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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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Musiu C, Adamo A, Caligola S, Agostini A, Frusteri C, Lupo F, Boschi F, Busato A, Poffe O, Anselmi C, Vella A, Wang T, Dusi S, Piro G, Carbone C, Tortora G, Marzola P, D'Onofrio M, Crinò SF, Corbo V, Scarpa A, Salvia R, Malleo G, Lionetto G, Sartoris S, Ugel S, Bassi C, Bronte V, Paiella S, De Sanctis F. Local ablation disrupts immune evasion in pancreatic cancer. Cancer Lett 2025; 609:217327. [PMID: 39580047 DOI: 10.1016/j.canlet.2024.217327] [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: 08/09/2024] [Revised: 11/04/2024] [Accepted: 11/12/2024] [Indexed: 11/25/2024]
Abstract
BACKGROUND Pancreatic cancer (PC) is characterised by late diagnosis, tumour heterogeneity, and a peculiar immunosuppressive microenvironment, leading to poor clinical outcomes. Local ablative techniques have been proposed to treat unresectable PC patients, although their impact on activating the host immune system and overcoming resistance to immunotherapy remains elusive. METHODS We dissected the immune-modulatory abilities triggered by local ablation in mouse and human PC models and human specimens, integrating phenotypic and molecular technologies with functional assays. RESULTS Local ablation treatment performed in mice bearing orthotopic syngeneic PC tumours triggered tumour necrosis and a short-term inflammatory process characterised by the prompt increase of HMGB1 plasma levels, coupled with an enhanced amount of circulating and tumour infiltrating myeloid cells and increased MHCII expression in splenic myeloid antigen-presenting cells. Local ablation synergised with immunotherapy to restrict tumour progression and improved the survival of PC-bearing mice by evoking a T lymphocyte-dependent anti-tumour immune response. By integrating spatial transcriptomics with histological techniques, we pinpointed how combination therapy could reshape TME towards an anti-tumour milieu characterised by the preferential entrance and colocalization of activated T lymphocytes and myeloid cells endowed with antigen presentation features instead of T regulatory lymphocytes and CD206-expressing tumour-associated macrophages. In addition, treatment-dependent TME repolarization extended to neoplastic cells, promoting a shift from squamous to a more differentiated classical phenotype. Finally, we validated the immune regulatory properties induced by local ablation in PC patients and identified an association of the short-term treatment-dependent increase of neutrophils, NLR and HMGB1 with a longer time to progression. CONCLUSION Therefore, local ablation might overcome the current limitations of immunotherapy in PC.
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Affiliation(s)
- Chiara Musiu
- Department of Medicine, Section of Immunology, University of Verona Hospital Trust, Verona, Italy
| | - Annalisa Adamo
- Department of Medicine, Section of Immunology, University of Verona Hospital Trust, Verona, Italy
| | | | - Antonio Agostini
- Medical Oncology, Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Cristina Frusteri
- Department of Medicine, Section of Immunology, University of Verona Hospital Trust, Verona, Italy
| | - Francesca Lupo
- Department of Engineering for Innovative Medicine University of Verona Hospital Trust, Verona, Italy
| | - Federico Boschi
- Department of Engineering for Innovative Medicine University of Verona Hospital Trust, Verona, Italy
| | - Alice Busato
- Assessment Department Aptuit S.r.l., an Evotec Company, Verona, Italy
| | - Ornella Poffe
- Department of Medicine, Section of Immunology, University of Verona Hospital Trust, Verona, Italy
| | - Cristina Anselmi
- Department of Medicine, Section of Immunology, University of Verona Hospital Trust, Verona, Italy
| | - Antonio Vella
- Department of Medicine, Section of Immunology, University of Verona Hospital Trust, Verona, Italy
| | - Tian Wang
- Department of Medicine, Section of Immunology, University of Verona Hospital Trust, Verona, Italy
| | - Silvia Dusi
- Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Geny Piro
- Medical Oncology, Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Carmine Carbone
- Medical Oncology, Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Giampaolo Tortora
- Medical Oncology, Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Department of Translational Medicine, Catholic University of the Sacred Heart, Rome, Italy
| | - Pasquina Marzola
- Department of Engineering for Innovative Medicine University of Verona Hospital Trust, Verona, Italy
| | - Mirko D'Onofrio
- Department of Diagnostics and Public Health, Radiology Section, University of Verona Hospital Trust, Verona, Italy
| | - Stefano Francesco Crinò
- Department of Surgery, Dentistry, Paediatrics and Gynaecology, Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Vincenzo Corbo
- Department of Engineering for Innovative Medicine University of Verona Hospital Trust, Verona, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Pathological Anatomy Section, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Salvia
- Department of Surgery, Dentistry, Paediatrics and Gynaecology, General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Giuseppe Malleo
- Department of Surgery, Dentistry, Paediatrics and Gynaecology, General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Gabriella Lionetto
- Department of Surgery, Dentistry, Paediatrics and Gynaecology, General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Silvia Sartoris
- Department of Medicine, Section of Immunology, University of Verona Hospital Trust, Verona, Italy
| | - Stefano Ugel
- Department of Medicine, Section of Immunology, University of Verona Hospital Trust, Verona, Italy.
| | - Claudio Bassi
- Department of Engineering for Innovative Medicine University of Verona Hospital Trust, Verona, Italy
| | | | - Salvatore Paiella
- Department of Surgery, Dentistry, Paediatrics and Gynaecology, General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Francesco De Sanctis
- Department of Medicine, Section of Immunology, University of Verona Hospital Trust, Verona, Italy.
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Martin RCG, White RR, Bilimoria MM, Kluger MD, Iannitti DA, Polanco PM, Hammil CW, Cleary SP, Heithaus RE, Welling T, Chan CHF. Effectiveness and Safety of Irreversible Electroporation When Used for the Ablation of Stage 3 Pancreatic Adenocarcinoma: Initial Results from the DIRECT Registry Study. Cancers (Basel) 2024; 16:3894. [PMID: 39682087 DOI: 10.3390/cancers16233894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 11/13/2024] [Accepted: 11/15/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND/OBJECTIVES Overall survival for patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) remains limited, with a median survival of 12 to 15 months. Irreversible electroporation (IRE) is a local tumor ablation method that induces cancerous cell death by disrupting cell membrane homeostasis. The DIRECT Registry study was designed to assess the effectiveness and safety of IRE when combined with standard of care (SOC) treatment for Stage 3 PDAC versus SOC alone in a real-world setting after at least 3 months of induction chemotherapy; Methods: Patients with Stage 3 PDAC treated with IRE plus SOC or SOC alone were prospectively enrolled in a multicenter registry study. Enrollment required 3 months of active multi-agent chemotherapy with no progression before enrollment. Endpoints were 30- and 90-day mortality and adverse events (AEs). RESULTS Eighty-seven IRE and 27 SOC subjects were enrolled in the registry. Mean ages were 64.0 ± 8.4 and 66.4 ± 9.9 years, and mean anterior/posterior tumor diameters were 2.2 ± 0.7 cm and 3.2 ± 1.3 for the IRE and SOC groups respectively (p = 0.0066). All IRE procedures were performed using an open approach. The 90-day all-cause mortality was 5/83 (6.0%) and 2/27 (7.4%) for the IRE and SOC groups, respectively. Two subjects in the IRE group died from treatment-related complications, and one patient in the SOC group died due to chemotherapy-related complications. CONCLUSIONS Initial results from the DIRECT registry study indicate the use of IRE for curative intent tumor ablation in combination with induction chemotherapy has equivalent morbidity and mortality rates when compared to standard-of-care chemotherapy alone.
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Affiliation(s)
- Robert C G Martin
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY 40202, USA
| | - Rebekah Ruth White
- San Diego Moores Cancer Center, University of California, La Jolla, CA 92037, USA
| | | | - Michael D Kluger
- Columbia University Herbert Irving Comprehensive Cancer Center, New York, NY 10032, USA
| | - David A Iannitti
- Atrium Health Carolinas Medical Center, Charlotte, NC 28203, USA
| | | | - Chet W Hammil
- Siteman Cancer Center, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA
| | - Sean P Cleary
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY 40202, USA
- Mayo Clinic, Rochester, MN 55905, USA
- University Health Network, University of Toronto, Toronto, ON M5G 2C4, Canada
| | - Robert Evans Heithaus
- Department of Radiology, College of Medicine, University of South Florida, Tampa, FL 33606, USA
| | - Theodore Welling
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY 40202, USA
- NYU Langone Health, New York, NY 10016, USA
- UC San Diego Health, San Diego, CA 92037, USA
| | - Carlos H F Chan
- University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA
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Fesmire CC, Williamson RH, Petrella RA, Kaufman JD, Topasna N, Sano MB. Integrated Time Nanosecond Pulse Irreversible Electroporation (INSPIRE): Assessment of Dose, Temperature, and Voltage on Experimental and Clinical Treatment Outcomes. IEEE Trans Biomed Eng 2024; 71:1511-1520. [PMID: 38145519 PMCID: PMC11035095 DOI: 10.1109/tbme.2023.3340718] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2023]
Abstract
OBJECTIVE This study sought to investigate a novel strategy using temperature-controlled delivery of nanosecond pulsed electric fields as an alternative to the 50-100 microsecond pulses used for irreversible electroporation. METHODS INSPIRE treatments were carried out at two temperatures in 3D tumor models using doses between 0.001 s and 0.1 s. The resulting treatment zones were quantified using viability staining and lethal electric field intensities were determined numerically. Computational modeling was then used to determine parameters necessary for INSPIRE treatments to achieve equivalent treatment zones to clinical electroporation treatments and evaluate the potential for these treatments to induce deleterious thermal damage. RESULTS Lethal thresholds between 1109 and 709 V/cm were found for nominal 0.01 s treatments with pulses between 350 ns and 2000 ns at physiological temperatures. Further increases in dose resulted in significant decreases in lethal thresholds. Given these experimental results, treatment zones comparable to clinical electroporation are possible by increasing the dose and voltage used with nanosecond duration pulses. Temperature-controlled simulations indicate minimal thermal cell death while achieving equivalent treatment volumes to clinical electroporation. CONCLUSION Nanosecond electrical pulses can achieve comparable outcomes to traditional electroporation provided sufficient electrical doses or voltages are applied. The use of temperature-controlled delivery may minimize thermal damage during treatment. SIGNIFICANCE Intense muscle stimulation and the need for cardiac gating have limited irreversible electroporation. Nanosecond pulses can alleviate these challenges, but traditionally have produced significantly smaller treatment zones. This study suggests that larger ablation volumes may be possible with the INSPIRE approach and that future in vivo studies are warranted.
