Ultrasound-guided Irreversible Electroporation Research Articles

Targeted Ablation Using Ultrasound-Guided Irreversible Electroporation of Index Tumors (TARGET Study): Prospective Development Study Evaluating Safety, Patient-Reported Outcomes, and Oncologic Efficacy.

We studied patient-reported functional outcomes, safety, and oncologic efficacy of focal irreversible electroporation as a primary treatment for intermediate-risk prostate cancer. Between February 2015 and April 2017, 20 consecutive patients elected irreversible electroporation and underwent 22 treatments. All underwent MRI-targeted and systematic transrectal biopsies. Eligibility criteria were grade group 2/3 prostate cancer in a maximum of 2 adjacent sextant prostate sectors in 1 hemigland without extraprostatic extension on MRI. Ablation was performed with a 5-mm cancer margin. Any grade group 1 cancer outside mapped index lesion was untreated. Outcome measures were based on the Prostate Quality of Life Survey, Male Sexual Health Questionnaire, and MRI-targeted and systematic biopsies at 3 and 12 months. Nineteen patients completed irreversible electroporation. One had electrocardiographic changes, and irreversible electroporation was aborted. No deterioration was detected in urinary or sexual domains (-0.2, 95% CI -1.4, 0.9, P = .7, and -1.9, 95% CI -10.1, 6.4, P = .6, respectively) or health-related quality of life (-0.2, 95% CI -1.4, 1.0, P = .7) at 6 months post ablation. Ejaculation volume decreased at 12 months (-1.5 points, 95% CI -2.4, -0.5, P = .003). At 12 months of follow-up, 14/19 patients (74%, 95% CI 49%, 91%) had no clinically significant cancer anywhere in the prostate. Radical treatment-free survival was 79% at 2 years (95% CI 53%, 92%) and 73% at 4 years (95% CI 47%, 88%). Our data show promising oncologic and functional outcomes following focal irreversible electroporation treatment for carefully selected patients with intermediate-risk prostate cancer. Further research should compare irreversible electroporation with active surveillance.

Combining intraoperative ultrasound-guided irreversible electroporation with chemotherapy for treating locally advanced pancreatic cancer: a clinical report of 64 cases

Objective: To examine the safety and clinical efficacy of ultrasound-guided irreversible electroporation (IRE) using the open surgery approach, after induction chemotherapy, in the treatment of locally advanced pancreatic cancer (LAPC) . Methods: The data of 64 LAPC patients who underwent ultrasound-guided IRE using the open surgery approach after induction chemotherapy at Department of Pancreatobiliary Surgery, Sun Yat-sen University Cancer Center from August 2015 to March 2019 were retrospectively analyzed. The study comprised of 30 males and 34 females, with median age of 58.5 years old (range: 34 to 87 years old) , were included in this study.The tumor was located in the pancreatic head and body/tail in 30 and 34 patients, respectively.The largest recorded tumor size was 6.1 cm (≤4.0 cm: n=35; >4.0 cm: n=29) .To create an electric field around the tumor, Two to six probes were parallelly inserted into each patient's tumor, based on the size of the tumor, at a distance of 2 cm apart through the transverse mesocolon in a caudal-to-cranial direction.According to the numerical sequence of patients undergoing ultrasound-guided IRE, the first 15 cases and following 49 patients were categorized as the primary and secondary treatment group, respectively.T text or χ(2) test was analyzed to the data between two groups.The study endpoints were overall survival (OS) and progression free survival (PFS) , which were investigated using Kaplan-Meier method, and their differences were compared using log-rank test. Results: The overall length of hospital stay was (8.9±2.7) days (range: 5 to 20 days) . Four patients were lost to follow-up.The study follow-up rate was 93.8%, with a median follow-up time of 29.3 months (range: 13.5 to 55.7 months) .The median OS and PFS of the entire cohort was 24.6 months (95% CI: 22.0 to 27.3 months) and 12.0 months (95%CI: 8.8 to 15.2 months) , respectively.One month after IRE, abdominal pain was significantly relieved in 95.3% of the patients (t=-28.55, P<0.01) .The rate of complications in the entire cohort was 20.3% and all were classified as grade B.Of them, pancreatic fistula, incisional infection, and upper gastrointestinal hemorrhage were observed in 7, 4, and 2 cases, respectively.The rate of complications for patients in the primary and secondary treatment groups were significantly different (10/15 vs. 6.1%) , respectively (χ(2)=26.01, P<0.01) .Further, two deaths were observed after IRE in the primary treatment group, while none was observed in the secondary treatment group. Conclusions: Ultrasound-guided IRE using the open surgery approach after induction chemotherapy is found to be safe and effective in treating patients with LAPC.However, these findings should be validated in prospective randomized trials before wide clinical application.

