Electroporation, a physical method that permeabilizes cell membranes, is increasingly used in cancer treatment. By enhancing the uptake of hydrophilic antitumor drugs, it boosts their cytotoxic effects and has proven effective in both human and veterinary medicine through electrochemotherapy. However, this treatment requires loco-regional or even general anesthesia, as electrical pulses cause muscle contractions and pain. Several clinical studies have demonstrated that application of high frequency pulses (above 5000 Hz) and short pulse duration (under 11 μs) causes much less discomfort to patients. In order to reduce the pain associated with contractions while maintaining the effectiveness of the treatment, we have developed new protocols using a high-frequency generator that delivers electric field pulses at a pulse repetition rate up to 2 MHz, associated to a multipolar electrode. In vitro tests on colorectal cancer cells were performed to assess the efficiency of cisplatin and bleomycin in inducing cell death. The efficiency obtained after one single treatment on both cell suspensions and on 3D multicellular spheroid models were similar to the ones obtained using ESOPE (European standard operating procedures for electrochemotherapy) protocol, which is currently used in clinics. In addition, as tumor cells die in an immunogenic cell death (ICD) mode and can release danger associated molecular patterns (DAMPs), major hallmarks of ICD were evaluated following the treatment by quantifying the apoptotic cell death, caspases 3/7 activation and key DAMPs. Subsequently, pilot studies on small number of conscious cats and horses under mild sedation confirmed that these protocols did not cause any noticeable muscle contractions and resulted in either partial or complete responses. New high-frequency electroporation protocols, described herein, show great promise in shifting electrochemotherapy into an effective and painless cancer treatment.

The therapeutic efficacy of irreversible electroporation (IRE) for treating subcapsular hepatocellular carcinoma (HCC) remains under-explored. The current study aimed to compare IRE and radiofrequency ablation (RFA) outcomes in an HCC patient group.

In this retrospective cohort study, we analyzed 213 patients with subcapsular HCC who met the Milan criteria and underwent either IRE (n = 80) or RFA (n = 133). We assessed local tumor progression (LTP), recurrence-free survival (RFS), overall survival (OS), and complications rates, using inverse probability of treatment weighting (IPTW).

After a median follow-up of 22 months, patients in the IRE group showed significantly lower LTP rates (1-year: 6.2% [95% CI: 2.1-14.0%], 2-year: 8.8% [95% CI: 3.6-17.2%] vs. RFA 18.0% [95% CI: 11.9-25.6%], 21.1% [95% CI: 14.5-29.0%]; P = 0.008) and higher RFS rates (1-year: 75.0% [95% CI: 64.1-84.0%], 2-year: 67.5% [95% CI: 56.1-77.6%] vs. RFA 60.9% [95% CI: 52.1-69.2%], 51.9% [95% CI: 43.1-60.6%]; P = 0.003). However, 2-year OS remained comparable across groups (IRE 100% [95.5-100%] vs. RFA 99.1% [95.9-100%]; P = 0.990). IPTW-adjusted analyses confirmed these findings. We determined that treatment modality was an independent influencing factor for LTP (RFA vs. IRE HR [95% CI]: 2.46 [1.05, 5.74], P = 0.037) and RFS (RFA vs. IRE HR [95% CI]: 1.62 [1.01, 2.61], P = 0.046). However, the complication rate (6.3% vs. 9.8%) and median hospital stay (3 vs. 3 days) were similar across groups (both P > 0.05).

For patients with subcapsular HCC meeting the Milan criteria, IRE demonstrated significantly improved LTP and RFS compared to RFA. These results may suggest that IRE is a viable therapeutic alternative for this tumor subtype.

This study aimed to assess the effectiveness and safety of conventional transarterial chemoembolization (c-TACE) followed by irreversible electroporation (IRE) for the treatment of hepatocellular carcinoma (HCC).

From January 2019 to September 2019, 12 patients with HCC who received c-TACE followed by IRE comprised the study group. The control group comprised 15 patients who received c-TACE followed by radiofrequency ablation (RFA). The 1-month, 3-month, 6-month, and 12-month local control rates and median progression-free survival (PFS) were compared between the two groups. Additionally, postoperative complications were assessed.