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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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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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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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Hendricks-Wenger A, Nagai-Singer MA, Uh K, Vlaisavljevich E, Lee K, Allen IC. Employing Novel Porcine Models of Subcutaneous Pancreatic Cancer to Evaluate Oncological Therapies. Methods Mol Biol 2022; 2394:883-895. [PMID: 35094364 DOI: 10.1007/978-1-0716-1811-0_47] [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: 06/14/2023]
Abstract
Immunocompromised mice are commonly utilized to study pancreatic cancer and other malignancies. The ability to xenograft tumors in either subcutaneous or orthotopic locations provides a robust model to study diverse biological features of human malignancies. However, there is a dire need for large animal models that better recapitulate human anatomy in terms of size and physiology. These models will be critical for biomedical device development, surgical optimization, and drug discovery. Here, we describe the generation and application of immunocompromised pigs lacking RAG2 and IL2RG as a novel model for human xenograft studies. These SCID-like pigs closely resemble NOD scid gamma mice and are receptive to human tumor tissue, cell lines, and organoid xenografts. However, due to their immunocompromised nature, these immunocompromised animals require housing and maintenance under germfree conditions. In this protocol, we describe the use of these pigs in a subcutaneous tumor injection study with human PANC1 cells. The tumors demonstrate a steady, linear growth curve, reaching 1.0 cm within 30 days post injection. The model described here is focused on subcutaneous injections behind the ear. However, it is readily adaptable for other locations and additional human cell types.
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Affiliation(s)
- Alissa Hendricks-Wenger
- Graduate Program in Translational Biology, Medicine and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, USA
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, USA
- Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Margaret A Nagai-Singer
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, USA
| | - Kyungjun Uh
- Department of Animal and Poultry Sciences, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA, USA
| | - Eli Vlaisavljevich
- Graduate Program in Translational Biology, Medicine and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, USA
- Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Kiho Lee
- Department of Animal and Poultry Sciences, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA, USA
| | - Irving C Allen
- Graduate Program in Translational Biology, Medicine and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, USA.
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, USA.
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10
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Oikonomou D, Karamouzis MV, Moris D, Dimitrokallis N, Papamichael D, Kountourakis P, Astras G, Davakis S, Papalampros A, Schizas D, Petrou AS, Felekouras E. Irreversible Electroporation (IRE) Combined With Chemotherapy Increases Survival in Locally Advanced Pancreatic Cancer (LAPC). Am J Clin Oncol 2021; 44:325-330. [PMID: 33979098 DOI: 10.1097/coc.0000000000000826] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Locally advanced pancreatic cancer (LAPC) is found in about 40% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a nonthermal ablative technique that provides an alternative in patients with LAPC and can be safely combined with chemotherapy. MATERIALS AND METHODS From 2015 until October of 2019, we performed laparotomic IRE in a total of 40 patients with stage III LAPC. The median age of these patients was 65.2 years (range: 46 to 81 y), and the median tumor size was 3.8 cm (range: 2 to 5.2 cm). 33 of 40 patients were treated preoperatively with FOLFIRINOX or nab-paclitaxel plus gemcitabine and in case of disease control, IRE was performed, whereas in 7 patients, IRE was performed without previous chemotherapy. RESULTS All patients were treated successfully with IRE as the tumor evaluation showed no disease progression after the completion of induction chemotherapy. No IRE-related deaths occurred. Two major grade III complications were reported: pancreatic fistula grade A in 8 patients and 3 patients diagnosed with delayed gastric emptying. Up to October 31, 2019, the median overall survival (OS) of all patients was 24.2 months (range: 6 to 36 mo), and the median progression-free survival was 10.3 months (range: 3 to 24 mo). After the completion of IRE, 30 patients (75%) continued with adjuvant chemotherapy. Fifteen patients (37%) have >24 months OS and 3 patients (8%) have reached 36 months OS and are still alive. CONCLUSION The combination of chemotherapy with IRE, which is a safe and effective procedure, may result in a survival benefit for patients with LAPC.
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Affiliation(s)
- Dimitrios Oikonomou
- First Department of Surgery, Athens University School of Medicine, Laiko General Hospital
| | - Michalis V Karamouzis
- Department of Biological Chemistry, Division of Molecular Oncology, Athens University School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Moris
- First Department of Surgery, Athens University School of Medicine, Laiko General Hospital
| | - Nikolaos Dimitrokallis
- First Department of Surgery, Athens University School of Medicine, Laiko General Hospital
| | | | | | - Georgios Astras
- Department of Medical Oncology, American Oncology Center, American Medical Center
| | - Spyridon Davakis
- First Department of Surgery, Athens University School of Medicine, Laiko General Hospital
| | - Alexandros Papalampros
- First Department of Surgery, Athens University School of Medicine, Laiko General Hospital
| | - Dimitrios Schizas
- First Department of Surgery, Athens University School of Medicine, Laiko General Hospital
| | - Athanasios S Petrou
- Department of Surgery, American Medical Center (AMC), Division of HPB and Surgical Oncology, American Institute of Minimal Invasive Surgery (AIMIS), Nicosia, Cyprus
| | - Evangelos Felekouras
- First Department of Surgery, Athens University School of Medicine, Laiko General Hospital
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11
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Iancu I, Bartoș A, Cioltean CL, Breazu C, Iancu C, Bartoș D. Role of radio-ablative technique for optimizing the survival of patients with locally advanced pancreatic adenocarcinoma (Review). Exp Ther Med 2021; 22:853. [PMID: 34178126 PMCID: PMC8220652 DOI: 10.3892/etm.2021.10285] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 05/05/2021] [Indexed: 12/19/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most common and frequently diagnosed malignant tumor of the pancreas with few treatment options and poor life expectancy. Despite the advances in the surgical field, 40% of the patients are diagnosed with locally advanced disease which is not suitable for surgery. Radio-frequency ablation (RFA) has been described as a new ‘weapon’ in the multimodal treatment of PDAC, representing a cytoreductive procedure which must be completed with radiotherapy or chemo-radiotherapy. A systematic research was carried out utilizing the PubMed database in regards to this subject, to evaluate the role of RFA in PDAC management. Abstracts, letters-to-the-editor and non-English language manuscripts were excluded. The literature showed that RFA can be used in open and laparoscopic surgery but it is also feasible for endoscopic ultrasound (EUS-guided RFA) or percutaneous approach. Even though we found optimistic and encouraging reports on overall survival (OS), randomized studies are still required to corroborate these findings. Our review research underline that surgical resection remains the only radical treatment option, RFA being a safe and feasible technique reserved for unresectable, non-metastatic pancreatic tumors. Its combination with oncological treatment can improve the OS of these patients.
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Affiliation(s)
- Ioana Iancu
- Department of Surgery, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania.,Anatomy and Embryology Department, 'Iuliu Hațieganu' University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Adrian Bartoș
- Department of Surgery, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania.,Department of Surgery, 'Iuliu Hațieganu' University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania
| | - Cristian Liviu Cioltean
- Department of Surgery, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Caius Breazu
- Department of Surgery, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania.,Department of Anesthesiology and Intensive Care, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Cornel Iancu
- Department of Surgery, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Dana Bartoș
- Department of Surgery, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania.,Anatomy and Embryology Department, 'Iuliu Hațieganu' University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
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12
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Combination of irreversible electroporation with sustained release of a synthetic membranolytic polymer for enhanced cancer cell killing. Sci Rep 2021; 11:10810. [PMID: 34031433 PMCID: PMC8144369 DOI: 10.1038/s41598-021-89661-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Accepted: 04/16/2021] [Indexed: 12/13/2022] Open
Abstract
Irreversible electroporation (IRE) is used clinically as a focal therapy to ablate solid tumors. A critical disadvantage of IRE as a monotherapy for cancer is the inability of ablating large tumors, because the electric field strength required is often too high to be safe. Previous reports indicate that cells exposed to certain cationic small molecules and surfactants are more vulnerable to IRE at lower electric field strengths. However, low-molecular-weight IRE sensitizers may suffer from suboptimal bioavailability due to poor stability and a lack of control over spatiotemporal accumulation in the tumor tissue. Here, we show that a synthetic membranolytic polymer, poly(6-aminohexyl methacrylate) (PAHM), synergizes with IRE to achieve enhanced cancer cell killing. The enhanced efficacy of the combination therapy is attributed to PAHM-mediated sensitization of cancer cells to IRE and to the direct cell killing by PAHM through membrane lysis. We further demonstrate sustained release of PAHM from embolic beads over 1 week in physiological medium. Taken together, combining IRE and a synthetic macromolecular sensitizer with intrinsic membranolytic activity and sustained bioavailability may present new therapeutic opportunities for a wide range of solid tumors.
