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1
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Jacobs EJ, Rubinsky B, Davalos RV. Pulsed field ablation in medicine: irreversible electroporation and electropermeabilization theory and applications. Radiol Oncol 2025; 59:1-22. [PMID: 40014783 PMCID: PMC11867574 DOI: 10.2478/raon-2025-0011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Accepted: 12/07/2024] [Indexed: 03/01/2025] Open
Abstract
BACKGROUND Focal ablation techniques are integral in the surgical intervention of diseased tissue, where it is necessary to minimize damage to the surrounding parenchyma and critical structures. Irreversible electroporation (IRE) and high-frequency IRE (H-FIRE), colloquially called pulsed-field ablation (PFA), utilize high-amplitude, low-energy pulsed electric fields (PEFs) to nonthermally ablate soft tissue. PEFs induce cell death through permeabilization of the cellular membrane, leading to loss of homeostasis. The unique nonthermal nature of PFA allows for selective cell death while minimally affecting surrounding proteinaceous structures, permitting treatment near sensitive anatomy where thermal ablation or surgical resection is contraindicated. Further, PFA is being used to treat tissue when tumor margins are not expected after surgical resection, termed margin accentuation. This review explores both the theoretical foundations of PFA, detailing how PEFs induce cell membrane destabilization and selective tissue ablation, the outcomes following treatment, and its clinical implications across oncology and cardiology. CONCLUSIONS Clinical experience is still progressing, but reports have demonstrated that PFA reduces complications often seen with thermal ablation techniques. Mounting oncology data also support that PFA produces a robust immune response that may prevent local recurrences and attenuate metastatic disease. Despite promising outcomes, challenges such as optimizing field delivery and addressing variations in tissue response require further investigation. Future directions include refining PFA protocols and expanding its application to other therapeutic areas like benign tissue hyperplasia and chronic bronchitis.
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Affiliation(s)
- Edward J Jacobs
- Wallace H Coulter School of Biomedical Engineering, Georgia Institute of Technology & Emory Medical School, Atlanta, Georgia, USA
| | - Boris Rubinsky
- Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, California, USA
| | - Rafael V Davalos
- Wallace H Coulter School of Biomedical Engineering, Georgia Institute of Technology & Emory Medical School, Atlanta, Georgia, USA
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2
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Seal R, Bararia A, Chattopadhyay BK, Sikdar N. Irreversible electroporation for metastatic pancreatic carcinoma with liver metastasis: What does the evidence say. World J Clin Cases 2025; 13:98452. [PMID: 39866648 PMCID: PMC11577528 DOI: 10.12998/wjcc.v13.i3.98452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 09/26/2024] [Accepted: 10/16/2024] [Indexed: 11/12/2024] Open
Abstract
Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies. However, higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice, which is chemotherapy alone. Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma, and such evidence is lacking at present.
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Affiliation(s)
- Ranit Seal
- Department of General Surgery, IPGME & R and SSKM Hospital, Kolkata 700020, West Bengal, India
| | - Akash Bararia
- Human Genetics Unit, Indian Statistical Institute, Kolkata 700108, West Bengal, India
| | | | - Nilabja Sikdar
- Human Genetics Unit, Indian Statistical Institute, Kolkata 700108, West Bengal, India
- Estaurine and Coastal Studies Foundation, Howrah 711101, India
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3
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Imran KM, Brock RM, Beitel-White N, Powar M, Orr K, Aycock KN, Alinezhadbalalami N, Salameh ZS, Eversole P, Tintera B, Markov Madanick J, Hendricks-Wenger A, Coutermarsh-Ott S, Davalos RV, Allen IC. Irreversible electroporation promotes a pro-inflammatory tumor microenvironment and anti-tumor immunity in a mouse pancreatic cancer model. Front Immunol 2024; 15:1352821. [PMID: 38711517 PMCID: PMC11070574 DOI: 10.3389/fimmu.2024.1352821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 04/09/2024] [Indexed: 05/08/2024] Open
Abstract
Pancreatic cancer is a significant cause of cancer-related mortality and often presents with limited treatment options. Pancreatic tumors are also notorious for their immunosuppressive microenvironment. Irreversible electroporation (IRE) is a non-thermal tumor ablation modality that employs high-voltage microsecond pulses to transiently permeabilize cell membranes, ultimately inducing cell death. However, the understanding of IRE's impact beyond the initiation of focal cell death in tumor tissue remains limited. In this study, we demonstrate that IRE triggers a unique mix of cell death pathways and orchestrates a shift in the local tumor microenvironment driven, in part, by reducing the myeloid-derived suppressor cell (MDSC) and regulatory T cell populations and increasing cytotoxic T lymphocytes and neutrophils. We further show that IRE drives induce cell cycle arrest at the G0/G1 phase in vitro and promote inflammatory cell death pathways consistent with pyroptosis and programmed necrosis in vivo. IRE-treated mice exhibited a substantial extension in progression-free survival. However, within a span of 14 days, the tumor immune cell populations reverted to their pre-treatment composition, which resulted in an attenuation of the systemic immune response targeting contralateral tumors and ultimately resulting in tumor regrowth. Mechanistically, we show that IRE augments IFN- γ signaling, resulting in the up-regulation of the PD-L1 checkpoint in pancreatic cancer cells. Together, these findings shed light on potential mechanisms of tumor regrowth following IRE treatment and offer insights into co-therapeutic targets to improve treatment strategies.
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Affiliation(s)
- Khan Mohammad Imran
- Medicine and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, United States
| | - Rebecca M. Brock
- Medicine and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, United States
| | - Natalie Beitel-White
- Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
- Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Manali Powar
- Medicine and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, United States
| | - Katie Orr
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, United States
| | - Kenneth N. Aycock
- Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Nastaran Alinezhadbalalami
- Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Zaid S. Salameh
- Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Paige Eversole
- Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Benjamin Tintera
- Department of Surgery, Carilion Clinic and Virginia Tech Carilion School of Medicine, Roanoke, VA, United States
| | - Justin Markov Madanick
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, United States
| | - Alissa Hendricks-Wenger
- Medicine and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, United States
| | - Sheryl Coutermarsh-Ott
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, United States
| | - Rafael V. Davalos
- Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Irving C. Allen
- Medicine and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, United States
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, United States
- Department of Basic Science Education, Virginia Tech Carilion School of Medicine, Roanoke, VA, United States
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4
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Campana LG, Daud A, Lancellotti F, Arroyo JP, Davalos RV, Di Prata C, Gehl J. Pulsed Electric Fields in Oncology: A Snapshot of Current Clinical Practices and Research Directions from the 4th World Congress of Electroporation. Cancers (Basel) 2023; 15:3340. [PMID: 37444450 PMCID: PMC10340685 DOI: 10.3390/cancers15133340] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 05/29/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
The 4th World Congress of Electroporation (Copenhagen, 9-13 October 2022) provided a unique opportunity to convene leading experts in pulsed electric fields (PEF). PEF-based therapies harness electric fields to produce therapeutically useful effects on cancers and represent a valuable option for a variety of patients. As such, irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumour-treating fields (TTF) are on the rise. Still, their full therapeutic potential remains underappreciated, and the field faces fragmentation, as shown by parallel maturation and differences in the stages of development and regulatory approval worldwide. This narrative review provides a glimpse of PEF-based techniques, including key mechanisms, clinical indications, and advances in therapy; finally, it offers insights into current research directions. By highlighting a common ground, the authors aim to break silos, strengthen cross-functional collaboration, and pave the way to novel possibilities for intervention. Intriguingly, beyond their peculiar mechanism of action, PEF-based therapies share technical interconnections and multifaceted biological effects (e.g., vascular, immunological) worth exploiting in combinatorial strategies.
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Affiliation(s)
- Luca G. Campana
- Department of Surgery, Manchester University NHS Foundation Trust, Oxford Rd., Manchester M13 9WL, UK;
| | - Adil Daud
- Department of Medicine, University of California, 550 16 Street, San Francisco, CA 94158, USA;
| | - Francesco Lancellotti
- Department of Surgery, Manchester University NHS Foundation Trust, Oxford Rd., Manchester M13 9WL, UK;
| | - Julio P. Arroyo
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA; (J.P.A.); (R.V.D.)
| | - Rafael V. Davalos
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA; (J.P.A.); (R.V.D.)
- Institute for Critical Technology and Applied Sciences, Virginia Tech, Blacksburg, VA 24061, USA
| | - Claudia Di Prata
- Department of Surgery, San Martino Hospital, 32100 Belluno, Italy;
| | - Julie Gehl
- Department of Clinical Oncology and Palliative Care, Zealand University Hospital, 4000 Roskilde, Denmark;
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark
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5
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Punzi E, Carrubba C, Contegiacomo A, Posa A, Barbieri P, De Leoni D, Mazza G, Tanzilli A, Cina A, Natale L, Sala E, Iezzi R. Interventional Radiology in the Treatment of Pancreatic Adenocarcinoma: Present and Future Perspectives. Life (Basel) 2023; 13:life13030835. [PMID: 36983990 PMCID: PMC10059735 DOI: 10.3390/life13030835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 03/07/2023] [Accepted: 03/18/2023] [Indexed: 03/30/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease; patients' long-term survival is strictly linked to the surgical resection of the tumor but only a minority of patients (2-3%) have a resectable disease at diagnosis. In patients with surgically unresectable disease, interventional radiology is taking on an increasing role in treatment with the application of loco-regional percutaneous therapies. The primary purposes of this narrative review are to analyze the safety and efficacy of ablative techniques in the management of borderline resectable and locally advanced diseases and to underline the role of the interventional radiologist in the management of patients with distant metastases. The secondary purpose is to focus on the synergy between immunotherapy and ablative therapies.
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Affiliation(s)
- Ernesto Punzi
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia-Istituto di Radiologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, l.go A gemelli 8, 00168 Rome, Italy
| | - Claudio Carrubba
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia-Istituto di Radiologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, l.go A gemelli 8, 00168 Rome, Italy
| | - Andrea Contegiacomo
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia-Istituto di Radiologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, l.go A gemelli 8, 00168 Rome, Italy
| | - Alessandro Posa
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia-Istituto di Radiologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, l.go A gemelli 8, 00168 Rome, Italy
| | - Pierluigi Barbieri
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia-Istituto di Radiologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, l.go A gemelli 8, 00168 Rome, Italy
| | - Davide De Leoni
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia-Istituto di Radiologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, l.go A gemelli 8, 00168 Rome, Italy
| | - Giulia Mazza
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia-Istituto di Radiologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, l.go A gemelli 8, 00168 Rome, Italy
| | - Alessandro Tanzilli
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia-Istituto di Radiologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, l.go A gemelli 8, 00168 Rome, Italy
| | - Alessandro Cina
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia-Istituto di Radiologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, l.go A gemelli 8, 00168 Rome, Italy
| | - Luigi Natale
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia-Istituto di Radiologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, l.go A gemelli 8, 00168 Rome, Italy
- Istituto di Radiodiagnostica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Evis Sala
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia-Istituto di Radiologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, l.go A gemelli 8, 00168 Rome, Italy
- Istituto di Radiodiagnostica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Roberto Iezzi
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia-Istituto di Radiologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, l.go A gemelli 8, 00168 Rome, Italy
- Istituto di Radiodiagnostica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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6
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Spiliopoulos S, Reppas L, Filippiadis D, Delvecchio A, Conticchio M, Memeo R, Inchingolo R. Irreversible electroporation for the management of pancreatic cancer: Current data and future directions. World J Gastroenterol 2023; 29:223-231. [PMID: 36687122 PMCID: PMC9846938 DOI: 10.3748/wjg.v29.i2.223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 11/13/2022] [Accepted: 12/21/2022] [Indexed: 01/06/2023] Open
Abstract
Pancreatic cancer is currently the seventh leading cause of cancer death (4.5% of all cancer deaths) while 80%-90% of the patients suffer from unresectable disease at the time of diagnosis. Prognosis remains poor, with a mean survival up to 15 mo following systemic chemotherapy. Loco-regional thermal ablative techniques are rarely implemented due to the increased risk of thermal injury to the adjacent structures, which can lead to severe adverse events. Irreversible electroporation, a promising novel non-thermal ablative modality, has been recently introduced in clinical practice for the management of inoperable pancreatic cancer as a safer and more effective loco-regional treatment option. Experimental and initial clinical data are optimistic. This review will focus on the basic principles of IRE technology, currently available data, and future directions.
