Atrial fibrillation (AF) management has historically relied on thermal ablation modalities—radiofrequency (RF) and cryoballoon—which have established a high benchmark for pulmonary vein isolation (PVI). However, the inherent risk of collateral thermal injury and lesion inconsistency has driven the search for alternative energy sources. The recent clinical adoption of pulsed-field ablation (PFA), based on irreversible electroporation, represents a significant technological evolution. This narrative review provides a critical appraisal of the transition from thermal to pulsed-field technologies. We synthesized data from pivotal trials and recent health-economic analyses to evaluate the biophysical mechanisms, clinical efficacy, and safety profiles of contemporary devices. We conduct a head-to-head comparison of all modalities regarding critical safety endpoints (esophageal, neurological, and vascular), real-world procedural challenges (anesthesia, lesion assessment), and economic sustainability. While PFA offers distinct advantages in procedural speed and tissue selectivity, we highlight that thermal modalities—particularly cryoballoon and very-high-power RF—retain competitive profiles in terms of cost-effectiveness and established long-term durability. This review aims to provide a balanced roadmap for clinicians navigating the complex choice between established thermal efficacy and the promising, yet evolving, landscape of electroporation.

The role of focal therapy for localized prostate cancer: From diagnosis to ablation.

Cancer vaccines face limitations due to the immunosuppressive tumor microenvironment (TME) and the low immunogenicity of tumor antigens. Immunogenic cell death (ICD), triggered by mitochondrial dysfunction, provides a promising strategy to enhance tumor antigen release and immune activation. However, actively amplifying mitochondrial damage-induced ICD remains challenging. In this study, we developed a vaccine in which liquid metal nanoparticles (LMPs) target tumor cells, undergo self-assembly and aggregation on the cell surface to achieve efficient uptake, fuse intracellularly to prolong retention, and release Ga3+ ions through an iron-substitution pathway to induce mitochondrial damage, thereby triggering ICD. In combination with irreversible electroporation (IRE), this approach mediates durable tumor-specific immunotherapy. Specifically, LMPs target tumor cell integrin αvβ6 to initiate self-assembly and aggregation, leading to efficient cellular internalization. Within the acidic lysosomal environment, LMPs undergo fusion and partially escape into the cytosol, enabling prolonged intracellular retention and sustained release of Ga3+ ions. The released Ga3+ disrupts mitochondrial structure and inhibits electron transport via iron substitution, resulting in pronounced mitochondrial damage. Synergistic IRE and LMPs increase the liberation of mitochondrial damage-associated DAMPs and tumor antigens, driving robust ICD and long-term systemic antitumor immunity. This dual-modality strategy provides a blueprint for nanomaterial-enabled amplification of ICD in cancer immunotherapy.

Nanosecond pulsed electric field (nsPEF) ablation has gradually been applied in clinical practice. However, no studies have reported its application in low-risk papillary thyroid microcarcinoma (PTMC). The study aimed to evaluate the efficacy and safety of nsPEF ablation for patients with low-risk PTMC. This prospective study (Chinese Clinical Trial Register: ChiCTR-2200064902) included consecutive low-risk PTMC patients who underwent nsPEF ablation at six hospitals in China. Technical feasibility was assessed by recording the technical success of the procedure and therapeutic efficacy at the 1-, 3-, 6-, and 12-month follow-up. Technical success was evaluated using contrast-enhanced ultrasound (CEUS) immediately after ablation, where the target ablation zone exceeded the tumor edge. Therapeutic complications were evaluated. From September 2022 to September 2024, 85 patients (median age, 38 years; IQR, 32-47 years; 58 females) with 85 PTMCs were included, all achieving successful nsPEF ablation. At 1-, 3-, 6-, and 12-month follow-up, median tumor volumes were 0.109, 0.054, 0.020, and 0.000 mL, and the associated median volume reduction ratios were -124.0%, -4.8%, 63.5%, and 100%, respectively. At 12 months, 88.0% (66/75) of PTMCs achieved complete disappearance. 56 (65.9%) patients experienced transient thyrotoxicosis. No recurrent tumors, cervical lymph node metastasis, or distant metastasis were observed during follow-up. nsPEF ablation under general anesthesia for low-risk PTMC is effective and safe, with the only major complication of transient thyrotoxicosis in more than 50% of patients, which might be caused by the release of thyroid hormones into the bloodstream due to irreversible electroporation. It appears to offer better absorption of the ablated lesions in the short term, potentially increasing its clinical use. Further short- and long-term study is needed.

