|
1
|
Lim JS, Heard J, Brant N, Malo J, Kong J, Osman H, Buell J, Jeyarajah DR. Irreversible Electroporation Margin Accentuation in Pancreaticoduodenectomy: A Propensity Score Matching Analysis. Ann Surg Oncol 2024; 31:8298-8307. [PMID: 39080139 DOI: 10.1245/s10434-024-15962-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 07/22/2024] [Indexed: 10/12/2024]
Abstract
BACKGROUND Margin accentuation using irreversible electroporation (MA-IRE) improves recurrence and overall survival (OS) in pancreatic cancer patients; however, there have been limited outcome comparisons to similarly risked patients who did not receive MA-IRE. METHODS Patients with borderline resectable or locally advanced pancreatic adenocarcinoma who underwent a pancreaticoduodenectomy (PD) between 2017 and 2022 were included. Those who did not receive neoadjuvant chemotherapy for major vessel involvement were excluded. One-to-one propensity score matching (PSM) was used to match the MA-IRE group with the corresponding non-MA-IRE control group with similar risk factors. RESULTS A total of 36 patients were included in this study. Seventeen (47.2%) patients who underwent MA-IRE matched with 19 control patients (52.8%) with similar risk factors who did not have MA-IRE. Before matching, OS and disease-free survival (DFS) were comparable between the MA-IRE and non-MA-IRE groups. After matching, the MA-IRE group showed improved OS (746 vs. 509 days, hazard ratio 0.313; p = 0.034) compared with the non-MA-IRE group. DFS (p = 0.768), negative margin status (p = 0.317), and 30-day complication rates (p = 1.000) remained statistically different between the groups. CONCLUSIONS MA-IRE in PD results in longer OS but does not impact margin status, DFS, or postoperative complication rates in our cohort. These findings suggest that MA-IRE is safe and potentially promotes immune cell activation rather than upfront margin mitigation.
Collapse
Affiliation(s)
- Joseph S Lim
- Department of Surgery, Methodist Health System, Dallas, TX, USA
| | - Jessica Heard
- Department of Surgery, Methodist Health System, Dallas, TX, USA
- Department of Surgery, University of Oklahoma School of Medicine, Tulsa, OK, USA
| | - Nick Brant
- Department of Surgery, University of Oklahoma School of Medicine, Tulsa, OK, USA
- Department of Surgery, Emory University, Atlanta, GA, USA
| | - Juan Malo
- Department of Surgery, Methodist Health System, Dallas, TX, USA
| | - Joshua Kong
- Department of Surgery, Methodist Health System, Dallas, TX, USA
| | - Houssam Osman
- Department of Surgery, Anne Burnett School of Medicine at, Texas Christian University, Fort Worth, TX, USA
| | - Joseph Buell
- Department of Surgery, Methodist Health System, Dallas, TX, USA
- Department of Surgery, Anne Burnett School of Medicine at, Texas Christian University, Fort Worth, TX, USA
| | - Dhiresh Rohan Jeyarajah
- Department of Surgery, Methodist Health System, Dallas, TX, USA.
- Department of Surgery, Anne Burnett School of Medicine at, Texas Christian University, Fort Worth, TX, USA.
| |
Collapse
|
|
2
|
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.
Collapse
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
| |
Collapse
|
|
3
|
Tasu JP, Tougeron D, Rols MP. Irreversible electroporation and electrochemotherapy in oncology: State of the art. Diagn Interv Imaging 2022; 103:499-509. [PMID: 36266192 DOI: 10.1016/j.diii.2022.09.009] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 09/29/2022] [Accepted: 09/30/2022] [Indexed: 01/10/2023]
Abstract
Thermal tumor ablation techniques including radiofrequency, microwave, LASER, high-intensity focused ultrasound and cryoablation are routinely used to treated liver, kidney, bone, or lung tumors. However, all these techniques are thermal and can therefore be affected by heat sink effect, which can lead to incomplete ablation, and thermal injuries of non-targeted tissues are possible. Under certain conditions, high voltage pulsed electric field can induce formation of pores in the cell membrane. This phenomenon, called electropermeabilization, is also known as "electroporation". Under certain conditions, electroporation can be irreversible, leading to cell death. Irreversible electroporation has demonstrated efficacy for the treatment of liver and prostate cancers, whereas data are scarce regarding pancreatic and renal cancers. During reversible electroporation, transient cell permeability can be used to introduce cytotoxic drugs into tumor cells (commonly bleomycin or cisplatin). Reversible electroporation used in conjunction with cytotoxic drugs shows promise in terms of oncological response, particularly for solid cutaneous and subcutaneous tumors such as melanoma. Irreversible and reversible electroporation are both not thermal ablation techniques and therefore open a new promising horizon for tumor ablation.