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Affiliation(s)
- Stavros Spiliopoulos
- Second Department of Radiology, School of Medicine, National and Kapodistrian University of Athens, Athens 12461, Attiki, Greece
| | - Lazaros Reppas
- Second Department of Radiology, School of Medicine, National and Kapodistrian University of Athens, Athens 12461, Attiki, Greece
| | - Dimitrios Filippiadis
- Second Department of Radiology, School of Medicine, National and Kapodistrian University of Athens, Athens 12461, Attiki, Greece
| | - Antonella Delvecchio
- Unit of Hepato-Pancreatic-Biliary Surgery, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Bari, Italy
| | - Maria Conticchio
- Unit of Hepato-Pancreatic-Biliary Surgery, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Bari, Italy
| | - Riccardo Memeo
- Unit of Hepato-Pancreatic-Biliary Surgery, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Bari, Italy
| | - Riccardo Inchingolo
- Interventional Radiology Unit, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Italy
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7
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Belfiore MP, De Chiara M, Reginelli A, Clemente A, Urraro F, Grassi R, Belfiore G, Cappabianca S. An overview of the irreversible electroporation for the treatment of liver metastases: When to use it. Front Oncol 2022; 12:943176. [PMID: 36119531 PMCID: PMC9477084 DOI: 10.3389/fonc.2022.943176] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 07/26/2022] [Indexed: 11/13/2022] Open
Abstract
Tumour ablation is an established therapy for local treatment of liver metastases and hepatocellular carcinoma. Most commonly two different kind of thermic ablation, radiofrequency ablation and microwave ablation, are used in clinical practice. The aim of both is to induce thermic damage to the malignant cells in order to obtain coagulative necrosis of the neoplastic lesions. Our main concerns about these procedures are the collateral thermic damage to adjacent structures and heat-sink effect. Irreversible electroporation (IRE) is a recently developed, non-thermal ablation procedure which works applying short pulses of direct current that generate an electric field in the lesion area. The electric field increase the transmembrane potential, changing its permeability to ions.Irreversible electroporation does not generate heat, giving the chance to avoid the heat-sink effect and opening the path to a better treatment of all the lesions located in close proximity to big vessels and bile ducts. Electric fields produced by the IRE may affect endothelial cells and cholangiocytes but they spare the collagen matrix, preserving re-epithelization process as well as the function of the damaged structures. Purpose of the authors is to identify the different scenarios where CT-guided percutaneous IRE of the liver should be preferred to other ablative techniques and why.
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Affiliation(s)
- Maria Paola Belfiore
- Division of Radiology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Napoli, Italy
- *Correspondence: Maria Paola Belfiore,
| | - Marco De Chiara
- Division of Radiology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Napoli, Italy
| | - Alfonso Reginelli
- Division of Radiology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Napoli, Italy
| | - Alfredo Clemente
- Division of Radiology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Napoli, Italy
| | - Fabrizio Urraro
- Division of Radiology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Napoli, Italy
| | - Roberto Grassi
- Division of Radiology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Napoli, Italy
| | - Giuseppe Belfiore
- Department of Diagnostic Imaging, Nursing home L.Cobellis, Vallo della Lucania Salerno, Italy
| | - Salvatore Cappabianca
- Division of Radiology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Napoli, Italy
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8
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Rai ZL, Ranieri V, Palmer DH, Littler P, Ghaneh P, Gurusamy K, Manas D, Pizzo E, Psarelli EE, Gilmore R, Peddu P, Bartlett DC, de Liguori Carino N, Davidson BR. Treatment of unresectable locally advanced pancreatic cancer with percutaneous irreversible electroporation (IRE) following initial systemic chemotherapy (LAP-PIE) trial: study protocol for a feasibility randomised controlled trial. BMJ Open 2022; 12:e050166. [PMID: 35551086 PMCID: PMC9109032 DOI: 10.1136/bmjopen-2021-050166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 01/17/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Approximately 30% of patients with pancreas cancer have unresectable locally advanced disease, which is currently treated with systemic chemotherapy. A new treatment option of irreversible electroporation (IRE) has been investigated for these patients since 2005. Cohort studies suggest that IRE confers a survival advantage, but with associated, procedure-related complications. Selection bias may account for improved survival and there have been no prospective randomised trials evaluating the harms and benefits of therapy. The aim of this trial is to evaluate the feasibility of a randomised comparison of IRE therapy with chemotherapy versus chemotherapy alone in patients with locally advanced pancreatic cancer (LAPC). METHODS AND ANALYSIS Eligible patients with LAPC who have undergone first-line 5-FluoroUracil, Leucovorin, Irinotecan and Oxaliplatin chemotherapy will be randomised to receive either a single session of IRE followed by (if indicated) further chemotherapy or to chemotherapy alone (standard of care). Fifty patients from up to seven specialist pancreas centres in the UK will be recruited over a period of 15 months. Trial follow-up will be 12 months. The primary outcome measure is ability to recruit. Secondary objectives include practicality and technical success of treatment, acceptability of treatment to patients and clinicians and safety of treatment. A qualitative study has been incorporated to evaluate the patient and clinician perspective of the locally advanced pancreatic cancer with percutaneous irreversible electroporation trial. It is likely that the data obtained will guide the structure, the primary outcome measure, the power and the duration of a subsequent multicentre randomised controlled trial aimed at establishing the clinical efficiency of pancreas IRE therapy. Indicative procedure-related costings will be collected in this feasibility trial, which will inform the cost evaluation in the subsequent study on efficiency. ETHICS AND DISSEMINATION The protocol has received approval by London-Brent Research Ethics Committee reference number 21/LO/0077.Results will be analysed following completion of trial recruitment and follow-up. Results will be presented to international conferences with an interest in oncology, hepatopancreaticobiliary surgery and interventional radiology and be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER ISRCTN14986389.
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Affiliation(s)
- Zainab L Rai
- Division of Surgery and Interventional Science, University College London, London, UK
- Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS), London, UK
| | - Veronica Ranieri
- Research & Development, Tavistock and Portman NHS Foundation Trust, London, UK
- Science & Technology Studies, University College London, London, UK
| | - Daniel H Palmer
- Hepato-Pancreatco-Biliary Disease, University of Liverpool, Liverpool, Merseyside, UK
| | - Peter Littler
- Hepato-Pancreatico-Biliary Surgery, Freeman Hospital, Newcastle Upon Tyne, UK
| | - Pauleh Ghaneh
- Hepato-Pancreatco-Biliary Disease, University of Liverpool, Liverpool, Merseyside, UK
| | - Kurinchi Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Derek Manas
- Hepato-Pancreatico-Biliary Surgery, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, UK
| | - Elena Pizzo
- Applied Health Research, University College London, London, UK
| | | | - Roopinder Gilmore
- Division of Surgery and Interventional Science, University College London, London, UK
- Oncology, Royal Free London NHS Foundation Trust, London, UK
| | - Praveen Peddu
- Department of Radiology, King's College Hospital NHS Trust, London, UK
| | - David C Bartlett
- Hepato-Pancreatico-Biliary Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Birmingham, UK
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9
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Imran KM, Nagai-Singer MA, Brock RM, Alinezhadbalalami N, Davalos RV, Allen IC. Exploration of Novel Pathways Underlying Irreversible Electroporation Induced Anti-Tumor Immunity in Pancreatic Cancer. Front Oncol 2022; 12:853779. [PMID: 35372046 PMCID: PMC8972192 DOI: 10.3389/fonc.2022.853779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 02/28/2022] [Indexed: 12/04/2022] Open
Abstract
Advancements in medical sciences and technologies have significantly improved the survival of many cancers; however, pancreatic cancer remains a deadly diagnosis. This malignancy is often diagnosed late in the disease when metastases have already occurred. Additionally, the location of the pancreas near vital organs limits surgical candidacy, the tumor's immunosuppressive environment limits immunotherapy success, and it is highly resistant to radiation and chemotherapy. Hence, clinicians and patients alike need a treatment paradigm that reduces primary tumor burden, activates systemic anti-tumor immunity, and reverses the local immunosuppressive microenvironment to eventually clear distant metastases. Irreversible electroporation (IRE), a novel non-thermal tumor ablation technique, applies high-voltage ultra-short pulses to permeabilize targeted cell membranes and induce cell death. Progression with IRE technology and an array of research studies have shown that beyond tumor debulking, IRE can induce anti-tumor immune responses possibly through tumor neo-antigen release. However, the success of IRE treatment (i.e. full ablation and tumor recurrence) is variable. We believe that IRE treatment induces IFNγ expression, which then modulates immune checkpoint molecules and thus leads to tumor recurrence. This indicates a co-therapeutic use of IRE and immune checkpoint inhibitors as a promising treatment for pancreatic cancer patients. Here, we review the well-defined and speculated pathways involved in the immunostimulatory effects of IRE treatment for pancreatic cancer, as well as the regulatory pathways that may negate these anti-tumor responses. By defining these underlying mechanisms, future studies may identify improvements to systemic immune system engagement following local tumor ablation with IRE and beyond.
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Affiliation(s)
- Khan Mohammad Imran
- Graduate Program in Translational Biology, Medicine and Health, Virginia Tech, Roanoke, VA, United States
| | - Margaret A. Nagai-Singer
- Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States
- Institute for Critical Technology and Applied Sciences, Virginia Tech, Blacksburg, VA, United States
| | - Rebecca M. Brock
- Graduate Program in Translational Biology, Medicine and Health, Virginia Tech, Roanoke, VA, United States
| | - Nastaran Alinezhadbalalami
- Institute for Critical Technology and Applied Sciences, Virginia Tech, Blacksburg, VA, United States
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA, United States
| | - Rafael V. Davalos
- Institute for Critical Technology and Applied Sciences, Virginia Tech, Blacksburg, VA, United States
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA, United States
- Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA, United States
| | - Irving Coy Allen
- Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, United States
- Institute for Critical Technology and Applied Sciences, Virginia Tech, Blacksburg, VA, United States
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Hendricks-Wenger A, Sereno J, Gannon J, Zeher A, Brock RM, Beitel-White N, Simon A, Davalos RV, Coutermarsh-Ott S, Vlaisavljevich E, Allen IC. Histotripsy Ablation Alters the Tumor Microenvironment and Promotes Immune System Activation in a Subcutaneous Model of Pancreatic Cancer. IEEE TRANSACTIONS ON ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL 2021; 68:2987-3000. [PMID: 33956631 PMCID: PMC9295194 DOI: 10.1109/tuffc.2021.3078094] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Abstract
Pancreatic cancer is a significant cause of cancer-related deaths in the United States with an abysmal five-year overall survival rate that is under 9%. Reasons for this mortality include the lack of late-stage treatment options and the immunosuppressive tumor microenvironment. Histotripsy is an ultrasound-guided, noninvasive, nonthermal tumor ablation therapy that mechanically lyses targeted cells. To study the effects of histotripsy on pancreatic cancer, we utilized an in vitro model of pancreatic adenocarcinoma and compared the release of potential antigens following histotripsy treatment to other ablation modalities. Histotripsy was found to release immune-stimulating molecules at magnitudes similar to other nonthermal ablation modalities and superior to thermal ablation modalities, which corresponded to increased innate immune system activation in vivo. In subsequent in vivo studies, murine Pan02 tumors were grown in mice and treated with histotripsy. Flow cytometry and rtPCR were used to determine changes in the tumor microenvironment over time compared to untreated animals. In mice with pancreatic tumors, we observed significantly increased tumor-progression-free and general survival, with increased activation of the innate immune system 24 h posttreatment and decreased tumor-associated immune cell populations within 14 days of treatment. This study demonstrates the feasibility of using histotripsy for pancreatic cancer ablation and provides mechanistic insight into the initial innate immune system activation following treatment. Further work is needed to establish the mechanisms behind the immunomodulation of the tumor microenvironment and immune effects.