Irreversible Electroporation for Prostate Tissue Ablation in Patients with Intermediate-risk Prostate Cancer: Results from the PRESERVE Trial.

Hilar cholangiocarcinoma (HCCA) is a rare, aggressive cancer often diagnosed at an unresectable stage. Patients commonly require systemic therapy and biliary stenting to manage symptoms and maintain liver function. Histotripsy is a novel, non-invasive, mechanical ablation technique recently FDA-approved for liver tumors. We report the case of a 77-year-old woman with recurrent HCCA who experienced progressive biliary obstruction despite chemotherapy and irreversible electroporation. She underwent 2 staged histotripsy treatments targeting tumors in the left and right biliary systems. Procedures were well-tolerated, with no complications, and led to normalization of bilirubin within 72 hours. Imaging at 6 months showed stable disease and sustained biliary patency, with only 1 stent exchange needed. This case highlights the potential role of histotripsy in relieving biliary obstruction and controlling local disease in patients with HCCA.

The objective of our study is to present our experience in Irreversible Electroporation (IRE) in the treatment of unresectable pancreas cancer in elderly patients.

Abstract Introduction Neuroendocrine tumours (NETs) of the small bowel are often indolent but typically present late with metastatic disease. Management becomes particularly complex in the presence of bilobar liver metastases and carcinoid heart disease. A multidisciplinary, multimodal approach is essential to achieve disease control and optimise patient outcomes in such challenging scenarios. Case Presentation A 58-year-old male was incidentally diagnosed with a DOTATATE-avid jejunal NET and extensive bilobar liver metastases during workup for elevated PSA. Further complexity was added by carcinoid heart disease requiring tricuspid valve replacement. Initial management involved bland embolisation of a dominant segment IVb/V liver lesion. This was followed by debulking surgery with non-anatomical resection of liver segments IVb, V, and VI, and cholecystectomy. Histology confirmed well-differentiated G1 NET with Ki-67 <2%. Residual left-lobe liver disease was treated with image-guided Irreversible Electroporation (IRE). Final surgical intervention included complete resection of the jejunal primary, mesenteric nodal clearance, and redo non-anatomical resection of liver segments VII and VIII. Discussion The case illustrates the value of a sequential, MDT-guided treatment strategy incorporating embolisation, surgical resection, and ablative therapies to manage extensive metastatic NET while addressing associated systemic disease. Conclusions The patient recovered well after surgery. Follow-up imaging shows no evidence of recurrence. Complete resection of the primary tumour has been achieved, and the case is currently pending further review at the specialist NET MDT.

This narrative review synthesizes current scientific evidence regarding oncological efficacy, functional outcomes, and safety profile of three leading focal therapy (FT) methods in the treatment of localized prostate cancer: high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and cryoablation. The analysis is based on 28 clinical studies published between 2022–2025, including prospective cohort studies, multicenter international trials, and meta-analyses. The results indicate that all analyzed ablative techniques offer acceptable oncological control while maintaining high patient quality of life. HIFU therapy provides the most established evidence, with a median biochemical recurrence-free survival (BCR-free survival) of 63 months and a low rate of clinically significant prostate cancer (csPCa) detection in control biopsy (6.5%). Oncological outcomes for IRE are more varied, with a csPCa detection rate of 24.1% in a multicenter study, suggesting strong dependence of efficacy on the extent of ablation (hemi-ablation vs. focal ablation). Cryoablation presents promising early oncological data, with 78.6% of patients free from csPCa at 12 months, but is associated with higher risk of erectile function impairment. Functionally, FT demonstrates clear superiority over radical treatment, with urinary incontinence rates at ~2% and significantly better preservation of potency. Key success factors for focal therapy include rigorous patient qualification based on advanced imaging techniques and precise procedure planning. Focal therapy represents a real and valuable therapeutic option for carefully selected groups of men with prostate cancer, offering a compromise between oncological radicality and preservation of vital functions.

