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Martin RC, Li Y, Shore EA, Malik DA, Li H, Hu X, Hayat T, Tan M, McMasters KM, Yan J. Irreversible Electroporation and Beta-Glucan-Induced Trained Innate Immunity for Treatment of Pancreatic Ductal Adenocarcinoma: A Phase II Study. J Am Coll Surg 2025; 240:351-361. [PMID: 39840846 PMCID: PMC11928255 DOI: 10.1097/xcs.0000000000001291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2025]
Abstract
BACKGROUND Irreversible electroporation (IRE) has augmented the effects of certain immunotherapies in pancreatic ductal adenocarcinoma (PDA). Yeast-derived particulate beta-glucan induces trained innate immunity and successfully reduced murine pancreatic cancer burden. This is a phase II study to test the hypothesis that IRE may augment beta-glucan-induced trained immunity in patients with PDA. STUDY DESIGN In this phase II clinical trial (NCT03080974), surgical ablative IRE was performed on clinical stage III PDA followed by oral beta-glucan administration for 12 months or until disease recurrence. Peripheral blood was taken preoperative, 14 days, and every 3 months and was evaluated by mass cytometry and compared with patients who received IRE alone. RESULTS Thirty consecutive patients with preoperative clinical stage III PDA were treated with IRE and then initiated on oral beta-glucan postoperatively were compared with 20 patients treated with IRE alone. There were no dose-limiting toxicities with oral beta-glucan, and compliance with therapy was 96% in all patients. Seven patients (23%) developed grade 3 or 4 treatment-related adverse events at 90 days; none required a dose modification of oral beta-glucan. A median disease-free interval (DFI) was 18 months (range 6 to 48 months), with a median overall survival (OS) of 32.5 months (range 4 to 53 months). At 12 months post-IRE, immunophenotyping was demonstrated a significant effect with improvement in the IRE-beta-glucan-treated group. This also resulted in a significant decrease on naive CD4 and CD8 T cells with increased CD4 and CD8 terminal effector cells in the IRE-beta-glucan-treated group, which correlated with a significant improvement in DFI and OS (p = 0.001). CONCLUSIONS Combined beta-glucan with IRE-ablated PDA tumor cells elicited a potent trained response and augmented antitumor functionality at 12 months post-IRE, which translated into an improved DFI and OS.
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Affiliation(s)
- Robert C.G. Martin
- Division of Surgical Oncology, The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA
| | - Yan Li
- Division of Surgical Oncology, The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA
| | - Emily A. Shore
- Division of Surgical Oncology, The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA
| | - Danial A Malik
- Division of Surgical Oncology, The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA
| | - Hong Li
- Functional Immunomics Core, Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA
| | - Xiaoling Hu
- Division of Immunotherapy, The Hiram C. Polk Jr., MD Department of Surgery, Immuno-Oncology Program, Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA
| | - Traci Hayat
- Division of Surgical Oncology, The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA
| | - Min Tan
- Division of Surgical Oncology, The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA
| | - Kelly M. McMasters
- Division of Surgical Oncology, The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA
| | - Jun Yan
- Division of Immunotherapy, The Hiram C. Polk Jr., MD Department of Surgery, Immuno-Oncology Program, Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA
- Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA
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Vos DJW, Ruarus AH, Timmer FEF, Geboers B, Bagla S, Belfiore G, Besselink MG, Leen E, Martin II RCG, Narayanan G, Nilsson A, Paiella S, Weintraub JL, Wiggermann P, Scheffer HJ, Meijerink MR. Consensus Guidelines of Irreversible Electroporation for Pancreatic Tumors: Protocol Standardization Using the Modified Delphi Technique. Semin Intervent Radiol 2024; 41:176-219. [PMID: 38993594 PMCID: PMC11236456 DOI: 10.1055/s-0044-1787164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/13/2024]
Abstract
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.
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Affiliation(s)
- Danielle J. W. Vos
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Alette H. Ruarus
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Florentine E. F. Timmer
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Bart Geboers
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Sandeep Bagla
- Vascular Institute of Virginia, Woodbridge, Virginia
| | - Giuseppe Belfiore
- Department of Diagnostic Imaging, S. Anna-S. Sebastiano Hospital, Caserta, Italy
| | - Marc G. Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Edward Leen
- Department of Experimental Medicine, Imperial College London, London, United Kingdom
| | | | - Govindarjan Narayanan
- Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Miami, Florida
| | - Anders Nilsson
- Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden
| | - Salvatore Paiella
- Department of General and Pancreatic Surgery, University of Verona Hospital Trust, G. B. Rossi Hospital, Verona, Italy
| | | | | | - Hester J. Scheffer
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University, Amsterdam, The Netherlands
- Department of Radiology and Nuclear Medicine, Northwest Hospital, Alkmaar, The Netherlands
| | - Martijn R. Meijerink
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University, Amsterdam, The Netherlands
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Stephens K, Philips PP, Egger ME, Scoggins CR, McMasters KM, Martin RCG. Multi-institutional review of adverse events associated with irreversible electroporation in the treatment of locally advanced pancreatic cancer. Surgery 2024; 175:704-711. [PMID: 37852831 DOI: 10.1016/j.surg.2023.08.042] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 08/14/2023] [Accepted: 08/16/2023] [Indexed: 10/20/2023]
Abstract
BACKGROUND Irreversible electroporation is a novel approach for treating locally advanced pancreatic adenocarcinoma. However, this ablative technique is not without risk and has the potential to precipitate adverse events. The aim of this study was to delineate risk factors that increase this risk, as well as to elucidate the risk profile associated with irreversible electroporation in the setting of locally advanced pancreatic adenocarcinoma. METHODS A review of our prospective multi-institutional database from December 2015 to March 2022 of patients with locally advanced pancreatic adenocarcinoma who underwent irreversible electroporation was analyzed for adverse events. These were then compared with a control population of patients undergoing pancreatectomy for adenocarcinoma. RESULTS Adverse events occurred in 51 patients of the 201 patients treated with irreversible electroporation compared with 78 of the 200 patients treated with pancreatectomy. The irreversible electroporation group had a significantly greater incidence of postoperative ascites in stage 3C patients. The most common complications in the irreversible electroporation group were infectious (n = 13), gastrointestinal bleed (n = 11), and ascites (n = 7). Multivariate analysis demonstrated increased risk of severe (grade ≥3) adverse events in the irreversible electroporation cohort who received high dose, neoadjuvant radiation (hazard ratio, 2.4; 95% confidence interval, 1.4-5.4), irreversible electroporation electrodes bracketing the superior mesenteric artery, superior mesenteric vein, and portal venous vein (hazard ratio, 1.9; 95% confidence interval, 1.3-3.4), and who had a bile duct stent in place for >6 months (hazard ratio, 1.7; 95% confidence interval, 1.2-5.6). There were similar rates of 90-day mortality in both groups, irreversible electroporation 2.4% vs pancreatectomy 2.8%. CONCLUSION This study revealed a 25% rate of adverse events associated with irreversible electroporation in locally advanced pancreatic adenocarcinoma, which was significantly less (P = .004) than the 39% rate of adverse events associated with pancreatectomy in early-stage disease. Certain unique adverse events in the irreversible electroporation group have been established and should be understood in the care of these patients.
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Affiliation(s)
- Kyle Stephens
- The Hiram C. Polk, Jr., MD Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY
| | - Prejesh P Philips
- The Hiram C. Polk, Jr., MD Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY
| | - Michael E Egger
- The Hiram C. Polk, Jr., MD Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY
| | - Charles R Scoggins
- The Hiram C. Polk, Jr., MD Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY
| | - Kelly M McMasters
- The Hiram C. Polk, Jr., MD Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY
| | - Robert C G Martin
- The Hiram C. Polk, Jr., MD Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY.
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Filson A, Martin RCG. Infection reporting in patients undergoing irreversible electroporation of locally advanced pancreatic cancer. J Surg Oncol 2023; 128:531-539. [PMID: 37165984 DOI: 10.1002/jso.27310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 04/01/2023] [Accepted: 04/28/2023] [Indexed: 05/12/2023]
Abstract
BACKGROUND Intraoperative bile cultures (IOBCs) taken during pancreatic surgery are commonly performed and there has been limited evidence that a positive IOBC could aid in perioperative adverse event (AE) management. Therefore, this study aims to describe infection management in patients undergoing irreversible electroporation (IRE). METHODS An Institutional Review Board (IRB)-approved prospective database was utilized from 8/2016 to 6/2022, with 127 pancreatic adenocarcinoma patients included. RESULTS A total of 28 patients that underwent IRE also had a simultaneous positive IOBC and the remaining 99 patients that underwent IRE had negative IOBC. A total of 11(39%) of the patients with a positive IOBC had AE's, and 38 (38%) of the patients with negative IOBC had AE's. Both groups had similar rates of AEs leading to new hospitalization and prolonged hospitalizations. Overall, there was no correlation between a positive IOBC and a patient developing an AE. CONCLUSIONS The findings of this study provide insights that improve the infectious management of patients undergoing IRE.
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Affiliation(s)
- Anthony Filson
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky, USA
| | - Robert C G Martin
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky, USA
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Shu C, Lim M, Fang A. Transarterial Embolization and Percutaneous Ablation of Primary and Metastatic Soft Tissue Tumors. Life (Basel) 2023; 13:1485. [PMID: 37511864 PMCID: PMC10381432 DOI: 10.3390/life13071485] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 06/25/2023] [Accepted: 06/26/2023] [Indexed: 07/30/2023] Open
Abstract
Soft tissue tumors (STTs) include a range of benign and malignant tumors originating from soft tissues. Transarterial and percutaneous therapies are image-guided and minimally invasive approaches for managing primary and metastatic STTs. The objective of this review is to discuss transarterial and percutaneous therapies by examining the current literature, including indications, patient selection, safety, and effectiveness. Transarterial therapies (e.g., transarterial bland embolization and transarterial chemoembolization) involve the delivery of either embolic or chemotherapeutic particles using a catheter into arteries feeding the tumor, resulting in localized tumor destruction. Percutaneous therapies (e.g., radiofrequency ablation, cryoablation, irreversible electroporation, laser ablation, and magnetic resonance-guided high-intensity focused ultrasound) involve the delivery of either hot or cold temperatures, electrical current, laser, or ultrasound to specifically target tumor cells. Both therapies have been shown to be safe and effective for reducing morbidity and local control of STTs, specifically in patients who are surgically inoperable or who are unresponsive to conventional therapies. Accurate diagnosis, staging, and histological subtype identification are crucial for treatment selection. A multidisciplinary approach, a thorough understanding of tissue anatomy and surrounding structures, as well as individualized strategies based on assessment are essential for optimal patient care.