The study group comprised 12 patients (median age: 57.5 years; range: 46-68 years), while the control group consisted of 15 patients (median age: 56 years; range: 31-69 years). Local control rates at 1, 3, 6, and 12 months were 91.7%, 91.7%, 83.3%, and 33.3%, respectively, for the study group, and 73.3%, 66.7%, 66.7%, and 20.0% for the control group. Statistical analysis revealed no significant differences between the two groups. In terms of survival, 9 patients (75%) in the study group and 11 patients (73.3%) in the control group were still alive at the last follow-up. The median PFS was 8 months in the study group and 7 months in the control group, with no significant difference between the two groups (p = 0.96). Notably, no severe surgery-related side effects were observed in either group, and also no significant differences were found in postoperative complications between the two groups (p = 0.64).

The long-term therapeutic outcomes of c-TACE followed by IRE were found to be similar to those of c-TACE followed by RFA in the study. The research suggests that c-TACE followed by IRE offered an effective and safe treatment option for HCC.

Irreversible electroporation (IRE) is a minimally thermal tissue ablation modality used to treat solid tumors adjacent to critical structures. Widespread clinical adoption of IRE has been limited due to complicated anesthetic management requirements and technical demands associated with placing multiple needle electrodes in anatomically challenging environments. High-frequency irreversible electroporation (H-FIRE) delivered using a novel single-insertion bipolar probe system could potentially overcome these limitations, but ablation volumes have remained small using this approach. While H-FIRE is minimally thermal in mode of action, high voltages or multiple pulse trains can lead to unwanted Joule heating. In this work, we improve the H-FIRE waveform design to increase the safe operating voltage using a single-insertion bipolar probe before electrical arcing occurs. By uniformly increasing interphase () and interpulse () delays, we achieved higher maximum operating voltages for all pulse lengths. Additionally, increasing pulse length led to higher operating voltages up to a certain delay length (25 μs), after which shorter pulses enabled higher voltages. We then delivered novel H-FIRE waveforms via an actively cooled single-insertion bipolar probe in swine liver in vivo to determine the upper limits to ablation volume possible using a single-needle H-FIRE device. Ablations up to 4.62 0.12 cm x 1.83 0.05 cm were generated in 5 minutes without a requirement for cardiac synchronization during treatment. Ablations were minimally thermal, easily visualized with ultrasound, and stimulated an immune response 24 hours post H-FIRE delivery. These data suggest H-FIRE can rapidly produce clinically relevant, minimally thermal ablations with a more user-friendly electrode design.

Background and Objectives: To report on the first results of safety, efficacy, and outcome of CT-navigated stereotactic percutaneous electrochemotherapy (SpECT) in patients with primary and secondary liver malignancies. Methods: This retrospective study included 23 consecutive lesions in 22 patients who underwent SpECT for primary and secondary malignant liver lesions with locally curative intention. The endpoints were primary technique efficacy (PTE), local tumor progression (LTP), time to progression (TTP), and occurrence of adverse events. Results: The mean maximum diameter of the treated lesions was 42 mm (range: 16 mm-72 mm). Eight lesions were hepatocellular carcinoma (34.8%), five lesions were colorectal liver metastases (21.7%), three lesions were cholangiocellular carcinoma (13.0%), and the other seven lesions were liver metastases from different primary cancers (30.4%). PTE was achieved for 22 lesions (95.7%). The mean follow-up time was 15 months (0-39 months). No LTP was observed. In six patients (27.3%), hepatic tumor progression was observed during follow-up with a mean TTP of 3.8 months (2-8 months). In 10 procedures (43.5%), minor complications (1 CIRSE Grade 2) and side effects occurred, but no major complications were observed. Conclusions: SpECT seems to be a safe and effective new local treatment modality for primary and secondary liver malignancies.

Irreversible electroporation has been proved as a feasible and safe method against tumor in liver. However, few studies focused on tumors adjacent to perihepatic important structure like vessels, biliary system and gall bladder. These structures limit the effectiveness of conventional treatments. The aim of this article is to analyze the clinical outcomes of patients with hepatic tumors at the special sites who received IRE treatment and provide reliable evidence for broadening the scope of IRE's clinical application.

The clinical information of patients who underwent IRE ablation for tumors adjacent to perihepatic important structure between February 2017 and December 2021 was collected and retrospectively analyzed. All patients underwent contrast-enhanced CT or MRI for further evaluation at the 1-month follow-up and every 3 months thereafter. Post-ablation complications, recurrence, progression-free survival and overall survival were evaluated to analyze the prognosis of IRE ablation adjacent to perihepatic important structure. Categorical variables are presented as numbers followed by percentages. Continuous data are presented as the mean ± deviation. The tumor size and IRE ablation size were evaluated by the maximum diameters.