Pulsed field ablation (PFA) represents one of the most significant technological advances in atrial fibrillation (AF) therapy in recent decades. By harnessing irreversible electroporation, PFA produces myocardial lesions within milliseconds, enabling rapid and efficient pulmonary vein (PV) isolation. Early clinical experience from pivotal investigational device exemption (IDE) trials has shown acute and one-year arrhythmia-free outcomes that are non-inferior to conventional radiofrequency (RF) and cryothermal ablation. The large MANIFEST-17 K registry, encompassing over 17 000 patients treated with the Farawave system, reported an exceptionally low 0.98% major complication rate with no atrio-oesophageal fistula, phrenic nerve injury, or PV stenosis. These findings have accelerated PFA adoption across many centres. However, as experience broadens, nuances in lesion formation and durability are becoming evident. Factors such as contact force, catheter rotation, pulse train configuration, and target tissue geometry influence lesion depth and transmurality. While PV isolation appears consistently durable, data remain limited for non-PV targets such as the posterior wall, mitral isthmus, and cavotricuspid isthmus. Moreover, novel PFA-specific complications including transient left atrial dysfunction, haemolysis, and coronary artery spasm warrant ongoing vigilance. PFA has undoubtedly transformed expectations for procedural safety and efficiency. Yet whether it should already be considered the standard technique for all AF ablation candidates remains an open question. This Controversy piece explores the balance between innovation and evidence, examining whether PFA's rapid rise represents the inevitable new standard or a technology still undergoing critical refinement.

Abstract Irreversible electroporation (IRE) is a focal ablative cancer therapy that destroys cells through membrane destabilization via pulsed electric fields. It also has the capacity to induce a systemic, anti‐tumor immune response, thus acting as an in situ vaccine. Although many studies characterize the immunogenicity of focal therapies by their released biochemical constituents, here we show that the biophysical context of the presentation of these immunogenic signals is vital to understanding downstream immune functions. Compared to thermal ablation or cryoablation, IRE generates similar numbers of exosome‐like particles (ELP, 50–200 nm) but significantly greater numbers of microparticles (MP, 200–1000 nm) and large debris particles (LDP, 2–6 μm) in both melanoma and pancreatic cancer cell lines. We show that LDPs contain antigen and tumor‐associated DNA, which dendritic cells (DCs) internalize in greater proportions from IRE‐treated cells compared to other treatments. For the submicron particles, we demonstrate both in vitro and in vivo that MPs induce greater T‐cell proliferation and differentiation compared to ELPs on a per‐particle basis. This novel biophysical analysis of the immunogenicity of IRE‐treated cancer cells opens a new avenue toward improving the systemic immune response to focal ablation‐based cancer immunotherapies via increasing cell fragmentation and particle generation.

