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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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Rouhezamin MR, Fintelmann FJ, Huang AJ, Arellano RS, Smolinski-Zhao S, Patel DM, Wehrenberg-Klee EP, Uppot RN. Limited Effectiveness in Early Human Clinical Experience with Pulsed Electrical Field Ablation. J Vasc Interv Radiol 2025; 36:274-281. [PMID: 39522867 DOI: 10.1016/j.jvir.2024.10.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 10/01/2024] [Accepted: 10/29/2024] [Indexed: 11/16/2024] Open
Abstract
PURPOSE To evaluate oncological outcomes, abscopal effect, and adverse events (AEs) of pulsed electrical field (PEF) ablation of tumors in the chest, abdomen, and pelvis. MATERIALS AND METHODS PEF ablations performed at an academic medical center between May 2023 and January 2024 were retrospectively analyzed. Eleven patients (4 males and 7 females; age, 58 years ± 19) underwent 11 PEF sessions targeting 13 tumors (lung metastasis from solitary fibrous tumor [n = 3] and colorectal carcinoma (CA) [n = 1], osteosarcoma pleural metastases [n = 2], hepatocellular CA [n = 2], liver metastasis from colorectal CA [n = 1] and leiomyosarcoma [n = 1], metastatic melanoma to the pancreas [n = 1], metastatic retroperitoneal lymph node from endometrial CA [n = 1], and recurrence of endometrial CA in the vaginal cuff [n = 1]) with the goal of complete coverage (n = 11/13) or debulking (n = 2/13). The mean tumor diameter was 1.9 cm (SD ± 1.0; range, 0.4-3.3 cm). Cross-sectional imaging follow-up was 5.3 months (SD ± 2.2; range, 1.9-7.9 months). Oncological outcomes, abscopal effect, and AEs categorized according to the Society of Interventional Radiology (SIR) guidelines were analyzed. RESULTS Of 11 tumors that underwent ablation for complete coverage, complete coverage was achieved for 1 (9%), and residual was detected in 9 (81%). Ten (91%) of 11 patients showed either residual, local, or distant progression within a median of 3 months. No abscopal effect was observed. There were 2 mild and 2 severe AEs. CONCLUSIONS PEF ablation showed a low rate of complete coverage (9%) and a high rate (91%) of residual, local, or distant progression. No abscopal effect was observed in any patient within a median of 5.1 months after the ablation.
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Affiliation(s)
- Mohammad Reza Rouhezamin
- Department of Radiology, Division of Interventional Radiology, Massachusetts General Hospital Boston & Harvard Medical School, Boston, Massachusetts.
| | - Florian J Fintelmann
- Department of Radiology, Division of Thoracic Imaging and Intervention, Massachusetts General Hospital Boston & Harvard Medical School, Boston, Massachusetts
| | - Ambrose J Huang
- Department of Radiology, Division of Musculoskeletal Imaging and Intervention, Massachusetts General Hospital Boston & Harvard Medical School, Boston, Massachusetts
| | - Ronald Steven Arellano
- Department of Radiology, Division of Interventional Radiology, Massachusetts General Hospital Boston & Harvard Medical School, Boston, Massachusetts
| | - Sara Smolinski-Zhao
- Department of Radiology, Division of Interventional Radiology, Massachusetts General Hospital Boston & Harvard Medical School, Boston, Massachusetts
| | - Dipesh M Patel
- Department of Radiology, Division of Interventional Radiology, Massachusetts General Hospital Boston & Harvard Medical School, Boston, Massachusetts
| | - Eric Paul Wehrenberg-Klee
- Department of Radiology, Division of Interventional Radiology, Massachusetts General Hospital Boston & Harvard Medical School, Boston, Massachusetts
| | - Raul N Uppot
- Department of Radiology, Division of Interventional Radiology, Massachusetts General Hospital Boston & Harvard Medical School, Boston, Massachusetts
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3
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Zhang H, Ji X, Zang L, Yan S, Wu X. Process Analysis and Parameter Selection of Cardiomyocyte Electroporation Based on the Finite Element Method. Cardiovasc Eng Technol 2024; 15:22-38. [PMID: 37919538 DOI: 10.1007/s13239-023-00694-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 10/18/2023] [Indexed: 11/04/2023]
Abstract
PURPOSE Pulsed-field ablation (PFA) has attracted attention for the treatment of atrial fibrillation. This study aimed to further explore the relationship between the transmembrane voltage, pore radius and the intensity and duration of pulsed electric fields, which are closely related to the formation of irreversible electroporation. The different mechanisms of microsecond and nanosecond pulses acting on cardiomyocyte cellular and nuclear membranes were studied. METHODS A 3-D cardiomyocyte model with a nucleus was constructed to simulate the process of electroporation in cells under an electric field. Cell membrane electroporation was used to simulate the effect of different pulse parameters on the process of electroporation. RESULTS Under a single pulse with a field strength of 1 kV/cm and width of 100 μs, the transmembrane potential (TMP) of the cell membrane reached 1.33 V, and the pore density and conductivity increased rapidly. The maximum pore radius of the cell membrane was 43.4 nm, and the electroporation area accounted for 4.6% of the total cell membrane area. The number of pores was positively correlated with the electric field intensity when the cell was exposed to electric fields of 0.5 to 6 kV/cm. Under a nanosecond pulse, the TMP of the nuclear and cell membranes exceeded 1 V after exposure to electric fields with strengths of 4 and 5 kV/cm, respectively. CONCLUSION This study simulated the electroporation process of cardiomyocyte, and provides a basis for the selection of parameters for the application of PFA for application toward arrhythmias.
