines of Irreversible Electroporation for Pancreatic Tumors: Protocol Standardization Using the Modified Delphi Technique.

Since no uniform treatment protocol for pancreatic irreversible electroporation (IRE) exists, the heterogeneity throughout literature complicates the comparison of results. To reach agreement among experts, a consensus study was performed. Eleven experts, recruited according to predefined criteria regarding previous IRE publications, participated anonymously in three rounds of questionnaires according to a modified Delphi technique. Consensus was defined as having reached ≥80% agreement. Response rates were 100, 64, and 64% in rounds 1 to 3, respectively; consensus was reached in 93%. Pancreatic IRE should be considered for stage III pancreatic cancer and inoperable recurrent disease after previous local treatment. Absolute contraindications are ventricular arrhythmias, implantable stimulation devices, congestive heart failure NYHA class 4, and severe ascites. The inter-electrode distance should be 10 to 20 mm and the exposure length should be 15 mm. After 10 test pulses, 90 treatment pulses of 1,500 V/cm should be delivered continuously, with a 90-µs pulse length. The first postprocedural contrast-enhanced computed tomography should take place 1 month post-IRE, and then every 3 months. This article provides expert recommendations regarding patient selection, procedure, and follow-up for IRE treatment in pancreatic malignancies through a modified Delphi consensus study. Future studies should define the maximum tumor diameter, response evaluation criteria, and the optimal number of preoperative FOLFIRINOX cycles.

One-year Follow-up Results of Transperineal Biopsy For Patients Undergoing Irreversible Electroporation Treatment in Localized Prostate Cancer.

This article reports on the early results of a 1-year follow-up study investigating the efficacy of irreversible electroporation in the treatment of localized prostate cancer. The study included 18 out of 40 patients diagnosed with low- and intermediate-risk prostate cancer who underwent irreversible electroporation. Treatment results were evaluated through confirmation biopsies, comparing prostate-specific antigen levels, international prostate symptom scoring, and international index of erectile dysfunction scores before irreversible electroporation and at the 12-month mark. The mean age of the patients was 61.1 years (SD ±6.5). Out of the 18 patients, 16 were tumor free (88.8%), while 2 experienced recurrences, one within the treatment field and the other outside of it (P < .001). Irreversible electroporation significantly reduced mean prostate-specific antigen levels (6.73 ng/mL vs. 2.05 ng/mL, P < .001), indicating a 69.5% reduction within 12 months. Furthermore, there was a significant improvement in mean international prostate symptom scores at the 12-month followup (10.05 vs. 7.52, P=.003). The mean international index of erectile dysfunction scores before treatment was 19.17 (SD ±5.85), and after irreversible electroporation, it was 18.67 (SD ±6.34), with no statistically significant change (P=.065). The short-term oncological results of irreversible electroporation treatment are promising, particularly for patients in the low- and intermediate-risk groups. Additionally, irreversible electroporation does not negatively impact the international index of erectile dysfunction; however, it may lead to a decrease in international prostate symptom scores.

Effect of Near-Infrared Pre-Irradiation on Irreversible Electroporation Treatment of Rat Gastric Tissues

Irreversible electroporation (IRE) is a recognized ablation technique that induces apoptosis via potent electric fields. Nonetheless, the heterogeneity of biological tissues often results in inconsistent treatment outcomes, leaving residual viable cells and leading to potential relapse. To address this, previous strategies incorporated chemical enhancers to IRE, but these faced limitations such as limited tissue diffusion and hyperpigmentation. In this study, we explore the synergistic application of near-infrared (NIR) irradiation with IRE. Using an in vivo rat gastric tissue model, we pre-irradiated samples with NIR at 3 J/cm2 prior to IRE. The combined treatment, termed NIRE, produced a change in tissue impedance of 13.5 Ohm compared to IRE alone, indicating NIR’s potential in modulating tissue electrical properties. Subsequent histopathological and molecular assessments revealed a 1.12-fold increase in apoptosis for NIRE over IRE. Notably, the apoptosis-related proteins BCL and p21 exhibited a 1.24-fold and 1.29-fold overexpression following NIRE treatment, respectively, emphasizing NIRE’s enhanced apoptotic activation. In essence, our findings underscore the augmented therapeutic efficacy of IRE when complemented with NIR, presenting a promising avenue for bolstering treatment outcomes in tissue ablation.