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13
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White RR, Murphy JD, Martin RCG. The Landmark Series: Locally Advanced Pancreatic Cancer and Ablative Therapy Options. Ann Surg Oncol 2021; 28:4173-4180. [PMID: 33586072 DOI: 10.1245/s10434-021-09662-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 01/15/2021] [Indexed: 12/11/2022]
Abstract
Locally advanced pancreatic cancer (LAPC) is a challenging disease to treat. There is consensus that systemic chemotherapy should be the first line of therapy for most patients. However, there is no consensus on how to manage those patients who do not have sufficient response to become candidates for resection but also do not have distant progression after weeks or months of systemic therapy. Radiation therapy is the most commonly used and best-studied local ablative therapy. One recent randomized controlled trial (LAP-07) failed to demonstrate an overall survival benefit for conventional chemoradiation therapy after induction chemotherapy versus chemotherapy alone. This study had several limitations, and ongoing studies are re-evaluating the role of chemoradiation after more effective chemotherapy regimens as well as more advanced radiation techniques. In parallel, there has been increasing interest in other thermal and non-thermal methods of ablation. In particular, irreversible electroporation has gained traction for treatment of LAPC, with at least one ongoing randomized controlled trial designed to address its role compared with systemic chemotherapy alone. Multiple preclinical and clinical studies are investigating combinations of local ablation and immunotherapy with the goal of generating immune responses that will meaningfully improve outcomes.
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Affiliation(s)
- Rebekah R White
- Department of Surgery, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
| | - James D Murphy
- Department of Radiation Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA, USA
| | - Robert C G Martin
- Department of Surgery, University of Louisville, Louisville, KY, USA
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14
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Kwon JH, Chung MJ, Park JY, Lee HS, Hwang HK, Kang CM, Lee WJ, Park MS, Kim N, Bang S, Kim MD. Initial experience of irreversible electroporation for locally advanced pancreatic cancer in a Korean population. Acta Radiol 2021; 62:164-171. [PMID: 32295390 DOI: 10.1177/0284185120917118] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Locally advanced pancreatic cancer (LAPC) is one of the most aggressive malignancies. Irreversible electroporation (IRE) is a novel technique that uses a non-thermal ablation to avoid vessel or duct injury. PURPOSE To investigate the safety and efficacy of IRE for the management of LAPC in a Korean population. MATERIAL AND METHODS Twelve patients (median age 64 years; age range 46-73 years) treated between December 2015 and March 2017 underwent intraoperative IRE for LAPC. Technical success and clinical outcomes, including complications, serum pancreatic enzyme levels, overall survival (OS), and progression-free survival (PFS), were evaluated. RESULTS Tumors were located in the pancreas head in 7 (58.3%) patients and in the body/tail in 5 (41.7%) patients. The median tumor diameter in the longest axis was 3.1 cm. Vascular invasion was observed in all patients and bowel abutment in 3 (25%) patients. Technical success was achieved in all patients. The median serum levels of amylase and lipase were 55 U/L and 31 U/L, respectively, at baseline, increased to 141.5 U/L (P = 0.008) and 53 U/L (P = 0.505), respectively, one day after IRE, and normalized after one week. The rate of 30-day mortality of unknown relation was 8.3% (one individual experienced massive hematemesis 12 days after IRE). The median OS from diagnosis and IRE was 24.5 months and 13.5 months, respectively. The median PFS from diagnosis and IRE was 19.2 months and 8.6 months, respectively. CONCLUSION For patients with LAPC, IRE appears to be a promising treatment modality with an acceptable safety profile.
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Affiliation(s)
- Joon Ho Kwon
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Moon Jae Chung
- Department of Internal Medicine, Severance Hospital, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jeong Youp Park
- Department of Internal Medicine, Severance Hospital, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hee Seung Lee
- Department of Internal Medicine, Severance Hospital, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ho Kyoung Hwang
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chang Moo Kang
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Woo Jung Lee
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Mi-Suk Park
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Namo Kim
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seungmin Bang
- Department of Internal Medicine, Severance Hospital, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Man-Deuk Kim
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Republic of Korea
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15
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Ma YY, Leng Y, Xing YL, Li HM, Chen JB, Niu LZ. Gemcitabine plus concurrent irreversible electroporation vs gemcitabine alone for locally advanced pancreatic cancer. World J Clin Cases 2020; 8:5564-5575. [PMID: 33344547 PMCID: PMC7716311 DOI: 10.12998/wjcc.v8.i22.5564] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 08/25/2020] [Accepted: 09/26/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Locally advanced pancreatic cancer (LAPC) is a common malignant digestive system tumor that ranks as the fourth leading cause of cancer-related death in the world. The prognosis of LAPC is poor even after standard treatment. Irreversible electroporation (IRE) is a novel ablative strategy for LAPC. Several studies have confirmed the safety of IRE. To date, no prospective studies have been performed to investigate the therapeutic efficacy of conventional gemcitabine (GEM) plus concurrent IRE. AIM To compare the therapeutic efficacy between conventional GEM plus concurrent IRE and GEM alone for LAPC. METHODS From February 2016 to September 2017, a total of 68 LAPC patients were treated with GEM plus concurrent IRE n = 33) or GEM alone n = 35). Overall survival (OS), progression free survival (PFS), and procedure-related complications were compared between the two groups. Multivariate analyses were performed to identify any prognostic factors. RESULTS There were no treatment-related deaths. The technical success rate of IRE ablation was 100%. The GEM + IRE group had a significantly longer OS from the time of diagnosis of LAPC (19.8 mo vs 9.3 mo, P < 0.0001) than the GEM alone group. The GEM + IRE group had a significantly longer PFS (8.3 mo vs 4.7 mo, P < 0.0001) than the GEM alone group. Tumor volume less than 37 cm3 and GEM plus concurrent IRE were identified as significant favorable factors for both the OS and PFS. CONCLUSION Gemcitabine plus concurrent IRE is an effective treatment for patients with LAPC.
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Affiliation(s)
- Yang-Yang Ma
- Central Laboratory, Affiliated Fuda Cancer Hospital, Jinan University, Guangzhou 510665, Guangdong Province, China
| | - Yin Leng
- Department of Oncology, Affiliated Fuda Cancer Hospital, Jinan University, Guangzhou 510665, Guangdong Province, China
| | - Yan-Li Xing
- Department of Oncology, Affiliated Fuda Cancer Hospital, Jinan University, Guangzhou 510665, Guangdong Province, China
| | - Hong-Mei Li
- Department of Oncology, Affiliated Fuda Cancer Hospital, Jinan University, Guangzhou 510665, Guangdong Province, China
| | - Ji-Bing Chen
- Central Laboratory, Affiliated Fuda Cancer Hospital, Jinan University, Guangzhou 510665, Guangdong Province, China
| | - Li-Zhi Niu
- Department of Interventional Radiology, Affiliated Fuda Cancer Hospital, Jinan University, Guangzhou 510665, Guangdong Province, China
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16
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Kwon JH, Kim MD, Kim SH, Lee EW, Kahlid SA. Effects of irreversible electroporation on femoral nerves in a rabbit model. MINIM INVASIV THER 2020; 31:306-312. [PMID: 32744129 DOI: 10.1080/13645706.2020.1799820] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
INTRODUCTION Irreversible electroporation (IRE) is a novel technique that uses a non-thermal ablation to avoid adjacent major structure injury. The aim of this study was to sequentially evaluate the effects of IRE on the femoral nerve during acute-to-delayed periods in a rabbit model. MATERIAL AND METHODS Ultrasound-guided IRE of femoral neurovascular bundles was performed in seven rabbits. Functional and histopathologic evaluation was performed sequentially after IRE. The extent of nerve fiber affected, and the proportion of perineurial inflammation and surrounding tissue injury were recorded. RESULTS After IRE, femoral nerve function was damaged before four weeks, but then gradually returned to normal. Perineural inflammatory cell infiltration was most severe three days after IRE (80-85%), and was normalized after eight weeks. Surrounding tissue injury was prominent at three days and one week after IRE (80-90%), and then gradually recovered. However, peripheral nerve fibers were markedly damaged at one and two weeks (80-100%). Nerve fibers then recovered and were normalized at eight weeks. CONCLUSION Nerve tissue injury with transient functional impairment can occur after IRE. However, endoneurial and epineurial extracellular matrix were preserved with Schwann cell regeneration, which could lead to regeneration of nerve tissues within eight weeks.
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Affiliation(s)
- Joon Ho Kwon
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Man-Deuk Kim
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Se Hoon Kim
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Edward W Lee
- Division of Interventional Radiology, Department of Radiology, Ronald Reagan Medical Center at UCLA Medical Center, Los Angeles, CA, USA
| | - Suliman Aljoqiman Kahlid
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Radiology, King Faisal University College of Medicine, Al-Ahsa, Saudi Arabia
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17
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Bhutiani N, Davidyuk V, Mortensen GF, Brown AN, Bahr MH, Martin RCG, Vitale GC. Safety, Efficacy, and Technical Details of Endoscopic Retrograde Cholangiopancreatography After Irreversible Electroporation for Locally Advanced Pancreatic Cancer. J Gastrointest Surg 2020; 24:1077-1081. [PMID: 31093898 DOI: 10.1007/s11605-019-04223-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 03/28/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Patients undergoing irreversible electroporation (IRE) for locally advanced pancreatic cancer (LAPC) may experience biliary obstruction owing to inflammation generated by tumor ablation. This study assessed the safety, efficacy, and technical details of endoscopic retrograde cholangiopancreatography (ERCP) for biliary decompression after IRE. METHODS A single-institution database of patients undergoing IRE for LAPC between 2012 and 2017 was queried for patients requiring post-IRE ERCP. Patients were evaluated along demographic, laboratory, procedural, and outcome measures. RESULTS Of 113 patients with LAPC who underwent IRE, 6 (5.3%) required subsequent ERCP for biliary obstruction. A total of 12 ERCPs were performed. Two patients (33%) had duodenal bulb narrowing requiring dilation, and one patient (17%) had a pancreatic head cyst complicating guidewire passage. Biliary cannulation was achieved in all patients in a median time of 30 min. Four patients (67%) underwent sphincterotomy, and 5 (83%) underwent stent placement. Post-procedurally, all showed liver test improvement. None developed pancreatitis. Four patients underwent a 2nd ERCP. All were successful and included stent placement. CONCLUSIONS For patients with biliary obstruction after IRE, ERCP with sphincterotomy and stent placement can safely relieve this obstruction. Duodenal dilation and careful guidewire manipulation may be required to maximize technical success in these patients.