Collapse
Affiliation(s)
- Jean-Pierre Tasu
- Department of Diagnosis and interventional radiology, University Hospital of Poitiers, 86021 Poitiers, France; LaTim, UBO and INSERM 1101, University of Brest, 29000 Brest, France.
| | - David Tougeron
- Department of Hepatogastroenterology, University Hospital of Poitiers, 86000 Poitiers, France
| | - Marie-Pierre Rols
- Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, 31000 Toulouse, France
| |
Collapse
|
|
4
|
Sugumar K, Hurtado A, Naik I, Hue JJ, Rothermel LD, Ammori JB, Hardacre JM, Winter JM, Ocuin LM. Multimodal therapy with or without irreversible electroporation for unresectable locally advanced pancreatic adenocarcinoma: a systematic review and meta-analysis. HPB (Oxford) 2022; 24:586-595. [PMID: 35000842 DOI: 10.1016/j.hpb.2021.12.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Revised: 10/29/2021] [Accepted: 12/20/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Irreversible electroporation (IRE) is used as a locoregional treatment modality for patients with locally advanced pancreatic cancer (LAPC), but is non-curative and is associated with postoperative morbidity and mortality. We performed a systematic review and meta-analysis comparing survival outcomes of multimodal therapy with or without IRE. METHODS Separate searches were performed for multimodal therapy + IRE and multimodal therapy alone given the lack of comparative literature using PubMed, SCOPUS, and Cochrane Library in 3/2021. We determined overall survival (OS) and progression-free survival (PFS) from diagnosis and time of IRE. Treatment-related morbidity and mortality was determined. RESULTS Of 585 published articles, 48 met inclusion criteria for IRE (n = 27) and without IRE (n = 21) with data for 1420 (IRE) and 1348 (without IRE) patients. The 6/12/24 months OS with IRE was 99%/84%/28%. The 6/12/24 months OS without IRE was 99%/80%/12%. At 12 months from IRE, OS was 55% and PFS was 12%. The mean major complication and 90-day mortality rates for IRE were 17.95% and 2.65%. CONCLUSION Multimodal therapy alone is associated with similar OS to multimodal therapy + IRE in patients with LAPC. Most patients progress and nearly half die within 1 year of the IRE procedure. Given the lack of quality prospective data, IRE should remain experimental and be used with caution in LAPC.
Collapse
Affiliation(s)
- Kavin Sugumar
- University Hospitals Seidman Cancer Center and the Department of Surgery, Cleveland, OH, USA
| | - Alex Hurtado
- Case Western Reserve University School of Medicine and the Case Comprehensive Cancer Center, Cleveland, OH, USA
| | - Ilora Naik
- Case Western Reserve University School of Medicine and the Case Comprehensive Cancer Center, Cleveland, OH, USA
| | - Jonathan J Hue
- University Hospitals Seidman Cancer Center and the Department of Surgery, Cleveland, OH, USA
| | - Luke D Rothermel
- University Hospitals Seidman Cancer Center and the Department of Surgery, Cleveland, OH, USA
| | - John B Ammori
- University Hospitals Seidman Cancer Center and the Department of Surgery, Cleveland, OH, USA
| | - Jeffrey M Hardacre
- University Hospitals Seidman Cancer Center and the Department of Surgery, Cleveland, OH, USA
| | - Jordan M Winter
- University Hospitals Seidman Cancer Center and the Department of Surgery, Cleveland, OH, USA
| | - Lee M Ocuin
- University Hospitals Seidman Cancer Center and the Department of Surgery, Cleveland, OH, USA.