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Affiliation(s)
- Chang Shu
- Post-Baccalaureate Premed Program, Goucher College, Baltimore, MD 21204, USA
| | - Maria Lim
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Adam Fang
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
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Martin RCG, Schoen EC, Philips P, Egger ME, McMasters KM, Scoggins CR. Impact of margin accentuation with intraoperative irreversible electroporation on local recurrence in resected pancreatic cancer. Surgery 2023; 173:581-589. [PMID: 36216618 PMCID: PMC9918678 DOI: 10.1016/j.surg.2022.07.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 07/08/2022] [Accepted: 07/12/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND The purpose of this study was to evaluate the rates of local recurrence and margin positivity in patients with borderline resectable pancreatic cancer after pancreatectomy with or without irreversible electroporation with margin accentuation. METHODS Prospective data for preoperative stages IIB (borderline resectable) and III were evaluated, with 75 patients undergoing pancreatectomy with irreversible electroporation with margin accentuation compared to 71 patients who underwent pancreatectomy alone from March 2010 to November 2020. RESULTS Both irreversible electroporation with margin accentuation and pancreatectomy-alone groups were similar for body mass index, Charleston comorbidity index, and sex. The irreversible electroporation with margin accentuation group had significantly greater preoperative stage III (irreversible electroporation 83% vs pancreatectomy alone 51%; P = .0001), with similar tumor location (head 64% vs 72%) and tumor size (median 2.9 vs 2.8). Neoadjuvant/induction chemotherapy and prior radiation therapy was similar in both groups (irreversible electroporation with margin accentuation 89% vs 72%). Surgical therapy included a greater percentage of pancreaticoduodenectomy in the pancreatectomy-alone group. Despite greater stage and greater percentage of margin positivity (irreversible electroporation with margin accentuation 27% vs 20%; P = not significant), rates of local recurrence were similar. The mean disease-free interval for local recurrence from time of diagnosis was similar (irreversible electroporation with margin accentuation 15.8 vs 16.5 pancreatectomy alone; P = not significant) and time of treatment (irreversible electroporation with margin accentuation 9.4 vs 10.5 months; P = not significant). Overall survival was improved with the irreversible electroporation with margin accentuation group, with a mean of 34.2 months versus 27.9 months in the pancreatectomy-alone group. CONCLUSION Irreversible electroporation with margin accentuation is safe and effective in stages IIB and III pancreatic adenocarcinomas that are technically resectable. Despite higher margin positivity rates, the time to local recurrence and the effects of recurrence were the same in the pancreatectomy-alone group.
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Affiliation(s)
- Robert C G Martin
- Division of Surgical Oncology, The Hiram C. Polk, Jr., MD Department of Surgery, University of Louisville School of Medicine, KY.
| | - Eric C Schoen
- Division of Surgical Oncology, The Hiram C. Polk, Jr., MD Department of Surgery, University of Louisville School of Medicine, KY
| | - Prejesh Philips
- Division of Surgical Oncology, The Hiram C. Polk, Jr., MD Department of Surgery, University of Louisville School of Medicine, KY
| | - Michael E Egger
- Division of Surgical Oncology, The Hiram C. Polk, Jr., MD Department of Surgery, University of Louisville School of Medicine, KY
| | - Kelly M McMasters
- Division of Surgical Oncology, The Hiram C. Polk, Jr., MD Department of Surgery, University of Louisville School of Medicine, KY
| | - Charles R Scoggins
- Division of Surgical Oncology, The Hiram C. Polk, Jr., MD Department of Surgery, University of Louisville School of Medicine, KY
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Zhao Y, McKillop IH, Davalos RV. Modeling of a single bipolar electrode with tines for irreversible electroporation delivery. Comput Biol Med 2022; 142:104870. [PMID: 35051854 PMCID: PMC10037907 DOI: 10.1016/j.compbiomed.2021.104870] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 08/24/2021] [Accepted: 09/12/2021] [Indexed: 01/07/2023]
Abstract
Irreversible electroporation (IRE) is a non-thermal tumor ablation technology employed to treat solid tumors not amenable to resection or thermal ablation. The IRE systems currently in clinical use deliver electrical pulses via multiple monopolar electrodes. This approach can present significant technical challenges due to the requirement for accurate placement of multiple electrodes and maintenance of parallel electrode alignment during pulse delivery. In this study, we sought to evaluate a novel IRE electrode configuration consisting of a single bipolar electrode with deployable tines. Using commercial finite element software predicted ablation outcomes, thermal damage, ablation sphericity, and energy delivery were calculated for existing monopolar and bipolar electrodes, and bipolar electrodes with either 4 or 8 deployable tines. The bipolar electrodes with tines generated larger predicted ablations compared to existing monopolar (>100%) and bipolar (>10%) arrangements, and the ablation shape using bipolar electrodes with tines were more spherical than those modeled for bipolar electrodes. Thermal damage modeled for bipolar electrodes and bipolar electrodes with tines was less than that of monopolar electrodes (using identical pulse parameters), and bipolar electrodes with tines delivered less energy than monopolar or bipolar electrodes. These studies using a single point of device insertion suggest the potential for developing alternative IRE delivery techniques, and may simplify clinical use and increase the predicted ablation shape/volume.
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Affiliation(s)
- Yajun Zhao
- College of Electrical Engineering and Control Science, Nanjing Tech. University, Nanjing, 211816, China; Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA, 24061, USA.
| | - Iain H McKillop
- Department of Surgery, Atrium Health, 1000 Blythe Boulevard, Charlotte, NC, 28203, USA
| | - Rafael V Davalos
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA, 24061, USA
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Woeste MR, Wilson KD, Kruse EJ, Weiss MJ, Christein JD, White RR, Martin RCG. Optimizing Patient Selection for Irreversible Electroporation of Locally Advanced Pancreatic Cancer: Analyses of Survival. Front Oncol 2022; 11:817220. [PMID: 35096621 PMCID: PMC8793779 DOI: 10.3389/fonc.2021.817220] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 12/17/2021] [Indexed: 12/12/2022] Open
Abstract
Background Irreversible 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. Methods A 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. Results 187 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. Conclusions Age, 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.
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Affiliation(s)
- Matthew R Woeste
- Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, KY, United States
| | - Khaleel D Wilson
- Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, KY, United States
| | - Edward J Kruse
- Department of Surgery, Section of Surgical Oncology, Augusta University Medical Center, Augusta, GA, United States
| | - Matthew J Weiss
- Department of Surgery, Division of Surgical Oncology, Johns Hopkins University, Baltimore, MD, United States
| | - John D Christein
- Department of Surgery, Division of Gastrointestinal Surgery, University of Alabama, Birmingham, AL, United States
| | - Rebekah R White
- Gastrointestinal Cancer Unit, University of California San Diego Moores Cancer Center, San Diego, CA, United States
| | - Robert C G Martin
- Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, KY, United States
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O’Neill CH, Tan M, Yan J, Li Y, Martin RCG. Perioperative systemic immunophenotype following irreversible electroporation (IRE) predicts recurrence. Am J Cancer Res 2022; 12:165-175. [PMID: 35141011 PMCID: PMC8822285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Accepted: 11/19/2021] [Indexed: 06/14/2023] Open
Abstract
Comprehensive understanding of the immunophenotypic response to local therapy will likely be required to improve outcomes for pancreatic ductal adenocarcinoma (PDAC). While the desmoplastic stroma has rendered PDAC resistant to immunotherapies, irreversible electroporation (IRE), a non-thermal method of tumor ablation, can overcome some of this resistance and immune suppression. We studied the systemic immunophenotype of patients following local treatment of PDAC. Stored lymphocytes from peripheral blood collected pre- and post-operatively for patients with PDAC who underwent surgical treatment from 12/2018 until 12/2019 were prepared for mass cytometry and a 30-marker panel identifying 37 immune-cell clusters were analyzed and compared to all clinical parameters. Stored lymphocytes from patient samples were collected pre-operatively postoperatively (Day 1, 3, 5 and 14) and during surveillance (Month 3, 6, 9 and 12). Thirty patients with locally advanced pancreatic cancer (LAPC) who underwent IRE were evaluated prospectively for changes in their immunophenotype. No significant differences in baseline demographics or tumor markers were identified. CA19-9 levels were significantly higher among patients who developed a recurrence (P=0.03). In the early perioperative period, CD4 and CD8 central memory cells were significantly higher among patients who did not recur (P=0.02 and 0.009 respectively). These findings were maintained in the late (>3 month) surveillance period. Early natural killer (NK) cells were significantly higher among those who did not recur (P=0.004) in the early postoperative period. The early immune-cell populations of CD4 and CD8 central memory cells and early NK cells were significantly higher among populations who did not recur following IRE for PDAC during the study period, with maintenance of the CD4 and CD8 central memory populations during later surveillance. Monitoring the early immunophenotype may offer opportunities to augment the immune response following tumor-disruptive IRE for PDAC.
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Affiliation(s)
- Conor H O’Neill
- Division of Surgical Oncology, Price Surgical Research Institute, Hiram Polk Department of Surgery, University of LouisvilleLouisville, KY 40202, USA
- Division of Immunotherapy, Hiram Polk Department of Surgery, University of LouisvilleLouisville, KY 40202, USA
| | - Min Tan
- Division of Surgical Oncology, Price Surgical Research Institute, Hiram Polk Department of Surgery, University of LouisvilleLouisville, KY 40202, USA
- Division of Immunotherapy, Hiram Polk Department of Surgery, University of LouisvilleLouisville, KY 40202, USA
| | - Jun Yan
- Division of Surgical Oncology, Price Surgical Research Institute, Hiram Polk Department of Surgery, University of LouisvilleLouisville, KY 40202, USA
- Division of Immunotherapy, Hiram Polk Department of Surgery, University of LouisvilleLouisville, KY 40202, USA
| | - Yan Li
- Division of Surgical Oncology, Price Surgical Research Institute, Hiram Polk Department of Surgery, University of LouisvilleLouisville, KY 40202, USA
- Division of Immunotherapy, Hiram Polk Department of Surgery, University of LouisvilleLouisville, KY 40202, USA
| | - Robert C G Martin
- Division of Surgical Oncology, Price Surgical Research Institute, Hiram Polk Department of Surgery, University of LouisvilleLouisville, KY 40202, USA
- Division of Immunotherapy, Hiram Polk Department of Surgery, University of LouisvilleLouisville, KY 40202, USA
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Zhang N, Li Z, Han X, Zhu Z, Li Z, Zhao Y, Liu Z, Lv Y. Irreversible Electroporation: An Emerging Immunomodulatory Therapy on Solid Tumors. Front Immunol 2022; 12:811726. [PMID: 35069599 PMCID: PMC8777104 DOI: 10.3389/fimmu.2021.811726] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 12/13/2021] [Indexed: 01/10/2023] Open
Abstract
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.
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Affiliation(s)
- Nana Zhang
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Zhuoqun Li
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Xuan Han
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Ziyu Zhu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Zhujun Li
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yan Zhao
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Zhijun Liu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yi Lv
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Rao S, Bui TL, Sasani A, Sadeghi B, Macherla A, Houshyar R, Abi-Jaoudeh N. Irreversible electroporation for pancreatic cancer using intraprocedural cone-beam computed tomography fusion navigation: a case report. J Med Case Rep 2021; 15:566. [PMID: 34819143 PMCID: PMC8613957 DOI: 10.1186/s13256-021-03152-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 10/15/2021] [Indexed: 11/12/2022] Open
Abstract
Background Patients diagnosed with locally advanced pancreatic cancer are usually not eligible for surgical resection because of significant vascular involvement. Stereotactic body radiation therapy and chemotherapy are the treatments recommended by the National Comprehensive Cancer Network criteria. For patients who do not respond to or tolerate stereotactic body radiation therapy and/or chemotherapy, a new option is irreversible electroporation. Irreversible electroporation is a nonthermal minimally invasive ablation technique that uses electrical pulses to induce apoptosis of tumor cells without damage to the extracellular matrix, thus preserving ducts and vessels. Irreversible electroporation requires very precise needle placement, which has limited its ubiquitous use. Intraprocedural cone-beam computed tomography with navigation can be fused with previous imaging to provide real-time tumor navigation capabilities during the procedure to allow for more accurate needle placement and treatment. Here, we present a patient who underwent percutaneous irreversible electroporation with intraprocedural cone-beam computed tomography fusion guidance to treat his pancreatic cancer. Case presentation The patient, an 88-year-old White male, initially presented with abdominal pain, and was ultimately diagnosed with locally advanced pancreatic cancer. He has an excellent performance status and no other comorbidities. He was started on chemotherapy and radiation therapy, with good response. However, continued vascular involvement of the tumors precluded him from safe surgical resection. The patient underwent irreversible electroporation with intraprocedural cone-beam computed tomography fusion navigation. The primary lesion demonstrates no residual tumor, and the soft tissue involvement of the adjacent vasculature has stabilized. Conclusions Although not curative on its own, irreversible electroporation holds promise as a treatment option for patients with locally advanced pancreatic cancer to increase downsizing to curative surgery or increase quality of life. Cone-beam computed tomography navigation can improve irreversible electroporation by providing guidance during needle guidance. Image fusion with previous advanced imaging can improve lesion visualization and targeting, thereby improving the effectiveness of irreversible electroporation.