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Affiliation(s)
- Hao Zhang
- Center for Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai, 200438, China
| | - Xingkai Ji
- Center for Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai, 200438, China
| | - Lianru Zang
- Center for Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai, 200438, China
| | - Shengjie Yan
- Center for Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai, 200438, China.
| | - Xiaomei Wu
- Center for Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai, 200438, China.
- Academy for Engineering and Technology, Fudan University, Shanghai, 200433, China.
- Yiwu Research Institute, Fudan University, Yiwu, 322000, China.
- Key Laboratory of Medical Imaging Computing and Computer-Assisted Intervention (MICCAI) of Shanghai, Fudan University, Shanghai, 200032, China.
- Shanghai Engineering Research Center of Assistive Devices, Shanghai, 200093, China.
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4
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Bi S, Jia F, Lv C, He Q, Xu X, Xue Z, Su S. Preclinical Study of Biphasic Asymmetric Pulsed Field Ablation. Front Cardiovasc Med 2022; 9:859480. [PMID: 35402543 PMCID: PMC8987372 DOI: 10.3389/fcvm.2022.859480] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 02/28/2022] [Indexed: 11/25/2022] Open
Abstract
Pulsed field ablation (PFA) is a novel method of pulmonary venous isolation in atrial fibrillation ablation and is featured by tissue-selective ablation. Isolation is achieved via the application of high-voltage microsecond pulses that create irreversible perforations in cell membranes (i.e., electroporation). We proposed a new biphasic asymmetric pulse mode and verified the lesion persistence and safety of this mode for pulmonary vein ostia ablation in preclinical studies. We found that biphasic asymmetric pulses can effectively reduce muscle contractions and drop ablation threshold. In the electroanatomic mapping, the ablation site showed a continuous low potential area, and the atrium was not captured after 30 days of pacing. Pathological staining showed that cardiomyocytes in the ablation area were replaced by fibroblasts and there was no damage outside the ablation zone. Our results show that pulmonary venous isolation using the biphasic asymmetric discharge mode is safe, durable, effective, and causes no damage to other tissues.
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Affiliation(s)
- Shengyu Bi
- School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, China
| | - Fenglin Jia
- School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, China
| | - Chang Lv
- School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, China
| | - Qiang He
- Department of Cardiology, Tianjin First Central Hospital, Tianjin, China
| | - Xinyu Xu
- School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, China
- *Correspondence: Xinyu Xu
| | - Zhixiao Xue
- School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, China
- Zhixiao Xue
| | - Siying Su
- Tianjin Intelligent Health Medical Co., Ltd., Tianjin, China
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5
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Ye X, Liu S, Yin H, He Q, Xue Z, Lu C, Su S. Study on Optimal Parameter and Target for Pulsed-Field Ablation of Atrial Fibrillation. Front Cardiovasc Med 2021; 8:690092. [PMID: 34621795 PMCID: PMC8490619 DOI: 10.3389/fcvm.2021.690092] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 08/16/2021] [Indexed: 12/21/2022] Open
Abstract
Pulsed-field ablation (PFA) had potential advantages in atrial fibrillation ablation, and we aim to confirm the optimal parameter and target of PFA for atrial fibrillation. Two ablation modes in vitro of single-cell system (ablation in electrode cup) and monolayer cell system (ablation in inserts with electrode tips) were established to perform PFA for myocardial cell H9C2 and smooth muscle cell A7r5. Ablation effect, calcium ion influx, the expression of Cx45, and surface morphological change were observed. Three Bama minipigs were used to verify the in vivo ablation effect of PFA. In monolayer cell system, H9C2 was significantly sensitive to PFA compared with A7r5, with shrinking of the whole monolayer. The ablation effect of bidirectional pulse was weaker than that of the two mono-polar pulses. Expressed Cx45 proteins were increased in H9C2 but decreased in A7r5 cells. Bidirectional PFA performed on Bama minipigs was able to effectively block electrical activity from the pulmonary vein to the atrium with week muscle contraction, not generating pulmonary vein stenosis. Bidirectional PFA was able to significantly ablate myocardial cells, maintain cell–cell connection, and reduce muscle contraction, which was a kind of optimized PFA strategy for atrial fibrillation.