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Bibok A, Kim DW, Malafa M, Kis B. Minimally invasive image-guided therapy of primary and metastatic pancreatic cancer. World J Gastroenterol 2021; 27:4322-4341. [PMID: 34366607 PMCID: PMC8316906 DOI: 10.3748/wjg.v27.i27.4322] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 05/21/2021] [Accepted: 06/23/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is a challenging malignancy with limited treatment options and poor life expectancy. The only curative option is surgical resection, but only 15%-20% of patients are resectable at presentation because more than 50% of patients has distant metastasis at diagnosis and the rest of them has locally advanced pancreatic cancer (LAPC). The standard of care first line treatment for LAPC patients is chemotherapy with or without radiation therapy. Recent developments in minimally invasive ablative techniques may add to the treatment armamentarium of LAPC. There are increasing number of studies evaluating these novel ablative techniques, including radiofrequency ablation, microwave ablation, cryoablation and irreversible electroporation. Most studies which included pancreatic tumor ablation, demonstrated improved overall survival in LAPC patients. However, the exact protocols are yet to set up to which stage of the treatment algorithm ablative techniques can be added and in what kind of treatment combinations. Patients with metastatic pancreatic cancer has dismal prognosis with 5-year survival is only 3%. The most common metastatic site is the liver as 90% of pancreatic cancer patients develop liver metastasis. Chemotherapy is the primary treatment option for patients with metastatic pancreatic cancer. However, when the tumor is not responding to chemotherapy or severe drug toxicity develops, locoregional liver-directed therapies can provide an opportunity to control intrahepatic disease progression and improve survival in selected patients. During the last decade new therapeutic options arose with the advancement of minimally invasive technologies to treat pancreatic cancer patients. These new therapies have been a topic of increasing interest due to the severe prognostic implications of locally advanced and metastatic pancreatic cancer and the low comorbid risk of these procedures. This review summarizes new ablative options for patients with LAPC and percutaneous liver-directed therapies for patients with liver-dominant metastatic disease.
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Affiliation(s)
- Andras Bibok
- Department of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, United States
- Department of Transplantation & Surgery, Radiology Unit, Semmelweis University, Budapest 1085, Hungary
| | - Dae Won Kim
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, United States
| | - Mokenge Malafa
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, United States
| | - Bela Kis
- Department of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, United States
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Flak RV, Fisker RV, Bruun NH, Stender MT, Thorlacius-Ussing O, Petersen LJ. Usefulness of Imaging Response Assessment after Irreversible Electroporation of Localized Pancreatic Cancer-Results from a Prospective Cohort. Cancers (Basel) 2021; 13:cancers13122862. [PMID: 34201272 PMCID: PMC8226515 DOI: 10.3390/cancers13122862] [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: 04/25/2021] [Revised: 05/28/2021] [Accepted: 06/04/2021] [Indexed: 01/05/2023] Open
Abstract
Simple Summary Irreversible electroporation (IRE) is a novel therapy that is being studied for the treatment of nonmetastatic pancreatic cancer. The current methods for evaluating the treatment response after IRE have been adapted from the Response Evaluation Criteria in Solid Tumors (RECIST). However, it is uncertain whether these methods are appropriate, because the methods have not been validated. The aim of the current study was to evaluate the correlation between survival time and the most commonly used imaging assessment methods on FDG-PET/CT scans. We confirmed that the Response Evaluation Criteria in Solid Tumors (RECIST) are correlated with survival, when applied as intended. However, no correlation was found when the often-used lesion-level method was used. FDG-PET-derived data did not provide any benefit over conventional CT data. Several novel methods for lesion-level analysis were explored. Abstract (1) Background: Irreversible electroporation (IRE) is a nonthermal ablation technique that is being studied in nonmetastatic pancreatic cancer (PC). Most published studies use imaging outcomes as an efficacy endpoint, but imaging interpretation can be difficult and has yet to be correlated with survival. The aim of this study was to examine the correlation of imaging endpoints with survival in a cohort of IRE-treated PC patients. (2) Methods: Several imaging endpoints were examined before and after IRE on 18F-fluorodeoxyglucose positron emission tomography (PET) with computed tomography. Separate analyses were performed at the patient and lesion levels. Mortality rate (MR) ratios for imaging endpoints after IRE were estimated. (3) Results: Forty-one patients were included. Patient-level analysis revealed that progressive disease (PD), as defined by RECIST 1.1, is correlated with a higher MR at all time intervals, but PD, as defined by EORTC PET response criteria, is only correlated with the MR in the longest interval. No correlation was found between PD, as defined by RECIST, and the MR in the lesion-level analysis. (4) Conclusions: Patient-level PD, as defined by RECIST, was correlated with poorer survival after IRE ablation, whereas no correlations were observed in the lesion-level analyses. Several promising lesion-level outcomes were identified.
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Affiliation(s)
- Rasmus V. Flak
- Department of Gastrointestinal Surgery, Aalborg University Hospital, DK-9000 Aalborg, Denmark; (M.T.S.); (O.T.-U.)
- Department of Clinical Science, Aalborg University, DK-9220 Aalborg Øst, Denmark;
- Clinical Cancer Research Center, Aalborg University Hospital, DK-9000 Aalborg, Denmark
- Correspondence: ; Tel.: +45-97-66-11-81
| | - Rune V. Fisker
- Department of Nuclear Medicine and Radiology, Aalborg University Hospital, DK-9000 Aalborg, Denmark;
| | - Niels H. Bruun
- Unit of Clinical Biostatistics, Aalborg University Hospital, DK-9000 Aalborg, Denmark;
| | - Mogens T. Stender
- Department of Gastrointestinal Surgery, Aalborg University Hospital, DK-9000 Aalborg, Denmark; (M.T.S.); (O.T.-U.)
- Department of Clinical Science, Aalborg University, DK-9220 Aalborg Øst, Denmark;
| | - Ole Thorlacius-Ussing
- Department of Gastrointestinal Surgery, Aalborg University Hospital, DK-9000 Aalborg, Denmark; (M.T.S.); (O.T.-U.)
- Department of Clinical Science, Aalborg University, DK-9220 Aalborg Øst, Denmark;
- Clinical Cancer Research Center, Aalborg University Hospital, DK-9000 Aalborg, Denmark
| | - Lars J. Petersen
- Department of Clinical Science, Aalborg University, DK-9220 Aalborg Øst, Denmark;
- Clinical Cancer Research Center, Aalborg University Hospital, DK-9000 Aalborg, Denmark
- Department of Nuclear Medicine and Radiology, Aalborg University Hospital, DK-9000 Aalborg, Denmark;
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Margin ACcentuation for resectable Pancreatic cancer using Irreversible Electroporation - Results from the MACPIE-I study. Eur J Surg Oncol 2021; 47:2571-2578. [PMID: 34039473 DOI: 10.1016/j.ejso.2021.05.024] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 04/27/2021] [Accepted: 05/06/2021] [Indexed: 01/11/2023] Open
Abstract
INTRODUCTION Margin accentuation (MA) using Irreversible electroporation (IRE) offers an unique opportunity to reduce the R1 resections in resectable pancreatic cancer (RPC). This study aims to assess the rate of margin positivity using IRE for MA during pancreaticoduodenectomy (PD) for resectable pancreatic head tumours. MATERIALS AND METHODS Following ethical approval, MA using IRE was carried out in 20 consecutive patients to posterior and superior mesenteric vein (SMV) margin, and the pancreatic neck, prior to the PD resection. The control group (non-IRE; n = 91) underwent PD without MA over the study period, March 2018 to March 2020. RESULTS There was no difference between the two groups in terms of patients' age, gender, pre-op biliary drainage, site of malignancy or pre-operative TNM stage. The overall margin positive rate for IRE group was lesser (35.0%) when compared to non-IRE group (51.6%; p = 0.177), with significantly less posterior pancreatic margin positivity (5.0% vs. 25.3%; p = 0.046). When only treated margins (SMA margin excluded) were compared, the IRE group had significantly lower margin positive rates (20.0% vs. 51.6%; p = 0.013). There was no difference between the two groups in terms of intra- or post-operative complications. With a median follow-up of 15.6 months, the median DFS and OS for IRE and non-IRE groups were 17 and 18 months (p = 0.306) and 19 and 22 months (p = 0.227) respectively. CONCLUSION Our pilot study confirms the safety of MA using IRE for RPC, with reduction in margin positivity. These results as a proof of concept are promising and need further validation with a randomised controlled trial.
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Timmer FE, Geboers B, Nieuwenhuizen S, Schouten EA, Dijkstra M, de Vries JJ, van den Tol MP, de Gruijl TD, Scheffer HJ, Meijerink MR. Locally Advanced Pancreatic Cancer: Percutaneous Management Using Ablation, Brachytherapy, Intra-arterial Chemotherapy, and Intra-tumoral Immunotherapy. Curr Oncol Rep 2021; 23:68. [PMID: 33864144 PMCID: PMC8052234 DOI: 10.1007/s11912-021-01057-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/11/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasms, bearing a terrible prognosis. Stage III tumors, also known as locally advanced pancreatic cancer (LAPC), are unresectable, and current palliative chemotherapy regimens have only modestly improved survival in these patients. At this stage of disease, interventional techniques may be of value and further prolong life. The aim of this review was to explore current literature on locoregional percutaneous management for LAPC. RECENT FINDINGS Locoregional percutaneous interventional techniques such as ablation, brachytherapy, and intra-arterial chemotherapy possess cytoreductive abilities and have the potential to increase survival. In addition, recent research demonstrates the immunomodulatory capacities of these treatments. This immune response may be leveraged by combining the interventional techniques with intra-tumoral immunotherapy, possibly creating a durable anti-tumor effect. This multimodality treatment approach is currently being examined in several ongoing clinical trials. The use of certain interventional techniques appears to improve survival in LAPC patients and may work synergistically when combined with immunotherapy. However, definitive conclusions can only be made when large prospective (randomized controlled) trials confirm these results.