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Affiliation(s)
- Sriram Rao
- Department of Radiological Sciences, University of California Irvine, 101 The City Drive South, Route 140, Orange, CA, 92868, USA
| | - Thanh-Lan Bui
- Department of Radiological Sciences, University of California Irvine, 101 The City Drive South, Route 140, Orange, CA, 92868, USA
| | - Ali Sasani
- Department of Radiological Sciences, University of California Irvine, 101 The City Drive South, Route 140, Orange, CA, 92868, USA
| | - Ben Sadeghi
- Department of Radiological Sciences, University of California Irvine, 101 The City Drive South, Route 140, Orange, CA, 92868, USA
| | - Anvesh Macherla
- Department of Radiological Sciences, University of California Irvine, 101 The City Drive South, Route 140, Orange, CA, 92868, USA
| | - Roozbeh Houshyar
- Department of Radiological Sciences, University of California Irvine, 101 The City Drive South, Route 140, Orange, CA, 92868, USA.
| | - Nadine Abi-Jaoudeh
- Department of Radiological Sciences, University of California Irvine, 101 The City Drive South, Route 140, Orange, CA, 92868, USA
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12
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Geboers B, Timmer FEF, Ruarus AH, Pouw JEE, Schouten EAC, Bakker J, Puijk RS, Nieuwenhuizen S, Dijkstra M, van den Tol MP, de Vries JJJ, Oprea-Lager DE, Menke-van der Houven van Oordt CW, van der Vliet HJ, Wilmink JW, Scheffer HJ, de Gruijl TD, Meijerink MR, on behalf of the Dutch Pancreatic Cancer Group. Irreversible Electroporation and Nivolumab Combined with Intratumoral Administration of a Toll-Like Receptor Ligand, as a Means of In Vivo Vaccination for Metastatic Pancreatic Ductal Adenocarcinoma (PANFIRE-III). A Phase-I Study Protocol. Cancers (Basel) 2021; 13:cancers13153902. [PMID: 34359801 PMCID: PMC8345515 DOI: 10.3390/cancers13153902] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/24/2021] [Accepted: 07/28/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Metastatic pancreatic ductal adenocarcinoma has a dismal prognosis, and to date no curative treatment options exist. The image guided tumor ablation technique irreversible electroporation (IRE) employs high-voltage electrical pulses through the application of several needle electrodes in and around the tumor in order to induce cell death. IRE ablation of the primary tumor has the ability to reduce pancreatic tumor induced immune suppression while allowing the expansion of tumor specific effector T cells, hereby possibly shifting the pancreatic tumor microenvironment into a more immune permissive state. The addition of immune enhancing therapies to IRE might work synergistically and could potentially induce a clinically significant treatment effect. This study protocol describes the rationale and design of the PANFIRE-III trial that aims to assess the safety of the combination of IRE with IMO-2125 (toll-like receptor 9 ligand) and/or nivolumab in patients with metastatic pancreatic ductal adenocarcinoma. Abstract Irreversible electroporation (IRE) is a novel image-guided tumor ablation technique with the ability to generate a window for the establishment of systemic antitumor immunity. IRE transiently alters the tumor’s immunosuppressive microenvironment while simultaneously generating antigen release, thereby instigating an adaptive immune response. Combining IRE with immunotherapeutic drugs, i.e., electroimmunotherapy, has synergistic potential and might induce a durable antitumor response. The primary objective of this study is to assess the safety of the combination of IRE with IMO-2125 (a toll-like receptor 9 ligand) and/or nivolumab in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). In this randomized controlled phase I clinical trial, 18 patients with mPDAC pretreated with chemotherapy will be enrolled in one of three study arms: A (control): nivolumab monotherapy; B: percutaneous IRE of the primary tumor followed by nivolumab; or C: intratumoral injection of IMO-2125 followed by percutaneous IRE of the primary tumor and nivolumab. Assessments include contrast enhanced computed tomography (ceCT), 18F-FDG and 18F-BMS-986192 (PD-L1) positron emission tomography (PET)-CT, biopsies of the primary tumor and metastases, peripheral blood samples, and quality of life and pain questionnaires. There is no curative treatment option for patients with mPDAC, and palliative chemotherapy regimens only moderately improve survival. Consequently, there is an urgent need for innovative and radically different treatment approaches. Should electroimmunotherapy establish an effective and durable anti-tumor response, it may ultimately improve PDAC’s dismal prognosis.
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Affiliation(s)
- Bart Geboers
- Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (F.E.F.T.); (A.H.R.); (E.A.C.S.); (R.S.P.); (S.N.); (M.D.); (J.J.J.d.V.); (D.E.O.-L.); (H.J.S.); (M.R.M.)
- Correspondence:
| | - Florentine E. F. Timmer
- Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (F.E.F.T.); (A.H.R.); (E.A.C.S.); (R.S.P.); (S.N.); (M.D.); (J.J.J.d.V.); (D.E.O.-L.); (H.J.S.); (M.R.M.)
| | - Alette H. Ruarus
- Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (F.E.F.T.); (A.H.R.); (E.A.C.S.); (R.S.P.); (S.N.); (M.D.); (J.J.J.d.V.); (D.E.O.-L.); (H.J.S.); (M.R.M.)
| | - Johanna E. E. Pouw
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (J.E.E.P.); (J.B.); (C.W.M.-v.d.H.v.O.); (H.J.v.d.V.); (J.W.W.); (T.D.d.G.)
| | - Evelien A. C. Schouten
- Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (F.E.F.T.); (A.H.R.); (E.A.C.S.); (R.S.P.); (S.N.); (M.D.); (J.J.J.d.V.); (D.E.O.-L.); (H.J.S.); (M.R.M.)
| | - Joyce Bakker
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (J.E.E.P.); (J.B.); (C.W.M.-v.d.H.v.O.); (H.J.v.d.V.); (J.W.W.); (T.D.d.G.)
| | - Robbert S. Puijk
- Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (F.E.F.T.); (A.H.R.); (E.A.C.S.); (R.S.P.); (S.N.); (M.D.); (J.J.J.d.V.); (D.E.O.-L.); (H.J.S.); (M.R.M.)
| | - Sanne Nieuwenhuizen
- Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (F.E.F.T.); (A.H.R.); (E.A.C.S.); (R.S.P.); (S.N.); (M.D.); (J.J.J.d.V.); (D.E.O.-L.); (H.J.S.); (M.R.M.)
| | - Madelon Dijkstra
- Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (F.E.F.T.); (A.H.R.); (E.A.C.S.); (R.S.P.); (S.N.); (M.D.); (J.J.J.d.V.); (D.E.O.-L.); (H.J.S.); (M.R.M.)
| | - M. Petrousjka van den Tol
- Department of Surgery, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands;
| | - Jan J. J. de Vries
- Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (F.E.F.T.); (A.H.R.); (E.A.C.S.); (R.S.P.); (S.N.); (M.D.); (J.J.J.d.V.); (D.E.O.-L.); (H.J.S.); (M.R.M.)
| | - Daniela E. Oprea-Lager
- Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (F.E.F.T.); (A.H.R.); (E.A.C.S.); (R.S.P.); (S.N.); (M.D.); (J.J.J.d.V.); (D.E.O.-L.); (H.J.S.); (M.R.M.)
| | - C. Willemien Menke-van der Houven van Oordt
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (J.E.E.P.); (J.B.); (C.W.M.-v.d.H.v.O.); (H.J.v.d.V.); (J.W.W.); (T.D.d.G.)
| | - Hans J. van der Vliet
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (J.E.E.P.); (J.B.); (C.W.M.-v.d.H.v.O.); (H.J.v.d.V.); (J.W.W.); (T.D.d.G.)
- Lava Therapeutics, Yalelaan 60, 3584 CM Utrecht, The Netherlands
| | - Johanna W. Wilmink
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (J.E.E.P.); (J.B.); (C.W.M.-v.d.H.v.O.); (H.J.v.d.V.); (J.W.W.); (T.D.d.G.)
| | - Hester J. Scheffer
- Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (F.E.F.T.); (A.H.R.); (E.A.C.S.); (R.S.P.); (S.N.); (M.D.); (J.J.J.d.V.); (D.E.O.-L.); (H.J.S.); (M.R.M.)
| | - Tanja D. de Gruijl
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (J.E.E.P.); (J.B.); (C.W.M.-v.d.H.v.O.); (H.J.v.d.V.); (J.W.W.); (T.D.d.G.)
| | - Martijn R. Meijerink
- Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Centers, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (F.E.F.T.); (A.H.R.); (E.A.C.S.); (R.S.P.); (S.N.); (M.D.); (J.J.J.d.V.); (D.E.O.-L.); (H.J.S.); (M.R.M.)
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Feasibility and effectiveness of endoscopic irreversible electroporation for the upper gastrointestinal tract: an experimental animal study. Sci Rep 2021; 11:15353. [PMID: 34321494 PMCID: PMC8319327 DOI: 10.1038/s41598-021-94583-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 07/09/2021] [Indexed: 02/07/2023] Open
Abstract
Irreversible electroporation (IRE) is a local non-thermal ablative technique currently used to treat solid tumors. Here, we investigated the clinical potency and safety of IRE with an endoscope in the upper gastrointestinal tract. Pigs were electroporated with recently designed endoscopic IRE catheters in the esophagus, stomach, and duodenum. Two successive strategies were introduced to optimize the electrical energy for the digestive tract. First, each organ was electroporated and the energy upscaled to confirm the upper limit energy inducing improper tissue results, including bleeding and perforation. Excluding the unacceptable energy from the first step, consecutive electroporations were performed with stepwise reductions in energy to identify the energy that damaged each layer. Inceptive research into inappropriate electrical intensity contributed to extensive hemorrhage and bowel perforation for each tissue above a certain energy threshold. However, experiments performed below the precluded energy accompanying hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays showed that damaged mucosal area and depth significantly decreased with decreased energy. Relevant histopathology showed infiltration of inflammatory cells with pyknotic nuclei at the electroporated lesion. This investigation demonstrated the possibility of endoscopic IRE in mucosal dysplasia or early malignant tumors of the hollow viscus.