Thirty-two patients who underwent IRE ablation for tumor adjacent to perihepatic important structure were studied in this research. There were 39 lesions in 32 patients treated with IRE ablation. Fourteen of them (35.9%) were located adjacent to the porta hepatis, and 8 of them (20.5%) were located adjacent to the hepatocaval confluence. Subcapsular lesions accounted for 15.4% (6 of 39 lesions). The other 11 lesions were in the para gallbladder (5 of 39 lesions, 12.8%), the caudate lobe (5 of 39 lesions, 12.8%) and the colonic hepatic flexure (1 of 39 lesions, 2.6%). According to the Clavien-Dindo classification system for complications, all relative patients with cancer experienced complications below class III except one patient who developed postoperative hemorrhagic shock and improved after timely treatment. Recurrence in situ was observed in 5 of 32 (15.6%) patients. The median PFS of the patients who received IRE ablation was 384 days, and the median OS was 571 days.

IRE ablation is a feasible and safe treatment strategy for tumors adjacent to perihepatic important structure. With improved equipment, optimized therapeutic parameters and long-term clinical trials, IRE will play an increasingly important role in the treatment of tumors in liver.

A nationwide multicenter study was performed to examine whether there is a correlation between decrease in tissue resistance and time to local tumor recurrence after irreversible electroporation (IRE) in patients with hepatocellular carcinoma (HCC) and colorectal cancer liver metastases (CRCLM).

All patients treated with IRE for liver tumors in Sweden from 2011 until 2018 were included. Patient characteristics and recurrence patterns were obtained from medical records and radiological imaging. All procedural data from the IRE hardware at the three hospitals performing IRE were retrieved. The resistance during each pulse and the change during each treatment were calculated. The electrode pair with the smallest decrease in tissue resistance was used and compared with the time to LTP.

149 patients with 206 tumors were treated. Exclusion due to missing and inaccurate data resulted in 124 patients with 170 tumors for the analyses. In a multivariable Cox regression model, a smaller decrease in tissue resistance and larger tumor size were associated with shorter time to local tumor recurrence for CRCLM, but not for HCC.

There was an association between a decrease in tissue resistance and time to local tumor recurrence for CRCLM. The decrease in resistance, in combination with a rise in current, may be the parameters the interventionist should use during IRE to decide if the treatment is successful.

Exposing cells to intense and brief electric field pulses can modulate cell permeability, a phenomenon termed electroporation. When applied in medical treatments of diseases like cancer and cardiac arrhythmias, depending on level of cellular destruction, it is also referred to as irreversible electroporation (IRE) or Pulsed Field Ablation (PFA). For ablation device testing, several pulse parameters need to be characterized in a comprehensive manner to assess lesion boundary and efficacy. Overly aggressive voltages and application numbers increase animal burden. The potato tuber is a widely used initial model for the early testing of electroporation. The aim of this study is to characterize and refine bench testing for the ablation outcomes of PFA in this simplistic vegetal model. For in vitro assays, several pulse parameters like voltage, duration, and frequency were modulated to study effects not only on 2D ablation area but also 3D depth and volume. As PFA is a relatively new technology with minimal thermal effects, we also measured temperature changes before, during, and after ablation. Data from experiments were supplemented with in silico modeling to examine E-field distribution. We have estimated the irreversible electroporation threshold in Solanum Tuberosum to be at 240 V/cm. This bench testing platform can screen several pulse recipes at early stages of PFA device development in a rapid and high-throughput manner before proceeding to laborious trials for IRE medical devices.

The prognosis of patients with perihilar-cholangiocarcinoma (PHC) is poor, with the majority presenting with unresectable disease at diagnosis. Palliative chemotherapy (CHT) is the standard treatment for unresectable PHC. Irreversible electroporation (IRE) has been introduced as a novel ablation technique, working predominantly nonthermal. This review aims to analyse the efficacy and safety of IRE in treating unresectable PHC.

This systematic review and meta-analysis was performed according to a specific protocol designed a priori, and reported according to the PRISMA. PubMed/MEDLINE, Scopus, and Cochrane CENTRAL were searched up to December 2023. Primary Outcome of interest of our meta-analysis was the mean Overall Survival (OS). Secondary outcomes were progression-free survival (PFS) and adverse event rate (AE).