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Affiliation(s)
- Florentine E.F. Timmer
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Bart Geboers
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Sanne Nieuwenhuizen
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Evelien A.C. Schouten
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Madelon Dijkstra
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Jan J.J. de Vries
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - M. Petrousjka van den Tol
- Department of Surgical Oncology, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Tanja D. de Gruijl
- Department of Medical Oncology, Amsterdam UMC (location VUmc)-Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Hester J. Scheffer
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Martijn R. Meijerink
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
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Rai ZL, Feakins R, Pallett LJ, Manas D, Davidson BR. Irreversible Electroporation (IRE) in Locally Advanced Pancreatic Cancer: A Review of Current Clinical Outcomes, Mechanism of Action and Opportunities for Synergistic Therapy. J Clin Med 2021; 10:1609. [PMID: 33920118 PMCID: PMC8068938 DOI: 10.3390/jcm10081609] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 04/04/2021] [Accepted: 04/07/2021] [Indexed: 12/11/2022] Open
Abstract
Locally advanced pancreatic cancer (LAPC) accounts for 30% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a novel cancer treatment that may improve survival and quality of life in LAPC. This narrative review will provide a perspective on the clinical experience of pancreas IRE therapy, explore the evidence for the mode of action, assess treatment complications, and propose strategies for augmenting IRE response. A systematic search was performed using PubMed regarding the clinical use and safety profile of IRE on pancreatic cancer, post-IRE sequential histological changes, associated immune response, and synergistic therapies. Animal data demonstrate that IRE induces both apoptosis and necrosis followed by fibrosis. Major complications may result from IRE; procedure related mortality is up to 2%, with an average morbidity as high as 36%. Nevertheless, prospective and retrospective studies suggest that IRE treatment may increase median overall survival of LAPC to as much as 30 months and provide preliminary data justifying the well-designed trials currently underway, comparing IRE to the standard of care treatment. The mechanism of action of IRE remains unknown, and there is a lack of data on treatment variables and efficiency in humans. There is emerging data suggesting that IRE can be augmented with synergistic therapies such as immunotherapy.
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Affiliation(s)
- Zainab L. Rai
- Centre of Surgical Innovation, Organ Regeneration and Transplantation, University College London (UCL), London NW3 2QG, UK;
- Wellcome/EPSRC Center for Interventional and Surgical Sciences (WEISS), London W1W 7TY, UK
- Royal Free NHS Foundation Trust, London NW3 2QG, UK;
| | - Roger Feakins
- Royal Free NHS Foundation Trust, London NW3 2QG, UK;
| | - Laura J. Pallett
- Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, London WC1E 6BT, UK;
| | - Derek Manas
- Newcastle Upon Tyne NHS Foundation Trust, Newcastle-Upon-Tyne NE7 7DN, UK;
| | - Brian R. Davidson
- Centre of Surgical Innovation, Organ Regeneration and Transplantation, University College London (UCL), London NW3 2QG, UK;
- Royal Free NHS Foundation Trust, London NW3 2QG, UK;
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Zhang H, Zhu X, Zeng Z, Gao X. Interventional therapy combined with radiotherapy for pancreatic carcinoma. INTEGRATIVE PANCREATIC INTERVENTION THERAPY 2021:523-539. [DOI: 10.1016/b978-0-12-819402-7.00023-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Lee KW, Lee JM, Choi HS, Kim ES, Keum B, Seo YS, Jeen YT, Um SH, Lee HS, Chun HJ, Kim CD, Oh CH, Kim HB. Novel Ablation Therapy Using Endoscopic Irreversible Electroporation in the Bile Duct: A Pilot Animal Study. Clin Endosc 2020; 54:413-419. [PMID: 33076633 PMCID: PMC8182241 DOI: 10.5946/ce.2020.126] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 07/09/2020] [Indexed: 12/18/2022] Open
Abstract
Background/Aims Irreversible electroporation (IRE) is a relatively new ablation method. However, the application of IRE ablation in the treatment of biliary disease has not been attempted. A minimally invasive approach using endoscopic retrograde cholangiopancreatography (ERCP) can be a novel therapeutic modality for IRE ablation. In this study, we aimed to investigate the feasibility of endoscopic IRE for the biliary tract using an animal model.
Methods A new catheter-type electrode was developed for endoscopic IRE ablation of the biliary tract. We performed ERCP and endoscopic IRE ablations in the normal common bile duct of Yorkshire pigs. The experimental setting of IRE was 500 V/cm (50 pulses, 100-µs length). The animals were sacrificed after 24 hr, and the ablated bile duct was examined.
Results Well-demarcated focal color changes were observed on the mucosa of the common bile duct. The depth of change after IRE was confined to the mucosal and submucosal layers. Apoptotic changes in the bile duct were observed only around the IRE ablation area. Immunohistochemistry assay showed cell death in the bile duct along the electrode.
Conclusions Endoscopic IRE ablation using ERCP was successfully performed in the common bile duct. It can be a potential option for the treatment of biliary tumors.
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Affiliation(s)
- Kang Won Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jae Min Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hyuk Soon Choi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Eun Sun Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Bora Keum
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Yeon Seok Seo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Yoon Tae Jeen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Soon Ho Um
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hong Sik Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hoon Jai Chun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Chang Duck Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Chi Hyuk Oh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea
| | - Hong Bae Kim
- Department of Biosystems and Biomaterials Science and Engineering, Seoul National University, Seoul, Korea
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Flak RV, Stender MT, Stenholt L, Thorlacius-Ussing O, Petersen LJ. Imaging response evaluation after local ablative treatments in locally advanced pancreatic cancer: an expedited systematic review. HPB (Oxford) 2020; 22:1083-1091. [PMID: 32451236 DOI: 10.1016/j.hpb.2020.04.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 04/15/2020] [Accepted: 04/20/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Several local ablative modalities have been introduced for the treatment of locally advanced pancreatic cancer (LAPC). However, there is no consensus on how to evaluate the imaging response after treatment. A systematic review was performed regarding the use of imaging for response assessment in LAPC. METHODS A systematic literature search was conducted in PubMed. Studies reporting imaging outcomes were included in the review. Studies were excluded if the imaging outcomes could not be differentiated between different disease stages, tumor histology or surgical approaches. RESULTS Thirty-four studies were included in the analysis. Fourteen studies used standardized response criteria, while six studies did not report the response evaluation method. The rest used self-determined criteria, absolute size comparisons or similar methods. One study found a correlation between early systemic progression (<6 months) and overall survival. CONCLUSION There was notable variation in the use of imaging for response assessment in LAPC. This significantly hinders cross-comparison of results among studies. There is currently only sparse evidence of an association between imaging responses and overall survival. The field calls for standardized recommendations regarding the choice of response assessment method, timing of scans, target definition and reporting of outcomes.
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Affiliation(s)
- R V Flak
- Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark; Department of Clinical Science, Aalborg University, Denmark.
| | - Mogens T Stender
- Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark; Department of Clinical Science, Aalborg University, Denmark
| | | | - Ole Thorlacius-Ussing
- Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark; Department of Clinical Science, Aalborg University, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Denmark
| | - Lars J Petersen
- Department of Clinical Science, Aalborg University, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Denmark; Department of Nuclear Medicine, Aalborg University Hospital, Denmark
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19
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He XF, Xiao YY, Zhang X, Zhang XB, Zhang X, Wei YT, Zhang ZL, Wiggermann P. Preliminary clinical application of the robot-assisted CT-guided irreversible electroporation ablation for the treatment of pancreatic head carcinoma. Int J Med Robot 2020; 16:e2099. [PMID: 32112493 DOI: 10.1002/rcs.2099] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 01/08/2020] [Accepted: 02/23/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND To evaluate the feasibility and safety of a robot-guided irreversible electroporation (IRE) ablation system for the treatment of pancreatic head carcinoma. METHODS A total of 20 cases with pancreatic head carcinoma were divided into two groups: 11 cases in group A with manual probe placement and 9 cases in group B with robotic navigated probe placement. The two groups were compared in terms of planning time before puncture, puncture time, the total time of electrode deployment, number of scans, and punctual accuracy of the single electrode. RESULTS Each probe was successfully punctured, and no complications were detected. P-values were calculated for all the parameters, using the SPSS 25.0 software and the t test. CONCLUSIONS The new robot can reduce the total operating time as compared to the manual probe placement with the same accuracy in the IRE of pancreatic head carcinoma.
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Affiliation(s)
- Xiao F He
- Department of Diagnostic Radiology, Medical School of Chinese PLA, Beijing, China
| | - Yue Y Xiao
- Department of Diagnostic Radiology, Medical School of Chinese PLA, Beijing, China
| | - Xiao Zhang
- Department of Diagnostic Radiology, Medical School of Chinese PLA, Beijing, China
| | - Xiao B Zhang
- Department of Diagnostic Radiology, Medical School of Chinese PLA, Beijing, China
| | - Xin Zhang
- Department of Diagnostic Radiology, Medical School of Chinese PLA, Beijing, China
| | - Ying T Wei
- Department of Diagnostic Radiology, Medical School of Chinese PLA, Beijing, China
| | - Zhong L Zhang
- Department of Diagnostic Radiology, Medical School of Chinese PLA, Beijing, China
| | - Philipp Wiggermann
- Chefarzt des Instituts für Röntgendiagnostik u. Nuklearmedizin Städtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany
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20
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Brock RM, Beitel-White N, Davalos RV, Allen IC. Starting a Fire Without Flame: The Induction of Cell Death and Inflammation in Electroporation-Based Tumor Ablation Strategies. Front Oncol 2020; 10:1235. [PMID: 32850371 PMCID: PMC7399335 DOI: 10.3389/fonc.2020.01235] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 06/16/2020] [Indexed: 12/17/2022] Open
Abstract
New therapeutic strategies and paradigms are direly needed for the treatment of cancer. While the surgical removal of tumors is favored in most cancer treatment plans, resection options are often limited based on tumor localization. Over the last two decades, multiple tumor ablation strategies have emerged as promising stand-alone or combination therapeutic options for patients. These strategies are often employed to treat tumors in areas where surgical resection is not possible or where chemotherapeutics have proven ineffective. The type of cell death induced by the ablation modality is a critical aspect of therapeutic success that can impact the efficacy of the treatment and systemic anti-tumor immune system responses. Electroporation-based ablation technologies include electrochemotherapy, irreversible electroporation, and other modalities that rely on pulsed electric fields to create pores in cell membranes. These pores can either be reversible or irreversible depending on the electric field parameters and can induce cell death either alone or in combination with a therapeutic agent. However, there have been many controversial findings among these technologies as to the cell death type initiated, from apoptosis to pyroptosis. As cell death mechanisms can impact treatment side effects and efficacy, we review the main types of cell death induced by electroporation-based treatments and summarize the impact of these mechanisms on treatment response. We also discuss potential reasons behind the variability of findings such as the similarities between cell death pathways, differences between cell-types, and the variation in electric field strength across the treatment area.
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Affiliation(s)
- Rebecca M. Brock
- Graduate Program in Translational Biology, Medicine, and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, United States
| | - Natalie Beitel-White
- Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
- Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Rafael V. Davalos
- Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Irving C. Allen
- Graduate Program in Translational Biology, Medicine, and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, United States
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Science, Blacksburg, VA, United States
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21
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O'Neill CH, Martin RCG. Cardiac synchronization and arrhythmia during irreversible electroporation. J Surg Oncol 2020; 122:407-411. [PMID: 32483842 DOI: 10.1002/jso.26041] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 05/17/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND OBJECTIVES Irreversible electroporation (IRE) is a nonthermal electrical tumor ablative strategy for unresectable tumors. IRE is relatively safe around critical structures but may induce cardiac arrhythmia when its delivery is not synchronized to the cardiac cycle. We performed a systematic literature review to determine rates of arrhythmia when IRE was utilized with or without cardiac synchronization. METHODS An online literature search was conducted with additional hand selection of articles. Data were extracted and pooled analyses were performed. RESULTS Twelve articles were included in analysis. IRE was performed for 481 patients; 46% hepatic tumors (n = 223), 36% pancreatic lesions (n = 168), and multiple other locations including prostate. Synchronization was performed on 422 patients. Arrhythmias were noted in 3.7% of cases (n = 18/481); cardiac synchronization: 1.2% (n = 5/422) vs unsynchronized: 22.0% (n = 13/59), P < .0001. These events occurred in every organ except the prostate. CONCLUSIONS IRE remains a potent technology for unresectable tumors, but arrhythmia is a clinical concern. This literature review confirms that cardiac gating should be used in all cases outside of prostate to prevent this potentially serious adverse event.