The Effect of Partial Electrical Insulation of the Tip and Active Needle Length of Monopolar Irreversible Electroporation Electrodes on the Electric Field Line Pattern and Temperature Gradient to Improve Treatment Control.

Unintentional local temperature effects can occur during irreversible electroporation (IRE) treatment, especially near the electrodes, and most frequently near the tip. Partial electrical insulation of the IRE electrodes could possibly control these temperature effects. This study investigated and visualized the effect of partial electrical insulation applied to the IRE electrodes on the electric field line pattern and temperature gradient. Six designs of (partial) electrical insulation of the electrode tip and/or active needle length (ANL) of the original monopolar 19G IRE electrodes were investigated. A semolina in castor oil model was used to visualize the electric field line pattern in a high-voltage static electric field. An optical method to visualize a change in temperature gradient (color Schlieren) was used to image the temperature development in a polyacrylamide gel. Computational models were used to support the experimental findings. Around the electrode tip, the highest electric field line density and temperature gradient were present. The more insulation was applied to the electrodes, the higher the resistance. Tip and ANL insulation together reduced the active area of and around the electrodes, resulting in a visually enlarged area that showed a change in temperature gradient. Electrically insulating the electrode tip together with an adjustment in IRE parameter settings could potentially reduce the uncontrollable influence of the tip and may improve the predictability of the current pathway development.

Irreversible electroporation for prostate cancer using PSMA PET-CT.

To demonstrate the clinical usefulness of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computerized tomography (CT) for irreversible electroporation (IRE) in prostate cancer patients. From January to May 2021, 17 men were diagnosed with localized prostate cancer through preoperative mpMRI and [18F] florastamin PSMA PET-CT imaging, followed by transperineal MRI-ultrasound fusion-guided biopsy. The patients underwent IRE focal therapy at the target lesions under general anesthesia. To evaluate the treatment outcome, serum prostate-specific antigen (PSA) levels were followed up in the 1st, 3rd, 6th, 9th, 12th months, and mpMRI was taken in the 1st and 12th months, followed by MR fusion biopsy in the 12th month post-IRE. The mean age of the patients was 66.1±9.3 with a median PSA of 7.5ng/ml. After the treatment, PSA nadir was 4.06±3.4, and 11 (64.7%) achieved decline of PSA more than 50% from the baseline. Rate of negative biopsy for prostate cancer is 88% (15/17) at 12monthsMR fusion biopsy after the IRE treatment. Among the relapsed cases, 1 (6.9%) patient recurred at margin of treated area, and 1 (6.9%) patient was from outfield recurrence. When excluding initial four patients, none of the patients had cancer recur. When treating with IRE focal therapy, PSMA-PET CT is a potentially valuable diagnostic approach for localizing prostate cancer; it supports the detection of lesions with conventional mpMRI, enabling to perform the procedure more completely.

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.

Abstract No. 5 ▪ FEATURED ABSTRACT Adjuvant Macrophage Repolarization to M1 Phenotype Augments Post-Ablation Local Tumor Control and Improves Overall Survival in a Murine Model of Bladder Tumors

To investigate the impact of adjuvant macrophage repolarization to inflammatory M1 phenotype on local tumor control and overall survival following irreversible electroporation (IRE) of murine bladder tumors. Mouse bladder cancer cell line (MB49) was used to induce subcutaneous tumors in C57BL/6 (n = 8/group) or NOD-SCID (n = 10/group) mice. Animals were randomized to receive (i) IRE, (ii) supramolecular nanotherapeutic for M1 repolarization (SNT), (iii) IRE+SNT or (iv) sham control. Mice assigned to IRE treatment received electric pulses (875 or 1500V/cm for C57BL/6 mice and 875V/cm for NOD-SCID mice, 90 pulses, 100 us duration) with tweezer electrodes. SNT treatment was administered by intravenous injection (40 mg/kg, 1,3- and 5-days post treatment). Mice were sacrificed at Day 1 or 6 for flow cytometry following IRE or were kept under observation in a survival study. Flow cytometry for macrophage markers (M1: CD80, M2: CD206) and T Cell markers (CD8, CD4 and FoxP3) from tumor samples was performed. Tumor samples underwent immunohistochemistry for cell death, macrophages (F4/80) or T cell markers. Local tumor volume and overall survival were evaluated and compared between cohorts and mouse strains to understand cross-interactions with adaptive immunity. Ablation of subcutaneous tumor with IRE stimulated robust macrophage infiltration that uniformly exhibited an immunosuppressive M2 phenotype at Day 3 and 5. SNT effectively repolarized macrophages at the site of ablation to M1 phenotype, with corresponding change in gene expression of NOS2 and IL-6. There was significantly higher population of CD80+ cells and reduced CD206+ cells at Day 1. Adjuvant SNT did not alter CD4+ and CD8+ cells but greatly reduced FoxP3+ population in vivo. IRE+SNT treated mice had greater reduction in local tumor growth, reduced lung metastases and high overall survival. These findings were reduced in NOD-SCID mice, indicating contribution of adaptive immunity under conditions of M1 repolarization. Repolarization of macrophages attracted to the site of ablation to a M1 phenotype promotes local tumor control, reducing the development of metastatic disease and prolonging survival in a mouse model of bladder cancer.