| |
Collapse
|
|
5
|
Barros AG, Pulido CF, Machado M, Brito MJ, Couto N, Sousa O, Melo SA, Mansinho H. Treatment optimization of locally advanced and metastatic pancreatic cancer (Review). Int J Oncol 2021; 59:110. [PMID: 34859257 PMCID: PMC8651228 DOI: 10.3892/ijo.2021.5290] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 10/12/2021] [Indexed: 12/12/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumor types, being the sixth leading cause of mortality worldwide and the fourth in Europe. Globally, it has a mortality/incidence ratio of 98%, and the 5‑year survival rate in Europe is only 3%. Although risk factors, such as obesity, diabetes mellitus, smoking, alcohol consumption and genetic factors, have been identified, the causes of PDAC remain elusive. Additionally, the only curative treatment for PDAC is surgery with negative margins. However, upon diagnosis, ~30% of the patients already present with locally advanced disease. In these cases, a multidisciplinary approach is required to improve disease‑related symptoms and prolong patient survival. In the present article, a comprehensive review of PDAC epidemiology, physiology and treatment is provided. Moreover, guidelines on patient treatment are suggested. Among the different available therapeutic options for the treatment of advanced PDAC, results are modest, most likely due to the complexity of the disease, and so the prognostic remains poor. Molecular approaches based on multi‑omics research are promising and will contribute to groundbreaking personalized medicine. Thus, economic investment that promotes research of pancreatic cancer will be critical to the development of more efficient diagnostic and treatment strategies.
Collapse
Affiliation(s)
- Anabela G. Barros
- Department of Medical Oncology, University Hospital of Coimbra, 3004-561 Coimbra, Portugal
| | - Catarina F. Pulido
- Department of Medical Oncology, Luz Lisbon Hospital, 1500-650 Lisbon, Portugal
| | - Manuela Machado
- Department of Medical Oncology, Entre o Douro e Vouga Hospital Center (CHEDV), 4520-211 Santa Maria da Feira, Portugal
| | - Maria José Brito
- Pathologic Anatomy Department, Garcia de Orta Hospital, 2805-267 Almada, Portugal
| | - Nuno Couto
- Digestive Unit, Champalimaud Clinical Centre, 4200-135 Porto, Portugal
- Champalimaud Research Centre, 1400-038 Lisbon, 4200-135 Porto, Portugal
| | - Olga Sousa
- Radiotherapy Department, Portuguese Institute of Oncology, 4200-072 Porto, 4200-135 Porto, Portugal
| | - Sónia A. Melo
- i3S-Institute for Research and Innovation in Health of University of Porto, 4200-135 Porto, Portugal
- IPATIMUP-Institute of Molecular Pathology and Immunology of University of Porto, 4200-135 Porto, Portugal
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
| | - Hélder Mansinho
- Hemato-Oncology Department, Garcia de Orta Hospital, 2805-267 Almada, Portugal
| |
Collapse
|
|
6
|
Ratnayake B, Al-Leswas D, Mohammadi-Zaniani G, Littler P, Sen G, Manas D, Pandanaboyana S. Margin Accentuation Irreversible Electroporation in Stage III Pancreatic Cancer: A Systematic Review. Cancers (Basel) 2021; 13:cancers13133212. [PMID: 34199031 PMCID: PMC8268790 DOI: 10.3390/cancers13133212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 06/14/2021] [Accepted: 06/24/2021] [Indexed: 11/17/2022] Open
Abstract