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Affiliation(s)
- Conor H O'Neill
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky
| | - Robert C G Martin
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky
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Timmer FEF, Geboers B, Ruarus AH, Schouten EAC, Nieuwenhuizen S, Puijk RS, de Vries JJJ, Meijerink MR, Scheffer HJ. Irreversible Electroporation for Locally Advanced Pancreatic Cancer. Tech Vasc Interv Radiol 2020; 23:100675. [PMID: 32591191 DOI: 10.1016/j.tvir.2020.100675] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Several minimally invasive image guided tumor ablation techniques have been added to the treatment spectrum for locally advanced pancreatic cancer (LAPC). Irreversible electroporation (IRE) might have a significant additive value in the management of this difficult-to-treat disease. As opposed to thermal ablative techniques, IRE induces cell death by the delivery of high-voltage electrical pulses. The electrical energy disrupts the cellular membrane integrity, causes loss of cellular homeostasis and ultimately results in cell death. The extracellular matrix of connective tissue in surrounding delicate structures such as bile ducts, bowel wall, and larger blood vessels is spared. The preservation of these structures makes IRE attractive for the treatment of pancreatic cancers that are unresectable due to their anatomical location (ie, LAPC and local recurrence after surgical resection). In addition to its cytoreductive abilities, evidence is emerging on IRE's capability to induce systemic immunomodulation through active in vivo vaccination against pancreatic cancer cells. These effects in combination with immunotherapy may offer a new treatment paradigm for tumors with low immunogenic potential like pancreatic ductal adenocarcinoma (PDAC). This review discusses several practical and technical issues of IRE for LAPC: clinical evaluation, indications, patient preparations, procedural steps, imaging characteristics, clinical results, and "tricks of the trade" used to improve the safety and efficacy of the treatment. Future directions such as the combination of IRE with immunotherapy will be shortly addressed.
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Affiliation(s)
- Florentine E F Timmer
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
| | - Bart Geboers
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands.
| | - Alette H Ruarus
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
| | - Evelien A C Schouten
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
| | - Sanne Nieuwenhuizen
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
| | - Robbert S Puijk
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
| | - Jan J J de Vries
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
| | - Martijn R Meijerink
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
| | - Hester J Scheffer
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
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Belfiore MP, Reginelli A, Maggialetti N, Carbone M, Giovine S, Laporta A, Urraro F, Nardone V, Grassi R, Cappabianca S, Brunese L. Preliminary results in unresectable cholangiocarcinoma treated by CT percutaneous irreversible electroporation: feasibility, safety and efficacy. Med Oncol 2020; 37:45. [PMID: 32270353 DOI: 10.1007/s12032-020-01360-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 03/10/2020] [Indexed: 12/12/2022]
Abstract
Cholangiocarcinoma (CC) accounts for about 3% of the gastrointestinal and 10-25% of all hepatobiliary malignancies. It arises from the epithelium of the bile duct and it can be classified in intrahaepatic (ICC), perihilar (PCC) and distal (DCC) cholangiocarcinoma, depending on the anatomical location. About 50-60% of the cases are PCC. Early detection is very difficult for the lack of symptoms, and most of the patients are not resectable at the time of diagnosis. IRE is a non-thermal ablation technique that determines cellular apoptosis by electrical impulses without involving extracellular matrix like MW or RF ablation (MWA and RFA). The aim of our study is to demonstrate the safety, feasibility and efficacy of this procedure in the treatment of cholangiocarcinoma according to our experience. From 2015 to 2019, fifteen patients with unre-sectable perhilar and intrahepatic colangiocarcinoma (7 female and 8 male, mean age 69.2) were referred to our department to be enrolled in our prospective study that was approved by local Ethical Committee. Eight lesions were defined iCC and seven of them pCC. Six patients had biliary STENT and four external percutaneous transhepatic biliary drainage (PTBD). The IRE procedure was performed to expert radiologist (G.B.) under CT guidance using the Nanoknife IRE device (Angiodynamics, Queensbury, NY). The data before and after treatment were compared using Wilcoxon Rank Test and the survival outcome was evaluated using Kaplan Meyer Test. All procedures performed under CT guidance have been successfully completed. Treated lesions were located seven perhilar and eight intrahepatic sites and showed a mean volume 66.3 (SD 70.9; IC ranged from 5.57 to 267.20 cm3). No major complications were observed. From 30 to 90 days, the mortality rate was around 0%. Progression of the disease in all cases were not observed. Only one patient was reported increase of the Ca19-9 without sign of pancreatitis and bile obstruction. The imaging follow-up showed the local disease control with a decrease of the entire volume of the lesion and a further reduction of the densitometric values. From the comparison between the mean volumes for each group (before and after treatment), the Wilcoxon Rank test demonstrated the statistical significant difference with a p value < 0.01. On the contrary, it is believed that this results encouraging in considering the IRE procedure the safe, feasible and effective method in the treatment of the CC.
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Affiliation(s)
- Maria Paola Belfiore
- Department of Precision Medicine, University of Campania "L. Vanvitelli", 80138, Naples, Italy
| | - Alfonso Reginelli
- Department of Precision Medicine, University of Campania "L. Vanvitelli", 80138, Naples, Italy.
| | - Nicola Maggialetti
- Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Via Francesco De Sanctis 1, Campobasso, Italy
| | - Mattia Carbone
- Department of Radiology, San Giovanni E Ruggi D'Aragona Hospital, Ospedale, Via San Leonardo, Salerno, Italy
| | - Sabrina Giovine
- Department of Radiology, SG Moscati Hospital, ASL Caserta, Aversa, Italy
| | | | - Fabrizio Urraro
- Department of Precision Medicine, University of Campania "L. Vanvitelli", 80138, Naples, Italy
| | - Valerio Nardone
- Unit of Radiation Oncology, Ospedale del Mare, 80147, Naples, Italy
| | - Roberta Grassi
- Department of Precision Medicine, University of Campania "L. Vanvitelli", 80138, Naples, Italy
| | - Salvatore Cappabianca
- Department of Precision Medicine, University of Campania "L. Vanvitelli", 80138, Naples, Italy
| | - Luca Brunese
- Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Via Francesco De Sanctis 1, Campobasso, Italy
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Moulla Y, Petersen TO, Maiwald B, Bailis N, Kreuser N, Lordick F, Seehofer D, Sucher R, Hecker M, Hoffmeister A, Jansen-Winkeln B, Gockel I. [Ablative treatment options for locally advanced unresectable and borderline resectable pancreatic carcinoma]. Chirurg 2020; 91:319-328. [PMID: 31828387 DOI: 10.1007/s00104-019-01072-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Locally advanced unresectable (nonmetastatic) and borderline resectable pancreatic carcinomas represent a therapeutic challenge. Several minimally invasive local ablative techniques are available for local treatment in these situations. OBJECTIVE Which interventional techniques and application options are currently available for pancreatic carcinoma and which oncological results could be achieved so far? MATERIAL AND METHODS An analysis of reviews and studies was carried out. The selection of literature was based on searches in PubMed and the Cochrane library. The studies analyzed were reviews, meta-analyses and original articles mainly from the period between 2013 and 2018. Single case reports were not included in this review. RESULTS Local ablative techniques are performed with various forms of energy and are associated with specific advantages and disadvantages. They have to be individually tailored to the specific patient and situation. Noninvasive thermal ablation with high-intensity focused ultrasound (HIFU) is primarily used for palliative pain relief. Solid tumors are the main indication for thermal necrosis with microwave ablation (MWA) and radiofrequency ablation (RFA). The use of irreversible electroporation (IRE) enables a selective destruction of tumor cells and can be performed in the vicinity of sensitive structures. This technique is applied for primary tumor control and also for accentuation of tumor margins during resection. CONCLUSION With local ablative techniques an improvement in the quality of life and possibly the prognosis can be achieved in patients with unresectable pancreatic cancer; however, the latter aspect has to be viewed with caution due to a current lack of well-founded data.
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Affiliation(s)
- Yusef Moulla
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Department für Operative Medizin (DOPM), Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
| | - Tim-Ole Petersen
- Klinik und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Leipzig, AöR, Leipzig, Deutschland
| | - Bettina Maiwald
- Klinik und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Leipzig, AöR, Leipzig, Deutschland
| | - Nikolaos Bailis
- Klinik und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Leipzig, AöR, Leipzig, Deutschland
| | - Nicole Kreuser
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Department für Operative Medizin (DOPM), Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
| | - Florian Lordick
- Universitäres Krebszentrum Leipzig (UCCL), Universitätsklinikum Leipzig, AöR, Leipzig, Deutschland
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Department für Operative Medizin (DOPM), Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
| | - Robert Sucher
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Department für Operative Medizin (DOPM), Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
| | - Martin Hecker
- Klinik und Poliklinik für Gastroenterologie, Universitätsklinikum Leipzig, AöR, Leipzig, Deutschland
| | - Albrecht Hoffmeister
- Klinik und Poliklinik für Gastroenterologie, Universitätsklinikum Leipzig, AöR, Leipzig, Deutschland
| | - Boris Jansen-Winkeln
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Department für Operative Medizin (DOPM), Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
| | - Ines Gockel
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Department für Operative Medizin (DOPM), Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland.
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He C, Wang J, Zhang Y, Lin X, Li S. Irreversible electroporation after induction chemotherapy versus chemotherapy alone for patients with locally advanced pancreatic cancer: A propensity score matching analysis. Pancreatology 2020; 20:477-484. [PMID: 32131993 DOI: 10.1016/j.pan.2020.02.009] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 02/12/2020] [Accepted: 02/15/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Locally advanced pancreatic cancer (LAPC) is a devastating disease and irreversible electroporation (IRE) is a non-thermal ablation method that is especially suitable for the treatment of LAPC. This study aimed to compare the long-term survival of LAPC patients after induction chemotherapy followed by IRE and chemotherapy alone. METHODS From August 2015 to August 2017, a total of 132 patients with LAPC were identified. The oncological outcomes of these two treatments were analyzed by propensity score matching (PSM) analysis. RESULTS Before PSM analysis, patients with LAPC had better overall survival (OS) and progression-free survival (PFS) after induction chemotherapy followed by IRE than those who received chemotherapy alone (2-year OS rates, 57.9% vs 19.8%, P < 0.001; 2-year PFS rates, 31.4% vs 9.3%, P < 0.001). The baseline clinicopathological factors were balanced between the 2 groups through PSM analysis. Even after PSM, the OS and PFS rates of patients after induction chemotherapy followed by IRE treatment were superior to those of patients who received chemotherapy treatment alone (2-year OS rates, 57.9% vs 18.1%, P < 0.001; 2-year PFS rates, 31.4% vs 7.1%, P < 0.001). Multivariate Cox regression analysis indicated that chemotherapy plus IRE was a significant prognostic factor for both OS and PFS in patients of both the whole cohort and the matched cohort. CONCLUSIONS Induction chemotherapy followed by IRE provided better OS and PFS than chemotherapy alone for patients with LAPC. This combination method may be a more suitable treatment for patients with LAPC.
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Affiliation(s)
- Chaobin He
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China.
| | - Jun Wang
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China; Department of Ultrasonics, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China.
| | - Yu Zhang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, PR China.
| | - Xiaojun Lin
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China.
| | - Shengping Li
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China.