The mean OS was estimated at 25.49 months (CI, 21.47-38.72, I2 81.37%), PFS 17.86 (CI, 13.00-22.72, I2 11.42%), with an AE incidence of 12% (CI, 7%-31%, I2 83.57%). High heterogeneity was found among studies, with no single study fully responsible for it, suggesting high variability among facilities/populations.

IRE is effective and relatively safe for unresectable PHC. However, the lack of prospective studies and randomized trials comparing chemotherapy or locoregional treatment with IRE prevents drawing sufficiently robust conclusions.

IRE appears a safe and effective technique for treating unresectable perihilar cholangiocarcinoma.

The relationships between burst number, reversible, irreversible, and calcium electroporation have not been comprehensively evaluated in tumor tissue-mimics. Our findings indicate that electroporation effects saturate with a rate constant (τ) of 20 bursts for both conventional and high frequency waveforms (R2 > 0.88), with the separation between reversible and irreversible electroporation thresholds converging at 50 bursts. We find the lethal thresholds for calcium electroporation are statistically similar to reversible electroporation (R2 > 0.99). We then develop a burst-dependent dynamic conductivity curve that now incorporates electroporation effects due to both the electric field magnitude and burst number. Simulated ablation and thermal damage volumes vary significantly between finite element models using either the conventional or new burst-dependent dynamic conductivity curve (p < 0.05). Lastly, for clinically relevant protocols, thermal damage is indicated to not begin until 50 bursts, with maximum nonthermal ablation volumes at 100 bursts (1.5-13% thermal damage by volume). We find that >100 bursts generated negligible increases in ablation volumes with 40-70% thermal damage by volume at 300 bursts. Our results illustrate the need for considering burst number in minimizing thermal damage, choosing adjuvant therapies, and in modeling electroporation effects at low burst numbers.

Irreversible Electroporation (IRE) is a non-thermal tumor ablation technique. High-voltage electrical pulses are applied between pairs of electrodes inserted around and/or inside a tumor. The generated electric current induces the creation of nanopores in the cell membrane, triggering apoptosis. As a result, IRE can be safely used in areas near delicate vascular structures where other thermal ablation methods are contraindicated. Currently, IRE has demonstrated to be a successful ablation technique for pancreatic, renal, and liver tumors and is widely used as a focal therapeutic option for prostate cancer. The need for specific anesthetic management and accurate parallel placement of multiple electrodes entails a high level of complexity and great expertise from the interventional team is required. Nevertheless, IRE is a very promising technique with a remarkable systemic immunological capability and may impact on distant metastases (abscopal effect).

Cancer has and continues to be a complex health crisis plaguing millions around the world. Alcohol ablation was one of the initial methods used for the treatment of liver lesions. It was surpassed by thermal ablation which has played a big role in the therapeutic arsenal for primary and metastatic liver tumors. However, thermal ablation has several shortcomings and limitations that prompted the development of alternative technologies including electroporation and histotripsy. Percutaneous alcohol injection in the liver lesion leads to dehydration and coagulative necrosis. This technology is limited to the lesion with relative sparing of the surrounding tissue, making it safe to use adjacent to sensitive structures. Electroporation utilizes short high-voltage pulses to permeabilize the cell membrane and can result in cell death dependent on the threshold reached. It can effectively target the tumor margins and has lower damage rates to surrounding structures due to the short pulse duration. Histotripsy is a novel technology, and although the first human trial was just completed, its results are encouraging, given the sharp demarcation of the targeted tissue, lack of thermal damage, and potential for immunomodulation of the tumor microenvironment. Herein, we discuss these techniques, their uses, and overall clinical benefit.

A nationwide multicenter study was performed to examine short- and long-term effects of irreversible electroporation (IRE) for hepatocellular carcinoma (HCC) and colorectal cancer liver metastases (CRCLM). IRE is an alternative method when thermal ablation is contraindicated because of risk for serious thermal complications.

All consecutive patients in Sweden treated with IRE because of HCC or CRCLM, were included between 2011 and 2018. We evaluated medical records and radiological imaging to obtain information regarding patient-, tumor-, and treatment characteristics. We also assessed local tumor progression, and survival.