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Affiliation(s)
- Neal Bhutiani
- University of Louisville Department of Surgery, 550 S. Jackson Street, Louisville, KY, 40202, USA
| | - Vladimir Davidyuk
- University of Louisville Department of Surgery, 550 S. Jackson Street, Louisville, KY, 40202, USA
| | - Garrett F Mortensen
- University of Louisville Department of Surgery, 550 S. Jackson Street, Louisville, KY, 40202, USA
| | - Amber N Brown
- University of Louisville Department of Surgery, 550 S. Jackson Street, Louisville, KY, 40202, USA
| | - Michael H Bahr
- University of Louisville Department of Surgery, 550 S. Jackson Street, Louisville, KY, 40202, USA
| | - Robert C G Martin
- University of Louisville Department of Surgery, 550 S. Jackson Street, Louisville, KY, 40202, USA
| | - Gary C Vitale
- University of Louisville Department of Surgery, 550 S. Jackson Street, Louisville, KY, 40202, USA.
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18
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Guenther E, Klein N, Mikus P, Botea F, Pautov M, Lugnani F, Macchioro M, Popescu I, Stehling MK, Rubinsky B. Toward a clinical real time tissue ablation technology: combining electroporation and electrolysis (E2). PeerJ 2020; 8:e7985. [PMID: 31998549 PMCID: PMC6977482 DOI: 10.7717/peerj.7985] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 10/03/2019] [Indexed: 01/05/2023] Open
Abstract
Background Percutaneous image-guided tissue ablation (IGA) plays a growing role in the clinical management of solid malignancies. Electroporation is used for IGA in several modalities: irreversible electroporation (IRE), and reversible electroporation with chemotoxic drugs, called electrochemotherapy (ECT). It was shown that the combination of electrolysis and electroporation—E2—affords tissue ablation with greater efficiency, that is, lower voltages, lower energy and shorter procedure times than IRE and without the need for chemotoxic additives as in ECT. Methods A new E2 waveform was designed that delivers optimal doses of electroporation and electrolysis in a single waveform. A series of experiments were performed in the liver of pigs to evaluate E2 in the context of clinical applications. The goal was to find initial parameter boundaries in terms of electrical field, pulse duration and charge as well as tissue behavior to enable real time tissue ablation of clinically relevant volumes. Results Histological results show that a single several hundred millisecond long E2 waveform can ablate large volume of tissue at relatively low voltages while preserving the integrity of large blood vessels and lumen structures in the ablation zone without the use of chemotoxic drugs or paralyzing drugs during anesthesia. This could translate clinically into much shorter treatment times and ease of use compared to other techniques that are currently applied.
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Affiliation(s)
- Enric Guenther
- Biophysics, Inter Science GmbH, Gisikon, Lucerne, Switzerland.,Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, CA, USA.,Institut fur Bildgebende Diagnostik, Offenbach, Germany
| | - Nina Klein
- Biophysics, Inter Science GmbH, Gisikon, Lucerne, Switzerland.,Institut fur Bildgebende Diagnostik, Offenbach, Germany.,Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain
| | - Paul Mikus
- Biophysics, Inter Science GmbH, Gisikon, Lucerne, Switzerland
| | - Florin Botea
- Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania.,Center of Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Mihail Pautov
- Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania.,Center of Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | | | | | - Irinel Popescu
- Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania.,Center of Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Michael K Stehling
- Biophysics, Inter Science GmbH, Gisikon, Lucerne, Switzerland.,Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, CA, USA.,Institut fur Bildgebende Diagnostik, Offenbach, Germany
| | - Boris Rubinsky
- Biophysics, Inter Science GmbH, Gisikon, Lucerne, Switzerland.,Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, CA, USA
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19
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Quality of life assessment for patients undergoing irreversible electroporation (IRE) for treatment of locally advanced pancreatic cancer (LAPC). Am J Surg 2019; 218:571-578. [DOI: 10.1016/j.amjsurg.2019.03.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 02/24/2019] [Accepted: 03/27/2019] [Indexed: 12/25/2022]
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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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A Conceivable Mechanism Responsible for the Synergy of High and Low Voltage Irreversible Electroporation Pulses. Ann Biomed Eng 2019; 47:1552-1563. [PMID: 30953220 DOI: 10.1007/s10439-019-02258-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Accepted: 03/29/2019] [Indexed: 12/12/2022]
Abstract
Irreversible electroporation (IRE), is a new non-thermal tissue ablation technology in which brief high electric field pulses are delivered across the target tissue to induce cell death by irreversible permeabilization of the cell membrane. A deficiency of conventional IRE is that the ablation zone is relatively small, bounded by the irreversible electroporation isoelectric field margin. In the previous studies we have introduced a new treatment protocol that combines few short high voltage (SHV) pulses with long low-voltage (LLV) pulses. In the previous studies, we also have shown that the addition of few SHV pulses increases by almost a factor of two the area ablated by a protocol that employs only the LLV pulses. This study employs potato and gel phantom to generate a plausible explanation for the mechanism. The study provides circumstantial evidence that the mechanism involved is the production of electrolytic compounds by the LLV pulse sequence, which causes tissue ablation beyond the margin of the irreversible electroporation isoelectric field generated by the SHV pulses, presumable to the reversible electroporation isoelectric field margin generated by the SHV pulses.
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Liu S, Qin Z, Xu J, Zeng J, Chen J, Niu L, Xu M. Irreversible electroporation combined with chemotherapy for unresectable pancreatic carcinoma: a prospective cohort study. Onco Targets Ther 2019; 12:1341-1350. [PMID: 30863100 PMCID: PMC6388995 DOI: 10.2147/ott.s186721] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Objective We aimed to determine the safety and efficacy of irreversible electroporation (IRE) combined with chemotherapy for unresectable pancreatic carcinoma (stage III/IV). Methods We prospectively enrolled 54 patients (30 men; median age 61.0 years; range 41-73 years) undergoing IRE with or without chemotherapy for pancreatic cancer between July 2015 and August 2016. Kaplan-Meier estimates were used to analyze progression-free survival (PFS) and overall survival (OS). Safety was assessed based on the occurrence of adverse events. Results All patients successfully underwent IRE. Major IRE-related complications were observed in four patients (7.4%). Gastrointestinal hemorrhage only developed in cases undergoing IRE via the open method, and was successfully managed with interventional embolization and/or vascular ligation. Any minor complications in the cases were alleviated within 14 days after symptomatic treatment. Overall, the performance status score decreased from 1.06 to 0.89 at 3 months after IRE (P<0.05). Among those with stage III disease, after a median follow-up of 18.8 months (range 9.6-28.7 months), the median OS from diagnosis was 16.2 and 20.3 months in the IRE and IRE + Chemo groups, respectively. Among those with stage IV disease, after a median follow-up of 13.3 months (range 3.7-23.1 months), the median OS from diagnosis was 11.6 and 13.56 months in the IRE and IRE + Chemo groups, respectively. The OS was significantly poorer in the IRE group than in the IRE + Chemo group (log-rank test, P=0.0398). Conclusion Patients with pancreatic carcinoma could benefit from IRE, which improved the OS in certain patients who had also undergone chemotherapy. Although some severe complications were noted, IRE was generally well tolerated.
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Affiliation(s)
- Shupeng Liu
- Department of Oncology, Fuda Cancer Hospital, Jinan University, Guangzhou 510665, China, .,Department of Oncology, First Affiliated Hospital of Jinan University, Guangzhou 510630, China,
| | - Zilin Qin
- Department of Oncology, Fuda Cancer Hospital, Jinan University, Guangzhou 510665, China,
| | - Jiongyuan Xu
- Department of Oncology, Fuda Cancer Hospital, Jinan University, Guangzhou 510665, China,
| | - Jianying Zeng
- Department of Oncology, Fuda Cancer Hospital, Jinan University, Guangzhou 510665, China,
| | - Jibing Chen
- Department of Oncology, Fuda Cancer Hospital, Jinan University, Guangzhou 510665, China,
| | - Lizhi Niu
- Department of Oncology, Fuda Cancer Hospital, Jinan University, Guangzhou 510665, China,
| | - Meng Xu
- Department of Oncology, First Affiliated Hospital of Jinan University, Guangzhou 510630, China,
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23
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Flak RV, Stender MT, Jensen TM, Andersen KL, Henriksen SD, Mortensen PB, Sall M, Thorlacius-Ussing O. Treatment of locally advanced pancreatic cancer with irreversible electroporation - a Danish single center study of safety and feasibility. Scand J Gastroenterol 2019; 54:252-258. [PMID: 30907286 DOI: 10.1080/00365521.2019.1575465] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Irreversible electroporation (IRE) is a novel non-thermal ablative technique applied in the treatment of unresectable locally advanced pancreatic cancer (LAPC). This paper reports on the initial experience with IRE of unresectable LAPC in our institution. METHODS From October 2013 to March 2018, patients with unresectable LAPC referred for IRE at the Department of Gastrointestinal Surgery, Aalborg University Hospital, were considered for inclusion in the study. Ninety-day morbidity, 30-day mortality, pain score, length of hospital stay (LOS) and overall survival (OS) were recorded. RESULTS We included 33 patients receiving 40 IRE ablations in total. The median visual analogue scale (VAS)-score was four (range 0-10) two hours after IRE, and one (range 0-8) eight hours after IRE. The median LOS was one day (range 1-13 days). Post-procedural complications occurred in 21 of 40 ablations (53%), of which eight (20%) were major (Clavien-Dindo grade III or more). A proportion of the observed complications might be attributed to disease progression and not IRE per se. Although not statistically significant, we observed increased severity of complications in tumors above 3.5 cm. The 30-day mortality was 5% (2/40). The median OS was 10.7 months (range 0.6-53.8 months) from the initial IRE procedure, and 18.5 months (range 4.9-65.8 months) from time of diagnosis. CONCLUSIONS In our institution, IRE seems as a feasible consolidative treatment of unresectable LAPC with an acceptable safety profile. The oncological outcome of IRE in patients with unresectable LAPC is to be further evaluated in a planned phase 2 clinical trial (CHEMOFIRE-2).