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14
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Wei Y, Xiao Y, Wang Z, Hu X, Chen G, Ding X, Fan Y, Han Y, Huang K, Huang X, Kuang M, Lang X, Li H, Li C, Li J, Li J, Li M, Lu Y, Ni C, Niu L, Sun J, Tian J, Wang H, Wang L, Wu P, Xie X, Xing W, Xu L, Yang P, Yu H, Yuan C, Zhai B, Zhang Y, Zheng J, Zhou Z, Zhu X, Jiang T, Zhang Y. Chinese expert consensus of image-guided irreversible electroporation for pancreatic cancer. J Cancer Res Ther 2021; 17:613-618. [PMID: 34269289 DOI: 10.4103/jcrt.jcrt_1663_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Pancreatic cancer (PC) is a lethal disease with extremely high mortality. Although surgical resection is the optimal therapeutic approach for PC, about 30%-40% of those patients are not candidates for surgical resection when diagnosed. Chemotherapy and radiotherapy also could not claim a desirable effect on PC. The application of interventional radiology approaches is limited by unavoidable damage to the surrounding vessels or organs. By the superiority of mechanism and technology, IRE could ablate the tumor by creating irreversible pores on the membrane of PC cells with other tissues like vessels and pancreatic ducts untouched. This consensus gathers the theoretical basis and clinical experience from multiple Chinese medical centers, to provide the application principles and experience from Chinese experts in the IRE field.
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Affiliation(s)
- Yingtian Wei
- Department of Radiology, First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yueyong Xiao
- Department of Radiology, First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Zhongmin Wang
- Department of Radiology, Ruijin Hospital/Lu Wan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaokun Hu
- Interventional Medical Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Guang Chen
- Department of Interventional Radiology, Tianjin Medical University General Hospital, Tianjin First Central Hospital, Tianjin, China
| | - Xiaoyi Ding
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Qingdao, China
| | - Yong Fan
- Department of Radiology, Tianjin Medical University General Hospital, Tianjin First Central Hospital, Tianjin, China
| | - Yue Han
- Department of Interventional Radiology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Kaiwen Huang
- Department of Surgery, National Taiwan University, Taipei, Taiwan, China
| | - Xuequan Huang
- Department of Radiology, First Hospital Affiliated to Army Medical University, Chongqing, China
| | - Ming Kuang
- Department of Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xu Lang
- Department of Radiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Hailiang Li
- Department of Radiology, Henan Cancer Hospital, Zhengzhou, China
| | - Chengli Li
- Department of Radiology, Shandong Medical Imaging Research Institute, Jinan, Shandong, China
| | - Jiakai Li
- Department of Interventional Radiology, Hainan Hospital, Chinese PLA General Hospital, Beijing, China
| | - Jiaping Li
- Interventional Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Maoquan Li
- Department of Interventional and Vascular Surgery, Affiliated Tenth People's Hospital of Tongji University, Interventional Vascular Institute of Tongji University, Shanghai, China
| | - Yinying Lu
- Comprehensive Liver Cancer Center, The 5th Medical Center of the PLA General Hospital, Beijing, China
| | - Caifang Ni
- Department of Interventional Radiology, First Affiliated Hospital of Soochow University, Suzhou, China
| | - Lizhi Niu
- Department of Surgical Oncology, Fuda Cancer Hospital, Guang Zhou, Fuda Cancer Hospital, Guangzhou, China
| | - Junhui Sun
- Interventional Diagnosis and Treatment Center of Hepatobiliary and Pancreatic Diseases, Affiliated First Hospital, Medical College of Zhejiang University, Zhejiang, China
| | - Jinlin Tian
- Department of Interventional Vascular Surgery, PLA 252 Hospital, Baoding, China
| | - Hao Wang
- Department of Interventional Radiology, Tianjin Medical University General Hospital, Tianjin First Central Hospital, Tianjin, China
| | - Liwei Wang
- Department of Oncology, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Peihong Wu
- Department of Minimally Invasive Intervention, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiaoyan Xie
- Ultrasound Medicine, The First Affiliated Hospital of Sun Yat-sen University, Zhengzhou, China
| | - Wenge Xing
- Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Linfeng Xu
- Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Po Yang
- Department of Interventional and Vascular Therapy, The 4th Hospital of Harbin Medical University, Harbin, China
| | - Haipeng Yu
- Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Chunwang Yuan
- Center of Interventional Oncology and Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Bo Zhai
- Department of Tumor Intervention, Affiliated Renji Hospital, Medical College of Shanghai Jiaotong University, Shanghai, China
| | - Yanfang Zhang
- Department of Interventional Radiology, Second Clinical Medical College, Shenzhen People's Hospital, Jinan University, Guangzhou, China
| | - Jiasheng Zheng
- Center of Interventional Oncology and Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Zhigang Zhou
- Department of Radiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiaoli Zhu
- IR Department of the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Tianan Jiang
- Department of Ultrasonic Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Harbin, China
| | - Yingxun Zhang
- Department of Nuclear Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, China
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15
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Margin ACcentuation for resectable Pancreatic cancer using Irreversible Electroporation - Results from the MACPIE-I study. Eur J Surg Oncol 2021; 47:2571-2578. [PMID: 34039473 DOI: 10.1016/j.ejso.2021.05.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 04/27/2021] [Accepted: 05/06/2021] [Indexed: 01/11/2023] Open
Abstract
INTRODUCTION Margin accentuation (MA) using Irreversible electroporation (IRE) offers an unique opportunity to reduce the R1 resections in resectable pancreatic cancer (RPC). This study aims to assess the rate of margin positivity using IRE for MA during pancreaticoduodenectomy (PD) for resectable pancreatic head tumours. MATERIALS AND METHODS Following ethical approval, MA using IRE was carried out in 20 consecutive patients to posterior and superior mesenteric vein (SMV) margin, and the pancreatic neck, prior to the PD resection. The control group (non-IRE; n = 91) underwent PD without MA over the study period, March 2018 to March 2020. RESULTS There was no difference between the two groups in terms of patients' age, gender, pre-op biliary drainage, site of malignancy or pre-operative TNM stage. The overall margin positive rate for IRE group was lesser (35.0%) when compared to non-IRE group (51.6%; p = 0.177), with significantly less posterior pancreatic margin positivity (5.0% vs. 25.3%; p = 0.046). When only treated margins (SMA margin excluded) were compared, the IRE group had significantly lower margin positive rates (20.0% vs. 51.6%; p = 0.013). There was no difference between the two groups in terms of intra- or post-operative complications. With a median follow-up of 15.6 months, the median DFS and OS for IRE and non-IRE groups were 17 and 18 months (p = 0.306) and 19 and 22 months (p = 0.227) respectively. CONCLUSION Our pilot study confirms the safety of MA using IRE for RPC, with reduction in margin positivity. These results as a proof of concept are promising and need further validation with a randomised controlled trial.
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Charalambous P, Moris D, Karachaliou GS, Papalampros A, Dimitrokallis N, Tsilimigras DI, Oikonomou D, Petrou A. The efficacy and safety of the open approach irreversible electroporation in the treatment of pancreatic cancer: A systematic review. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:1565-1572. [PMID: 32536525 DOI: 10.1016/j.ejso.2020.05.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 05/04/2020] [Accepted: 05/19/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Irreversible Electroporation (IRE) is a novel non-thermal ablation technique used in patients with locally advanced pancreatic cancer (LAPC), in the proximity of sensitive structures such as vessels, intestinal wall and the bile duct. Currently, it is only used in the setting of clinical trials. This systematic review aimed to tackle the knowledge gap in the literature, in relation to the safety and efficacy of the open approach IRE. METHODS MEDLINE, EMBASE and Cochrane libraries were searched for English language articles published from January 2000 to December 2019. Data related to safety and efficacy were extracted. RESULTS Nine studies involving 460 patients with LAPC were included. Open approach IRE was associated with high morbidity (29.4%) but with a survival benefit compared to traditional treatment. Median overall survival (OS) was at 17.15 months. Major morbidity was at 10.2% and mortality at 3.4%. CONCLUSIONS Despite the paucity of literature and the low quality of evidence, the results regarding safety and efficacy appear to be encouraging. The high morbidity seems to be mitigated by a demonstrated improvement in OS. The potential of this technique is more evident when mortality and major morbidity are considered, since they are at acceptable levels. The limitations of this review have made it difficult to extract definitive conclusions. Higher quality evidence is needed in the form of large-scale multicentre randomized controlled trials. It remains to be elucidated whether the rate of adverse events decreases as our experience with this technique increases.
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Affiliation(s)
- Pabos Charalambous
- Department of General Surgery, Nicosia Teaching Hospital, Strovolos, Cyprus
| | - Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, NC, USA.
| | | | - Alexandros Papalampros
- 1st Department of Surgery, Laikon General Hospital, University of Athens, Athens, Greece
| | - Nikolaos Dimitrokallis
- 1st Department of Surgery, Laikon General Hospital, University of Athens, Athens, Greece
| | - Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Dimitrios Oikonomou
- 1st Department of Surgery, Laikon General Hospital, University of Athens, Athens, Greece
| | - Athanasios Petrou
- Department of General Surgery, Nicosia Teaching Hospital, Strovolos, Cyprus
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He C, Huang X, Zhang Y, Lin X, Li S. A Novel Prediction Tool Based on Large Cohorts to Determine the Cancer-Specific Survival Probability of Patients With Locally Advanced Pancreatic Cancer After Irreversible Electroporation Treatment. Front Oncol 2020; 10:952. [PMID: 32695671 PMCID: PMC7339950 DOI: 10.3389/fonc.2020.00952] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 05/14/2020] [Indexed: 12/14/2022] Open
Abstract
Irreversible electroporation (IRE) is a novel method which was especially suitable for the treatment of locally advanced pancreatic cancer (LAPC). The purpose of this study was to evaluate probabilities of overall survival (OS) and cancer-specific survival (CSS) in patients with LAPC after IRE treatment and to construct nomograms to predict survival for these patients. Data of patients were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database and medical records of Sun Yat-sen University Cancer Center (SYSUCC). A total of 312 LAPC patients after IRE treatment were included into this study. The 3-year cumulative incidence of cancer-specific mortality for patients with LAPC after IRE treatment was 74.3%. Nomograms for predicting probabilities of OS, CSS, and non-cancer-specific survival (NCSS) were built and calibrated with the concordance index (C-index) and the area under receiver operating characteristic (ROC) curve (AUC). The established nomograms were well-calibrated, with C-indexes of 0.782 for OS prediction, 0.729 for CSS prediction, and 0.730 for NCSS prediction. Compared with the TNM stage system, the established nomograms displayed higher values of AUC and showed better discriminatory power for predicting OS, CSS, and NCSS. These nomograms were well-calibrated and could serve to guide management of LAPC patients after IRE treatment.
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Affiliation(s)
- Chaobin He
- State Key Laboratory of Oncology in South China, Department of Pancreatobiliary Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xin Huang
- State Key Laboratory of Oncology in South China, Department of Pancreatobiliary Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yu Zhang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Xiaojun Lin
- State Key Laboratory of Oncology in South China, Department of Pancreatobiliary Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shengping Li
- State Key Laboratory of Oncology in South China, Department of Pancreatobiliary Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
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18
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O'Neill CH, Martin RCG. Cardiac synchronization and arrhythmia during irreversible electroporation. J Surg Oncol 2020; 122:407-411. [PMID: 32483842 DOI: 10.1002/jso.26041] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 05/17/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND OBJECTIVES Irreversible electroporation (IRE) is a nonthermal electrical tumor ablative strategy for unresectable tumors. IRE is relatively safe around critical structures but may induce cardiac arrhythmia when its delivery is not synchronized to the cardiac cycle. We performed a systematic literature review to determine rates of arrhythmia when IRE was utilized with or without cardiac synchronization. METHODS An online literature search was conducted with additional hand selection of articles. Data were extracted and pooled analyses were performed. RESULTS Twelve articles were included in analysis. IRE was performed for 481 patients; 46% hepatic tumors (n = 223), 36% pancreatic lesions (n = 168), and multiple other locations including prostate. Synchronization was performed on 422 patients. Arrhythmias were noted in 3.7% of cases (n = 18/481); cardiac synchronization: 1.2% (n = 5/422) vs unsynchronized: 22.0% (n = 13/59), P < .0001. These events occurred in every organ except the prostate. CONCLUSIONS IRE remains a potent technology for unresectable tumors, but arrhythmia is a clinical concern. This literature review confirms that cardiac gating should be used in all cases outside of prostate to prevent this potentially serious adverse event.