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Affiliation(s)
- Xuying Ye
- The First Central Clinical College of Tianjin Medical University, Tianjin, China.,Department of cardiology, Tianjin First Central Hospital, Tianjin, China
| | - Shangzhong Liu
- School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, China
| | - Huijuan Yin
- Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Qiang He
- Department of cardiology, Tianjin First Central Hospital, Tianjin, China
| | - Zhixiao Xue
- School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, China.,Tianjin Intelligent Health Medical Co., Ltd, Tianjin, China
| | - Chengzhi Lu
- The First Central Clinical College of Tianjin Medical University, Tianjin, China.,Department of cardiology, Tianjin First Central Hospital, Tianjin, China
| | - Siying Su
- Tianjin Intelligent Health Medical Co., Ltd, Tianjin, China
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6
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Burbach BJ, O'Flanagan SD, Shao Q, Young KM, Slaughter JR, Rollins MR, Street TJL, Granger VE, Beura LK, Azarin SM, Ramadhyani S, Forsyth BR, Bischof JC, Shimizu Y. Irreversible electroporation augments checkpoint immunotherapy in prostate cancer and promotes tumor antigen-specific tissue-resident memory CD8+ T cells. Nat Commun 2021; 12:3862. [PMID: 34162858 PMCID: PMC8222297 DOI: 10.1038/s41467-021-24132-6] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 06/02/2021] [Indexed: 01/04/2023] Open
Abstract
Memory CD8+ T cells populate non-lymphoid tissues (NLTs) following pathogen infection, but little is known about the establishment of endogenous tumor-specific tissue-resident memory T cells (TRM) during cancer immunotherapy. Using a transplantable mouse model of prostate carcinoma, here we report that tumor challenge leads to expansion of naïve neoantigen-specific CD8+ T cells and formation of a small population of non-recirculating TRM in several NLTs. Primary tumor destruction by irreversible electroporation (IRE), followed by anti-CTLA-4 immune checkpoint inhibitor (ICI), promotes robust expansion of tumor-specific CD8+ T cells in blood, tumor, and NLTs. Parabiosis studies confirm that TRM establishment following dual therapy is associated with tumor remission in a subset of cases and protection from subsequent tumor challenge. Addition of anti-PD-1 following dual IRE + anti-CTLA-4 treatment blocks tumor growth in non-responsive cases. This work indicates that focal tumor destruction using IRE combined with ICI is a potent in situ tumor vaccination strategy that generates protective tumor-specific TRM.
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Affiliation(s)
- Brandon J Burbach
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
- Center for Immunology, University of Minnesota, Minneapolis, USA.
- Masonic Cancer Center, University of Minnesota, Minneapolis, USA.
- Institute for Engineering in Medicine, University of Minnesota, Minneapolis, USA.
| | - Stephen D O'Flanagan
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
- Center for Immunology, University of Minnesota, Minneapolis, USA
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, USA
| | - Qi Shao
- Masonic Cancer Center, University of Minnesota, Minneapolis, USA
- Institute for Engineering in Medicine, University of Minnesota, Minneapolis, USA
- Department of Mechanical Engineering, University of Minnesota, Minneapolis, USA
| | - Katharine M Young
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
- Center for Immunology, University of Minnesota, Minneapolis, USA
| | - Joseph R Slaughter
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
- Center for Immunology, University of Minnesota, Minneapolis, USA
| | - Meagan R Rollins
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
- Center for Immunology, University of Minnesota, Minneapolis, USA
- Boston Scientific Corporation, Maple Grove, MN, USA
| | - Tami Jo L Street
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
- Center for Immunology, University of Minnesota, Minneapolis, USA
| | - Victoria E Granger
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
- Center for Immunology, University of Minnesota, Minneapolis, USA
| | - Lalit K Beura
- Center for Immunology, University of Minnesota, Minneapolis, USA
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, USA
- Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, USA
| | - Samira M Azarin
- Masonic Cancer Center, University of Minnesota, Minneapolis, USA
- Institute for Engineering in Medicine, University of Minnesota, Minneapolis, USA
- Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, USA
| | | | | | - John C Bischof
- Masonic Cancer Center, University of Minnesota, Minneapolis, USA
- Institute for Engineering in Medicine, University of Minnesota, Minneapolis, USA
- Department of Mechanical Engineering, University of Minnesota, Minneapolis, USA
- Department of Biomedical Engineering, University of Minnesota, Minneapolis, USA
| | - Yoji Shimizu
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
- Center for Immunology, University of Minnesota, Minneapolis, USA.