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Affiliation(s)
- Rasmus Virenfeldt Flak
- a Department of Gastrointestinal Surgery , Aalborg University Hospital , Aalborg , Denmark
| | - Mogens Tornby Stender
- a Department of Gastrointestinal Surgery , Aalborg University Hospital , Aalborg , Denmark
| | | | - Kasper Lenni Andersen
- a Department of Gastrointestinal Surgery , Aalborg University Hospital , Aalborg , Denmark
| | - Stine Dam Henriksen
- a Department of Gastrointestinal Surgery , Aalborg University Hospital , Aalborg , Denmark
| | | | - Mogens Sall
- a Department of Gastrointestinal Surgery , Aalborg University Hospital , Aalborg , Denmark
| | - Ole Thorlacius-Ussing
- a Department of Gastrointestinal Surgery , Aalborg University Hospital , Aalborg , Denmark.,c Clinical Cancer Research Center, Aalborg University Hospital , Aalborg , Denmark.,d Department of Clinical Medicine , Aalborg University , Aalborg , Denmark
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24
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Pandit H, Hong YK, Li Y, Rostas J, Pulliam Z, Li SP, Martin RCG. Evaluating the Regulatory Immunomodulation Effect of Irreversible Electroporation (IRE) in Pancreatic Adenocarcinoma. Ann Surg Oncol 2019; 26:800-806. [PMID: 30610562 DOI: 10.1245/s10434-018-07144-3] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Irreversible electroporation (IRE) has been demonstrated as an effective local method for locally advanced (stage 3) pancreatic adenocarcinoma. Immune regulatory T cells (Tregs) induce immunosuppression of tumors by inhibiting patients' anti-tumor adaptive immune response. This study aimed to evaluate the immunomodulation effect of IRE to identify an ideal time point for potential adjuvant immunotherapy. METHODS This study prospectively evaluated an institutional review board-approved study of patients undergoing either in situ IRE or pancreatectomy. Patient blood samples were collected at different time points (before surgery [preOP] and on postoperative day [POD] 1, POD3, and POD5). Peripheral blood mononuclear cells (PBMCs) were isolated and evaluated for three different CD4 + Treg subsets (CD25 + CD4 +, CD4 + CD25 + FoxP3 +, CD4 + CD25 + FoxP3 -) by flow cytometry and analyzed for median fold change (MFC) between each two consecutive time points (MFC = log2(T2/T1)). RESULTS The study analyzed 15 patients with in situ IRE (n = 11) or pancreatectomy (PAN) (n = 4). In both groups, CD25 + CD4 + Tregs decreased on POD1 followed by a steady increase in pancreatectomy, whereas the trend in the IRE group reversed between D3 and D5 (MFC: IRE [- 0.01], PAN [+ 0.39]). For each period, CD4 + CD25 + FoxP3 + Tregs showed the most dramatic inverse effect, with D3 to D5 showing the most change (MFC: IRE [- 0.18], PAN [+ 0.39]). Also, CD4 + CD25 + FoxP3 - Tregs showed an inverse effect between D3 and D5 (MFC: IRE [- 0.25], PAN [+ 0.49]). Altogether, the Treg trend was inversely affected by the in situ IRE procedure, with the greatest cumulative significant change for all three Treg subsets between D3 and D5 (MFC ± SEM: IRE [- 0.24 ± 0.05], PAN [+ 0.37 ± 0.02]; p = 0.016). CONCLUSIONS The study data suggest that in situ IRE procedure-mediated Treg attenuation between POD3 and POD5 can provide a clinical window of opportunity for potentiating clinical efficacy in combination with immunotherapy.
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Affiliation(s)
- Harshul Pandit
- Division of Surgical Oncology, Hiram C. Polk Jr. M.D. Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA.,Department of Pharmacology & Toxicology, University of Louisville School of Medicine, Louisville, KY, USA
| | - Young K Hong
- Division of Surgical Oncology, Hiram C. Polk Jr. M.D. Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA
| | - Yan Li
- Division of Surgical Oncology, Hiram C. Polk Jr. M.D. Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA
| | - Jack Rostas
- Division of Surgical Oncology, Hiram C. Polk Jr. M.D. Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA
| | - Zachary Pulliam
- Division of Surgical Oncology, Hiram C. Polk Jr. M.D. Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA
| | - Su Ping Li
- Division of Surgical Oncology, Hiram C. Polk Jr. M.D. Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA
| | - Robert C G Martin
- Division of Surgical Oncology, Hiram C. Polk Jr. M.D. Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA. .,Department of Pharmacology & Toxicology, University of Louisville School of Medicine, Louisville, KY, USA.
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25
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Zhao Y, Liu H, Bhonsle SP, Wang Y, Davalos RV, Yao C. Ablation outcome of irreversible electroporation on potato monitored by impedance spectrum under multi-electrode system. Biomed Eng Online 2018; 17:126. [PMID: 30236121 PMCID: PMC6148960 DOI: 10.1186/s12938-018-0562-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Accepted: 09/17/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Irreversible electroporation (IRE) therapy relies on pulsed electric fields to non-thermally ablate cancerous tissue. Methods for evaluating IRE ablation in situ are critical to assessing treatment outcome. Analyzing changes in tissue impedance caused by electroporation has been proposed as a method for quantifying IRE ablation. In this paper, we assess the hypothesis that irreversible electroporation ablation outcome can be monitored using the impedance change measured by the electrode pairs not in use, getting more information about the ablation size in different directions. METHODS Using a square four-electrode configuration, the two diagonal electrodes were used to electroporate potato tissue. Next, the impedance changes, before and after treatment, were measured from different electrode pairs and the impedance information was extracted by fitting the data to an equivalent circuit model. Finally, we correlated the change of impedance from various electrode pairs to the ablation geometry through the use of fitted functions; then these functions were used to predict the ablation size and compared to the numerical simulation results. RESULTS The change in impedance from the electrodes used to apply pulses is larger and has higher deviation than the other electrode pairs. The ablation size and the change in resistance in the circuit model correlate with various linear functions. The coefficients of determination for the three functions are 0.8121, 0.8188 and 0.8691, respectively, showing satisfactory agreement. The functions can well predict the ablation size under different pulse numbers, and in some directions it did even better than the numerical simulation method, which used different electric field thresholds for different pulse numbers. CONCLUSIONS The relative change in tissue impedance measured from the non-energized electrodes can be used to assess ablation size during treatment with IRE according to linear functions.
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Affiliation(s)
- Yajun Zhao
- State Key Laboratory of Power Transmission Equipment and System Security and New Technology, School of Electrical Engineering, Chongqing University, No. 174 Shazhengjie, Shapingba District, Chongqing, 400044, China.,Department of Biomedical Engineering and Mechanics, Virginia Tech, 329 ICTAS Stanger St (0298), Blacksburg, VA, 24061, USA
| | - Hongmei Liu
- State Key Laboratory of Power Transmission Equipment and System Security and New Technology, School of Electrical Engineering, Chongqing University, No. 174 Shazhengjie, Shapingba District, Chongqing, 400044, China
| | - Suyashree P Bhonsle
- Department of Biomedical Engineering and Mechanics, Virginia Tech, 329 ICTAS Stanger St (0298), Blacksburg, VA, 24061, USA
| | - Yilin Wang
- State Key Laboratory of Power Transmission Equipment and System Security and New Technology, School of Electrical Engineering, Chongqing University, No. 174 Shazhengjie, Shapingba District, Chongqing, 400044, China
| | - Rafael V Davalos
- Department of Biomedical Engineering and Mechanics, Virginia Tech, 329 ICTAS Stanger St (0298), Blacksburg, VA, 24061, USA.
| | - Chenguo Yao
- State Key Laboratory of Power Transmission Equipment and System Security and New Technology, School of Electrical Engineering, Chongqing University, No. 174 Shazhengjie, Shapingba District, Chongqing, 400044, China.
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Abstract
The vast majority of patients who present with pancreatic adenocarcinoma have locally advanced or metastatic disease at the time of presentation without possibility of cure. Although in recent years there have been some new promising chemotherapy regimens that improve overall survival by a few months, the prognosis remains dismal. There is, however, a subset of patients who experience durable stable disease or partial responses after initial courses of chemotherapy with locally advanced disease. In these select patients, there remains interest in local ablative therapy with or without resection as a means for local control, palliation of symptoms, and possible improved survival. This review describes the techniques, complications, and expected benefits of several ablative techniques as a treatment modality for locally advanced pancreatic cancer.