The effect of endoscopic ultrasound-guided irreversible electroporation of pancreas: An experimental study in porcine model

The effect of endoscopic ultrasound-guided irreversible electroporation of pancreas: An experimental study in porcine model

Percutaneous Irreversible Electroporation as First-line Treatment of Locally Advanced Pancreatic Cancer.

Irreversible electroporation (IRE) has recently been used as an experimental ablation treatment following systemic chemotherapy in locally advanced pancreatic cancer (LAPC). The primary aim of this study was to evaluate survival of LAPC patients after IRE prior to chemotherapy. The secondary aim was to examine the complication rates. Twenty-four patients with LAPC were included and treated with percutaneous ultrasound-guided IRE under general anesthesia. Survival data from the National Quality Registry for Pancreatic and Periampullary Cancer for LAPC during the same period were used for comparison. The median survival after diagnosis was 13.3 months in the IRE group compared to 9.9 months in the registry group (p=0.511). Six patients had a severe complication after IRE treatment. No obvious gain in survival was observed with IRE as the first line treatment of LAPC and IRE was associated with severe complications. This study does not support percutaneous IRE in this setting.

Surgical Irreversible Electroporation for Locally Advanced Pancreatic Cancer after Chemoradiotherpay

Introduction: Irreversible electroporation (IRE) is a non-thermal focal therapy that utilizes high voltage electric pulses to permanently rupture the cellular membrane and induce cell death resembling apoptosis. In the multicentric study from Asia, we evaluated the safety and efficacy of a protocol based on intra-operative ultrasound-guided IRE in patients with locally advanced pancreatic cancer (LAPC). Methods: From 2013-2016, we performed surgical IRE under US guidance in a total of 42 patients presenting with stage III LAPC smaller than 3 cm in diameter. Adjuvant chemoradiotherapy had been applicated for at least 3 months before IRE treatment, and tumor response was observed. Results: No IRE-related deaths occurred. A median follow-up of 31 months showed that 11.9% of patients sustained complications with a median Grade of II (range I–III). Three patients (7.1%) experienced local recurrence and 6 (14.3%) experienced distant progression. Overall mean survival from the time of treatment was 28.4 months. Conclusions: Our study suggests that IRE after effective chemoradiotherapy is safe and effective in the control of locally advanced pancreatic cancer. We surmise that the addition of IRE to a chemoradiotherpay for small localized pancreatic cancer may provide a survival advantage.

Ablation with irreversible electroporation in patients with advanced perihilar cholangiocarcinoma (ALPACA): a multicentre phase I/II feasibility study protocol

IntroductionThe majority of patients with perihilar cholangiocarcinoma (PHC) has locally advanced disease or distant lymph node metastases on presentation or exploratory laparotomy, which makes them not eligible for resection. As...