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Affiliation(s)
- Conor H O'Neill
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky
| | - Robert C G Martin
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky
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Ridouani F, Srimathveeravalli G. Percutaneous image-guided ablation: From techniques to treatments. Presse Med 2019; 48:e219-e231. [PMID: 31447333 DOI: 10.1016/j.lpm.2019.06.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 06/11/2019] [Indexed: 02/06/2023] Open
Abstract
Image-guided ablation is performed by percutaneously introducing ablation probes to deliver energy into a tumor to destroy it in a controlled and localized fashion. Ablation modalities can be broadly classified as thermal or non-thermal based on the mechanism of tumor destruction and are performed using different types of image guidance for planning, delivering and follow-up of the treatment. Ablation is performed in a minimally invasive fashion, providing greater residual organ preservation with minimal morbidity to the patient. Image-guided ablation is being used in the clinic for the treatment of primary and metastatic tumors, and this article reviews state of the art for the treatment of malignancies in the liver, lung, kidney and musculoskeletal tissue.
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Affiliation(s)
- Fourat Ridouani
- Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, USA
| | - Govindarajan Srimathveeravalli
- University of Massachusetts, Institute for Applied Life Sciences, Department of Mechanical and Industrial Engineering, Amherst, USA.
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20
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Holland MM, Bhutiani N, Kruse EJ, Weiss MJ, Christein JD, White RR, Huang KW, Martin RCG. A prospective, multi-institution assessment of irreversible electroporation for treatment of locally advanced pancreatic adenocarcinoma: initial outcomes from the AHPBA pancreatic registry. HPB (Oxford) 2019; 21:1024-1031. [PMID: 30737097 DOI: 10.1016/j.hpb.2018.12.004] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Revised: 12/11/2018] [Accepted: 12/28/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND The optimal treatment and management of locally advanced pancreatic cancer (LAPC) remains unclear and controversial. This study aimed to report the initial outcomes of the AHPBA Registry and evaluate the reproducibility of existing evidence that the addition of Irreversible Electroporation (IRE), a nonthermal ablative treatment, confers survival benefits beyond standard therapeutic options for patients with LAPC. METHODS From December 2015 to October 2017, patients with LAPC were treated with open-technique IRE following the AHPBA Registry Protocols. Patient demographics, long-term outcomes, and adverse events were recorded. Survival analyses were performed using Kaplan-Meier (KM) curves for overall survival (OS), progression free survival (PFS) and time to progression (TTP). RESULTS A total of 152 patients underwent successful IRE. Morbidity and mortality were 18% and 2% respectively, with 19 (13%) patients experiencing severe adverse events. Nine (6%) patients presented with local recurrence. Median TTP, PFS, and OS from diagnosis were 27.3 months, 22.8 months, and 30.7 months respectively. CONCLUSION The combination of IRE with established multiagent therapy is safe and demonstrates encouraging survival among patients with LAPC. IRE is associated with a low rate of serious adverse events and has been optimized for more widespread adoption through the standardized protocols available through the AHPBA registry.
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Affiliation(s)
- Michelle M Holland
- University of Louisville, Hiram C. Polk Jr, MD Department of Surgery, Division of Surgical Oncology, Louisville, KY, USA
| | - Neal Bhutiani
- University of Louisville, Hiram C. Polk Jr, MD Department of Surgery, Division of Surgical Oncology, Louisville, KY, USA
| | - Edward J Kruse
- Augusta University Medical Center, Department of Surgery, Section of Surgical Oncology, Augusta, GA, USA
| | - Matthew J Weiss
- Johns Hopkins University, Department of Surgery, Division of Surgical Oncology, Baltimore, MD, USA
| | - John D Christein
- University of Alabama, Department of Surgery, Division of Gastrointestinal Surgery, Birmingham, AL, USA
| | - Rebekah R White
- University of California San Diego Moores Cancer Center, Gastrointestinal Cancer Unit, San Diego, CA, USA
| | - Kai-Wen Huang
- National Taiwan University Hospital, Department of Surgery, Zhongzheng, Taipei, Taiwan
| | - Robert C G Martin
- University of Louisville, Hiram C. Polk Jr, MD Department of Surgery, Division of Surgical Oncology, Louisville, KY, USA.
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21
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Niessen C, Beyer L, Haimerl M, Schicho A, Stroszczynski C, Wiggermann P, Jung E. Percutaneous irreversible electroporation of hepatocellular carcinoma: Contrast-enhanced ultrasound-findings during 1-year follow-up. Clin Hemorheol Microcirc 2019; 72:85-93. [DOI: 10.3233/ch-180449] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- C. Niessen
- Institute for Radiology, University Hospital Regensburg, Regensburg, Germany
| | - L.P. Beyer
- Institute for Radiology, University Hospital Regensburg, Regensburg, Germany
| | - M. Haimerl
- Institute for Radiology, University Hospital Regensburg, Regensburg, Germany
| | - A. Schicho
- Institute for Radiology, University Hospital Regensburg, Regensburg, Germany
| | - C. Stroszczynski
- Institute for Radiology, University Hospital Regensburg, Regensburg, Germany
| | - P. Wiggermann
- Institute for Radiology, University Hospital Regensburg, Regensburg, Germany
| | - E.M. Jung
- Institute for Radiology, University Hospital Regensburg, Regensburg, Germany
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22
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Martin EK, Bhutiani N, Egger ME, Philips P, Scoggins CR, McMasters KM, Kelly LR, Vitale GC, Martin RCG. Safety and efficacy of irreversible electroporation in the treatment of obstructive jaundice in advanced hilar cholangiocarcinoma. HPB (Oxford) 2018; 20:1092-1097. [PMID: 30057125 DOI: 10.1016/j.hpb.2018.06.1806] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 06/20/2018] [Accepted: 06/23/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Irreversible electroporation (IRE) has successfully been used for palliation of pancreatic and liver cancers due to its ability to ablate tumors without destroying nearby vital structures. To date, it has not been evaluated in patients with advanced hilar cholangiocarcinoma (AHC). This study presents a single-institution experience with IRE for management of obstructive jaundice in AHC. METHODS A single-institution database was queried for patients undergoing IRE for AHC after PTBD placement for relief of obstructive jaundice from 2010 to 2017 and compared to a control group treated with standard of care only (No IRE). RESULTS Twenty-six patients underwent IRE for AHC after PTBD replacement. Three patients experienced complications, with two experiencing severe (≥ grade 3) complications. After IRE, median time to PTBD removal was 122 days (range 0-305 days) and median catheter-free time before requiring PTBD replacement was 305 days (range 92-458 days). In comparison, the 137 control patients had an admission rate of 59% (N = 80 patients) for PTBD infection, occlusion, or catheter related problem. CONCLUSION IRE safely achieves biliary decompression via tumor electroporation and allows PTBD removal for an extended period of time. In appropriately selected patients with obstructive jaundice in the setting of AHC, IRE can be used to increase catheter-free days and optimize overall quality of life.
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Affiliation(s)
- Emily K Martin
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
| | - Neal Bhutiani
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
| | - Michael E Egger
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
| | - Prejesh Philips
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
| | - Charles R Scoggins
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
| | - Kelly M McMasters
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
| | | | - Gary C Vitale
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
| | - Robert C G Martin
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA.
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23
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Lin M, Xie X, Xu M, Feng S, Tian W, Zhuang B, Su L, Ye J, Lin J, Liang P, Yu J, Kuang M. Non-enhanced Pattern on Contrast-Enhanced Ultrasound in the Local Efficacy Assessment of Irreversible Electroporation Ablation of Pancreatic Adenocarcinoma. ULTRASOUND IN MEDICINE & BIOLOGY 2018; 44:1986-1995. [PMID: 30055820 DOI: 10.1016/j.ultrasmedbio.2018.05.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 05/01/2018] [Accepted: 05/19/2018] [Indexed: 06/08/2023]
Abstract
The objective was to evaluate the diagnostic value of contrast-enhanced ultrasound in the assessment of the local efficacy after irreversible electroporation (IRE) ablation of pancreatic adenocarcinoma 1 mo after ablation. Fifteen patients with pancreatic adenocarcinoma were treated with IRE and then examined by contrast-enhanced ultrasound 1 mo after ablation. The contrast agent was SonoVue. Technical efficacy was assessed at 3 mo after IRE and classified as technical efficiency (TE) and technical inefficiency (TIE). Diagnostic performance was analyzed using a receiver operating characteristic curve. Ten patients were considered as having TE, and five, TIE. Complete non-enhancement was observed in seven ablation zones (70.0%) in the TE group, and peripheral heterogeneous enhancement, in all five ablation zones (100.0%) in the TIE group. The non-enhancement pattern differed significantly between the TE and TIE groups (p = 0.026), with significant correlation with technical efficacy (p = 0.007). The area under the receiver operating characteristic curve was 0.85 (p = 0.008, 95% confidence interval: 0.65-1.05). A non-enhancement pattern using contrast-enhanced ultrasound was useful in the assessment of local efficacy after IRE ablation of pancreatic adenocarcinoma.
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Affiliation(s)
- Manxia Lin
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital, Institute for the Study of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China
| | - Xiaoyan Xie
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital, Institute for the Study of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China
| | - Ming Xu
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital, Institute for the Study of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China
| | - Shiting Feng
- Department of Radiology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Wenshuo Tian
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital, Institute for the Study of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China
| | - Bowen Zhuang
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital, Institute for the Study of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China
| | - Liya Su
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital, Institute for the Study of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China
| | - Jieyi Ye
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital, Institute for the Study of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China
| | - Jinhua Lin
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital, Institute for the Study of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Jie Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Ming Kuang
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, First Affiliated Hospital, Institute for the Study of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China; Department of Liver Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
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24
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Korem M, Goldberg NS, Cahan A, Cohen MJ, Nissenbaum I, Moses AE. Clinically applicable irreversible electroporation for eradication of micro-organisms. Lett Appl Microbiol 2018; 67:15-21. [PMID: 29679390 DOI: 10.1111/lam.12996] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2017] [Revised: 04/15/2018] [Accepted: 04/16/2018] [Indexed: 12/18/2022]
Abstract
Irreversible electroporation (IRE) damages cell membranes and is used in medicine for nonthermal ablation of malignant tumours. Our aim was to evaluate the antimicrobial effect of IRE. The pathogenic micro-organisms, Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa and Candida albicans were subjected to IRE. Survival was measured as a function of voltage and the number of pulses applied. Combined use of IRE and oxacillin for eradication of Staph. aureus was also tested. Log10 reduction in micro-organisms positively correlated with the number of applied pulses. The colony count of Strep. pyogenes and E. coli declined by 3·38 and 3·05 orders of magnitude, respectively, using an electric field of 2000 V and 100 pulses. Killing of Staph. aureus and P. aeruginosa was achieved with a double cycle of IRE (2000, 1500 V and repeated 1250 V respectively) of 50-100 IRE pulses. The addition of subclinical inhibitory concentrations of oxacillin to the Staph. aureus suspension prior to IRE led to total bacterial death, demonstrating synergism between oxacillin and IRE. Our results demonstrate that using IRE with clinically established parameters has a marked in vitro effect on pathogenic micro-organisms and highlights the potential of IRE as a treatment modality for deep-seated infections, particularly when combined with low doses of antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY Irreversible electroporation (IRE) is utilized in interventional radiology to treat cancer patients. In this study we evaluated in vitro the antimicrobial effect of IRE. We demonstrated that using IRE with clinically established parameters has a marked effect on pathogenic micro-organisms and is synergistic to antimicrobials when both are combined. Our results point to the potential of IRE as a treatment modality for deep-seated infections.
