irreversible electroporation
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2022 ◽  
Vol 11 ◽  
Author(s):  
Matthew R. Woeste ◽  
Khaleel D. Wilson ◽  
Edward J. Kruse ◽  
Matthew J. Weiss ◽  
John D. Christein ◽  
...  

BackgroundIrreversible electroporation (IRE) has emerged as a viable consolidative therapy after induction chemotherapy, in which this combination has improved overall survival of locally advanced pancreatic cancer (LAPC). Optimal timing and patient selection for irreversible electroporation remains a clinically unmet need. The aim of this study was to investigate preoperative factors that may assist in predicting progression-free and overall survival following IRE.MethodsA multi-institutional, prospectively maintained database was reviewed for patients with LAPC treated with induction chemotherapy followed by open-technique irreversible electroporation from 7/2015-5/2019. RECIST 1.1 criteria were used to assess tumor response and radiological progression. Overall survival (OS) and progression-free survival (PFS) were recorded. Survival analyses were performed using Kaplan Meier and Cox multivariable regression analyses.Results187 LAPC patients (median age 62 years range, 21 – 91, 65% men, 35% women) were treated with IRE. Median PFS was 21.7 months and median OS from diagnosis was 25.5 months. On multivariable analysis, age ≤ 61 (HR 0.41, 95%CI 0.21-0.78, p<0.008) and no prior radiation (HR 0.49, 95%CI 0.26-0.94, p=0.03) were positive predictors of OS after IRE. Age ≤ 61(HR 0.53, 95%CI, 0.28-.99, p=0.046) and FOLFIRINOX followed by gemcitabine/abraxane induction chemotherapy (HR 0.37,95%CI 0.15-0.89, p=0.027) predicted prolonged PFS after IRE. Abnormal CA19-9 values at the time of surgery negatively impacted both OS (HR 2.46, 95%CI 1.28-4.72, p<0.007) and PFS (HR 2.192, 95%CI 1.143-4.201, p=0.018) following IRE.ConclusionsAge, CA 19-9 response, avoidance of pre-IRE radiation, and FOLFIRINOX plus gemcitabine/abraxane induction chemotherapy are prominent factors to consider when referring or selecting LAPC patients to undergo IRE.


2022 ◽  
Vol 12 ◽  
Author(s):  
Nana Zhang ◽  
Zhuoqun Li ◽  
Xuan Han ◽  
Ziyu Zhu ◽  
Zhujun Li ◽  
...  

Irreversible electroporation (IRE), a novel non-thermal ablation technique, is utilized to ablate unresectable solid tumors and demonstrates favorable safety and efficacy in the clinic. IRE applies electric pulses to alter the cell transmembrane voltage and causes nanometer-sized membrane defects or pores in the cells, which leads to loss of cell homeostasis and ultimately results in cell death. The major drawbacks of IRE are incomplete ablation and susceptibility to recurrence, which limit its clinical application. Recent studies have shown that IRE promotes the massive release of intracellular concealed tumor antigens that become an “in-situ tumor vaccine,” inducing a potential antitumor immune response to kill residual tumor cells after ablation and inhibiting local recurrence and distant metastasis. Therefore, IRE can be regarded as a potential immunomodulatory therapy, and combined with immunotherapy, it can exhibit synergistic treatment effects on malignant tumors, which provides broad application prospects for tumor treatment. This work reviewed the current status of the clinical efficacy of IRE in tumor treatment, summarized the characteristics of local and systemic immune responses induced by IRE in tumor-bearing organisms, and analyzed the specific mechanisms of the IRE-induced immune response. Moreover, we reviewed the current research progress of IRE combined with immunotherapy in the treatment of solid tumors. Based on the findings, we present deficiencies of current preclinical studies of animal models and analyze possible reasons and solutions. We also propose possible demands for clinical research. This review aimed to provide theoretical and practical guidance for the combination of IRE with immunotherapy in the treatment of malignant tumors.


Author(s):  
Ross Aaron Petrella ◽  
Shani Leah Levit ◽  
Christopher C. Fesmire ◽  
Christina Tang ◽  
Michael B. Sano

2021 ◽  
Vol 12 ◽  
Author(s):  
Kunpeng Wang ◽  
Cong Wang ◽  
Hao Jiang ◽  
Yaqiong Zhang ◽  
Weidong Lin ◽  
...  

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and is increasing in incidence. Local ablative therapy plays a leading role in HCC treatment. Radiofrequency (RFA) is one of the first-line therapies for early local ablation. Other local ablation techniques (e.g., microwave ablation, cryoablation, irreversible electroporation, phototherapy.) have been extensively explored in clinical trials or cell/animal studies but have not yet been established as a standard treatment or applied clinically. On the one hand, single treatment may not meet the needs. On the other hand, ablative therapy can stimulate local and systemic immune effects. The combination strategy of immunotherapy and ablation is reasonable. In this review, we briefly summarized the current status and progress of ablation and immunotherapy for HCC. The immune effects of local ablation and the strategies of combination therapy, especially synergistic strategies based on biomedical materials, were discussed. This review is hoped to provide references for future researches on ablative immunotherapy to arrive to a promising new era of HCC treatment.