Irreversible Electroporation in Pancreatic Cancer-An Evolving Experimental and Clinical Method.

Pancreatic cancer has no symptoms until the disease has advanced and is aggressive cancer with early metastasis. Up to now, the only curative treatment is surgical resection, which is possible in the early stages of the disease. Irreversible electroporation treatment offers new hope for patients with unresectable tumors. Irreversible electroporation (IRE) is a type of ablation therapy that has been explored as a potential treatment for pancreatic cancer. Ablation therapies involve the use of energy to destroy or damage cancer cells. IRE involves using high-voltage, low-energy electrical pulses to create resealing in the cell membrane, causing the cell to die. This review summarizes experiential and clinical findings in terms of the IRE applications. As was described, IRE can be a non-pharmacological approach (electroporation) or combined with anticancer drugs or standard treatment methods. The efficacy of irreversible electroporation (IRE) in eliminating pancreatic cancer cells has been demonstrated through both in vitro and in vivo studies, and it has been shown to induce an immune response. Nevertheless, further investigation is required to assess its effectiveness in human subjects and to comprehensively understand IRE's potential as a treatment option for pancreatic cancer.

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.

The Influence of Irreversible Electroporation Parameters on the Size of the Ablation Zone and Thermal Effects: A Systematic Review.

Introduction: The aim of this study was to review the effect of irreversible electroporation parameter settings on the size of the ablation zone and the occurrence of thermal effects. This insight would help to optimize treatment protocols and effectively ablate a tumor while controlling the occurrence of thermal effects. Methods: Various individual studies report the influence of variation in electroporation parameters on the ablation zone size or occurrence of thermal effects. However, no connections have yet been established between these studies. With the aim of closing the gap in the understanding of and personalizing irreversible electroporation parameter settings, a systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A quality assessment was performed using an in-house developed grading tool based on components of commonly used grading domains. Data on the electroporation parameters voltage, number of electrodes, inter-electrode distance, active needle length, pulse length/number/protocol/frequency, and pulse interval were extracted. Ablation zone size and temperature data were grouped per parameter. Spearman correlation and linear regression were used to define the correlation with outcome measures. Results: A total of 7661 articles were screened, of which 18 preclinical studies (animal and phantom studies) met the inclusion criteria. These studies were graded as moderate (4/18) and low (14/18) quality. Only the applied voltage appeared to be a significant linear predictor of ablation zone size: length, surface, and volume. The pulse number was moderately but nonlinearly correlated with the ablation zone length. Thermal effects were more likely to occur for higher voltages (≥2000 V), higher number of electrodes, and increased active needle length. Conclusion: Firm conclusions are limited since studies that investigated and precisely reported the influence of electroporation parameters on the ablation zone size and thermal effects were scarce and mostly graded low quality. High-quality studies are needed to improve the predictability of the combined effect of variation in parameter combinations and optimize irreversible electroporation treatment protocols.

Synergism between SUMO inhibition and irreversible electroporation for pancreatic cancer

Background: Irreversible electroporation (IRE) is being studied as a treatment option for patients with locally advanced pancreatic cancer (PC). Our laboratory has shown that combination of IRE with immunotherapy optimizes the local and distant effects of IRE treatment. Post-translational protein modification by small ubiquitin-like modifier (SUMO ) is upregulated in cancer and is important for the function of immune checkpoints. TAK-981 is a novel inhibitor of SUMO ylation that inhibits PC cell proliferation and also upregulates type I interferon responses, boosting anti-tumor immunity. We hypothesized that there would be synergistic effects of combining IRE with TAK-981 treatment.

Histological Response to 5 kHz Irreversible Electroporation in a Porcine Liver Model.