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Affiliation(s)
- Rupen Shah
- From the Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY
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27
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Lin M, Liang S, Wang X, Liang Y, Zhang M, Chen J, Niu L, Xu K. Percutaneous irreversible electroporation combined with allogeneic natural killer cell immunotherapy for patients with unresectable (stage III/IV) pancreatic cancer: a promising treatment. J Cancer Res Clin Oncol 2017; 143:2607-2618. [PMID: 28871458 DOI: 10.1007/s00432-017-2513-4] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Accepted: 08/31/2017] [Indexed: 12/11/2022]
Abstract
PURPOSE This study was attempted to investigate the safety and clinical efficacy of percutaneous irreversible electroporation combined with allogeneic natural killer cell therapy for treating stage III/IV pancreatic cancer, evaluate median progression-free survival (PFS), and overall survival (OS). METHODS Between March 2016 and February 2017, we enrolled 67 patients who met the enrollment criteria. According to the latest NCCN Guidelines, the patients were divided into stage III (35 patients, 16 patients received only irreversible electroporation (IRE) and 19 patients received IRE-NK: 8 patients underwent one course NK and 11 patients underwent ≥3 courses) and stage IV (32 patients, 14 patients received only IRE and 18 patients received IRE-NK: 8 patients underwent one course NK and 10 patients underwent ≥3 courses). The safety and short-term effects were evaluated first, then the median PFS, median OS, response rate (RR) and disease control rate (DCR) were assessed. RESULTS Adverse events of all patients were limited to grades A and B, included local (mainly cough 12.7%, nausea and emesis 6.8%, pain of puncture point 25.3% and duodenum and gastric retention 5.9%) and systemic (mainly fatigue 21.5, fever 33.5%, and blood pressure intraoperative transient reduction 27.4% and white cell count reduction 22.6%) reactions, fever was most frequent. The serum amylase level at 24 h and 7 d after IRE was not significantly changed compared to those before IRE (P > 0.05). CA19-9 value was lower in IRE-NK group than in IRE at 1 month after treatment (P < 0.05). After a median follow-up of 7.9 months (3.8-12.1 months): in stage III group, median PFS was higher in IRE-NK group (9.1 months) than in IRE group (7.9 months, P = 0.0432), median OS was higher in IRE-NK (13.6 months) than in IRE (12.2 months; P = 0.0327), and median PFS was higher in who received multiple NK than single NK (9.9 vs. 8.2 months; P = 0.0387, respectively), median OS who received multiple NK was higher than single NK (13.7 vs. 12.1 months; P = 0.0451, respectively), the RR in IRE-NK (63.2%) was higher than in IRE (50.0%; P < 0.05); in stage IV group, median OS was higher in IRE-NK (10.2 months) than in IRE (9.1 months; P = 0.0367), the DCR in IRE-NK (66.7%) was higher than in IRE (42.9%; P < 0.05). CONCLUSION Percutaneous irreversible electroporation combined with allogeneic natural killer cell immunotherapy significantly increased median PFS and median OS in stage III pancreatic cancer and extended the median OS of stage IV pancreatic cancer. Multiple allogeneic natural killer cells infusion was associated with better prognosis to stage III pancreatic cancer.
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Affiliation(s)
- Mao Lin
- Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School, Guangzhou, China
- Fuda Cancer Institute, Guangzhou, China
| | - Shuzhen Liang
- Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School, Guangzhou, China
| | - Xiaohua Wang
- Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School, Guangzhou, China
| | - Yinqing Liang
- Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School, Guangzhou, China
| | | | - Jibing Chen
- Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School, Guangzhou, China.
- Fuda Cancer Institute, Guangzhou, China.
| | - Lizhi Niu
- Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School, Guangzhou, China.
- Fuda Cancer Institute, Guangzhou, China.
- Department of Oncology, Fuda Cancer Hospital, Jinan University School, Guangzhou, China.
| | - Kecheng Xu
- Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School, Guangzhou, China
- Fuda Cancer Institute, Guangzhou, China
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28
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Lin M, Alnaggar M, Liang SZ, Shi J, Niu LZ, Chen JB, Xu KC. Using circulating tumor cells to evaluate the efficacy of irreversible electroporation for unresectasble pancreatic cancer. Immunol Res 2017; 66:172-178. [DOI: 10.1007/s12026-017-8959-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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29
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Lin M, Alnaggar M, Liang S, Wang X, Liang Y, Zhang M, Chen J, Niu L, Xu K. An important discovery on combination of irreversible electroporation and allogeneic natural killer cell immunotherapy for unresectable pancreatic cancer. Oncotarget 2017; 8:101795-101807. [PMID: 29254205 PMCID: PMC5731915 DOI: 10.18632/oncotarget.21974] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 09/23/2017] [Indexed: 12/11/2022] Open
Abstract
Purpose To study the safety and clinical efficacy on combination of irreversible electroporation and allogeneic natural killer cell therapy for treating Stage III/IV pancreatic cancer, evaluating median progression free survival (PFS), and overall survival (OS). Results Adverse events of all patients were limited to grades 1 and 2, including local (mainly tussis 13.4%, nausea and emesis 7.1%, pain of puncture point 29.6% and duodenum and gastric retention 4.3%) and systemic (mainly fatigue 22.3%, fever 31.6%, and transient reduction of intraoperative blood pressure 25.1% and white cell count reduction 18.3%) reactions, fever was the most frequent. The serum amylase level at 24 h and 7 d after IRE was not significantly changed compared to those before IRE (P > 0.05). CA19–9 value was lower in IRE-NK group than in IRE at 1 month after treatment (P < 0.05). After a median follow-up of 7.4 months (3.6–11.2 months): in stage III group, median PFS was higher in IRE-NK group (9.3 months) than in IRE group (8.1 months, P = 0.0465), median OS was higher in IRE-NK (13.2 months) than in IRE (11.4 months, P = 0.0411), and median PFS was higher in who received multiple NK than single NK (9.8 months vs.8.1 months, P = 0.0423, respectively), median OS who received multiple NK was higher than single NK (13.9 months vs.12.3 months, P = 0.0524, respectively), the RR in IRE-NK (63.2%) was higher than in IRE (50.0%, P < 0.05); in stage IV group, median OS was higher in IRE-NK (9.8 months) than in IRE (8.7 months, P = 0.0397), the DCR in IRE-NK (66.7%) was higher than in IRE (42.9%, P < 0.05). Materials and Methods Between July 2016 and May 2017, we enrolled 71 patients who met the enrollment criteria. The patients were divided into stage III (32 patients, 17 patients received only IRE and 15 patients received IRE-NK (Irreversible electroporation- natural killer): 8 patients underwent a course of NK and 7 patients underwent ≥ 3 courses) and stage IV (39 patients, 22 patients received only IRE and 17 patients received IRE-NK: 9 patients underwent a course of NK and 8 patients underwent ≥ 3 courses). The safety and short-term effects were evaluated firstly, then the median PFS, median OS, response rate (RR) and disease control rate (DCR) were assessed. Conclusions Combination of irreversible electroporation and allogeneic natural killer cell immunotherapy significantly increased median PFS and median OS in stage III pancreatic cancer and extended the median OS of stage IV pancreatic cancer. Multiple allogeneic natural killer cells infusion was associated with better prognosis to stage III pancreatic cancer.
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Affiliation(s)
- Mao Lin
- Fuda Cancer Hospital, School of Medicine, Jinan University, Guangzhou, China.,Fuda Cancer Institute, Guangzhou, China
| | - Mohammed Alnaggar
- Fuda Cancer Hospital, School of Medicine, Jinan University, Guangzhou, China
| | - Shuzhen Liang
- Fuda Cancer Hospital, School of Medicine, Jinan University, Guangzhou, China
| | - Xiaohua Wang
- Fuda Cancer Hospital, School of Medicine, Jinan University, Guangzhou, China
| | - Yinqing Liang
- Fuda Cancer Hospital, School of Medicine, Jinan University, Guangzhou, China
| | | | - Jibing Chen
- Fuda Cancer Hospital, School of Medicine, Jinan University, Guangzhou, China.,Fuda Cancer Institute, Guangzhou, China
| | - Lizhi Niu
- Fuda Cancer Hospital, School of Medicine, Jinan University, Guangzhou, China.,Fuda Cancer Institute, Guangzhou, China
| | - Kecheng Xu
- Fuda Cancer Hospital, School of Medicine, Jinan University, Guangzhou, China.,Fuda Cancer Institute, Guangzhou, China
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30
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Short-term clinical efficacy of percutaneous irreversible electroporation combined with allogeneic natural killer cell for treating metastatic pancreatic cancer. Immunol Lett 2017; 186:20-27. [DOI: 10.1016/j.imlet.2017.03.018] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 03/31/2017] [Accepted: 03/31/2017] [Indexed: 02/07/2023]
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31
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Martin RCG. Multi-disciplinary management of locally advanced pancreatic cancer with irreversible electroporation. J Surg Oncol 2017; 116:35-45. [PMID: 28475814 DOI: 10.1002/jso.24640] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Accepted: 03/22/2017] [Indexed: 12/13/2022]
Abstract
The essential diagnosis for LAPC is based on high-quality cross-sectional imaging, which demonstrates tumor invasion into the celiac/superior mesenteric arteries and/or superior mesenteric/portal venous system that is not reconstructable. The optimal management of these patients is evolving quickly with the advent of newer chemotherapeutics, radiation, and non-thermal ablation modalities. This review will present the current status of initial chemotherapy, surgical therapy, ablative therapy, and radiation therapy for patients with nonmetastatic locally advanced unresectable pancreatic cancer.
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Affiliation(s)
- Robert C G Martin
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky
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32
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Sánchez-Velázquez P, Clavien PA. The role of the irreversible electroporation in the hepato-pancreatico-biliary surgery. Cir Esp 2017; 95:307-312. [PMID: 28318494 DOI: 10.1016/j.ciresp.2017.01.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2017] [Accepted: 01/26/2017] [Indexed: 12/19/2022]
Abstract
Irreversible electroporation is a novel technique growing in popularity over the last years among the ablative modalities. Its unique action mechanism produces irreversible nanopores in the membrane of the cell leading to apoptosis; therefore irreversible electroporation can be used to ablate substantial volumes of tissue without the undesirable thermal effects as the "heat sink effect". Moreover the extracellular matrix is left unperturbed, thus sparing the structural architecture of surrounding structures such as bile ducts and blood vessels. In the last years its use has been widespread in both liver and pancreatic ablation. Irreversible electroporation has shown its safety with however some caution, feasibility and favorable outcomes in clinical settings such as unresectable locally advanced disease in which the surgical and therapeutic options are very limited.
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Affiliation(s)
| | - Pierre-Alain Clavien
- Departmento de cirugía y transplante, Hospital universitario de Zürich, Zúrich, Suiza.