In total 206 tumors in 149 patients were treated with IRE. Eighty-seven patients (58.4%) had colorectal cancer liver metastases, and 62 patients (41.6%) had hepatocellular carcinoma. Median tumor size was 20 mm (i.q.r. 14-26 mm). Median overall survival for CRCLM and HCC, were 27.0 months (95% CI 22.2-31.8 months), and 35.0 months (95% CI 13.8-56.2 months), respectively. Median follow-up time was 58 months (95% CI 50.6-65.4). Local ablation success at six and twelve months for HCC was 58.3% and 40.3%, and for CRCLM 37.7% and 25.4%. The median time to local tumor progression (LTP) for HCC was 21.0 months (95% CI: 9.5-32.5 months), and for CRCLM 6.0 months (95% CI: 4.5-7.5 months). At 30-day follow-up, 15.4% (n = 23) of patients suffered from a complication rated as Clavien-Dindo grade 1-3a. Three patients (2.0%) had grade 3b-5 with one death in a thromboembolic event.

IRE is a safe ablation modality for patients with liver tumors that are located in such a way that other treatment options are unsuitable.

Irreversible electroporation (IRE) is a novel local tumor ablation approach with the potential to stimulate an antitumor immune response. However, it is not effective in preventing distant metastasis in isolation. This study aimed to compare the potential of augmenting the antitumor immune response in patients with locally advanced pancreatic cancer (LAPC) who underwent IRE combined with chemotherapy and PD-1/PD-L1 blockade with those who underwent IRE combined with chemotherapy.

A retrospective review was conducted on LAPC patients treated either with IRE in combination with chemotherapy and PD-1/PD-L1 blockade (group A) or with IRE with chemotherapy alone (group B) from July 2015 to June 2021. The primary outcomes were overall survival (OS) and progression-free survival (PFS), with immune responses and adverse events serving as secondary endpoints. Risk factors for OS and PFS were identified using univariate and multivariate analyses.

A total of 103 patients were included in the final analysis, comprising 25 in group A and 78 in group B. The median duration of follow-up was 18.2 months (3.0-38.6 months). Group A patients demonstrated improved survival compared to group B (median OS: 23.6 vs. 19.4 months, p = 0.001; median PFS: 18.2 vs. 14.7 months, p = 0.022). The data suggest a robust immune response in group A, while adverse events related to the treatment were similar in both groups. The multivariate analysis identified the combination of IRE, chemotherapy, and PD-1/PD-L1 blockade as an independent prognostic factor for OS and PFS.

The addition of PD-1/PD-L1 blockade to the regimen of IRE combined with chemotherapy enhanced antitumor immunity and extended survival in LAPC patients.

The 4th World Congress of Electroporation (Copenhagen, 9-13 October 2022) provided a unique opportunity to convene leading experts in pulsed electric fields (PEF). PEF-based therapies harness electric fields to produce therapeutically useful effects on cancers and represent a valuable option for a variety of patients. As such, irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumour-treating fields (TTF) are on the rise. Still, their full therapeutic potential remains underappreciated, and the field faces fragmentation, as shown by parallel maturation and differences in the stages of development and regulatory approval worldwide. This narrative review provides a glimpse of PEF-based techniques, including key mechanisms, clinical indications, and advances in therapy; finally, it offers insights into current research directions. By highlighting a common ground, the authors aim to break silos, strengthen cross-functional collaboration, and pave the way to novel possibilities for intervention. Intriguingly, beyond their peculiar mechanism of action, PEF-based therapies share technical interconnections and multifaceted biological effects (e.g., vascular, immunological) worth exploiting in combinatorial strategies.

Applicator-based local ablations under computed tomography (CT) guidance for the treatment of malignant tumors have found their way into clinical routine.

The basic principles of the different ablation technologies and their specific clinical field of application are described.

A comprehensive literature review regarding applicator-based ablation techniques was carried out.

Radiofrequency (RFA) and microwave ablation (MWA) represent two image-guided hyperthermal treatment modalities that have been established for the treatment of primary and secondary liver malignancies. In addition, both techniques are also applied for local ablative therapy of lung- and kidney tumors. Cryoablation is mainly used for the local ablation of T1 kidney cancer and due to its intrinsic analgetic characteristics for application in the musculoskeletal system. Nonresectable pancreatic tumors and centrally located liver malignancies can be treated with irreversible electroporation. This nonthermal ablation modality preserves the structure of the extracellular matrix including blood vessels and ducts. Technical advancements in the field of CT-guided interventions include the use of robotics, different tracking and navigation technologies and the use of augmented reality with the goal to achieve higher precision, shorter intervention time and thereby reduce radiation exposure.