Unlike necrosis by thermal ablation, irreversible electroporation (IRE) is known to induce apoptosis by disrupting plasma membrane integrity with electric pulses while preserving the structure of blood vessels and bile ducts in liver tissue without a heat sink effect. This study aimed to investigate thermal damage and histopathological effects in the porcine liver by high-frequency electric pulses (5 kHz) which is much higher than the widely used 1 Hz. The electric field and thermal distributions of 5 kHz electric pulses were compared with those of 1 Hz in numerical simulations. 5 kHz-IRE was applied on pigs under ultrasound imaging to guide the electrode placement. The animals underwent computed tomography (CT) examination immediately and 1 day after IRE. After CT, IRE-treated tissues were taken and analyzed histologically. CT revealed that hepatic veins were intact for 1-day post-IRE. Histopathologically, the structure of the portal vein was intact, but endothelial cells were partially removed. In addition, the hepatic artery structure from which endothelial cells were removed were not damaged, while the bile duct structure and cholangiocytes were intact. The thermal injury was observed only in the vicinity of the electrodes as simulated in silico. 5 kHz-IRE generated high heat due to its short pulse interval, but the thermal damage was limited to the tissue around the electrodes. The histopathological damage caused by 5 kHz-IRE was close to that caused by 1 Hz-IRE. If a short-time treatment is required for reasons such as anesthesia, high-frequency IRE treatment is worth considering. Our observations will contribute to a better understanding of the IRE phenomena and search for advanced therapeutic conditions.

Enhanced Therapeutic Potential of Irreversible Electroporation under Combination with Gold-Doped Mesoporous Silica Nanoparticles against EMT-6 Breast Cancer Cells

Irreversible electroporation (IRE) is a non-thermal tumor ablation technique that delivers short pulses of strong electric fields to cancer tissues and induces cell death through the destruction of cell membranes. Here, we synthesized gold-doped mesoporous silica nanoparticles (Au-MSNs) via incipient wetness impregnation and evaluated the therapeutic potentials of combination therapy with IRE. The fabricated Au-MSNs had around 80-100 nm of particle size and were successfully end-doped with Au nanoparticles. Combination treatment of IRE (800 V/cm) and Au-MSNs (100 μg/mL) increased cell membrane permeability by 25-fold compared with single IRE treatment. Cellular reactive oxygen species (ROS) and lipid peroxidation of EMT-6 cells were significantly increased by 14- and 265-fold, respectively, under combination treatment of IRE (800 V/cm) and Au-MSNs (100 µg/mL). Cytotoxic cell death increased by 28% under a combination treatment of IRE (800 V/cm) and Au-MSNs (100 ug/mL) over single IRE. Our studies suggest that the combination treatment of IRE with Au-MSNs can enhance the therapeutic efficacy of IRE for breast cancer.

Comparison of the efficacy of irreversible electroporation and conversional resection for locally advanced pancreatic cancer

Objective: To compare the short-term and long-term prognosis of irreversible electroporation(IRE) and conversional resection for locally advanced pancreatic cancer(LAPC). Methods: The clinical and pathological data of 98 LAPC patients who underwent IRE or conversional resection at the Department of Pancreatobiliary Surgery,Sun Yat-sen University Cancer Center from August 2015 to December 2020 were retrospectively collected and analyzed.The study comprised of 53 males and 45 females, with age(M(IQR)) of 57.5(13.5)years old(range:20 to 87 years old). Fifty-three patients received IRE treatment(IRE group) and 45 patients received surgical resection(resection group). The differences of clinical and pathological data between both groups were not significant(all P<0.05). The Mann-Whitney U test was used for quantitative data and the χ2 test was used for categorical data.Survival was analyzed using Kaplan-Meier method and compared using Log-rank test. Results: The operation time and intraoperative blood loss were 5.0(2.4)hours and 50(100) ml in the IRE group,respectively,which were significantly less than those of resection group(7.0(3.3)hours and 400(200)ml,both P<0.05).The hospital stay and hospitalization cost were 9.0(3.0)days and 79 154 (83 738) yuan in the IRE group,respectively,which were also significantly less than those in the resection group(16.0(8.5)days and 109 557(37 795)yuan,both P<0.05).The complication rate of IRE group was significantly lower than that of the resection group(18.8% vs. 55.6%,χ2=14.270,P<0.01).The median overall survival(OS) time of IRE group was 28.9 months(95%CI:23.2 to 34.6 months),with the 1-,2-,and 3-year OS rates of 91.6%,61.7%,and 24.6%,respectively.The median survival of OS of resection group was 27.1 months(95%CI:20.9 to 33.3 months),with the 1-,2-,and 3-year OS rates of 81.8%,53.9%,and 30.3%,respectively.There was no significant difference in OS between the two groups(χ2=0.900,P=0.760).The median progression free survival(PFS) time of IRE group was 18.0 months(95%CI:14.7 to 21.3 months),with the 1-,2-,and 3-year PFS rates of 68.3%,29.7%,and 9.9%,respectively.The median survival of PFS of resection group was 11.1 months(95%CI:6.1 to 16.2 months),with the 1-,2-,and 3-year PFS rates of 45.2%,21.9%,and 14.6%,respectively.There was no significant difference in PFS between the two groups(χ2=1.850,P=0.170). Conclusion: IRE can achieve similar survival for LAPC and may has less complications compared to those with conversion resection.