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33
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Percutaneous Irreversible Electroporation for Ablation of Locally Advanced Pancreatic Cancer: Experience From a Chinese Institution. Pancreas 2017; 46:e12-e14. [PMID: 28085755 DOI: 10.1097/mpa.0000000000000703] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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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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Abstract
The purpose of this study was to investigate the safety and efficacy of irreversible electroporation (IRE) for the management of unresectable pancreatic vasoactive intestinal peptide tumor (VIPoma) in a 34-year-old male patient. The initial symptom was watery diarrhea, which could not be stopped by fasting. Laboratory tests revealed high vasoactive intestinal peptide (VIP) hormone levels, hypokalemia, and metabolic acidosis. Computed tomography examination showed a 6.0 × 5.0-cm, contrast-enhanced lesion in the neck and body of the pancreas and obliteration of the portal vein. Pathological and immunohistochemical findings were indicative of pancreatic VIPoma. The patient was treated with octreotide and IRE, and had no obvious IRE-related complications, except for moderate pain at the puncture sites. The patient reported that the watery diarrhea had decreased gradually; moreover, the VIP hormone level was normalized 15 days after IRE. Computed tomography scans showed a large area of necrosis in the pancreatic lesion. The findings from this case indicated that IRE could be a feasible and safe technique in controlling pancreatic VIPoma; however, additional follow-up and findings from more cases are required to further confirm the efficacy of IRE ablation therapy for pancreatic VIPoma.
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Yan L, Chen YL, Su M, Liu T, Xu K, Liang F, Gu WQ, Lu SC. A Single-institution Experience with Open Irreversible Electroporation for Locally Advanced Pancreatic Carcinoma. Chin Med J (Engl) 2016; 129:2920-2925. [PMID: 27958223 PMCID: PMC5198526 DOI: 10.4103/0366-6999.195476] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Locally advanced pancreatic carcinoma (LAPC) is characterized by poor prognosis despite recommended concurrent chemoradiotherapy. Irreversible electroporation (IRE) has emerged as a potential option for the management of unresectable pancreatic cancer. This study was conducted to evaluate the safety and short-term efficacy of open IRE for the treatment of LAPC. METHODS Retrospective data of 25 consecutive patients receiving IRE for T3 lesions from July 2015 to June 2016 at a single center were analyzed. The perioperative and long-term IRE-related complications were reviewed to evaluate the safety of the procedure. The tumor reduction and biological response were analyzed through computed tomography/magnetic resonance imaging; the serum level of CA19-9 was measured as a secondary endpoint to evaluate the short-term efficacy of IRE. RESULTS All patients were successfully treated; the median tumor size was 4.2 cm and the median IRE time was 36 min. Four intraoperative procedure-related complications were observed (16%): two transient hypertensive episodes, one hypotension case, and one transient supraventricular tachycardia case. Nine postoperative complications were described, including three Grade A pancreatic fistulas, three delayed gastric emptying, one acute pancreatitis, one upper gastrointestinal hemorrhage, and one portal vein thrombosis. The overall rate of stable disease was 28%, 36% achieved partial response, and lower serum CA19-9 levels were recorded in all patients at discharge. CONCLUSIONS IRE is feasible for the treatment of LAPC and is a reasonable intervention strategy owing to its combined attributes of safety and efficacy.
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Affiliation(s)
- Li Yan
- Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Yong-Liang Chen
- Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Ming Su
- Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Tian Liu
- Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Kai Xu
- Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Feng Liang
- Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
- Department of General Surgery, People's Hospital of Rizhao, Rizhao, Shandong 276800, China
| | - Wan-Qing Gu
- Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Shi-Chun Lu
- Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
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38
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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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Schulz B, Ou J, Van Meter T, Martin RCG. Early nontumorous CT findings after irreversible electroporation of locally advanced pancreatic cancer. Abdom Radiol (NY) 2016; 41:2142-2149. [PMID: 27351439 DOI: 10.1007/s00261-016-0815-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE The use of irreversible electroporation (IRE) has been a relatively recent development in the palliative treatment of locally advanced pancreatic cancer. With CT as a key modality in patient follow-up, recognition of nontumorous imaging findings is paramount after IRE. METHODS A retrospective review of patients having undergone IRE for locally advanced pancreatic adenocarcinoma was performed. A total of 36 patients met inclusion criteria and their imaging studies were reviewed by two radiologists. Nontumorous abnormalities identified in the peri-electroporation bed on Computed Tomography (CT) during the early postoperative period (within 30 days) were characterized and classified into categories. RESULTS Our results indicate that the most common nontumorous findings in the peri-electroporation bed were vascular, followed by changes involving the gastrointestinal tract, peritoneal cavity, and, infrequently, the biliary tree. CONCLUSIONS Interpretation of CT imaging of the postoperative peri-electroporation bed is challenging. This review of CT findings allows the radiologist to recognize and anticipate significant nontumorous findings in the peri-electroporation bed during early follow-up after IRE.
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An update on the role of irreversible electroporation in locally advanced pancreatic adenocarcinoma. HPB (Oxford) 2016; 18:791-792. [PMID: 27542589 PMCID: PMC5061020 DOI: 10.1016/j.hpb.2016.07.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Revised: 06/22/2016] [Accepted: 07/08/2016] [Indexed: 12/12/2022]
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Beyer LP, Pregler B, Michalik K, Niessen C, Dollinger M, Müller M, Schlitt HJ, Stroszczynski C, Wiggermann P. Evaluation of a robotic system for irreversible electroporation (IRE) of malignant liver tumors: initial results. Int J Comput Assist Radiol Surg 2016; 12:803-809. [PMID: 27653615 DOI: 10.1007/s11548-016-1485-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Accepted: 09/01/2016] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Comparison of conventional CT-guided manual irreversible electroporation (IRE) of malignant liver tumors and a robot-assisted approach regarding procedural accuracy, intervention time, dose, complications, and treatment success. METHODS A retrospective single-center analysis of 40 cases of irreversible electroporation of malignant liver tumors in 35 patients (6 females, 29 males, average age 60.3 years). Nineteen of these ablation procedures were performed manually and 21 with robotic assistance. A follow-up (ultrasound, CT, and MRI) was performed after 6 weeks in all patients. RESULTS The time from the planning CT scan to the start of the ablation as well as the dose-length product were significantly lower under robotic assistance (63.5 vs. 87.4 min, [Formula: see text]; 2132 vs. 4714 mGy cm, [Formula: see text]). The procedural accuracy, measured as the deviation of the IRE probes with respect to a defined reference probe, was significantly higher using robotic guidance (2.2 vs. 3.1 mm, [Formula: see text]). There were no complications. There was one incomplete ablation in the manual group. CONCLUSION Robotic assistance for IRE of liver tumors allows for faster procedure times with higher accuracy while reducing radiation dose as compared to the manual placement of IRE probes.
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Affiliation(s)
- L P Beyer
- Department of Radiology, University Medical Center Regensburg, 93053, Regensburg, Germany.
| | - B Pregler
- Department of Radiology, University Medical Center Regensburg, 93053, Regensburg, Germany
| | - K Michalik
- Department of Radiology, University Medical Center Regensburg, 93053, Regensburg, Germany
| | - C Niessen
- Department of Radiology, University Medical Center Regensburg, 93053, Regensburg, Germany
| | - M Dollinger
- Department of Radiology, University Medical Center Regensburg, 93053, Regensburg, Germany
| | - M Müller
- Department of Internal Medicine I, University Medical Center Regensburg, Regensburg, Germany
| | - H J Schlitt
- Department of Surgery, University Medical Center Regensburg, Regensburg, Germany
| | - C Stroszczynski
- Department of Radiology, University Medical Center Regensburg, 93053, Regensburg, Germany
| | - P Wiggermann
- Department of Radiology, University Medical Center Regensburg, 93053, Regensburg, Germany
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Paiella S, Salvia R, Girelli R, Frigerio I, Giardino A, D'Onofrio M, De Marchi G, Bassi C. Role of local ablative techniques (Radiofrequency ablation and Irreversible Electroporation) in the treatment of pancreatic cancer. Updates Surg 2016; 68:307-311. [PMID: 27535401 DOI: 10.1007/s13304-016-0385-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Accepted: 07/15/2016] [Indexed: 02/08/2023]
Abstract
Thanks to continuous research and investment in technology, the ablation of tumors has become common. Through the application of different types of energy is possible to induce cellular injury of the neoplastic tissue, leading to cellular death. Radiofrequency ablation (RFA) and irreversible electroporation (IRE) represent the most applied ablative techniques on pancreatic cancer. RFA and IRE, causing necrosis and apoptosis of neoplastic cells, are able to destroy neoplastic tissue, to drastically modify the neoplastic microenvironment and, possibly, to stimulate both directly and indirectly the anti-tumor immune system. This article provides part of our experience with the application of RFA and IRE on pancreatic adenocarcinoma (PDAC).
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Affiliation(s)
- Salvatore Paiella
- General and Pancreatic Surgery Department, The Pancreas Institute, University of Verona Hospital Trust, Piazzale L.A. Scuro 10, 37134, Verona, Italy
| | - Roberto Salvia
- General and Pancreatic Surgery Department, The Pancreas Institute, University of Verona Hospital Trust, Piazzale L.A. Scuro 10, 37134, 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
| | - Mirko D'Onofrio
- Radiology Department, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Giulia De Marchi
- Gastroenterology B Department, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Bassi
- General and Pancreatic Surgery Department, The Pancreas Institute, University of Verona Hospital Trust, Piazzale L.A. Scuro 10, 37134, Verona, Italy.