Numerical evaluation of irreversible electroporation (IRE) holds significant potential to assist practitioners in planning and guiding these complex procedures. We aimed to establish a correlation between the results of retrospective numerical simulations of IRE and clinical outcomes in the treatment of hepatocellular carcinoma (HCC). IRE procedures conducted at our center for HCCs < 5 cm were reconstructed. Per-procedural imaging was used to generate a 3D geometric model of the tumor and its surroundings. The spatial coordinates of electrodes and treatment parameters were used to retrospectively simulate the EF using the static linear model. The proportion of tumor volume encompassed by 3D mappings of different EF magnitudes was correlated with clinical efficacy using a logistic regression algorithm. 31 IRE procedures were included. HCCs had a median diameter of 20 mm (range: 7-45 mm). At 1 month, 29/31 tumors (93.5%) showed complete ablation, but 10 of these recurred later (median delay: 7 months). The percentages of tumor coverage by EF isolines were significantly lower in the 12 cases of local IRE failure compared to the 19 cases of IRE success: 97.7% vs. 100% at 300 V/cm (p < 0.001); 89.7% vs. 100% at 400 V/cm (p < 0.001) and 82.8% vs. 95.4% at 500 V/cm (p < 0.01) with 400 V/cm being the most discriminative threshold dose (ROC-AUC: 0.904). Tumor coverage < 95% by the 400 V/cm isoline was associated with IRE failure (2-year incidence: 89% vs. 21.7%, p < 0.0001). Numerical simulations of IRE correlate with local treatment outcomes. This study suggests that, in HCC, inadequate tumor coverage by the 400 V/cm isoline predicts and localizes recurrence. Question Can the clinical outcomes of irreversible electroporation for hepatocellular carcinoma be predicted using numerical simulation of the electric field (EF) distribution? Findings Inadequate tumor coverage by simulated EF maps predicts and localizes recurrence, with 400 V/cm being the most discriminative isodose threshold (ROC-AUC > 0.9). Clinical relevance Numerical simulations of the electric field correlate with local treatment outcomes of irreversible electroporation for hepatocellular carcinoma within a computational framework compatible with clinical use. Real-time identification of insufficient tumor coverage can enable operators to adapt and optimize treatment delivery.

Pulsed field ablation (PFA) is a cutting-edge treatment for arrhythmias that targets cardiac tissue with rapid, high-voltage electric current pulses, resulting in irreversible electroporation. Freed from the constraints of traditional radiofrequency (RF) ablation, the non-thermal mechanism and myocardial selectivity of PFA has improved procedural safety aspects and efficiency over RF ablation. However, catheter development thus far has focused on waveforms and voltage, such that critical aspects related to the physics of energy delivery at the tissue-blood interface were often overlooked. When delivering high-voltage pulsed electric fields, differences in electrical impedance, catheter geometry, and field strength impact the resulting precision and durability of lesions; principles that warrant a deeper understanding to inform and optimize future catheter designs. This article examines the engineering considerations behind the success of the first industrial iterations of PFA, with a comparison of catheter form factors for current systems that impact energy delivery, workflow, safety, and performance. We also address the initial assumptions and misconceptions related to PFA design and the development of current generation catheters as considerations for the future of ablation and mapping.

The Canady Helios Cold Plasma (CHCP) system is a non-thermal, non-contact cold atmospheric plasma technology that generates transient electric fields and reactive species capable of disrupting cancer cell membranes. This study investigated the voltage-dependent membrane irreversible electroporation (IRE) dynamics induced by CHCP across biologically distinct breast cancer subtypes. Four breast cancer cell lines, triple-negative (MDA-MB-231 and Hs578T), ER+/PR+/HER2- (MCF-7), and ER+/PR+/HER2+ (BT-474), were exposed to CHCP for 5 min at 25 V (~1675 V/cm PTEF) or 30 V (~2010 V/cm), either directly or with Plasma Activated Media (PAM). Membrane permeability was assessed by propidium iodide (PI) uptake over 120 min. Morphological changes were evaluated microscopically. Functional electroporation was examined via BCL2A1-targeting siRNA delivery and clonogenic survival. Ex vivo analyses of Phase I clinical trial tumor specimens (NCT04267575) were performed to characterize CHCP-induced tissue responses. CHCP produced voltage- and time-dependent membrane permeabilization in all breast cancer cell lines, with 30 V generating robust and sustained PI uptake compared to transient effects at 25 V. Treated cells exhibited morphological features consistent with membrane disruption. CHCP enabled intracellular siRNA delivery and significantly reduced clonogenic potential, confirming functional pore formation. Ex vivo CHCP treatment selectively damaged tumor cells while sparing adjacent non-cancerous tissue. This study demonstrates CHCP as a non-thermal (24 °C), non-contact plasma-based IRE platform which induces controlled membrane permeabilization and selective cancer cell death. CHCP offers a translational strategy to eradicate residual tumor cells at the surgical margins, and prevent local recurrence, positioning it as a versatile adjunct in precision surgical oncology.