Simple Summary This literature review shows preliminary evidence to suggest that electroporation, the use of electricity to cause the death of cells around the tumour, may be associated with an improved survival and complete resection rates following pancreatic surgery for higher stage pancreatic cancer. However, one in five patients have a complication from the procedure that alters their normal course in hospital. Moreover, the number of patients who underwent this technique is small and further data is needed to support the preliminary evidence. The results therefore should be interpreted with caution. Abstract The present systematic review aimed to summarise the available evidence on indications and oncological outcomes after MA IRE for stage III pancreatic cancer (PC). A literature search was performed in the Pubmed, MEDLINE, EMBASE, SCOPUS databases using the PRISMA framework to identify all MA IRE studies. Nine studies with 235 locally advanced (LA) (82%, 192/235) or Borderline resectable (BR) PC (18%, 43/235) patients undergoing MA IRE pancreatic resection were included. Patients were mostly male (56%) with a weighted-mean age of 61 years (95% CI: 58–64). Pancreatoduodenectomy was performed in 51% (120/235) and distal pancreatectomy in 49% (115/235). R0 resection rate was 73% (77/105). Clavien Dindo grade 3–5 postoperative complications occurred in 19% (36/187). Follow-up intervals ranged from 3 to 29 months. Local and systematic recurrences were noted in 8 and 43 patients, respectively. The weighted-mean progression free survival was 11 months (95% CI: 7–15). The weighted-mean overall survival was 22 months (95% CI 20–23 months) and 8 months (95% CI 1–32 months) for MA IRE and IRE alone, respectively. Early non-randomised data suggest MA IRE during pancreatic surgery for stage III pancreatic cancer may result in increased R0 resection rates and improved OS with acceptable postoperative morbidity. Further, larger studies are warranted to corroborate this evidence.
Collapse
Affiliation(s)
- Bathiya Ratnayake
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand;
| | - Dhya Al-Leswas
- Hepato-Pancreato-Biliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK; (D.A.-L.); (G.M.-Z.); (G.S.); (D.M.)
| | - Ghazaleh Mohammadi-Zaniani
- Hepato-Pancreato-Biliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK; (D.A.-L.); (G.M.-Z.); (G.S.); (D.M.)
| | - Peter Littler
- Department of Interventional Radiology, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK;
| | - Gourab Sen
- Hepato-Pancreato-Biliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK; (D.A.-L.); (G.M.-Z.); (G.S.); (D.M.)
| | - Derek Manas
- Hepato-Pancreato-Biliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK; (D.A.-L.); (G.M.-Z.); (G.S.); (D.M.)
| | - Sanjay Pandanaboyana
- Hepato-Pancreato-Biliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK; (D.A.-L.); (G.M.-Z.); (G.S.); (D.M.)
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE2 4AX, UK
- Correspondence:
| |
Collapse
|
|
7
|
Granata V, Grassi R, Fusco R, Belli A, Palaia R, Carrafiello G, Miele V, Grassi R, Petrillo A, Izzo F. Local ablation of pancreatic tumors: State of the art and future perspectives. World J Gastroenterol 2021; 27:3413-3428. [PMID: 34163121 PMCID: PMC8218359 DOI: 10.3748/wjg.v27.i23.3413] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 03/28/2021] [Accepted: 05/08/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Currently, the technologies most commonly used to treat locally advanced pancreatic cancer are radiofrequency ablation (RFA), microwave ablation, and irreversible (IRE) or reversible electroporation combined with low doses of chemotherapeutic drugs.
AIM To report an overview and updates on ablative techniques in pancreatic cancer.
METHODS Several electronic databases were searched. The search covered the years from January 2000 to January 2021. Moreover, the reference lists of the found papers were analysed for papers not indexed in the electronic databases. All titles and abstracts were analysed.