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Beyer LP, Pregler B, Nießen C, Schicho A, Haimerl M, Jung EM, Stroszczynski C, Wiggermann P. Stereotactically-navigated percutaneous Irreversible Electroporation (IRE) compared to conventional IRE: a prospective trial. PeerJ 2016; 4:e2277. [PMID: 27602266 PMCID: PMC4991851 DOI: 10.7717/peerj.2277] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Accepted: 07/01/2016] [Indexed: 12/18/2022] Open
Abstract
Purpose. The purpose of this study was to compare CT-navigated stereotactic IRE (SIRE) needle placement to non-navigated conventional IRE (CIRE) for percutaneous ablation of liver malignancies. Materials and Methods. A prospective trial including a total of 20 patients was conducted with 10 patients in each arm of the study. IRE procedures were guided using either CT fluoroscopy (CIRE) or a stereotactic planning and navigation system (SIRE). Primary endpoint was procedure time. Secondary endpoints were accuracy of needle placement, technical success rate, complication rate and dose-length product (DLP). Results. A total of 20 IRE procedures were performed to ablate hepatic malignancies (16 HCC, 4 liver metastases), 10 procedures in each arm. Mean time for placement of IRE electrodes in SIRE was significantly shorter with 27 ± 8 min compared to 87 ± 30 min for CIRE (p < 0.001). Accuracy of needle placement for SIRE was higher than CIRE (2.2 mm vs. 3.3 mm mean deviation, p < 0.001). The total DLP and the fluoroscopy DLP were significantly lower in SIRE compared to CIRE. Technical success rate and complication rates were equal in both arms. Conclusion. SIRE demonstrated a significant reduction of procedure length and higher accuracy compared to CIRE. Stereotactic navigation has the potential to reduce radiation dose for the patient and the radiologist without increasing the risk of complications or impaired technical success compared to CIRE.
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Affiliation(s)
- Lukas P Beyer
- Department of Radiology, University Hospital Regensburg , Regensburg , Germany
| | - Benedikt Pregler
- Department of Radiology, University Hospital Regensburg , Regensburg , Germany
| | - Christoph Nießen
- Department of Radiology, University Hospital Regensburg , Regensburg , Germany
| | - Andreas Schicho
- Department of Radiology, University Hospital Regensburg , Regensburg , Germany
| | - Michael Haimerl
- Department of Radiology, University Hospital Regensburg , Regensburg , Germany
| | - Ernst Michael Jung
- Department of Radiology, University Hospital Regensburg , Regensburg , Germany
| | | | - Philipp Wiggermann
- Department of Radiology, University Hospital Regensburg , Regensburg , Germany
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Comparative Effects of Irreversible Electroporation, Radiofrequency Ablation, and Partial Nephrectomy on Renal Function Preservation in a Porcine Solitary Kidney Model. Urology 2016; 94:281-7. [DOI: 10.1016/j.urology.2016.04.035] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 04/21/2016] [Accepted: 04/26/2016] [Indexed: 12/12/2022]
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Rubinsky L, Guenther E, Mikus P, Stehling M, Rubinsky B. Electrolytic Effects During Tissue Ablation by Electroporation. Technol Cancer Res Treat 2016; 15:NP95-NP103. [PMID: 26323571 DOI: 10.1177/1533034615601549] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2015] [Accepted: 07/22/2015] [Indexed: 11/17/2022] Open
Abstract
Nonthermal irreversible electroporation is a new tissue ablation technique that consists of applying pulsed electric fields across cells to induce cell death by creating permanent defects in the cell membrane. Nonthermal irreversible electroporation is of interest because it allows treatment near sensitive tissue structures such as blood vessels and nerves. Two recent articles report that electrolytic reaction products at electrodes can be combined with electroporation pulses to augment and optimize tissue ablation. Those articles triggered a concern that the results of earlier studies on nonthermal irreversible electroporation may have been tainted by unaccounted for electrolytic effects. The goal of this study was to reexamine previous studies on nonthermal irreversible electroporation in the context of these articles. The study shows that the results from some of the earlier studies on nonthermal irreversible electroporation were affected by unaccounted for electrolysis, in particular the research with cells in cuvettes. It also shows that tissue ablation ascribed in the past to irreversible electroporation is actually caused by at least 3 different cytotoxic effects: irreversible electroporation without electrolysis, irreversible electroporation combined with electrolysis, and reversible electroporation combined with electrolysis. These different mechanisms may affect cell and tissue ablation in different ways, and the effects may depend on various clinical parameters such as the polarity of the electrodes, the charge delivered (voltage, number, and length of pulses), and the distance of the target tissue from the electrodes. Current clinical protocols employ ever-increasing numbers of electroporation pulses to values that are now an order of magnitude larger than those used in our first fundamental nonthermal irreversible electroporation studies in tissues. The different mechanisms of cell death, and the effect of the clinical parameters on the mechanisms may explain discrepancies between results of different clinical studies and should be taken into consideration in the design of optimal electroporation ablation protocols.
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Affiliation(s)
| | | | | | - Michael Stehling
- Interscience, Luzern, Switzerland
- Boston University School of Medicine, MA, USA
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Irreversible Electroporation as an Effective Technique for Ablating Human Metastatic Osteosarcoma. J Pediatr Hematol Oncol 2016; 38:182-6. [PMID: 26950088 DOI: 10.1097/mph.0000000000000516] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Irreversible electroporation (IRE) induces apoptosis in tumor cells with electric energy, allowing treatment of unresectable tumors. One potential application is metastatic osteosarcoma (OS) in the pediatric population. A 12-year-old underwent thoracotomy with resection of metastatic OS. IRE was applied to 1 resected tumor section. Using 2 probes, 100 pulses with width of 90 ms were delivered. Efficacy was measured by increase in current draw during treatment. The treated sample was analyzed with hematoxylin and eosin and transmission electron microscopy. Default voltage of 1800 kV was ineffective. Voltage of 2700 kV caused excessive current draw and was aborted to prevent thermal injury. At 2200 kV, current draw rise was 9 amps, signifying successful treatment. Untreated specimen showed viable OS, normal surrounding lung tissue. Treated tumor had edema within the tumor and in surrounding lung tissue, with intra-alveolar hemorrhage and cellular architecture destruction. There was also evidence for cellular destruction such as disruption of lipid bilayer and release of intracellular fluid. Optimal voltage for treatment was 2200 kV, likely higher due to electrical conduction variation in the aerated lung. IRE may be an option for pediatric patients with unresectable metastatic OS.
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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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Synergistic Combination of Electrolysis and Electroporation for Tissue Ablation. PLoS One 2016; 11:e0148317. [PMID: 26866693 PMCID: PMC4750947 DOI: 10.1371/journal.pone.0148317] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Accepted: 01/15/2016] [Indexed: 01/04/2023] Open
Abstract
Electrolysis, electrochemotherapy with reversible electroporation, nanosecond pulsed electric fields and irreversible electroporation are valuable non-thermal electricity based tissue ablation technologies. This paper reports results from the first large animal study of a new non-thermal tissue ablation technology that employs "Synergistic electrolysis and electroporation" (SEE). The goal of this pre-clinical study is to expand on earlier studies with small animals and use the pig liver to establish SEE treatment parameters of clinical utility. We examined two SEE methods. One of the methods employs multiple electrochemotherapy-type reversible electroporation magnitude pulses, designed in such a way that the charge delivered during the electroporation pulses generates the electrolytic products. The second SEE method combines the delivery of a small number of electrochemotherapy magnitude electroporation pulses with a low voltage electrolysis generating DC current in three different ways. We show that both methods can produce lesion with dimensions of clinical utility, without the need to inject drugs as in electrochemotherapy, faster than with conventional electrolysis and with lower electric fields than irreversible electroporation and nanosecond pulsed ablation.
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CT Findings of Patients Treated with Irreversible Electroporation for Locally Advanced Pancreatic Cancer. JOURNAL OF ONCOLOGY 2015; 2015:680319. [PMID: 26649039 PMCID: PMC4651710 DOI: 10.1155/2015/680319] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/26/2015] [Revised: 10/14/2015] [Accepted: 10/15/2015] [Indexed: 12/17/2022]
Abstract
Introduction. In patients with locally advanced pancreatic cancer (LAPC), IRE has been shown to be safe for local disease control and palliation. As IRE continues to gain acceptance it is important to characterize the expected imaging findings. Materials and Methods. A review of our prospective soft tissue ablation registry from July 2010 to June 2013 was performed on patients who had undergone IRE for LAPC. Five masses treated with intraoperative IRE ablation for pancreatic tumors that underwent CT imaging before and after ablation were reviewed. Results and Discussion. Following IRE, the postablation bed is larger than the original ablated tumor. This ablation zone may get smaller in size (due to decreased edema and hyperemia) in the following months and more importantly remains stable provided there is no recurrence. In cases of recurrent disease there is increased size of the ablation bed, mass effect, and new or worsening vascular encasement or occlusion. Conclusion. CT imaging remains the best current imaging modality to assess post-IRE ablation changes. Serial imaging over at least 2-6 months must be employed to detect recurrence by comparing with prior studies in conjunction with clinical and serum studies. Larger imaging studies are underway to evaluate a more ideal imaging modality for this unique patient population.
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Bonakdar M, Latouche EL, Mahajan RL, Davalos RV. The Feasibility of a Smart Surgical Probe for Verification of IRE Treatments Using Electrical Impedance Spectroscopy. IEEE Trans Biomed Eng 2015; 62:2674-84. [PMID: 26057529 DOI: 10.1109/tbme.2015.2441636] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
SIGNIFICANCE Irreversible electroporation (IRE) is gaining popularity as a focal ablation modality for the treatment of unresectable tumors. One clinical limitation of IRE is the absence of methods for real-time treatment evaluation, namely actively monitoring the dimensions of the induced lesion. This information is critical to ensure a complete treatment and minimize collateral damage to the surrounding healthy tissue. GOAL In this study, we are taking advantage of the biophysical properties of living tissues to address this critical demand. METHODS Using advanced microfabrication techniques, we have developed an electrical impedance microsensor to collect impedance data along the length of a bipolar IRE probe for treatment verification. For probe characterization and interpretation of the readings, we used potato tuber, which is a suitable platform for IRE experiments without having the complexities of in vivo or ex vivo models. We used the impedance spectra, along with an electrical model of the tissue, to obtain critical parameters such as the conductivity of the tissue before, during, and after completion of treatment. To validate our results, we used a finite element model to simulate the electric field distribution during treatments in each potato. RESULTS It is shown that electrical impedance spectroscopy could be used as a technique for treatment verification, and when combined with appropriate FEM modeling can determine the lesion dimensions. CONCLUSIONS This technique has the potential to be readily translated for use with other ablation modalities already being used in clinical settings for the treatment of malignancies.
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