2021 ◽  
Author(s):  
Kenneth N Aycock ◽  
Sabrina N. Campelo ◽  
Rafael V. Davalos

Abstract Irreversible electroporation (IRE), otherwise known as non-thermal pulsed field ablation (PFA), is an attractive focal ablation modality due to its ability to destroy aberrant cells with limited disruption of extracellular tissue architecture. Despite its non-thermal cell death mechanism, application of electrical energy results in Joule heating that, if ignored, can cause undesired thermal injury. Engineered thermal mitigation (TM) technologies including phase change materials (PCMs) and active cooling (AC) have been reported and tested in isolated preliminary studies to limit the risk of thermal damage, but their performance compared to one another is relatively unknown. Further, the effects of pulsing paradigm, electrode geometry, PCM composition, and chosen active cooling parameters have not been examined. Here, we develop a computational model of conventional bipolar and monopolar probes with solid, PCM-filled, or actively cooled cores and simulate clinical IRE treatments in pancreatic tissue. We find that probes with integrated PCM cores can be tuned to drastically limit thermal damage compared to traditional solid probes. Actively cooled probes, on the other hand, provide even more control over thermal effects within the probe vicinity and can altogether eliminate thermal damage. In practice, these differences in performance are tempered by the increased time, expense, and effort necessary to use actively cooled probes compared to traditional solid probes or those containing a PCM core.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Li ◽  
Jingjing Wang ◽  
Xiaobo Zhang ◽  
Xiao Zhang ◽  
Hongmei Gao ◽  
...  

Abstract Background High-Frequency Irreversible Electroporation (H-FIRE) is a novel technology for non-thermal ablation. Different from Irreversible electroporation (IRE), H-FIRE delivers bipolar electrical pulses without muscle contraction and does not cause electrolysis. Currently, little is known regarding the cardiac safety during the administration of H-FIRE on liver. The aim of this study was to evaluate the changes of electrocardiogram (ECG) and biomarkers of cardiac damage during asymmetrical waveform of H-FIRE therapy in vivo. Methods The swines (n = 7) in IRE group, which used 100 pulses (2200 V, 100–100 μs configuration), were administrated with muscle relaxant under anesthesia. In the absence of muscle relaxant, 7 swines in H-FIRE group were performed with 2400 pulses (3000 V, 5–3–3–5 μs configuration). Midazolam (0.5 mg/kg) and xylazine hydrochloride (20 mg/kg) were given to induce sedation, followed by Isoflurane (2.5%, 100% oxygen, 3 L/min) to maintain sedation in all the swines. Limb lead ECG recordings were analyzed by two electrophysiologists to judge the arrhythmia. Cardiac and liver tissue was examined by pathology technique. Results The ablation zones were larger in H-FIRE than IRE. Both IRE and H-FIRE did not affect the autonomous cardiac rhythm. Even when the electrical signal of IRE and H-FIRE fell on ventricular vulnerable period. Moreover, cTnI in IRE group showed an increase in 4 h after ablation, and decreased to baseline 72 h after ablation. However, cTnI showed no significant change during the administration of H-FIRE. Conclusions The study suggests an asymmetrical waveform for H-FIRE is a promising measure for liver ablation. The results were based on normal liver and the swines without potential cardiac diseases. With the limitations of these facts, asymmetrical waveform for H-FIRE of liver tissue seems relatively safe without major cardiac complications. The safety of asymmetrical waveform for H-FIRE needs to evaluate in future.


2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Dhya Al-Leswas ◽  
Bathiya Ratnayake ◽  
Ghazaleh Mohammadi-Zaniani ◽  
Peter Peter Littler ◽  
Gourab Sen ◽  
...  

Abstract Background The present systematic review aimed to summarise the available evidence on indications and oncological outcomes after MA IRE for stage III pancreatic cancer (PC). Methods A literature search was performed in the Pubmed, MEDLINE, EMBASE, SCOPUS databases using the PRISMA framework to identify all MA IRE studies.  Results Nine studies with 235 locally advanced (LA) (82%, 192/235) or Borderline resectable (BR) PC (18%, 43/235) patients undergoing MA IRE pancreatic resection were included. Patients were mostly male (56%) with a weighted-mean age of 61 years (95% CI: 58–64). Pancreatoduodenectomy was performed in 51% (120/235) and distal pancreatectomy in 49% (115/235). R0 resection rate was 73% (77/105). Clavien Dindo grade 3–5 postoperative complications occurred in 19% (36/187). Follow-up intervals ranged from 3 to 29 months. Local and systematic recurrences were noted in 8 and 43 patients, respectively. The weighted-mean progression free survival was 11 months (95% CI: 7–15). The weighted-mean overall survival was 22 months (95% CI 20–23 months) and 8 months (95% CI 1–32 months) for MA IRE and IRE alone, respectively. Conclusions Early non-randomised data suggest MA IRE during pancreatic surgery for stage III pancreatic cancer may result in increased R0 resection rates and improved OS with acceptable postoperative morbidity. Further, larger studies are warranted to corroborate this evidence.


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