RESULTS We found 30 studies (14 studies for RFA, 3 for microwave therapy, 10 for IRE, and 3 for electrochemotherapy), comprising 1047 patients, which were analysed further. Two randomized trials were found for IRE. Percutaneous and laparotomy approaches were performed. In the assessed patients, the median maximal diameter of the lesions was in the range of 2.8 to 4.5 cm. All series included patients unfit for surgical treatment, but Martin et al assessed a subgroup of patients with borderline resectable tumours who underwent resection with margin attenuation with IRE. Most studies administered chemotherapy prior to ablative therapies. However, several studies suggest that the key determinant of improved survival is attributable to ablative treatment alone. Nevertheless, the authors suggested chemotherapy before local therapies for several reasons. This strategy may not only downstage a subgroup of patients to curative-intent surgery but also support to recognize patients with biologically unfavourable tumours who would likely not benefit from ablation treatments. Ablation therapies seem safe based on the 1047 patients assessed in this review. The mortality rate ranged from 1.8% to 2%. However, despite the low mortality, the reported rates of severe post procedural complications ranged from 0%-42%. Most reported complications have been self-limiting and manageable. Median overall survival varied between 6.0 and 33 mo. Regarding the technical success rate, assessed papers reported an estimated rate in the range of 85% to 100%. However, the authors reported early recurrence after treatment. A distinct consideration should be made on whether local treatments induce an immune response in the ablated area. Preclinical and clinical studies have shown that RFA is a promising mechanism for inducing antigen-presenting cell infiltration and enhancing the systemic antitumour T-cell immune response and tumour regression.
CONCLUSION In the management of patients with pancreatic cancer, the possibility of a multimodal approach should be considered, and conceptually, the combination of RFA with immunotherapy represents a novel angle of attack against this tumour.
Collapse
Affiliation(s)
- Vincenza Granata
- Department of Radiology, Istituto Nazionale Tumori –IRCCS- Fondazione G. Pascale, Naples 80131, Italy
| | - Roberta Grassi
- Department of Radiology, Università degli Studi della Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Roberta Fusco
- Department of Radiology, Istituto Nazionale Tumori –IRCCS- Fondazione G. Pascale, Naples 80131, Italy
| | - Andrea Belli
- Department of Surgery, Istituto Nazionale Tumori –IRCCS- Fondazione G. Pascale, Naples 80131, Italy
| | - Raffaele Palaia
- Department of Surgery, Istituto Nazionale Tumori –IRCCS- Fondazione G. Pascale, Naples 80131, Italy
| | | | - Vittorio Miele
- Italian Society of Medical and Interventional Radiology SIRM, SIRM Foundation Milan 20122, Italy
- Department of Emergency Radiology, San Camillo Hospital, Firenze 50139, Italy
| | - Roberto Grassi
- Department of Radiology, Università degli Studi della Campania Luigi Vanvitelli, Naples 80127, Italy
- Italian Society of Medical and Interventional Radiology SIRM, SIRM Foundation Milan 20122, Italy
| | - Antonella Petrillo
- Department of Radiology, Istituto Nazionale Tumori –IRCCS- Fondazione G. Pascale, Naples 80131, Italy
| | - Francesco Izzo
- Department of Surgery, Istituto Nazionale Tumori –IRCCS- Fondazione G. Pascale, Naples 80131, Italy
| |
Collapse
|
|
8
|
Margin ACcentuation for resectable Pancreatic cancer using Irreversible Electroporation - Results from the MACPIE-I study. Eur J Surg Oncol 2021; 47:2571-2578. [PMID: 34039473 DOI: 10.1016/j.ejso.2021.05.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 04/27/2021] [Accepted: 05/06/2021] [Indexed: 01/11/2023] Open
Abstract
INTRODUCTION Margin accentuation (MA) using Irreversible electroporation (IRE) offers an unique opportunity to reduce the R1 resections in resectable pancreatic cancer (RPC). This study aims to assess the rate of margin positivity using IRE for MA during pancreaticoduodenectomy (PD) for resectable pancreatic head tumours. MATERIALS AND METHODS Following ethical approval, MA using IRE was carried out in 20 consecutive patients to posterior and superior mesenteric vein (SMV) margin, and the pancreatic neck, prior to the PD resection. The control group (non-IRE; n = 91) underwent PD without MA over the study period, March 2018 to March 2020. RESULTS There was no difference between the two groups in terms of patients' age, gender, pre-op biliary drainage, site of malignancy or pre-operative TNM stage. The overall margin positive rate for IRE group was lesser (35.0%) when compared to non-IRE group (51.6%; p = 0.177), with significantly less posterior pancreatic margin positivity (5.0% vs. 25.3%; p = 0.046). When only treated margins (SMA margin excluded) were compared, the IRE group had significantly lower margin positive rates (20.0% vs. 51.6%; p = 0.013). There was no difference between the two groups in terms of intra- or post-operative complications. With a median follow-up of 15.6 months, the median DFS and OS for IRE and non-IRE groups were 17 and 18 months (p = 0.306) and 19 and 22 months (p = 0.227) respectively. CONCLUSION Our pilot study confirms the safety of MA using IRE for RPC, with reduction in margin positivity. These results as a proof of concept are promising and need further validation with a randomised controlled trial.