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Abstract
Irreversible electroporation (IRE) is a relatively recent method of ablation. In contrast to many ablation devices that use thermal methods to induce cell death, IRE employs the use of an electric field to cause irreversible permeability of the cell membrane, thus inducing apoptosis. Since its use in the pancreas was first described in 2012, IRE has become established as part of the armamentarium of ablation devices currently available. The crucial advantage of IRE compared with other devices employing thermal ablation is the safety around vital structures such as vessels and ducts. This is especially important in the pancreas due to the close proximity of multiple major vascular structures, biliary ducts, and adjacent gastrointestinal organs. This article will explore the current evidence regarding the use of IRE in the pancreas.
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Affiliation(s)
- Gabriel Chan
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore
| | - Uei Pua
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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27
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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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Moris D, Machairas N, Tsilimigras DI, Prodromidou A, Ejaz A, Weiss M, Hasemaki N, Felekouras E, Pawlik TM. Systematic Review of Surgical and Percutaneous Irreversible Electroporation in the Treatment of Locally Advanced Pancreatic Cancer. Ann Surg Oncol 2019; 26:1657-1668. [PMID: 30843163 DOI: 10.1245/s10434-019-07261-7] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The aim of the present systematic review was to collect, analyze, and critically evaluate the role of irreversible electroporation (IRE) in locally advanced pancreatic cancer (LAPC). Furthermore, we sought to analyze the different approaches of IRE (open, laparoscopic, and percutaneous) and assess the relative outcomes. METHODS A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Using the MEDLINE (1966-2018), Scopus (2004-2018), Google Scholar (2004-2018) and ClinicalTrials.gov databases, eligible articles published up to August 2018 were included. The following keywords were applied: 'irreversible electroporation', 'IRE', 'LAPC', 'unresectable pancreatic cancer', 'palliative treatment', 'locally advanced pancreatic cancer', 'ablation' and 'ablative treatment'. RESULTS IRE for LAPC was feasible and safe; however, it was associated with morbidity in approximately one in three patients, some of whom experienced serious complications, particularly after surgical IRE. In addition, while mortality following IRE was uncommon, it did occur in 2% of patients. While some studies suggested a survival benefit, others failed to note an improvement in long-term outcomes following IRE compared with other therapies. CONCLUSIONS Providers and patients need to be aware of the potential morbidity and mortality associated with IRE. In addition, based on the literature to date, the survival benefit of IRE for LAPC remains to be elucidated. Conclusive and definitive evidence to support a survival benefit of IRE does not currently exist. Future multicenter, randomized, prospective trials are needed to clarify the role of IRE in patients with LAPC.
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Affiliation(s)
- Dimitrios Moris
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Wexner Medical Center, James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH, USA
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Nikolaos Machairas
- First Department of Surgery, Laikon General Hospital, University of Athens Medical School, Athens, Greece
| | - Diamantis I Tsilimigras
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Wexner Medical Center, James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH, USA
- First Department of Surgery, Laikon General Hospital, University of Athens Medical School, Athens, Greece
| | - Anastasia Prodromidou
- First Department of Surgery, Laikon General Hospital, University of Athens Medical School, Athens, Greece
| | - Aslam Ejaz
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Wexner Medical Center, James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH, USA
| | - Matthew Weiss
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Natasha Hasemaki
- First Department of Surgery, Laikon General Hospital, University of Athens Medical School, Athens, Greece
| | - Evangelos Felekouras
- First Department of Surgery, Laikon General Hospital, University of Athens Medical School, Athens, Greece
| | - Timothy M Pawlik
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Wexner Medical Center, James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH, USA.
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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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Irreversible Electroporation in pancreatic ductal adenocarcinoma: Is there a role in conjunction with conventional treatment? Eur J Surg Oncol 2018; 44:1486-1493. [PMID: 30146253 DOI: 10.1016/j.ejso.2018.07.047] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 07/09/2018] [Accepted: 07/20/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The incidence of pancreatic ductal adenocarcinoma (PDAC) is rapidly increasing. Up to 30% of patients present with locally advanced disease and therefore are not candidates for surgery. Locally advanced pancreatic cancer (LAPC) is an emerging entity lacking in level III evidence-based recommendations for its treatment. Currently, systemic chemotherapy is the main treatment for LAPC. However, due to lack of response or disease progression, downsizing of the tumour, making it resectable is successful in only a small proportion of patients. Radiotherapy is often advocated to improve local disease control if there is stability following chemotherapy. Recently, Irreversible Electroporation (IRE), a novel non-thermal ablation technique, has been proposed for the treatment of LAPC. AIMS AND METHODS This narrative review aims to explore the potential role and timing for the use of IRE in patients with LAPC. RESULTS To date, there is limited and inconsistent level I and II evidence available in the literature regarding the use of IRE for the treatment of PDAC. DISCUSSION Although some of the preliminary experience of the use of IRE in patients with LAPC is encouraging, it should only be used after conventional evidence-based treatments and/or within the research context.
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Shankara Narayanan JS, Ray P, Naqvi I, White R. A Syngeneic Pancreatic Cancer Mouse Model to Study the Effects of Irreversible Electroporation. J Vis Exp 2018. [PMID: 29939178 DOI: 10.3791/57265] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Pancreatic cancer (PC), a disease which kills approximately 40,000 patients each year in the US, has successfully evaded several therapeutic approaches including the promising immunotherapeutic strategies. Irreversible electroporation (IRE) is a non-thermal ablation technique that induces tumor cell death without destruction of adjacent collagenous structures, thus enabling the procedure to be performed in tumors very close to blood vessels. Unlike thermal ablation techniques, IRE results in gradual apoptotic cell death, along with immediate ablation induced necrosis, and is currently in clinical use for selected patients with locally advanced PC. An ablative, non-target specific procedure like IRE can induce a myriad of responses in the tumor microenvironment. A few studies have addressed the effects of IRE on tumor growth in other tumor types, but none have focused on PC. We have developed a syngeneic mouse model of PC in which subcutaneous (SQ) and orthotopic tumors can be successfully treated with IRE in a highly controlled setting, facilitating various longitudinal studies post procedure. This animal model serves as a robust system to study the effects of IRE and ways to improve the clinical efficacy of IRE.
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Affiliation(s)
| | - Partha Ray
- Moores Cancer Center, University California San Diego
| | | | - Rebekah White
- Moores Cancer Center, University California San Diego;
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Irreversible Electroporation in Patients with Pancreatic Cancer: How Important Is the New Weapon? BIOMED RESEARCH INTERNATIONAL 2018; 2018:5193067. [PMID: 29854763 PMCID: PMC5944201 DOI: 10.1155/2018/5193067] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 03/12/2018] [Indexed: 12/23/2022]
Abstract
Background Pancreatic cancer (PC) is a deadly disease with poor prognosis in the general population. We aimed to quantitate overall survival of patients with PC after irreversible electroporation (IRE) and the incidence of relevant complications. Methods We performed a literature search via five electronic databases (PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases) up to August 2017. The primary outcomes were overall survival and prognosis. Secondary outcomes included the response of post-IRE complications. Fixed-effects or random-effects meta-analysis was conducted to pool these data. Results A total of 15 eligible articles involving 535 patients were included. The primary outcomes showed that the pooled prevalence estimates of overall survival were 94.1% (95% CI: 90.7–97.5), 80.9% (95% CI: 72.5–89.4), 54.5% (95% CI: 38.3–70.6), and 33.8% (95% CI: 14.2–53.5) at 3, 6, 12, and 24 months, and the pooled prevalence data of complete response (CR) at 2 months, partial response (PR) at 3 months, and progression at 3 months were 12.5% (95% CI: 2.9–22.2), 48.5% (95% CI: 39.4–57.6), and 19.7% (95% CI: 7.3–32.2), respectively. The secondary outcomes showed that the pooled prevalence values of post-IRE complications were abscess 6.6% (95% CI: 0.2–13), fistula 10.6% (95% CI: 2.5–18.7), pain 33.5% (95% CI: 14.5–52.5), infection 16.1% (95% CI: 3.9–28.4), thrombosis 4.9% (95% CI: 1.2–8.5), pancreatitis 7.2% (95% CI: 3.1–11.2), bleeding 4.2% (95% CI: −0.5–8.9), cholangitis 4.2% (95% CI: −0.5–8.9), nausea 9.6% (95% CI: 4.4–14.8), biliary obstruction 13.8% (95% CI: 4.2–23.3), chest tightness 7.6% (95% CI: 0.5–14.6), and hypoglycemia 5.9% (95% CI: −0.4–12.2). Conclusions This meta-analysis indicated a clear survival benefit for PC patients who received irreversible electroporation therapy, although future safety and effectivity monitoring from more large-scale studies will be needed.
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Ruarus A, Vroomen L, Puijk R, Scheffer H, Zonderhuis B, Kazemier G, van den Tol M, Berger F, Meijerink M. Irreversible Electroporation in Hepatopancreaticobiliary Tumours. Can Assoc Radiol J 2018; 69:38-50. [DOI: 10.1016/j.carj.2017.10.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Accepted: 10/25/2017] [Indexed: 12/18/2022] Open
Abstract
Hepatopancreaticobiliary tumours are often diagnosed at an advanced disease stage, in which encasement or invasion of local biliary or vascular structures has already occurred. Irreversible electroporation (IRE) is an image-guided tumour ablation technique that induces cell death by exposing the tumour to high-voltage electrical pulses. The cellular membrane is disrupted, while sparing the extracellular matrix of critical tubular structures. The preservation of tissue integrity makes IRE an attractive treatment option for tumours in the vicinity of vital structures such as splanchnic blood vessels and major bile ducts. This article reviews current data and discusses future trends of IRE for hepatopancreaticobiliary tumours.
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Affiliation(s)
- A.H. Ruarus
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - L.G.P.H. Vroomen
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - R.S. Puijk
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - H.J. Scheffer
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - B.M. Zonderhuis
- Department of Surgery, VU University Medical Center, Amsterdam, the Netherlands
| | - G. Kazemier
- Department of Surgery, VU University Medical Center, Amsterdam, the Netherlands
| | - M.P. van den Tol
- Department of Surgery, VU University Medical Center, Amsterdam, the Netherlands
| | - F.H. Berger
- Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - M.R. Meijerink
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands
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Rashid MF, Hecht EM, Steinman JA, Kluger MD. Irreversible electroporation of pancreatic adenocarcinoma: a primer for the radiologist. Abdom Radiol (NY) 2018; 43:457-466. [PMID: 29051982 DOI: 10.1007/s00261-017-1349-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Irreversible electroporation (IRE) is increasingly used for the ablation of unresectable locally advanced pancreatic adenocarcinoma. Unlike other ablation technologies that cannot be safely used around critical vasculature or ducts for risk of thermal damage, IRE uses high-voltage pulses to disrupt cellular membranes. This causes cell death by apoptosis and inflammation. IRE has been deployed by both open and percutaneous approaches. Generator parameters are the same for both approaches, and settings are pancreas specific. Variations in settings, probe placement, and probe exposure can result in thermal damage or reversible electroporation and resultant treatment failure, morbidity, or mortality. When used properly, IRE appears to improve overall survival and local recurrence, but does not influence the rate of distant recurrence. However, studies of both open and percutaneous approaches have been relatively small, non-controlled, and without appropriate comparisons. It is challenging for the radiologist to interpret treatment effects after IRE because of a dearth of guiding literature and pathologic correlates. This primer describes technical aspects, pathology correlates, post-IRE imaging, and outcomes for percutaneous and open approaches.
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Affiliation(s)
- M Farzan Rashid
- Division of Gastrointestinal and Endocrine Surgery, Department of Surgery, Columbia University College of Physicians and Surgeons, 161 Fort Washington Ave - 8th Floor, New York, NY, USA
| | - Elizabeth M Hecht
- Division of Abdominal Imaging, Department of Radiology, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA
| | - Jonathan A Steinman
- Division of Abdominal Imaging, Department of Radiology, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA
| | - Michael D Kluger
- Division of Gastrointestinal and Endocrine Surgery, Department of Surgery, Columbia University College of Physicians and Surgeons, 161 Fort Washington Ave - 8th Floor, New York, NY, USA.