Percutaneous ablation techniques under CT guidance are an essential part of interventional radiology and they are suited for local treatment of malignancies in most organ systems.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the fifth leading cause of cancer death worldwide and the third leading cause of all diseases worldwide. Liver transplantation, surgical resection and ablation are the three main curative treatments for HCC. Liver transplantation is the optimal treatment option for HCC, but its usage is limited by the shortage of liver sources. Surgical resection is considered the first choice for early-stage HCC, but it does not apply to patients with poor liver function. Therefore, more and more doctors choose ablation for HCC. However, intrahepatic recurrence occurs in up to 70% patients within 5 years after initial treatment. For patients with oligo recurrence after primary treatment, repeated resection and local ablation are both alternative. Only 20% patients with recurrent HCC (rHCC) indicate repeated surgical resection because of limitations in liver function, tumor location and intraperitoneal adhesions. Local ablation has become an option for the waiting period when liver transplantation is unavailable. For patients with intrahepatic recurrence after liver transplantation, local ablation can reduce the tumor burden and prepare them for liver transplantation. This review systematically describes the various ablation treatments for rHCC, including radiofrequency ablation, microwave ablation, laser ablation, high-intensity focused ultrasound ablation, cryablation, irreversible electroporation, percutaneous ethanol injection, and the combination of ablation and other treatment modalities.

Irreversible electroporation (IRE) is a non-thermal form of ablation based on the delivery of pulsed electrical fields. It has been used to treat liver lesions, particularly those in proximity to major hepatic vasculature. The role of this technique in the portfolio of treatments for colorectal hepatic metastases has not been clearly defined. This study undertakes a systematic review of IRE for treatment of colorectal hepatic metastases.

The study protocol was registered with the PROSPERO register of systematic reviews (CRD42022332866) and reports in compliance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The Ovid MEDLINE^®, EMBASE, Web of Science and Cochrane databases were queried in April 2022. The search terms 'irreversible electroporation', 'colon cancer', 'rectum cancer' and 'liver metastases' were used in combinations. Studies were included if they provided information on the use of IRE for patients with colorectal hepatic metastases and reported procedure and disease-specific outcomes. The searches returned 647 unique articles and the exclusions left a total of eight articles. These were assessed for bias using the methodological index for nonrandomized studies (MINORS criteria) and reported using the synthesis without meta-analysis guideline (SWiM).

One hundred eighty patients underwent treatment for liver metastases from colorectal cancer. The median transverse diameter of tumours treated by IRE was <3 cm. Ninety-four (52%) tumours were adjacent to major hepatic inflow/outflow structures or the vena cava. IRE was undertaken under general anaesthesia with cardiac cycle synchronisation and with the use of either CT or ultrasound for lesion localisation. Probe spacing was less than 3.2 cm for all ablations. There were two (1.1%) procedure-related deaths in 180 patients. There was one (0.5%) post-operative haemorrhage requiring laparotomy, one (0.5%) bile leak, five (2.8%) post-procedure biliary strictures and a zero incidence of post-IRE liver failure.

This systematic review shows that IRE for colorectal liver metastases can be accomplished with low procedure-related morbidity and mortality. Further prospective study is required to assess the role of IRE in the portfolio of treatments for patients with liver metastases from colorectal cancer.

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.

Thermal tumor ablation techniques including radiofrequency, microwave, LASER, high-intensity focused ultrasound and cryoablation are routinely used to treated liver, kidney, bone, or lung tumors. However, all these techniques are thermal and can therefore be affected by heat sink effect, which can lead to incomplete ablation, and thermal injuries of non-targeted tissues are possible. Under certain conditions, high voltage pulsed electric field can induce formation of pores in the cell membrane. This phenomenon, called electropermeabilization, is also known as "electroporation". Under certain conditions, electroporation can be irreversible, leading to cell death. Irreversible electroporation has demonstrated efficacy for the treatment of liver and prostate cancers, whereas data are scarce regarding pancreatic and renal cancers. During reversible electroporation, transient cell permeability can be used to introduce cytotoxic drugs into tumor cells (commonly bleomycin or cisplatin). Reversible electroporation used in conjunction with cytotoxic drugs shows promise in terms of oncological response, particularly for solid cutaneous and subcutaneous tumors such as melanoma. Irreversible and reversible electroporation are both not thermal ablation techniques and therefore open a new promising horizon for tumor ablation.