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Affiliation(s)
- M Korem
- Department of Clinical Microbiology and Infectious Diseases, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - N S Goldberg
- Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - A Cahan
- IBM Research, Yorktown, NY, USA
| | - M J Cohen
- Clalit Health Services, Jerusalem, Israel
| | - I Nissenbaum
- Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - A E Moses
- Department of Clinical Microbiology and Infectious Diseases, Hadassah Hebrew University Medical Center, Jerusalem, Israel
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25
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Vogel JA, Rombouts SJ, de Rooij T, van Delden OM, Dijkgraaf MG, van Gulik TM, van Hooft JE, van Laarhoven HW, Martin RC, Schoorlemmer A, Wilmink JW, van Lienden KP, Busch OR, Besselink MG. Induction Chemotherapy Followed by Resection or Irreversible Electroporation in Locally Advanced Pancreatic Cancer (IMPALA): A Prospective Cohort Study. Ann Surg Oncol 2017; 24:2734-2743. [PMID: 28560601 DOI: 10.1245/s10434-017-5900-9] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Following induction chemotherapy, both resection or irreversible electroporation (IRE) may further improve survival in patients with locally advanced pancreatic cancer (LAPC). However, prospective studies combining these strategies are currently lacking, and available studies only report on subgroups that completed treatment. This study aimed to determine the applicability and outcomes of resection and IRE in patients with nonprogressive LAPC after induction chemotherapy. METHODS This was a prospective, single-center cohort study in consecutive patients with LAPC (September 2013 to March 2015). All patients were offered 3 months of induction chemotherapy (FOLFIRINOX or gemcitabine depending on performance status), followed by exploratory laparotomy for resection or IRE in patients with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 nonprogressive, IRE-eligible tumors. RESULTS Of 132 patients with LAPC, 70% (n = 93) started with chemotherapy (46% [n = 61] FOLFIRINOX). After 3 months, 59 patients (64%) had nonprogressive disease, of whom 36 (27% of the entire cohort) underwent explorative laparotomy, resulting in 14 resections (11% of the entire cohort, 39% of the explored patients) and 15 IREs (11% of the entire cohort, 42% of the explored patients). After laparotomy, 44% (n = 16) of patients had Clavien-Dindo grade 3 or higher complications, and 90-day all-cause mortality was 11% (n = 4). With a median follow-up of 24 months, median overall survival after resection, IRE, and for all patients with nonprogressive disease without resection/IRE (n = 30) was 34, 16, and 15 months, respectively. The resection rate in 61 patients receiving FOLFIRINOX treatment was 20%. CONCLUSION Induction chemotherapy followed by IRE or resection in nonprogressive LAPC led to resection or IRE in 22% of all-comers, with promising survival rates after resection but no apparent benefit of IRE, despite considerable morbidity. Registered at Netherlands Trial Register (NTR4230).
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Affiliation(s)
- Jantien A Vogel
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Steffi J Rombouts
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Thijs de Rooij
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Otto M van Delden
- Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands
| | - Marcel G Dijkgraaf
- Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands
| | - Thomas M van Gulik
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Jeanin E van Hooft
- Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands
| | | | - Robert C Martin
- Department of Surgery, University of Louisville, Louisville, KY, USA
| | | | - Johanna W Wilmink
- Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands
| | - Krijn P van Lienden
- Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands
| | - Olivier R Busch
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Marc G Besselink
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.
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26
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Tasu JP, Vesselle G, Herpe G, Richer JP, Boucecbi S, Vélasco S, Debeane B, Carretier M, Tougeron D. Irreversible Electroporation for Locally Advanced Pancreatic Cancer: Where Do We Stand in 2017? Pancreas 2017; 46:283-287. [PMID: 28187107 DOI: 10.1097/mpa.0000000000000793] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Pancreatic adenocarcinoma has a very poor prognosis. Complete surgical resection remains the only current curative treatment. Locally advanced pancreatic cancers are considered as unresectable because of involvement of celiac and/or mesenteric vessels. Irreversible electroporation has recently been introduced to induce permanent cell death by apoptosis. Irreversible electroporation is a nonthermal cell-destruction technique that was claimed to allow destruction of cancerous cells with less damage to surrounding supporting connective tissues with collagenic structure (such as nearby blood vessels, biliary ducts, and nerves) than other types of treatment. Applications on pancreatic adenocarcinoma seem promising, and this article is an up-to-date review of the first results.
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Affiliation(s)
- Jean Pierre Tasu
- From the *Department of Imaging, †Laboratory of Simulations and Anatomy Department, ‡Abdominal Surgery Department, §Anesthesiology Department, and ∥Abdominal Oncology Department, University Hospital of Poitiers, Poitiers, France
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27
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Latouche EL, Sano MB, Lorenzo MF, Davalos RV, Martin RCG. Irreversible electroporation for the ablation of pancreatic malignancies: A patient-specific methodology. J Surg Oncol 2017; 115:711-717. [PMID: 28185295 DOI: 10.1002/jso.24566] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Accepted: 01/07/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND OBJECTIVES Irreversible Electroporation (IRE) is a focal ablation technique highly attractive to surgical oncologists due to its non-thermal nature that allows for eradication of unresectable tumors in a minimally invasive procedure. In this study, our group sought to address the challenge of predicting the ablation volume with IRE for pancreatic procedures. METHODS In compliance with HIPAA and hospital IRB approval, we established a pre-treatment planning methodology for IRE procedures in pancreas, which optimized treatment protocols for individual cases of locally advanced pancreatic cancer (LAPC). A new method for confirming treatment plans through intraoperative monitoring of tissue resistance was also proved feasible in three patients. RESULTS Results from computational models showed good correlation with experimental data available in the literature. By implementing the proposed resistance measurement system 210 ± 26.1 (mean ± standard deviation) fewer pulses were delivered per electrode-pair. CONCLUSION The proposed physics-based pre-treatment plan through finite element analysis and system for actively monitoring resistance changes can be paired to significantly reduce ablation times and risk of thermal effects during IRE procedures for LAPC.
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Affiliation(s)
- Eduardo L Latouche
- Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Michael B Sano
- Radiation Oncology, Stanford University School of Medicine, Stanford, California.,UNC/NCSU Joint Department of Biomedical Engineering, Chapel Hill, North Carolina
| | - Melvin F Lorenzo
- Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Rafael V Davalos
- Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
| | - Robert C G Martin
- Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky
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28
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Martin RCG, Agle S, Schlegel M, Hayat T, Scoggins CR, McMasters KM, Philips P. Efficacy of preoperative immunonutrition in locally advanced pancreatic cancer undergoing irreversible electroporation (IRE). Eur J Surg Oncol 2017; 43:772-779. [PMID: 28162818 DOI: 10.1016/j.ejso.2017.01.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Revised: 12/22/2016] [Accepted: 01/04/2017] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Improved preoperative immunonutrition has been shown to decrease the length of stay (LOS) and complications among patients undergoing elective gastrointestinal cancer surgeries. The purpose of this study was to determine whether preoperative immunonutrition supplementation decreases postoperative LOS, infectious complications, and morbidity in patients undergoing irreversible electroporation (IRE) surgery for locally advanced pancreatic cancer (LAPC). METHODS At a regional hepatopancreatobiliary referral center within an academic medical center 71 patients receiving IRE treatment of LAPC were included in the study. The participants were divided into those receiving preoperative immunonutrition (n = 44) and those receiving no supplemental preoperative immunonutrition (n = 27). Main outcomes and measures were LOS, postoperative complications, nutritional risk index (NRI), and albumin levels. RESULTS Patients in both groups were similar for preoperative nutrition parameters and operative therapy. Patients in the immunonutrition group experienced a statistically significant decrease in postoperative complications (p = 0.05) and LOS (10.7 vs. 17.4, p = 0.01), and less of a decrease in nutritional risk index (-12.6 vs. -16.2, p = 0.03) and albumin levels (-1.1 vs. -1.5, p < 0.01). CONCLUSION Preoperative immunonutrition was clinically significant in decreasing postoperative complications, LOS, and improving post-surgery NRI and albumin levels in patients receiving elective IRE treatment of non-resectable pancreatic cancer. These results indicate that preoperative immunonutrition is effective and feasible in this subset of cancer patients.
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Affiliation(s)
- R C G Martin
- Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.
| | - S Agle
- Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA
| | - M Schlegel
- Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA
| | - T Hayat
- Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA
| | - C R Scoggins
- Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA
| | - K M McMasters
- Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA
| | - P Philips
- Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA
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Martin RCG, Durham AN, Besselink MG, Iannitti D, Weiss MJ, Wolfgang CL, Huang KW. Irreversible electroporation in locally advanced pancreatic cancer: A call for standardization of energy delivery. J Surg Oncol 2016; 114:865-871. [PMID: 27546233 DOI: 10.1002/jso.24404] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Accepted: 07/30/2016] [Indexed: 02/06/2023]
Abstract
Irreversible Electroporation (IRE) is used to treat locally advanced cancers, commonly of the pancreas, liver, kidney, and other soft tissues. Precise eligibility for IRE should be established in each individual patient by a multidisciplinary team based on comprehensive clinical, imaging, and laboratory assessment. Standardization of IRE technique and protocols is expected to improve safety, lead to reproducible outcomes, and facilitate further research into IRE. The present article provides a set of technical recommendations for the use of IRE in the treatment of locally advanced pancreatic cancer. J. Surg. Oncol. 2016;114:865-871. © 2016 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Robert C G Martin
- Division of Surgical Oncology, Hiram C Polk Jr Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky.
| | - Alan North Durham
- Division of Surgical Oncology, Hiram C Polk Jr Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky
| | - Marc G Besselink
- Department of Surgery, Academic Medical Center Amsterdam, Amsterdam, The Netherlands
| | | | | | - Christopher L Wolfgang
- Department of Surgery and Hepatitis Research Center, National Taiwan University Hospital, China and Singapore Universities Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
| | - Kai-Wen Huang
- Department of Surgery and Hepatitis Research Center, National Taiwan University Hospital, China and Singapore Universities Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
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D’Onofrio M, Ciaravino V, De Robertis R, Barbi E, Salvia R, Girelli R, Paiella S, Gasparini C, Cardobi N, Bassi C. Percutaneous ablation of pancreatic cancer. World J Gastroenterol 2016; 22:9661-9673. [PMID: 27956791 PMCID: PMC5124972 DOI: 10.3748/wjg.v22.i44.9661] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Revised: 09/13/2016] [Accepted: 10/19/2016] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma is a highly aggressive tumor with an overall 5-year survival rate of less than 5%. Prognosis and treatment depend on whether the tumor is resectable or not, which mostly depends on how quickly the diagnosis is made. Chemotherapy and radiotherapy can be both used in cases of non-resectable pancreatic cancer. In cases of pancreatic neoplasm that is locally advanced, non-resectable, but non-metastatic, it is possible to apply percutaneous treatments that are able to induce tumor cytoreduction. The aim of this article will be to describe the multiple currently available treatment techniques (radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation), their results, and their possible complications, with the aid of a literature review.