Collapse
|
|
9
|
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.
Collapse
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;
| |
Collapse
|
|
10
|
Charalambous P, Moris D, Karachaliou GS, Papalampros A, Dimitrokallis N, Tsilimigras DI, Oikonomou D, Petrou A. The efficacy and safety of the open approach irreversible electroporation in the treatment of pancreatic cancer: A systematic review. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:1565-1572. [PMID: 32536525 DOI: 10.1016/j.ejso.2020.05.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 05/04/2020] [Accepted: 05/19/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Irreversible Electroporation (IRE) is a novel non-thermal ablation technique used in patients with locally advanced pancreatic cancer (LAPC), in the proximity of sensitive structures such as vessels, intestinal wall and the bile duct. Currently, it is only used in the setting of clinical trials. This systematic review aimed to tackle the knowledge gap in the literature, in relation to the safety and efficacy of the open approach IRE. METHODS MEDLINE, EMBASE and Cochrane libraries were searched for English language articles published from January 2000 to December 2019. Data related to safety and efficacy were extracted. RESULTS Nine studies involving 460 patients with LAPC were included. Open approach IRE was associated with high morbidity (29.4%) but with a survival benefit compared to traditional treatment. Median overall survival (OS) was at 17.15 months. Major morbidity was at 10.2% and mortality at 3.4%. CONCLUSIONS Despite the paucity of literature and the low quality of evidence, the results regarding safety and efficacy appear to be encouraging. The high morbidity seems to be mitigated by a demonstrated improvement in OS. The potential of this technique is more evident when mortality and major morbidity are considered, since they are at acceptable levels. The limitations of this review have made it difficult to extract definitive conclusions. Higher quality evidence is needed in the form of large-scale multicentre randomized controlled trials. It remains to be elucidated whether the rate of adverse events decreases as our experience with this technique increases.
Collapse
Affiliation(s)
- Pabos Charalambous
- Department of General Surgery, Nicosia Teaching Hospital, Strovolos, Cyprus
| | - Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, NC, USA.
| | | | - Alexandros Papalampros
- 1st Department of Surgery, Laikon General Hospital, University of Athens, Athens, Greece
| | - Nikolaos Dimitrokallis
- 1st Department of Surgery, Laikon General Hospital, University of Athens, Athens, Greece
| | - Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Dimitrios Oikonomou
- 1st Department of Surgery, Laikon General Hospital, University of Athens, Athens, Greece
| | - Athanasios Petrou
- Department of General Surgery, Nicosia Teaching Hospital, Strovolos, Cyprus
| |
Collapse
|
|
11
|
Lafranceschina S, Brunetti O, Delvecchio A, Conticchio M, Ammendola M, Currò G, Piardi T, de'Angelis N, Silvestris N, Memeo R. Systematic Review of Irreversible Electroporation Role in Management of Locally Advanced Pancreatic Cancer. Cancers (Basel) 2019; 11:1718. [PMID: 31684186 PMCID: PMC6896066 DOI: 10.3390/cancers11111718] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Revised: 10/25/2019] [Accepted: 10/29/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Ablative techniques provide in patients with locally advanced pancreatic cancer (LAPC) symptomatic relief, survival benefit and potential downsizing. Irreversible Electroporation (IRE) represents potentially an ideal solution as no thermal tissue damage occurs. The purpose of this review is to present an overview on safety, feasibility, oncological results, survival and quality of life improvement obtained by IRE. METHODS A systematic search was performed in PubMed, regarding the use of IRE on PC in humans for studies published in English up to March 2019. RESULTS 15 original studies embodying 691 patients with unresectable LAPC who underwent IRE were included. As emerged, IRE works better on tumour sizes between 3-4 cm. Oncological results are promising: median OS from diagnosis or treatment up to 27 months. Two groups investigated borderline resectable tumours treated with IRE before resection with margin attenuation, whereas IRE has proved to be effective in pain control. CONCLUSIONS Electroporation is bringing new hopes in LAPC management. The first aim of IRE is to offer a palliative treatment. Further efforts are needed for patient selection, as well as the use of IRE for 'margin accentuation' during surgical resection. Even if promising, IRE needs to be validated in large, randomized, prospective series.