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy. Irreversible electroporation (IRE) is an ablative modality that uses high-voltage electrical pulses to permeabilize the cell membrane leading to cell necrosis. Unlike traditional thermal ablation, IRE is hardly affected by the "heat-sink" effect and can prevent damage of the adjacent vital structures. Nanosecond pulsed electric field (nsPEF) is a new IRE technique using ultra-short pulses (nanosecond duration), can not only penetrate the cell membranes, but also act on the organelles. Sufficient preclinical researches have shown that nsPEF can eliminate HCC without damaging vital organs, and elicit potent anti-tumor immune response.

This is the first clinical study to evaluate feasibility, efficacy, and safety of nsPEF for the treatment of HCC, where thermal ablation is unsuitable due to proximity to critical structures.

We will conduct an open-labeled, single-arm, prospective, multicenter, and objective performance criteria trial. One hundred and ninety-two patients with HCC, in which the tumor is located immediately (<0.5 cm) adjacent to the portal vein, hepatic veins, bile duct, gastrointestinal tract, or diaphragm, will be enrolled among 4 academic medical centers. The primary outcomes are the rate of complete ablation at 1 month and adverse events. Secondary outcomes include technical success, technique efficacy, nsPEF procedural characteristics, local tumor progression, and local progression-free survival.

The trial will be conducted according to the ethical principles of the Declaration of Helsinki and has been approved by the ethics committee of all participating centers. The results of this study will be published in peer-reviewed scientific journals and presented at relevant academic conferences.

This study is the Phase 1 clinical trial to evaluate the efficacy and safety of nsPEF in patients with HCC at high-risk locations where thermal ablation is contra-indicated. The results may expand the options and offer an alternative therapy for HCC.

ClinicalTrials.gov, identifier NCT04309747.

 Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. Because many hepatocellular carcinomas are already unresectable at the time of initial diagnosis, percutaneous tumor ablation has become established in recent decades as a curative therapeutic approach for very early (BCLC 0) and early (BCLC A) HCC. The aim of this paper is to provide a concise overview of the percutaneous local ablative procedures currently in use, based on their technical characteristics as well as clinical relevance, taking into account the current body of studies.

 The literature search included all original papers, reviews, and meta-analyses available via MEDLINE and Pubmed on the respective percutaneous ablation procedures; the primary focus was on randomized controlled trials and publications from the last 10 years.

 Radiofrequency ablation (RFA) and microwave ablation (MWA) are well-established procedures that are considered equal to surgical resection in the treatment of stage BCLC 0 and A HCC with a diameter up to 3 cm due to their strong evidence in international and national guidelines. For tumors with a diameter between 3 and 5 cm, the current S3 guidelines recommend a combination of transarterial chemoembolization (TACE) and thermal ablation using RFA or MWA as combination therapy is superior to thermal ablation alone in tumors of this size and shows comparable results to surgical resection in terms of overall survival. Alternative, less frequently employed thermal procedures include cryotherapy (CT) and laser ablation (LA). Non-thermal procedures include irreversible electroporation (IRE), interstitial brachytherapy (IBT), and most recently, electrochemotherapy (ECT). Due to insufficient evidence, these have only been used in individual cases and within the framework of studies. However, the nonthermal methods are a reasonable alternative for ablation of tumors adjacent to large blood vessels and bile ducts because they cause significantly less damage to these structures than thermal ablation methods. With advances in the technology of the respective procedures, increasingly good evidence, and advancements in supportive techniques such as navigation devices and fusion imaging, percutaneous ablation procedures may expand their indications for the treatment of larger and more advanced tumors in the coming years.

· RFA and MWA are considered equal to surgical resection as a first-line therapy for the curative treatment of stage BCLC 0 and A HCCs with a diameter of up to 3 cm.. · For HCCs with a diameter between 3 and 5 cm, a combination of TACE and RFA or MWA is recommended. This combination therapy yields results comparable to those of surgical resection in terms of overall survival.. · Due to insufficient evidence, alternative ablation methods have only been used in individual cases and within the framework of studies. However, nonthermal methods, such as IRE, IBT, and, most recently, ECT, are a reasonable alternative for ablation of HCCs adjacent to large blood vessels and bile ducts because they cause significantly less damage to these structures than thermal ablation methods..

· Luerken L, Haimerl M, Doppler M et al. Update on Percutaneous Local Ablative Procedures for the Treatment of Hepatocellular Carcinoma. Fortschr Röntgenstr 2022; DOI: 10.1055/a-1768-0954.