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Ekici Y, Tezcaner T, Aydın HO, Boyvat F, Moray G. Arterial complication of irreversible electroporation procedure for locally advanced pancreatic cancer. World J Gastrointest Oncol 2016; 8:751-756. [PMID: 27795815 PMCID: PMC5064053 DOI: 10.4251/wjgo.v8.i10.751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 06/08/2016] [Accepted: 08/16/2016] [Indexed: 02/05/2023] Open
Abstract
Irreversible electroporation (IRE) is a non-thermal ablation technique used especially in locally advanced pancreatic carcinomas that are considered surgically unresectable. We present the first case of acute superior mesenteric artery (SMA) occlusion secondary to pancreatic IRE procedure that has not been reported before in the literature. A 66-year-old man underwent neoadjuvant chemoradiotherapy for locally advanced pancreatic ductal adenocarcinoma. IRE procedure was applied to the patient during laparotomy under general anesthesia. After finishing the procedure, an acute intestinal ischemia was detected. A conventional vascular angiography was performed and a metallic stent was successfully placed to the SMA and blood flow was maintained. It is important to be careful in such cases of tumor involvement of SMA when evaluating for IRE procedure of pancreatic tumor.
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Evaluation of tolerability and efficacy of irreversible electroporation (IRE) in treatment of Child-Pugh B (7/8) hepatocellular carcinoma (HCC). HPB (Oxford) 2016; 18:593-9. [PMID: 27346140 PMCID: PMC4925804 DOI: 10.1016/j.hpb.2016.03.609] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Accepted: 03/24/2016] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Few studies have assessed the tolerability and efficacy of irreversible electroporation (IRE) in the treatment of Child-Pugh B (7/8) patients with hepatocellular carcinoma (HCC). Based on its mechanism of action, we hypothesized that IRE would be superior to microwave (MW) ablation and compared the liver tolerance and ablation success rates of these therapies in Child-Pugh B patients with HCC. METHODS 55 patients with Child-Pugh B (7/8) HCC were treated with either MW ablation (n = 25) or IRE (n = 30). Tolerance and ablation success were evaluated at 30 and 90 days and 90 days and 6 months, respectively. Tolerance was defined as stable liver function and absence of increased ascites or worsening portal hypertension. Ablation success was defined as tumor eradication on triple phase contrasted computed tomography (CT). RESULTS Patients undergoing IRE had shorter length of stay (p = 0.05) and 90 day readmission rate (p = 0.03) than those undergoing MW ablation. Additionally, IRE was better tolerated than MW ablation at 30 and 90 days. IRE and MW ablation resulted in 6 month success rates of 97% and 100%. CONCLUSION Treatment of Child-Pugh B (7/8) HCC with IRE results in equivalent ablation success with improved liver tolerance compared with MW ablation and other ablative modalities.
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Wendler JJ, Fischbach K, Ricke J, Jürgens J, Fischbach F, Köllermann J, Porsch M, Baumunk D, Schostak M, Liehr UB, Pech M. Irreversible Electroporation (IRE): Standardization of Terminology and Reporting Criteria for Analysis and Comparison. Pol J Radiol 2016; 81:54-64. [PMID: 26966472 PMCID: PMC4760650 DOI: 10.12659/pjr.896034] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2015] [Accepted: 09/22/2015] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Irreversible electroporation (IRE) as newer ablation modality has been introduced and its clinical niche is under investigation. At present just one IRE system has been approved for clinical use and is currently commercially available (NanoKnife® system). In 2014, the International Working Group on Image-Guided Tumor Ablation updated the recommendation about standardization of terms and reporting criteria for image-guided tumor ablation. The IRE method is not covered in detail. But the non-thermal IRE method and the NanoKnife System differ fundamentally from established ablations techniques, especially thermal approaches, e.g. radio frequency ablation (RFA). MATERIAL/METHODS As numerous publications on IRE with varying terminology exist so far - with numbers continuously increasing - standardized terms and reporting criteria of IRE are needed urgently. The use of standardized terminology may then allow for a better inter-study comparison of the methodology applied as well as results achieved. RESULTS Thus, the main objective of this document is to supplement the updated recommendation for image-guided tumor ablation by outlining a standardized set of terminology for the IRE procedure with the NanoKnife Sytem as well as address essential clinical and technical informations that should be provided when reporting on IRE tumor ablation. CONCLUSIONS We emphasize that the usage of all above recommended reporting criteria and terms can make IRE ablation reports comparable and provide treatment transparency to assess the current value of IRE and provide further development.
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Affiliation(s)
- Johann J Wendler
- Department of Urology, University of Magdeburg, Magdeburg, Germany
| | | | - Jens Ricke
- Department of Radiology, University of Magdeburg, Magdeburg, Germany
| | - Julian Jürgens
- Department of Radiology, University of Magdeburg, Magdeburg, Germany
| | - Frank Fischbach
- Department of Radiology, University of Magdeburg, Magdeburg, Germany
| | - Jens Köllermann
- Department of Pathology, Sana Klinikum Offenbach a. M., Offenbach Am Main, Germany
| | - Markus Porsch
- Department of Urology, University of Magdeburg, Magdeburg, Germany
| | - Daniel Baumunk
- Department of Urology, University of Magdeburg, Magdeburg, Germany
| | - Martin Schostak
- Department of Radiology, University of Magdeburg, Magdeburg, Germany
| | - Uwe-Bernd Liehr
- Department of Urology, University of Magdeburg, Magdeburg, Germany
| | - Maciej Pech
- Department of Radiology, University of Magdeburg, Magdeburg, Germany
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Bimonte S, Leongito M, Granata V, Barbieri A, Del Vecchio V, Falco M, Nasto A, Albino V, Piccirillo M, Palaia R, Amore A, Giacomo RD, Lastoria S, Setola SV, Fusco R, Petrillo A, Izzo F. Electrochemotherapy in pancreatic adenocarcinoma treatment: pre-clinical and clinical studies. Radiol Oncol 2016; 50:14-20. [PMID: 27069445 PMCID: PMC4825336 DOI: 10.1515/raon-2016-0003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Accepted: 12/13/2015] [Indexed: 12/18/2022] Open
Abstract
Background Pancreatic adenocarcinoma is currently one of the deadliest cancers with high mortality rate. This disease leads to an aggressive local invasion and early metastases, and is poorly responsive to treatment with chemotherapy or chemo-radiotherapy. Radical resection is still the only curative treatment for pancreatic cancer, but it is generally accepted that a multimodality strategy is necessary for its management. Therefore, new alternative therapies have been considered for local treatment. Conclusions Chemotherapeutic resistance in pancreatic cancer is associated to a low penetration of drugs into tumour cells due to the presence of fibrotic stroma surrounding cells. In order to increase the uptake of chemotherapeutic drugs into tumour cells, electrochemotherapy can be used for treatment of pancreatic adenocarcinoma leading to an increased tumour response rate. This review will summarize the published papers reported in literature on the efficacy and safety of electrochemotherapy in pre-clinical and clinical studies on pancreatic cancer.
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Affiliation(s)
- Sabrina Bimonte
- Division of Abdominal Surgical Oncology, Hepatobiliary Unit, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
| | - Maddalena Leongito
- Division of Abdominal Surgical Oncology, Hepatobiliary Unit, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
| | - Vincenza Granata
- Division of Radiology, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
| | - Antonio Barbieri
- S.S.D Sperimentazione Animale, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
| | - Vitale Del Vecchio
- S.S.D Sperimentazione Animale, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
| | - Michela Falco
- S.S.D Sperimentazione Animale, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
| | - Aurelio Nasto
- Division of Abdominal Surgical Oncology, Hepatobiliary Unit, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
| | - Vittorio Albino
- Division of Abdominal Surgical Oncology, Hepatobiliary Unit, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
| | - Mauro Piccirillo
- Division of Abdominal Surgical Oncology, Hepatobiliary Unit, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
| | - Raffaele Palaia
- Division of Abdominal Surgical Oncology, Hepatobiliary Unit, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
| | - Alfonso Amore
- Division of Abdominal Surgical Oncology, Hepatobiliary Unit, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
| | - Raimondo di Giacomo
- Division of Abdominal Surgical Oncology, Hepatobiliary Unit, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
| | - Secondo Lastoria
- Division of Nuclear Medicine, Department of Diagnostic Imaging and Radiotherapy, Istituto Nazionale Tumori "Fondazione G.Pascale" IRCCS, Naples, Italy
| | - Sergio Venanzio Setola
- Division of Radiology, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
| | - Roberta Fusco
- Division of Radiology, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
| | - Antonella Petrillo
- Division of Radiology, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
| | - Francesco Izzo
- Division of Abdominal Surgical Oncology, Hepatobiliary Unit, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy
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Paiella S, Salvia R, Ramera M, Girelli R, Frigerio I, Giardino A, Allegrini V, Bassi C. Local Ablative Strategies for Ductal Pancreatic Cancer (Radiofrequency Ablation, Irreversible Electroporation): A Review. Gastroenterol Res Pract 2016; 2016:4508376. [PMID: 26981115 PMCID: PMC4770121 DOI: 10.1155/2016/4508376] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Revised: 10/28/2015] [Accepted: 01/13/2016] [Indexed: 02/07/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has still a dismal prognosis. Locally advanced pancreatic cancer (LAPC) accounts for the 40% of the new diagnoses. Current treatment options are based on chemo- and radiotherapy regimens. Local ablative techniques seem to be the future therapeutic option for stage-III patients with PDAC. Radiofrequency Ablation (RFA) and Irreversible Electroporation (IRE) are actually the most emerging local ablative techniques used on LAPC. Initial clinical studies on the use of these techniques have already demonstrated encouraging results in terms of safety and feasibility. Unfortunately, few studies on their efficacy are currently available. Even though some reports on the overall survival are encouraging, randomized studies are still required to corroborate these findings. This study provides an up-to-date overview and a thematic summary of the current available evidence on the application of RFA and IRE on PDAC, together with a comparison of the two procedures.