Irreversible electroporation with intratumoral plant virus immunotherapy induces systemic immunity in a metastatic model of pancreatic cancer.

FocalONE high-intensity focused ultrasound for localized prostate cancer: A systematic review of oncologic outcomes, functional preservation, and technological evolution.

BackgroundElectroporation-based therapies are being explored in glioblastoma (GB) treatment, as means of enhancing drug delivery or achieving nonthermal ablation. Yet, little is known about how sublethal exposure affects the invasive behaviour of GB tumour cells.Materials and methodsFive patient-derived GB cell lines were initially screened for intrinsic invasive potential, and two most invasive (NIB140 CORE and NIB216 CORE) were selected for further experiments with electroporation treatment. Cells in suspension were exposed to bursts of high-frequency biphasic electric pulses resulting in electric field strength of 1 kV/cm, which corresponded to conditions of reversible electroporation. Changes in cell invasion and gene regulation were assessed 24 hours after electroporation using transwell assay and RNA transcriptome analysis, respectively.ResultsReversible electroporation at 1.0 kV/cm enhanced invasion in a cell line-dependent manner. NIB140 CORE showed a consistent and pronounced increase, with a median of 3.74-fold (274%) higher number of invading cells compared to sham control. In contrast, NIB216 CORE exhibited only a modest increase in invasion (1.30-fold; 30%). Transcriptomic profiling identified modulation of genes linked to extracellular matrix organization and ion channel activity in NIB140 CORE, and cytoskeletal remodelling in NIB216 CORE, indicating the activation of invasion-related pathways.ConclusionsThese findings highlight a potential risk of pro-invasive responses in GB cells. In tumour ablation with irreversible electroporation, this concern relates to cells in the peripheral zone that may experience only sublethal electric fields, while in electrochemotherapy, a similar risk may arise if permeabilized cells are not effectively eliminated due to insufficient local drug delivery. Nevertheless, the two tested cell lines responded differently, underscoring patient-specific heterogeneity and the need for validation in more physiologically relevant models.

Irreversible Electroporation and Whipple Procedure in the Management of Pancreatic Tumors: A Descriptive Study in a Tertiary Referral Center

ABSTRACTMulti‐Resistant Bacteria (MRB) is a threatening biomedical problem, whose solution is of paramount importance. Due to the antibiotics resistance there is an emerging need for novel treatment strategies and protocolls. As bacteria tolerance in modern chemotherapeytic agents expands, the introduction of alternative methods is fundamental. The use of High voltage Electric Pulses, through a process known as Irreversible Electroporation (IRE), is an effective alternative bacterial control method. This paper describes a new prototype high voltage nanosecond pulser and validates its effectiveness in the in‐vitro growth inhibition of a clinical resistant Staphylococcus aureus strain. Radiofrequency (RF) pulses of 100 ns and 450 ns pulse width and 1 Hz and 1 kHz repetition rate respectively were tested for therapy time in the range of 20–200 s. Increasing the electric field strength up to 11.5 kV/cm and the duration of therapy time up to 200 s results in 3.5 log scale reduction in bacterial cells. Nanosecond electric pulsed fields from our prototype device inhibite S. aureus growth in in‐vitro test. It is sugested to test our prototype device in ex‐vivo studies and propose a therapeutic protocol for infected skin wounds.

Mitigating muscle contractions during pulsed field ablation by utilizing intersegment delays.