Collapse
Affiliation(s)
- Stefano Lafranceschina
- Department of Emergency and Organ Transplantation, University "Aldo Moro" of Bary, 70124 Bary, Italy.
| | - Oronzo Brunetti
- Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II 2", 70124 Bari, Italy.
| | - Antonella Delvecchio
- Department of Emergency and Organ Transplantation, University "Aldo Moro" of Bary, 70124 Bary, Italy.
| | - Maria Conticchio
- Department of Emergency and Organ Transplantation, University "Aldo Moro" of Bary, 70124 Bary, Italy.
| | - Michele Ammendola
- Department of Health Science, General Surgery, Magna Graecia University, Medicine School of Germaneto, 88100 Catanzaro, Italy.
| | - Giuseppe Currò
- Department of Health Science, General Surgery, Magna Graecia University, Medicine School of Germaneto, 88100 Catanzaro, Italy.
| | - Tullio Piardi
- Department of Surgery, Hôpital Robert Debré, University of Champagne-Ardenne, 51100 Reims, France.
| | - Nicola de'Angelis
- Department of Digestive and Hepato-Pancreato-Biliary Surgery, Henri Mondor University Hospital, AP-HP, Université Paris-Est Créteil (UPEC), 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France.
| | - Nicola Silvestris
- Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II 2", 70124 Bari, Italy.
- Department of Biomedical Sciences and Human Oncology, University of Bari 'Aldo Moro', 70124 Bari, Italy.
| | - Riccardo Memeo
- Department of Emergency and Organ Transplantation, University "Aldo Moro" of Bary, 70124 Bary, Italy.
| |
Collapse
|
|
12
|
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.
Collapse
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
| |
Collapse
|
|
13
|
Foreword to the special issue “Electroporation for biomedical applications”. Med Biol Eng Comput 2017. [DOI: 10.1007/s11517-017-1643-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
|
|
14
|
Tian G, Jiang T. US-guided percutaneous laser ablation of refractory metastatic retroperitoneal lesions: A care-compliant case report. Medicine (Baltimore) 2017; 96:e6597. [PMID: 28403099 PMCID: PMC5403096 DOI: 10.1097/md.0000000000006597] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
RATIONALE Retroperitoneal metastatic lymph node is rare but severe, which has important structures like the gastrointestinal tract and large blood vessels around and may challenge excision, inducing serious complications like hemorrhage, intestinal adhesion, and even death after injury. PATIENT CONCERNS We described the case of a 60-year-old man with a history of right liver resection in 2010, pulmonary wedge resection in 2012, and transarterial chemoembolization twice in 2014, in which the postoperative pathology suggested the mixed liver cancer, and poorly differentiated lung cancer from liver metastasis. DIAGNOSES Preoperative magnetic resonance (MR) imaging scan showed a refractory retroperitoneal metastatic lymph node. INTERVENTIONS Then this patient repeatedly received 4 ablations with US-guided laser ablation within a month. OUTCOMES After 4 ablations due to residual tumor, MR, and CT images of 5-month follow-up showed the partial response. No obvious side effects were discovered in this case during these procedures. LESSONS This suggested US-guided laser ablation appears to be a useful technique for retroperitoneal metastatic lymph node with poor general condition or those refusing surgical therapy.
Collapse
Affiliation(s)
- Guo Tian
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
| | - Tian’an Jiang
- Department of Ultrasound Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
| |
Collapse
|