- Masonic Cancer Center, University of Minnesota, Minneapolis, USA.
- Institute for Engineering in Medicine, University of Minnesota, Minneapolis, USA.
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7
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Motta G, Ferraresso M, Lamperti L, Di Paolo D, Raison N, Perego M, Favi E. Treatment options for localised renal cell carcinoma of the transplanted kidney. World J Transplant 2020; 10:147-161. [PMID: 32742948 PMCID: PMC7360528 DOI: 10.5500/wjt.v10.i6.147] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Revised: 04/07/2020] [Accepted: 05/26/2020] [Indexed: 02/06/2023] Open
Abstract
Currently, there is no consensus among the transplant community about the treatment of renal cell carcinoma (RCC) of the transplanted kidney. Until recently, graftectomy was universally considered the golden standard, regardless of the characteristics of the neoplasm. Due to the encouraging results observed in native kidneys, conservative options such as nephron-sparing surgery (NSS) (enucleation and partial nephrectomy) and ablative therapy (radiofrequency ablation, cryoablation, microwave ablation, high-intensity focused ultrasound, and irreversible electroporation) have been progressively used in carefully selected recipients with early-stage allograft RCC. Available reports show excellent patient survival, optimal oncological outcome, and preserved renal function with acceptable complication rates. Nevertheless, the rarity and the heterogeneity of the disease, the number of options available, and the lack of long-term follow-up data do not allow to adequately define treatment-specific advantages and limitations. The role of active surveillance and immunosuppression management remain also debated. In order to offer a better insight into this difficult topic and to help clinicians choose the best therapy for their patients, we performed and extensive review of the literature. We focused on epidemiology, clinical presentation, diagnostic work up, staging strategies, tumour characteristics, treatment modalities, and follow-up protocols. Our research confirms that both NSS and focal ablation represent a valuable alternative to graftectomy for kidney transplant recipients with American Joint Committee on Cancer stage T1aN0M0 RCC. Data on T1bN0M0 lesions are scarce but suggest extra caution. Properly designed multi-centre prospective clinical trials are warranted.
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Affiliation(s)
- Gloria Motta
- Urology, IRCCS Policlinico San Donato, San Donato Milanese 27288, Italy
| | - Mariano Ferraresso
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan 20122, Italy
| | - Luca Lamperti
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy
| | - Dhanai Di Paolo
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy
| | - Nicholas Raison
- MRC Centre for Transplantation, King’s College London, London WC2R 2LS, United Kingdom
| | - Marta Perego
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy
| | - Evaldo Favi
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan 20122, Italy
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8
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Wośkowiak P, Lewicka K, Bureta A, Salagierski M. Active surveillance and focal ablation for small renal masses: a better solution for comorbid patients. Arch Med Sci 2020; 16:1111-1118. [PMID: 32864000 PMCID: PMC7444719 DOI: 10.5114/aoms.2019.86190] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 09/01/2018] [Indexed: 01/04/2023] Open
Abstract
The natural history of small renal masses (SRM) is still not well understood and they are frequently incidentally diagnosed in elderly patients. Therefore, there is a need for less invasive options sparing the patient from the side-effects related to conventional surgical treatment. PubMed and Medline database search was performed to look for new findings on active surveillance and focal therapy for SRM. Sixty-one articles published between 2002 and 2018 were selected for the purpose of the review. There is growing evidence confirming the safety of active surveillance in patients at surgical risk and there appears to be a satisfactory intermediate-term outcome of focal treatment of SRM. In the group of elderly patients with a decreased life expectancy active surveillance appears to be the most appropriate approach. The future of minimally invasive therapy appears bright, especially with the improvement of new imaging modalities.