P0250 : Effect of irreversible electroporation (IRE) on the porcine liver: comparison with radiofrequency ablation

Background and Aims: Irreversible electroporation (IRE) is a promising, non-thermal ablation therapy for hepatocellular carcinoma, which, unlike radiofrequency thermal ablation (RFA), induces apoptosis through irreversible formation of nanoscale pores in the cell membrane with delivery of high-voltage electric current and is considered to improve safety in the vicinity of heat-sensitive blood vessel and bile duct. The aim of the present study is to clarify the acute pathological effect of IRE on the liver and also to compare with effect of RFA. Methods: Three pigs underwent ultrasound-guided IRE and RFA of normal liver under general anesthesia and at laparotomy. A total of 9 IRE ablated areas and 3 RFA ablated areas were created. We examined histopathologic findings of ablated areas at 4 hours after therapy with immunohistochemical methods. The pathologic findings according to IRE ablation conditions were compared with findings of RFA. Results: In IRE zones, various degree of congestion and hemorrhage, apoptotic change of hepatocytes, defluxion of portal endothelial cells and cholangitis were observed in hepatic lobules. With the increase in the total pulse number of IRE delivered, these pathological findings became remarkable. NADPH-diaphorase enzyme histochemistry performed in IRE zones demonstrated the stainability is very weak in the hepatic lobule, which reflecting defluxion of hepatocytes and reduced activity of viable hepatocytes in acute phase, while the stainability is lost in the central portion of RFA. Silver impregnation stain and collagen type 4 immunohistochemistry showed that reticular fibers and collagen fibers around the sinusoid remain well-preserved in IRE zones, on the other hand, those in RFA zones are very poorly stained. The vessels in IRE zones demonstrated a relatively intact configuration of positive smooth muscle cells for Caldesmon staining and endothelial cells for Factor 8 staining, with the minimal endothelial damage, while the vessels in RFA zones demonstrated a negative or weakened reaction. Bile duct epithelial cells showed a positive reaction for cytokeratin 7 staining in IRE zones with desquamated cells, while an entirely negative reaction in RFA zones, revealing protein denaturation. Conclusions: Unlike RFA, IRE induces apoptosis of hepatocytes, endothelium of the blood vessels and mucosal membrane of the bile ducts, whereas preservation of sinusoidal framework and vascular structure may have the potential for liver regeneration.

Percutaneous ultrasound-guided irreversible electroporation: A goat liver study

Irreversible electroporation (IRE) is a new tumor ablation technique. Pulsed electric fields (PEFs) with permanent duration (100 μsec) permanently permeabilize the cell membrane, causing the formation of innumerable permanent nanopores in the cell membrane and leading to cell death. In this study, percutaneous IRE was performed on 24 goat livers under the guidance of ultrasonography (US). IRE-exposed tissues were pathologically examined and glucose-6-phosphatase (G-6-P) and succinodehydrogenase (SDH) staining were used to detect the activity and function of the endoplasmic reticulum and mitochondria of liver tissues at 0 and 24 h after IRE ablation. Tissue ablation responses were monitored in real-time with US in the percutaneous IRE group; the largest diameter of the ablation zones was measured immediately (D1) and after 24 h (D2). Following D2 measurement, the animals were sacrificed and the gross sections (D3) were measured. The pathological examination results showed complete tissue necrosis after 24 h instead of immediately following IRE. The largest long diameters measured by intraprocedural US immediately after IRE (D1, 39.58±2.13 mm) were larger than those measured by US after 24 h (D2, 37.07±3.51 mm) and in gross section measurements (D3, 36.44±2.04 mm; P<0.05). D1 showed a good linear correlation with D3 (r=0.949). We conclude from these studies that IRE is not an acute ablating effect which leads to cell death. If US-guided percutaneous IRE focused on the target liver areas accurately, physicians would be able to assess the extent of necrosis through the regression equation during the IRE ablation procedure, and evaluate whether sufficient electric field energy had been applied to the desired tissue. Assisted with US guiding and monitoring, the minimally invasive IRE procedure in intraperitoneal lesions may become an important tumor ablation technique.