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Affiliation(s)
- Salvatore Paiella
- Unit of General Surgery B, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Salvia
- Unit of General Surgery B, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy
| | - Marco Ramera
- Unit of General Surgery B, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Girelli
- Pancreatic Surgical Unit, Casa di Cura Pederzoli, Peschiera del Garda, Verona, Italy
| | - Isabella Frigerio
- Pancreatic Surgical Unit, Casa di Cura Pederzoli, Peschiera del Garda, Verona, Italy
| | - Alessandro Giardino
- Pancreatic Surgical Unit, Casa di Cura Pederzoli, Peschiera del Garda, Verona, Italy
| | - Valentina Allegrini
- Unit of General Surgery B, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Bassi
- Unit of General Surgery B, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy
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Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy. Ann Surg 2015; 262:486-94; discussion 492-4. [PMID: 26258317 DOI: 10.1097/sla.0000000000001441] [Citation(s) in RCA: 292] [Impact Index Per Article: 29.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Ablative therapies have been increasingly utilized in the treatment of locally advanced pancreatic cancer (LAPC). Irreversible electroporation (IRE) is an energy delivery system, effective in ablating tumors by inducing irreversible membrane destruction of cells. We aimed to demonstrate efficacy of treatment with IRE as part of multimodal treatment of LAPC. METHODS From July 2010 to October 2014, patients with radiographic stage III LAPC were treated with IRE and monitored under a multicenter, prospective institutional review board-approved registry. Perioperative 90-day outcomes, local failure, and overall survival were recorded. RESULTS A total of 200 patients with LAPC underwent IRE alone (n = 150) or pancreatic resection plus IRE for margin enhancement (n = 50). All patients underwent induction chemotherapy, and 52% received chemoradiation therapy as well for a median of 6 months (range, 5-13 months) before IRE. IRE was successfully performed in all patients. Thirty-seven percent of patients sustained complications, with a median grade of 2 (range, 1-5). Median length of stay was 6 days (range, 4-36 days). With a median follow-up of 29 months, 6 patients (3%) have experienced local recurrence. Median overall survival was 24.9 months (range: 4.9-85 months). CONCLUSIONS For patients with LAPC (stage III), the addition of IRE to conventional chemotherapy and radiation therapy results in substantially prolonged survival compared with historical controls. These results suggest that ablative control of the primary tumor may prolong survival.
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Young SJ. Irreversible electroporation and the pancreas: What we know and where we are going? World J Gastrointest Surg 2015; 7:138-144. [PMID: 26328033 PMCID: PMC4550840 DOI: 10.4240/wjgs.v7.i8.138] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Revised: 06/02/2015] [Accepted: 07/02/2015] [Indexed: 02/06/2023] Open
Abstract
Pancreatic adenocarcinoma continues to have a poor prognosis with 1 and 5 years survival rates of 27% and 6% respectively. The gold standard of treatment is resection, however, only approximately 10% of patients present with resectable disease. Approximately 40% of patients present with disease that is too locally advanced to resect. There is great interest in improving outcomes in this patient population and ablation techniques have been investigated as a potential solution. Unfortunately early investigations into thermal ablation techniques, particularly radiofrequency ablation, resulted in unacceptably high morbidity rates. Irreversible electroporation (IRE) has been introduced and is promising as it does not rely on thermal energy and has shown an ability to leave structural cells such as blood vessels and bile ducts intact during animal studies. IRE also does not suffer from heat sink effect, a concern given the large number of blood vessels surrounding the pancreas. IRE showed significant promise during preclinical animal trials and as such has moved on to clinical testing. There are as of yet only a few studies which look at the applications of IRE within humans in the setting of pancreatic adenocarcinoma. This paper reviews the basic principles, techniques, and current clinical data available on IRE.
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Groselj A, Kos B, Cemazar M, Urbancic J, Kragelj G, Bosnjak M, Veberic B, Strojan P, Miklavcic D, Sersa G. Coupling treatment planning with navigation system: a new technological approach in treatment of head and neck tumors by electrochemotherapy. Biomed Eng Online 2015; 14 Suppl 3:S2. [PMID: 26355773 PMCID: PMC4565575 DOI: 10.1186/1475-925x-14-s3-s2] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Electrochemotherapy provides highly effective local treatment for a variety of tumors. In deep-seated tumors of the head and neck, due to complex anatomy of the region or inability to cover the whole tumor with standard electrodes, the use of long single needle electrodes is mandatory. In such cases, a treatment plan provides the information on the optimal configuration of the electrodes to adequately cover the tumor with electric field, while the accurate placement of the electrodes in the surgical room in patients can remain a problem. Therefore, during electrochemotherapy of two head and neck lymph-node metastases of squamous cell carcinoma origin, a navigation system for placement of electrodes was used. PATIENT AND METHODS Electrochemotherapy of two lymph-node metastases of cutaneous squamous cell carcinoma, one in the left parotid gland and the other in the neck just behind the left mandibular angle, was performed using intravenous administration of bleomycin and long single needle electrodes. The tumors were treated according to the prepared treatment plan, and executed with the use of navigation system. RESULTS Coupling of treatment plan with the navigation system aided to an accurate placement of the electrodes. The navigation system helped the surgeon to identify the exact location of the tumors, and helped with the positioning of the long needle electrodes during their insertion, according to treatment plan. Five electrodes were inserted for each metastasis, one centrally in the tumor and four in the periphery of the tumor. Five weeks after electrochemotherapy, computed tomography images demonstrated partial response of the first metastasis and complete response of the second one. Six weeks after electrochemotherapy, fine-needle aspiration biopsy specimen obtained from the treated lesions revealed necrosis and inflammatory cells, without any viable tumor cells. CONCLUSION We describe a new technological approach for electrochemotherapy of deep-seated head and neck tumors, coupling of the treatment planning with navigation system for accurate placement of the single long needle electrodes into and around the tumors, according to the treatment plan. Evidence of its effectiveness on two lymph-node metastases of cutaneous squamous cell carcinoma origin in neck lymph is provided.
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Sugimoto K, Moriyasu F, Kobayashi Y, Saito K, Takeuchi H, Ogawa S, Ando M, Sano T, Mori T, Furuichi Y, Nakamura I. Irreversible electroporation for nonthermal tumor ablation in patients with hepatocellular carcinoma: initial clinical experience in Japan. Jpn J Radiol 2015; 33:424-432. [PMID: 26032929 DOI: 10.1007/s11604-015-0442-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Accepted: 05/20/2015] [Indexed: 12/15/2022]
Abstract
PURPOSE This clinical study was conducted to evaluate the safety and short-term outcomes of irreversible electroporation (IRE) for the treatment of patients with hepatocellular carcinoma (HCC) in Japan. MATERIALS AND METHODS The study was designed in a prospective setting. Five patients (3 men and 2 women; mean age, 66.6 ± 5.8 years) with 6 HCCs were enrolled and treated using percutaneous ultrasound (US)-guided IRE. Safety was assessed based on adverse events and laboratory values. Local control was assessed using contrast-enhanced US with a perflubutane microbubble contrast agent, contrast-enhanced multiphase CT, and gadoxetic acid-enhanced MRI (EOB-MRI) at designated points. RESULTS The tumors ranged in diameter from 11 to 28 mm (mean diameter, 17.5 ± 6.3 mm). Five of the 6 tumors (83 %) were successfully treated, with no local recurrence to date (mean follow-up 244 ± 55 days). In 1 lesion located in liver segment 1, residual tumor was diagnosed at 7 days after intervention by follow-up EOB-MRI. No serious complications related to the IRE procedure were observed. CONCLUSION The results of this study suggest that image-guided percutaneous IRE can achieve satisfactory local disease control, particularly for small HCCs, and is well tolerated by patients.
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Affiliation(s)
- Katsutoshi Sugimoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan,
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Niessen C, Igl J, Pregler B, Beyer L, Noeva E, Dollinger M, Schreyer AG, Jung EM, Stroszczynski C, Wiggermann P. Factors associated with short-term local recurrence of liver cancer after percutaneous ablation using irreversible electroporation: a prospective single-center study. J Vasc Interv Radiol 2015; 26:694-702. [PMID: 25812712 DOI: 10.1016/j.jvir.2015.02.001] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2014] [Revised: 01/26/2015] [Accepted: 02/01/2015] [Indexed: 02/08/2023] Open
Abstract
PURPOSE To evaluate the risk factors associated with short-term local recurrence of malignant liver lesions after irreversible electroporation (IRE). MATERIALS AND METHODS Thirty-nine consecutive patients (79 malignant liver lesions) were treated with IRE, of whom 14 were excluded from the analysis (including 12 without 6 mo of follow-up and two with incomplete ablation). The remaining 25 patients (aged 59.4 y ± 11.2) had 48 malignant liver lesions, including 22 hepatocellular carcinomas (HCCs), six cholangiocellular carcinomas, and 20 metastatic liver cancers. Multivariate analyses were used to evaluate the associations of risk factors with early recurrence. The characteristics of patients, lesions, and IRE procedures were assessed by logistic regression. RESULTS Fourteen of the 48 treated lesions (29.2%) showed early local recurrence after 6 months. Tumor volume (< 5 cm(3) vs ≥ 5 cm(3); P = .022) and underlying disease type (HCC, cholangiocellular carcinoma, or metastatic disease; P = .023) were independently associated with early local recurrence. However, distances to the surrounding portal veins (< 0.5 cm vs ≥ 0.5 cm; P = .810), hepatic veins (P = .170), hepatic arteries (P = .761), and bile ducts (P = .226) were not significantly associated with local recurrence. CONCLUSIONS Because short distances to the surrounding vessels were not associated with early local recurrence, percutaneous IRE might provide an alternative treatment option for perivascular tumors. However, patients with larger tumor volumes appeared to be poor candidates for percutaneous IRE. Regarding the different types of treated lesions, patients with HCC had significantly better outcomes.
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Affiliation(s)
- Christoph Niessen
- Department of Radiology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany..
| | - Juliane Igl
- Department of Radiology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany
| | - Benedikt Pregler
- Department of Radiology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany
| | - Lukas Beyer
- Department of Radiology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany
| | - Ekaterina Noeva
- Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany
| | - Marco Dollinger
- Department of Radiology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany
| | - Andreas G Schreyer
- Department of Radiology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany
| | - Ernst M Jung
- Department of Radiology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany
| | - Christian Stroszczynski
- Department of Radiology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany
| | - Philipp Wiggermann
- Department of Radiology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany
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Paiella S, Butturini G, Frigerio I, Salvia R, Armatura G, Bacchion M, Fontana M, D'Onofrio M, Martone E, Bassi C. Safety and feasibility of Irreversible Electroporation (IRE) in patients with locally advanced pancreatic cancer: results of a prospective study. Dig Surg 2015; 32:90-97. [PMID: 25765775 DOI: 10.1159/000375323] [Citation(s) in RCA: 97] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2014] [Accepted: 01/14/2015] [Indexed: 12/13/2022]
Abstract
PURPOSE To evaluate the safety of the NanoKnife Low Energy Direct Current (LEDC) System (Irreversible Electroporation, IRE) in order to treat patients with unresectable pancreatic adenocarcinoma. METHODS Prospective, nonrandomized, single-center clinical evaluation of ten patients with a cytohystological diagnosis of unresectable locally advanced pancreatic cancer (LAPC) that was no further responsive to standard treatments. The primary outcome was the rate of procedure-related abdominal complications. The secondary endpoints included the evaluation of the short-term efficacy of IRE through the evaluation of tumor reduction at imaging and biological tumor response as shown by CA 19-9, clinical assessments and patient quality of life. RESULTS Ten patients (5 males, 5 females) were enrolled, with a median age of 66 and median tumor size of 30 mm. All patients were treated successfully with a median procedure time of 79.5 min. Two procedure-related complications were described in one patient (10%): a pancreatic abscess with a pancreoduodenal fistula. Three patients had early progression of disease: one patient developed pulmonary metastases 30 days post-IRE and two patients had liver metastases 60 days after the procedure. We registered an overall survival of 7.5 months (range: 2.9-15.9). CONCLUSIONS IRE is a safe procedure in patients with LAPC and may represent a new technological option in the treatment and multimodality management of this disease.
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Affiliation(s)
- Salvatore Paiella
- Unit of Pancreatic and General Surgery, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy
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