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Affiliation(s)
- Piotr Wośkowiak
- The Faculty of Medicine and Health Sciences, University of Zielona Gora, Zielona Gora, Poland
| | - Katarzyna Lewicka
- The Faculty of Medicine and Health Sciences, University of Zielona Gora, Zielona Gora, Poland
| | - Adrianna Bureta
- The Faculty of Medicine and Health Sciences, University of Zielona Gora, Zielona Gora, Poland
| | - Maciej Salagierski
- The Faculty of Medicine and Health Sciences, University of Zielona Gora, Zielona Gora, Poland
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9
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Yoon YE, Lee HH, Kim KH, Park SY, Moon HS, Lee SR, Hong YK, Park DS, Kim DK. Focal therapy versus robot-assisted partial nephrectomy in the management of clinical T1 renal masses: A systematic review and meta-analysis. Medicine (Baltimore) 2018; 97:e13102. [PMID: 30407321 PMCID: PMC6250551 DOI: 10.1097/md.0000000000013102] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Robot-assisted partial nephrectomy (RPN) and focal therapy (FT) have both been successfully employed in the management of small renal masses. However, despite this being the era of minimally invasive surgery, few comparative studies exist on RPN and FT. The aim of our study is to review perioperative, renal functional and oncologic outcomes of FT and RPN in cT1 renal masses. METHODS Literature published in Medline, EMBASE, and Cochrane Library databases up to April 22, 2018, was systematically searched. We included literature comparing outcomes of FT (radiofrequency ablation, cryoablation, microwave ablation, and irreversible electroporation) and RPN. Studies that reported only on laparoscopic partial nephrectomy or open partial nephrectomy, and review articles, editorials, letters, or cost analyses were excluded. In total, data from 1166 patients were included. RESULTS From 858 total articles, 7 nonrandomized, observational studies were included. Compared with RPN, FT was associated with a significantly lower decrease of estimated glomerular filtration rate (weighted mean difference [WMD] -8.06 mL/min/1.73 m; confidence interval [CI] -15.85 to -0.26; P = .04), and lower estimated blood loss (WMD -49.61 mL; CI -60.78 to -38.45; P < .001). However, patients who underwent FT had a significantly increased risk of local recurrence (risk ratio [RR] 9.89; CI 4.24-23.04; P < .001) and distant metastasis (RR 6.42; CI 1.70-24.33; P = .006). However, operative times, lengths of stay, and complication rates were revealed to be similar between FT and RPN. CONCLUSION RPN has a substantial advantage in preventing cancer recurrence. However, in the era of minimally invasive surgery, FT has advantages in renal function preservation and less bleeding. Long-term follow-up for survival rates and comparative analysis of microwave ablation and irreversible electroporation are needed to extend FT for patients with significant morbidities and for those who need sufficient renal function preservation with minimal bleeding.
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Affiliation(s)
- Young Eun Yoon
- Department of Urology, Hanyang University College of Medicine, Seoul
| | - Hyung Ho Lee
- Department of Urology, National Health Insurance Corporation Ilsan Hospital, Gyeonggi-do
| | - Ki Hong Kim
- Department of Urology, Soonchunhyang University College of Medicine, Cheonan
| | - Sung Yul Park
- Department of Urology, Hanyang University College of Medicine, Seoul
| | - Hong Sang Moon
- Department of Urology, Hanyang University College of Medicine, Seoul
| | - Seung Ryeol Lee
- Department of Urology, CHA Bundang Medical Center, CHA University, Seongnam
| | - Young Kwon Hong
- Department of Urology, CHA Bundang Medical Center, CHA University, Seongnam
| | - Dong Soo Park
- Department of Urology, CHA Bundang Medical Center, CHA University, Seongnam
| | - Dae Keun Kim
- Department of Urology, CHA Seoul Station Medical Center, CHA University
- Department of Urology, School of Medicine, Graduate School, Hanyang University, Seoul, Korea
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10
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Salagierski M, Wojciechowska A, Zając K, Klatte T, Thompson RH, Cadeddu JA, Kaouk J, Autorino R, Ahrar K, Capitanio U. The Role of Ablation and Minimally Invasive Techniques in the Management of Small Renal Masses. Eur Urol Oncol 2018; 1:395-402. [PMID: 31158078 DOI: 10.1016/j.euo.2018.08.029] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 08/14/2018] [Accepted: 08/31/2018] [Indexed: 12/25/2022]
Abstract
CONTEXT Nephron-sparing approaches are increasingly recommended for incidental small renal masses. Herein, we review the current literature regarding the safety and efficacy of focal therapy, including percutaneous ablation, for small renal masses. OBJECTIVE To summarize the application of ablative therapy in the management of small renal masses. EVIDENCE ACQUISITION PubMed and Medline database search was performed to look for findings published since 2000 on focal therapy for small renal masses. After literature review, 64 articles were selected and discussed. EVIDENCE SYNTHESIS Radiofrequency ablation and cryotherapy are the most widely used procedures with intermediate-term oncological outcome comparable with surgical series. Cost effectiveness seems excellent and side effects appear acceptable. To date, no randomized trial comparing percutaneous focal therapy with standard surgical approach or active surveillance has been performed. CONCLUSIONS Focal ablative therapies are now accepted as effective treatment for small renal tumors. For tumors <3cm, oncological effectiveness of ablative therapies is comparable with that of partial nephrectomy. Percutaneous ablation has fewer complications and a better postoperative profile when compared with minimally invasive partial nephrectomy. PATIENT SUMMARY Focal ablative therapies are now accepted as effective treatment for small renal tumors. For tumors <3cm, oncological effectiveness of ablative therapies is comparable with that of partial nephrectomy.