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Locally Advanced Pancreatic Cancer: A Review of Local Ablative Therapies. Cancers (Basel) 2018; 10:cancers10010016. [PMID: 29320420 PMCID: PMC5789366 DOI: 10.3390/cancers10010016] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 01/03/2018] [Accepted: 01/04/2018] [Indexed: 12/17/2022] Open
Abstract
Pancreatic cancer is typically characterized by its aggressive tumor growth and dismal prognosis. Approximately 30% of patients with pancreatic cancer present with locally advanced disease, broadly defined as having a tumor-to-artery interface >180°, having an unreconstructable portal vein or superior mesenteric vein and no signs of metastatic disease. These patients are currently designated to palliative systemic chemotherapy, though median overall survival remains poor (approximately 11 months). Therefore, several innovative local therapies have been investigated as new treatment options for locally advanced pancreatic cancer (LAPC). This article provides an overview of available data with regard to morbidity and oncological outcome of novel local therapies for LAPC.
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Ansari D, Kristoffersson S, Andersson R, Bergenfeldt M. The role of irreversible electroporation (IRE) for locally advanced pancreatic cancer: a systematic review of safety and efficacy. Scand J Gastroenterol 2017; 52:1165-1171. [PMID: 28687047 DOI: 10.1080/00365521.2017.1346705] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2017] [Revised: 06/19/2017] [Accepted: 06/19/2017] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Irreversible electroporation (IRE) is a new modality for tumor ablation. Electrodes are placed around the tumor, and a pulsed, direct current with a field strength of 2000 V/cm is delivered. The direct current drives cells into apoptosis and cell death without causing significant heating of the tissues, which spares the extracellular matrix and proteins. The purpose of this review was to evaluate current experience of IRE for the ablation of pancreatic cancer. MATERIAL AND METHODS We searched PubMed for all studies of IRE in human pancreatic cancer in English reporting at least 10 patients. RESULTS The search yielded 10 studies, comprising a total of 446 patients. Percutaneous IRE was done in 142 patients, while 304 patients were treated during laparotomy. Tumor sizes ranged from median 2.8 to 4.5 cm. Post-procedural complications occurred in 35% of patients, most of them were less severe. Nine patients (2.0%) died after the procedure. The technical success rate was 85-100%. The median recurrence-free survival was 2.7-12.4 months after IRE treatment. The median overall survival was 7-23 months postoperatively. The longest overall survival was noted when IRE was used in conjunction with pancreatic resection. CONCLUSIONS IRE seems feasible and safe with a low post-procedural mortality. Further efforts are needed to address patient selection and efficacy of IRE, as well as the use of IRE for 'margin accentuation' during surgical resection.
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Affiliation(s)
- Daniel Ansari
- a Department of Surgery, Clinical Sciences Lund , Lund University, Skåne University Hospital , Lund , Sweden
| | - Stina Kristoffersson
- a Department of Surgery, Clinical Sciences Lund , Lund University, Skåne University Hospital , Lund , Sweden
| | - Roland Andersson
- a Department of Surgery, Clinical Sciences Lund , Lund University, Skåne University Hospital , Lund , Sweden
| | - Magnus Bergenfeldt
- a Department of Surgery, Clinical Sciences Lund , Lund University, Skåne University Hospital , Lund , Sweden
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Coelen RJS, Vogel JA, Vroomen LGPH, Roos E, Busch ORC, van Delden OM, Delft FV, Heger M, van Hooft JE, Kazemier G, Klümpen HJ, van Lienden KP, Rauws EAJ, Scheffer HJ, Verheul HM, Vries JD, Wilmink JW, Zonderhuis BM, Besselink MG, van Gulik TM, Meijerink MR. Ablation with irreversible electroporation in patients with advanced perihilar cholangiocarcinoma (ALPACA): a multicentre phase I/II feasibility study protocol. BMJ Open 2017; 7:e015810. [PMID: 28864693 PMCID: PMC5588990 DOI: 10.1136/bmjopen-2016-015810] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION The majority of patients with perihilar cholangiocarcinoma (PHC) has locally advanced disease or distant lymph node metastases on presentation or exploratory laparotomy, which makes them not eligible for resection. As the prognosis of patients with locally advanced PHC or lymph node metastases in the palliative setting is significantly better compared with patients with organ metastases, ablative therapies may be beneficial. Unfortunately, current ablative options are limited. Photodynamic therapy causes skin phototoxicity and thermal ablative methods, such as stereotactic body radiation therapy and radiofrequency ablation, which are affected by a heat/cold-sink effect when tumours are located close to vascular structures, such as the liver hilum. These limitations may be overcome by irreversible electroporation (IRE), a relatively new ablative method that is currently being studied in several other soft tissue tumours, such as hepatic and pancreatic tumours. METHODS AND ANALYSIS In this multicentre phase I/II safety and feasibility study, 20 patients with unresectable PHC due to vascular or distant lymph node involvement will undergo IRE. Ten patients who present with unresectable PHC will undergo CT-guided percutaneous IRE, whereas ultrasound-guided IRE will be performed in 10 patients with unresectable tumours detected at exploratory laparotomy. The primary outcome is the total number of clinically relevant complications (Common Terminology Criteria for Adverse Events, score of≥3) within 90 days. Secondary outcomes include quality of life, tumour response, metal stent patency and survival. Follow-up will be 2 years. ETHICS AND DISSEMINATION The protocol has been approved by the local ethics committees. Data and results will be submitted to a peer-reviewed journal. CONCLUSION The Ablation with irreversible eLectroportation in Patients with Advanced perihilar CholangiocarcinomA (ALPACA) study is designed to assess the feasibility of IRE for advanced PHC. The main purpose is to inform whether a follow-up trial to evaluate safety and effectiveness in a larger cohort would be feasible.
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Affiliation(s)
- Robert J S Coelen
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Jantien A Vogel
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | | | - Eva Roos
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Olivier R C Busch
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Otto M van Delden
- Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands
| | - Foke van Delft
- Department of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands
| | - Michal Heger
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Jeanin E van Hooft
- Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands
| | - Geert Kazemier
- Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands
| | - Heinz-Josef Klümpen
- Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands
| | - Krijn P van Lienden
- Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands
| | - Erik A J Rauws
- Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands
| | - Hester J Scheffer
- Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands
| | - Henk M Verheul
- Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
| | - Jan de Vries
- Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands
| | - Johanna W Wilmink
- Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands
| | | | - Marc G Besselink
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Thomas M van Gulik
- Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands
| | - Martijn R Meijerink
- Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands
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Vogel JA, Rombouts SJ, de Rooij T, van Delden OM, Dijkgraaf MG, van Gulik TM, van Hooft JE, van Laarhoven HW, Martin RC, Schoorlemmer A, Wilmink JW, van Lienden KP, Busch OR, Besselink MG. Induction Chemotherapy Followed by Resection or Irreversible Electroporation in Locally Advanced Pancreatic Cancer (IMPALA): A Prospective Cohort Study. Ann Surg Oncol 2017; 24:2734-2743. [PMID: 28560601 DOI: 10.1245/s10434-017-5900-9] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Following induction chemotherapy, both resection or irreversible electroporation (IRE) may further improve survival in patients with locally advanced pancreatic cancer (LAPC). However, prospective studies combining these strategies are currently lacking, and available studies only report on subgroups that completed treatment. This study aimed to determine the applicability and outcomes of resection and IRE in patients with nonprogressive LAPC after induction chemotherapy. METHODS This was a prospective, single-center cohort study in consecutive patients with LAPC (September 2013 to March 2015). All patients were offered 3 months of induction chemotherapy (FOLFIRINOX or gemcitabine depending on performance status), followed by exploratory laparotomy for resection or IRE in patients with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 nonprogressive, IRE-eligible tumors. RESULTS Of 132 patients with LAPC, 70% (n = 93) started with chemotherapy (46% [n = 61] FOLFIRINOX). After 3 months, 59 patients (64%) had nonprogressive disease, of whom 36 (27% of the entire cohort) underwent explorative laparotomy, resulting in 14 resections (11% of the entire cohort, 39% of the explored patients) and 15 IREs (11% of the entire cohort, 42% of the explored patients). After laparotomy, 44% (n = 16) of patients had Clavien-Dindo grade 3 or higher complications, and 90-day all-cause mortality was 11% (n = 4). With a median follow-up of 24 months, median overall survival after resection, IRE, and for all patients with nonprogressive disease without resection/IRE (n = 30) was 34, 16, and 15 months, respectively. The resection rate in 61 patients receiving FOLFIRINOX treatment was 20%. CONCLUSION Induction chemotherapy followed by IRE or resection in nonprogressive LAPC led to resection or IRE in 22% of all-comers, with promising survival rates after resection but no apparent benefit of IRE, despite considerable morbidity. Registered at Netherlands Trial Register (NTR4230).
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Affiliation(s)
- Jantien A Vogel
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Steffi J Rombouts
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Thijs de Rooij
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Otto M van Delden
- Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands
| | - Marcel G Dijkgraaf
- Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands
| | - Thomas M van Gulik
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Jeanin E van Hooft
- Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands
| | | | - Robert C Martin
- Department of Surgery, University of Louisville, Louisville, KY, USA
| | | | - Johanna W Wilmink
- Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands
| | - Krijn P van Lienden
- Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands
| | - Olivier R Busch
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Marc G Besselink
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.
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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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Narayanan G, Hosein PJ, Beulaygue IC, Froud T, Scheffer HJ, Venkat SR, Echenique AM, Hevert EC, Livingstone AS, Rocha-Lima CM, Merchan JR, Levi JU, Yrizarry JM, Lencioni R. Percutaneous Image-Guided Irreversible Electroporation for the Treatment of Unresectable, Locally Advanced Pancreatic Adenocarcinoma. J Vasc Interv Radiol 2016; 28:342-348. [PMID: 27993507 DOI: 10.1016/j.jvir.2016.10.023] [Citation(s) in RCA: 85] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Revised: 10/18/2016] [Accepted: 10/25/2016] [Indexed: 02/07/2023] Open
Abstract
PURPOSE To describe safety and effectiveness of percutaneous irreversible electroporation (IRE) for treatment of unresectable, locally advanced pancreatic adenocarcinoma (LAPC). MATERIALS AND METHODS This retrospective study included 50 patients (23 women, 27 men; age range, 46-91 y; median age, 62.5 y) with biopsy-proven, unresectable LAPC who received percutaneous computed tomography (CT)-guided IRE. The primary objective was to assess the safety profile of the procedure; the secondary objective was to determine overall survival (OS). All patients had prior chemotherapy (1-5 lines, median 2), and 30 (60%) of 50 patients had prior radiation therapy. Follow-up included CT at 1 month and at 3-month intervals thereafter. RESULTS There were no treatment-related deaths and no 30-day mortality. Serious adverse events occurred in 10 (20%) of 50 patients (abdominal pain [n = 7], pancreatitis [n = 1], sepsis [n = 1], gastric leak [n = 1]). Median OS was 27.0 months (95% confidence interval [CI], 22.7-32.5 months) from time of diagnosis and 14.2 months (95% CI, 9.7-16.2 months) from time of IRE. Patients with tumors ≤ 3 cm (n = 24) had significantly longer median OS than patients with tumors > 3 cm (n = 26): 33.8 vs 22.7 months from time of diagnosis (P = .002) and 16.2 vs 9.9 months from time of IRE (P = .031). Tumor size was confirmed as the only independent predictor of OS at multivariate analysis. CONCLUSIONS Percutaneous image-guided IRE of unresectable LAPC is associated with an acceptable safety profile.