Real-Time Temperature Rise Estimation during Irreversible Electroporation Treatment through State-Space Modeling

To evaluate the feasibility of real-time temperature monitoring during an electroporation-based therapy procedure, a data-driven state-space model was developed. Agar phantoms mimicking low conductivity (LC) and high conductivity (HC) tissues were tested under the influences of high (HV) and low (LV) applied voltages. Real-time changes in impedance, measured by Fourier Analysis SpecTroscopy (FAST) along with the known tissue conductivity and applied voltages, were used to train the model. A theoretical finite element model was used for external validation of the model, producing model fits of 95.8, 88.4, 90.7, and 93.7% at 4 mm and 93.2, 58.9, 90.0, and 90.1% at 10 mm for the HV-HC, LV-LC, HV-LC, and LV-HC groups, respectively. The proposed model suggests that real-time temperature monitoring may be achieved with good accuracy through the use of real-time impedance monitoring.

Early Single-Center Experience With Irreversible Electroporation for Stage 2, 3, and 4 Pancreatic Adenocarcinomas.

Irreversible electroporation (IRE) is an ablation technology that uses electrical energy delivered between electrodes. If the electrodes are placed atraumatically, there is little to no risk of collateral injury, making IRE appealing for the treatment of pancreatic tumors. We report on 20 patients with pancreatic adenocarcinoma (PAC) who underwent 21 IRE in our center. There were 6 IRE for stage 2 PAC, 11 for stage 3 PAC, 1 for stage 4 PAC, and 2 patients treated with IRE for recurrence after pancreaticoduodenectomy. One patient had local progression 18 months after IRE and received a second IRE treatment. Using propensity score matching (age, sex, stage, tumor size, and chemotherapy), cases were matched 2 to 1 with patients from the Surveillance, Epidemiology, and End Results database. A total of 7 cases experienced 8 complications; 4 complications were mild, and 4 were severe. Significant survival benefit was seen for patients with stage 3 PAC (27.5 vs 14.6 months for the matched group, P = 0.003); for stage 2, median survival was 15 months, and the single stage 4 patient survived 9 months after IRE treatment. Pancreatic cancers were safely and effectively treated with image-guided IRE in our medium-sized center.

Polymer Nanoparticles Enhance Irreversible Electroporation In Vitro

Expanding the volume of an irreversible electroporation treatment typically necessitates an increase in pulse voltage, number, duration, or repetition. This study investigates the addition of polyethylenimine nanoparticles (PEI-NP) to pulsed electric field treatments, determining their combined effect on ablation size and voltages. U118 cells in an in vitro 3D cell culture model were treated with one of three pulse parameters (with and without PEI-NPs) which are representative of irreversible electroporation (IRE), high frequency irreversible electroporation (H-FIRE), or nanosecond pulsed electric fields (nsPEF). The size of the ablations were compared and mapped onto an electric field model to describe the electric field required to induce cell death. Analysis was conducted to determine the role of PEI-NPs in altering media conductivity, the potential for PEI-NP degradation following pulsed electric field treatment, and PEI-NP uptake. Results show there was a statistically significant increase in ablation diameter for IRE and H-FIRE pulses with PEI-NPs. There was no increase in ablation size for nsPEF with PEI-NPs. This all occurs with no change in cell media conductivity, no observable degradation of PEI-NPs, and moderate particle uptake. These results demonstrate the synergy of a combined cationic polymer nanoparticle and pulsed electric field treatment for the ablation of cancer cells. These results set the foundation for polymer nanoparticles engineered specifically for irreversible electroporation.