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Affiliation(s)
- Maciej Salagierski
- Urology Department, The Faculty of Medicine and Health Sciences, University of Zielona Góra, Zielona Góra, Poland.
| | - Adrianna Wojciechowska
- Urology Department, The Faculty of Medicine and Health Sciences, University of Zielona Góra, Zielona Góra, Poland
| | - Kinga Zając
- Urology Department, The Faculty of Medicine and Health Sciences, University of Zielona Góra, Zielona Góra, Poland
| | - Tobias Klatte
- Department of Urology, Royal Bournemouth and Christchurch Hospitals, Bournemouth, UK
| | | | | | - Jihad Kaouk
- Department of Urology, Cleveland Clinic Foundation, Cleveland, OH, USA
| | | | - Kamran Ahrar
- Interventional Radiology, The University of Texas MD Anderson Cancer Center, TX, USA
| | - Umberto Capitanio
- Unit of Urology, Division of Experimental Oncology, Urological Research Institute (URI), IRCCS Ospedale San Raffaele, Milan, Italy
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11
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Abstract
With the ubiquitous use of cross-sectional abdominal imaging in recent years, the incidence of small renal masses (SRMs) has increased, and the evaluation and management of SRMs have become important clinical issues. Diagnosing a mass in the early stages theoretically allows for high rates of cure but simultaneously risks overtreatment. In the past 20 years, surgical treatment of SRMs has transitioned from radical nephrectomy for all renal tumors, regardless of size, to elective partial nephrectomy whenever technically feasible. Additionally, newer approaches, including renal mass biopsy, active surveillance for select patients, and renal mass ablation, have been increasingly used. In this chapter, we review the current evidence-based papers covering aspects of the diagnosis and management of SRMs.
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Affiliation(s)
- Avinash Chenam
- Department of Surgery, Division of Urology and Urologic Oncology, City of Hope National Medical Center, 1500 E. Duarte Rd, MOB L002H, Duarte, CA, 91010, USA
| | - Clayton Lau
- Department of Surgery, Division of Urology and Urologic Oncology, City of Hope National Medical Center, 1500 E. Duarte Rd, MOB L002H, Duarte, CA, 91010, USA.
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Percutaneous radiofrequency and microwave ablation in the treatment of renal tumors - 10 years of experience. Wideochir Inne Tech Maloinwazyjne 2017; 12:394-402. [PMID: 29362655 PMCID: PMC5776489 DOI: 10.5114/wiitm.2017.72322] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 10/02/2017] [Indexed: 01/18/2023] Open
Abstract
Introduction The standard radical treatment of renal cell carcinoma is surgical resection, but it is not suitable for patients with serious medical comorbidities and solitary kidney tumors. Minimally invasive ablation techniques could be an appropriate therapeutic alternative. Aim To retrospectively evaluate the technical success, mid-term and long-term efficacy and safety of radiofrequency and microwave ablation in patients with small renal tumors. Material and methods Over the course of 10 years, 91 ablation procedures in 64 patients for 68 tumors, of size 12–60 mm, were performed using only conscious sedation. These ablations were done under the guidance of computed tomography. We treated 41 males and 23 females with solitary kidney tumors (14 cases) and tumors in non-surgical candidates (54 cases). Results In 50 (73.5%) tumors single treatment was successful; in 13 (19.1%) cases a second procedure was used successfully, and in the 5 largest tumors (sizes 45–60 mm, 7.4%) a third treatment was necessary. Within the follow-up 10 (15.6%) patients died, but none due to metastatic renal cell carcinoma. Only 1 serious complication was observed – retroperitoneal and psoatic hematoma. Early recurrence occurred in 18 (26.5%) tumors. Late recurrence was detected in 5 (7.4%) cases. In all cases complete local control of the renal tumors was reached. Conclusions Percutaneous ablation is a very effective treatment for patients with small renal tumors of the T1a group with a minimal complication rate.