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Affiliation(s)
- Govindarajan Narayanan
- Department of Interventional Radiology, University of Miami Miller School of Medicine, 1475 NW 12th Avenue, C-080, Miami, FL 33136.
| | - Peter J Hosein
- Division of Medical Oncology, Department of Medicine, University of Kentucky, Lexington, Kentucky
| | - Isabelle C Beulaygue
- Department of Interventional Radiology, University of Miami Miller School of Medicine, 1475 NW 12th Avenue, C-080, Miami, FL 33136
| | - Tatiana Froud
- Department of Interventional Radiology, University of Miami Miller School of Medicine, 1475 NW 12th Avenue, C-080, Miami, FL 33136
| | - Hester J Scheffer
- Department of Radiology and Nuclear Medicine, VU University Medical Center Amsterdam, Amsterdam, The Netherlands
| | - Shree R Venkat
- Department of Interventional Radiology, University of Miami Miller School of Medicine, 1475 NW 12th Avenue, C-080, Miami, FL 33136
| | - Ana M Echenique
- Department of Interventional Radiology, University of Miami Miller School of Medicine, 1475 NW 12th Avenue, C-080, Miami, FL 33136
| | | | - Alan S Livingstone
- Department of Medicine, Sylvester Comprehensive Cancer Center, and Department of Surgery, University of Miami Miller School of Medicine, 1475 NW 12th Avenue, C-080, Miami, FL 33136
| | - Caio M Rocha-Lima
- Division of Oncology, Gibbs Cancer Center & Research Institute, Spartanburg, South Carolina
| | - Jaime R Merchan
- Division of Medical Oncology, University of Miami Miller School of Medicine, 1475 NW 12th Avenue, C-080, Miami, FL 33136
| | - Joseph U Levi
- Department of Medicine, Sylvester Comprehensive Cancer Center, and Department of Surgery, University of Miami Miller School of Medicine, 1475 NW 12th Avenue, C-080, Miami, FL 33136
| | - Jose M Yrizarry
- Department of Interventional Radiology, University of Miami Miller School of Medicine, 1475 NW 12th Avenue, C-080, Miami, FL 33136
| | - Riccardo Lencioni
- Department of Interventional Radiology, University of Miami Miller School of Medicine, 1475 NW 12th Avenue, C-080, Miami, FL 33136
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Pain Analysis in Patients with Pancreatic Carcinoma: Irreversible Electroporation versus Cryoablation. BIOMED RESEARCH INTERNATIONAL 2016; 2016:2543026. [PMID: 28074177 PMCID: PMC5198095 DOI: 10.1155/2016/2543026] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 10/31/2016] [Accepted: 11/29/2016] [Indexed: 12/18/2022]
Abstract
The aim of this article is to evaluate and compare the postprocedure pain in patients with pancreatic carcinoma treated with irreversible electroporation (IRE) and cryoablation (CRYO). We compared 22 patients with 22 lesions in pancreas treated with IRE and 26 patients with 27 lesions treated with cryosurgery. All the patients in the two groups were under celiac plexus block (CPB) treatment to alleviate the postprocedure pain. A numerical rating scale (VAS) consisting of 11-point scales and the 24 h total hydromorphone use were recorded for the analysis of the pain level in the patients who underwent these two technologies separately. Other parameters, such as the complications and the ECOG performance status, were also noted. Statistical analysis was performed by Fisher's exact test, the Chi-square test, and Student's t-test. All the pancreatic carcinoma patients in our study were reported to have postprocedure pain in the two groups. But there was no significant difference in the mean pain score (4.95 (IRE) versus 4.85 (CRYO); P = 0.52) and 24 h total hydromorphone use (3.89 mg (IRE) versus 3.97 mg (CRYO); P = 0.30). IRE is comparable to cryotherapy in the amount of pain that patients with pancreatic carcinoma experience.
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Martin RCG, Durham AN, Besselink MG, Iannitti D, Weiss MJ, Wolfgang CL, Huang KW. Irreversible electroporation in locally advanced pancreatic cancer: A call for standardization of energy delivery. J Surg Oncol 2016; 114:865-871. [PMID: 27546233 DOI: 10.1002/jso.24404] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Accepted: 07/30/2016] [Indexed: 02/06/2023]
Abstract
Irreversible Electroporation (IRE) is used to treat locally advanced cancers, commonly of the pancreas, liver, kidney, and other soft tissues. Precise eligibility for IRE should be established in each individual patient by a multidisciplinary team based on comprehensive clinical, imaging, and laboratory assessment. Standardization of IRE technique and protocols is expected to improve safety, lead to reproducible outcomes, and facilitate further research into IRE. The present article provides a set of technical recommendations for the use of IRE in the treatment of locally advanced pancreatic cancer. J. Surg. Oncol. 2016;114:865-871. © 2016 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Robert C G Martin
- Division of Surgical Oncology, Hiram C Polk Jr Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky.
| | - Alan North Durham
- Division of Surgical Oncology, Hiram C Polk Jr Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky
| | - Marc G Besselink
- Department of Surgery, Academic Medical Center Amsterdam, Amsterdam, The Netherlands
| | | | | | - Christopher L Wolfgang
- Department of Surgery and Hepatitis Research Center, National Taiwan University Hospital, China and Singapore Universities Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
| | - Kai-Wen Huang
- Department of Surgery and Hepatitis Research Center, National Taiwan University Hospital, China and Singapore Universities Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
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Tasu JP, Vesselle G, Herpe G, Richer JP, Boucebci S, Vélasco S, Carretier M, Debeane B, Tougeron D. Irreversible electroporation for locally advanced pancreatic cancer. Diagn Interv Imaging 2016; 97:1297-1304. [PMID: 27856215 DOI: 10.1016/j.diii.2016.10.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Accepted: 10/04/2016] [Indexed: 12/18/2022]
Abstract
Pancreatic adenocarcinoma is one of the solid cancers associated with the poorest prognosis; the only curative treatment remains surgical resection but in most cases, this treatment is not possible because of distant metastasis or local extension. Irreversible electroporation is a new tumor ablation technique, which provides cellular apoptosis without any thermal coagulation effect. This technique helps preserve the ducts, vessels or nerves located in the treatment area. This article reviews the current knowledge regarding the use of electroporation for the treatment of pancreatic adenocarcinoma.
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Affiliation(s)
- J-P Tasu
- Department of Imaging, University Hospital of Poitiers, rue de la Milétrie, 86000 Poitiers, France.
| | - G Vesselle
- Department of Imaging, University Hospital of Poitiers, rue de la Milétrie, 86000 Poitiers, France
| | - G Herpe
- Department of Imaging, University Hospital of Poitiers, rue de la Milétrie, 86000 Poitiers, France
| | - J-P Richer
- Laboratory of Simulations and Anatomy Department, University of Poitiers, rue de la Milétrie, 86000 Poitiers, France; Abdominal Surgery Department, University of Poitiers, rue de la Milétrie, 86000 Poitiers, France
| | - S Boucebci
- Department of Imaging, University Hospital of Poitiers, rue de la Milétrie, 86000 Poitiers, France
| | - S Vélasco
- Department of Imaging, University Hospital of Poitiers, rue de la Milétrie, 86000 Poitiers, France
| | - M Carretier
- Abdominal Surgery Department, University of Poitiers, rue de la Milétrie, 86000 Poitiers, France
| | - B Debeane
- Anaesthesiology Department, University Hospital of Poitiers, rue de la Milétrie, 86000 Poitiers, France
| | - D Tougeron
- Abdominal Oncology Department, University Hospital of Poitiers, rue de la Milétrie, 86000 Poitiers, France
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Zager Y, Kain D, Landa N, Leor J, Maor E. Optimization of Irreversible Electroporation Protocols for In-vivo Myocardial Decellularization. PLoS One 2016; 11:e0165475. [PMID: 27893744 PMCID: PMC5125564 DOI: 10.1371/journal.pone.0165475] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Accepted: 10/12/2016] [Indexed: 12/18/2022] Open
Abstract
Background Irreversible electroporation (IRE) is a non-thermal cell ablation approach that induces selective damage to cell membranes only. The purpose of the current study was to evaluate and optimize its use for in-vivo myocardial decellularization. Methods Forty-two Sprague-Dawley rats were used to compare myocardial damage of seven different IRE protocols with anterior myocardial infarction damage. An in-vivo open thoracotomy model was used, with two-needle electrodes in the anterior ventricular wall. IRE protocols included different combinations of pulse lengths (70 vs. 100 μseconds), frequency (1, 2, 4 Hz), and number (10 vs. 20 pulses), as well as voltage intensity (50, 250 and 500 Volts). All animals underwent baseline echocardiographic evaluation. Degree of myocardial ablation was determined using repeated echocardiography measurements (days 7 and 28) as well as histologic and morphometric analysis at 28 days. Results All animals survived 28 days of follow-up. Compared with 50V and 250V, electroporation with 500V was associated with significantly increased myocardial scar and reduction in ejection fraction (67.4%±4% at baseline vs. 34.6%±20% at 28 days; p <0.01). Also, compared with pulse duration of 70 μsec, pulses of 100 μsec were associated with markedly reduced left ventricular function and markedly increased relative scar area ratio (28%±9% vs. 16%±3%, p = 0.02). Decreasing electroporation pulse frequency (1Hz vs. 2Hz, 2Hz vs. 4Hz) was associated with a significant increase in myocardial damage. Electroporation protocols with a greater number of pulses (20 vs. 10) correlated with more profound tissue damage (p<0.05). When compared with myocardial infarction damage, electroporation demonstrated a considerable likeness regarding the extent of the inflammatory process, but with relatively higher levels of extra-cellular preservation. Conclusions IRE has a graded effect on the myocardium. The extent of ablation can be controlled by changing pulse length, frequency and number, as well as by changing electric field intensity.
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Affiliation(s)
- Yaniv Zager
- Tamman Cardiovascular Research Institute, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel
| | - David Kain
- Tamman Cardiovascular Research Institute, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Natalie Landa
- Tamman Cardiovascular Research Institute, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Jonathan Leor
- Tamman Cardiovascular Research Institute, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Elad Maor
- Tamman Cardiovascular Research Institute, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel
- Pinchas Borenstein Talpiot Medical Leadership Program, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel
- * E-mail:
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Li J, Liu F, Gupta S, Li C. Interventional Nanotheranostics of Pancreatic Ductal Adenocarcinoma. Am J Cancer Res 2016; 6:1393-402. [PMID: 27375787 PMCID: PMC4924507 DOI: 10.7150/thno.15122] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 05/19/2016] [Indexed: 12/13/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) accounts for over 90% of all pancreatic cancer. Nanoparticles (NPs) offer new opportunities for image-guided therapy owing to the unique physicochemical properties of the nanoscale effect and the multifunctional capabilities of NPs. However, major obstacles exist for NP-mediated cancer theranostics, especially in PDAC. The hypovascular nature of PDAC may impede the deposition of NPs into the tumor after systemic administration, and most NPs localize predominantly in the mononuclear phagocytic system, leading to a relatively poor tumor-to-surrounding-organ uptake ratio. Image guidance combined with minimally invasive interventional procedures may help circumvent these barriers to poor drug delivery of NPs in PDAC. Interventional treatments allow regional drug delivery, targeted vascular embolization, direct tumor ablation, and the possibility of disrupting the stromal barrier of PDAC. Interventional treatments also have potentially fewer complications, faster recovery, and lower cost compared with conventional therapies. This work is an overview of current image-guided interventional cancer nanotheranostics with specific attention given to their applications for the management of PDAC.
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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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