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Campelo S, Valerio M, Ahmed HU, Hu Y, Arena SL, Neal RE, Emberton M, Arena CB. An evaluation of irreversible electroporation thresholds in human prostate cancer and potential correlations to physiological measurements. APL Bioeng 2017; 1:016101. [PMID: 31069281 PMCID: PMC6481690 DOI: 10.1063/1.5005828] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 06/26/2017] [Indexed: 12/18/2022] Open
Abstract
Irreversible electroporation (IRE) is an emerging cancer treatment that utilizes non-thermal electric pulses for tumor ablation. The pulses are delivered through minimally invasive needle electrodes inserted into the target tissue and lead to cell death through the creation of nanoscale membrane defects. IRE has been shown to be safe and effective when performed on tumors in the brain, liver, kidneys, pancreas, and prostate that are located near critical blood vessels and nerves. Accurate treatment planning and prediction of the ablation volume require a priori knowledge of the tissue-specific electric field threshold for cell death. This study addresses the challenge of defining an electric field threshold for human prostate cancer tissue. Three-dimensional reconstructions of the ablation volumes were created from one week post-treatment magnetic resonance imaging (MRIs) of ten patients who completed a clinical trial. The ablation volumes were incorporated into a finite element modeling software that was used to simulate patient-specific treatments, and the electric field threshold was calculated by matching the ablation volume to the field contour encompassing the equivalent volume. Solutions were obtained for static tissue electrical properties and dynamic properties that accounted for electroporation. According to the dynamic model, the electric field threshold was 506 ± 66 V/cm. Additionally, a potentially strong correlation (r = −0.624) was discovered between the electric field threshold and pre-treatment prostate-specific antigen levels, which needs to be validated in higher enrollment studies. Taken together, these findings can be used to guide the development of future IRE protocols.
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Affiliation(s)
- Sabrina Campelo
- Laboratory for Therapeutic Directed Energy, Department of Physics, Elon University, Elon, North Carolina 27244, USA
| | | | | | - Yipeng Hu
- Centre for Medical Image Computing, University College London, London WC1E 6BT, United Kingdom
| | | | - Robert E Neal
- AngioDynamics, Marlborough, Massachusetts 01752, USA
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Hsiao CY, Huang KW. Irreversible Electroporation: A Novel Ultrasound-guided Modality for Non-thermal Tumor Ablation. J Med Ultrasound 2017; 25:195-200. [PMID: 30065492 PMCID: PMC6029329 DOI: 10.1016/j.jmu.2017.08.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Accepted: 08/10/2017] [Indexed: 12/18/2022] Open
Abstract
Ultrasound-guided tumor ablation techniques have been proven to be highly effective and minimally invasive in the treatment of many diseases. Traditional approaches to ablation include microwave and radiofrequency techniques, cryotherapy, and high-intensity focused ultrasound. However, these methods are prone to heat-sink effects that can diminish the effectiveness of treatment and damage adjacent structures, such as bile ducts, blood vessels, the gallbladder, or bowel. Irreversible electroporation (IRE) is a non-thermal ablation modality that induces cell apoptosis through the application of high-voltage current. IRE is not limited by many of the limitation which affects conventional tumor ablation techniques, and is particularly useful in treating sensitive areas of the body. The article reviews the basics of ultrasound-guided technology, including its clinical applications and effectiveness in the treatment of tumors.
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Affiliation(s)
- Chih-Yang Hsiao
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Kai-Wen Huang
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
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15
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Focal ablation therapy for renal cancer in the era of active surveillance and minimally invasive partial nephrectomy. Nat Rev Urol 2017; 14:669-682. [PMID: 28895562 DOI: 10.1038/nrurol.2017.143] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Partial nephrectomy is the optimal surgical approach in the management of small renal masses (SRMs). Focal ablation therapy has an established role in the modern management of SRMs, especially in elderly patients and those with comorbidities. Percutaneous ablation avoids general anaesthesia and laparoscopic ablation can avoid excessive dissection; hence, these techniques can be suitable for patients who are not ideal surgical candidates. Several ablation modalities exist, of which radiofrequency ablation and cryoablation are most widely applied and for which safety and oncological efficacy approach equivalency to partial nephrectomy. Data supporting efficacy and safety of ablation techniques continue to mature, but they originate in institutional case series that are confounded by cohort heterogeneity, selection bias, and lack of long-term follow-up periods. Image guidance and surveillance protocols after ablation vary and no consensus has been established. The importance of SRM biopsy, its optimal timing, the type of biopsy used, and its role in treatment selection continue to be debated. As safety data for active surveillance and experience with minimally invasive partial nephrectomy are expanding, the role of focal ablation therapy in the treatment of patients with SRMs requires continued evaluation.
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[Image-guided tumor ablation]. Prog Urol 2017; 27:853-864. [PMID: 28864163 DOI: 10.1016/j.purol.2017.07.244] [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: 07/20/2017] [Accepted: 07/22/2017] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Ablatives techniques for destroying in situ a tumoral process aim tissular necrosis by the application of several physical principles. MATERIAL AND METHODS We searched MEDLINE®, Embase®, using (MeSH) words; from January 2005 through May 2017, and we looked for all the studies. Investigators graded the strength of evidence in terms of methodology, language and relevance. RESULTS Forty-seven articles were analyzed. We described ablative techniques and sorted them in thermal and non-thermal therapies according to the used physical principle and their frequency of use in the urological pathology. CONCLUSION Percutaneous ablative therapies are mini-invasive techniques, which have an important role in tumors focal treatment. This article is a review of the ablative therapies and describes their physical principles, their equipment and their recent technological modifications, which have been developed to improve the clinical success of these techniques.
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Abstract
BACKGROUND The rising incidence of renal cell carcinoma, its more frequent early detection (stage T1a) and the increasing prevalence of chronic renal failure with higher morbidity and shorter life expectancy underscore the need for multimodal focal nephron-sparing therapy. DISCUSSION During the past decade, the gold standard shifted from radical to partial nephrectomy. Depending on the surgeon's experience, the patient's constitution and the tumor's location, the intervention can be performed laparoscopically with the corresponding advantages of lower invasiveness. A treatment alternative can be advantageous for selected patients with high morbidity and/or an increased risk of complications associated with anesthesia or surgery. Corresponding risk stratification necessitates previous confirmation of the small renal mass (cT1a) by histological examination of biopsy samples. Active surveillance represents a controlled delay in the initiation of treatment. RESULTS Percutaneous radiofrequency ablation (RFA) and laparoscopic cryoablation are currently the most common treatment alternatives, although there are limitations particularly for renal tumors located centrally near the hilum. More recent ablation procedures such as high intensity focused ultrasound (HIFU), irreversible electroporation, microwave ablation, percutaneous stereotactic ablative radiotherapy and high-dose brachytherapy have high potential in some cases but are currently regarded as experimental for the treatment of renal cell carcinoma.
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Chang L, Li L, Shi J, Sheng Y, Lu W, Gallego-Perez D, Lee LJ. Micro-/nanoscale electroporation. LAB ON A CHIP 2016; 16:4047-4062. [PMID: 27713986 DOI: 10.1039/c6lc00840b] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Electroporation has been one of the most popular non-viral technologies for cell transfection. However, conventional bulk electroporation (BEP) shows significant limitations in efficiency, cell viability and transfection uniformity. Recent advances in microscale-electroporation (MEP) resulted in improved cell viability. Further miniaturization of the electroporation system (i.e., nanoscale) has brought up many unique advantages, including negligible cell damage and dosage control capabilities with single-cell resolution, which has enabled more translational applications. In this review, we give an insight into the fundamental and technical aspects of micro- and nanoscale/nanochannel electroporation (NEP) and go over several examples of MEP/NEP-based cutting-edge research, including gene editing, adoptive immunotherapy, and cellular reprogramming. The challenges and opportunities of advanced electroporation technologies are also discussed.
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Affiliation(s)
- Lingqian Chang
- Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA.
| | - Lei Li
- School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164, USA
| | - Junfeng Shi
- Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH 43210, USA
| | - Yan Sheng
- William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43209, USA
| | - Wu Lu
- Department of Electrical and Computer Engineering, The Ohio State University, Columbus, OH 43209, USA
| | - Daniel Gallego-Perez
- Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA. and Department of Surgery, The Ohio State University, Columbus, OH 43210, USA
| | - Ly James Lee
- Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA. and Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH 43210, USA and William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43209, USA
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Diehl SJ, Rathmann N, Kostrzewa M, Ritter M, Smakic A, Schoenberg SO, Kriegmair MC. Irreversible Electroporation for Surgical Renal Masses in Solitary Kidneys: Short-Term Interventional and Functional Outcome. J Vasc Interv Radiol 2016; 27:1407-1413. [DOI: 10.1016/j.jvir.2016.03.044] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Revised: 03/28/2016] [Accepted: 03/28/2016] [Indexed: 12/15/2022] Open
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