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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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Wang Y, Qian K, Liu X, Yang Q, Lei Y, Zhu L, Yao C, Zhou Q, Liu H, Dong S. Synergistic Bipolar Irreversible Electroporation for Tumor Ablation Without Muscle Contraction. IEEE Trans Biomed Eng 2024; 71:3505-3514. [PMID: 39028604 DOI: 10.1109/tbme.2024.3431013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/21/2024]
Abstract
Irreversible electroporation (IRE) has emerged as a promising modality for tumor ablation, leveraging the controlled application of electrical pulses to induce cell death. However, the associated muscle contractions during the procedure pose challenges. This study introduces a novel approach, termed Synergistic Bipolar Irreversible Electroporation (SBIRE), aimed at achieving tumor ablation without the undesirable side effect of muscle contraction. SBIRE involves the simultaneous application of nanosecond bipolar electrical pulses (±1600 V per 0.2 cm or ±8000 V per 1 cm, ±500 ns, "+" to "-" delay 1 µs, "-" to "+" delay 200 µs, 5 cycles) and microsecond bipolar electrical pulses (±300 V per 0.2 cm or ±1500 V per 1 cm, ±2 µs, "+" to "-" delay 2 µs, "-" to "+" delay 1000 µs, 25 cycles), strategically designed to synergistically target tumor cells while minimizing the impact on adjacent muscle tissue. The experimental setup includes in vitro and in vivo studies utilizing tumor cells and animal models to assess the efficacy of SBIRE. Preliminary results demonstrate the effectiveness of SBIRE in inducing irreversible electroporation within the tumor, leading to cell death, and the ablation effect is better than other parameter forms (24.41 ± 0.23 mm2 (SBIRE group) vs 12.93 ± 0.31 mm2 (ns group), 6.55 ± 0.23 mm2 (µs group), 19.54 ± 0.25 mm2 (ns+µs group), p<0.0001). Notably, muscle contraction is significantly reduced compared to traditional IRE procedures, highlighting the potential of SBIRE to enhance patient comfort and procedural success. The development of SBIRE represents a significant advancement in the field of tumor ablation, addressing a fundamental limitation associated with muscle contraction during IRE. This technique not only offers a valuable and promising approach to tumor treatment but also holds promise for minimizing procedural side effects.
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Ndhlovu E, Zhang BX, Chen XP, Zhu P. Thermal ablation for hepatic tumors in high-risk locations. Clin Res Hepatol Gastroenterol 2024; 48:102300. [PMID: 38367803 DOI: 10.1016/j.clinre.2024.102300] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 01/21/2024] [Accepted: 02/10/2024] [Indexed: 02/19/2024]
Abstract
Thermal ablative techniques such as radiofrequency and microwave ablation are minimally invasive and cost-effective approaches that are currently being adopted as alternatives to surgical resection for primary and metastatic liver malignancies. However, they are considered to be relatively contraindicated for tumors in high-risk locations due to technical difficulties and a perceived increased risk of perioperative complications. Several techniques, including artificial ascites, non-touch multibipolar ablation, and laparoscopically assisted ablation, can be used to improve the outcomes of ablation for high-risk tumors. This review aims to provide a comprehensive summary of the techniques currently used to improve thermal ablation outcomes for high-risk liver tumors.
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Affiliation(s)
- Elijah Ndhlovu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan 430030, China
| | - Bi-Xiang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan 430030, China
| | - Xiao-Ping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan 430030, China
| | - Peng Zhu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan 430030, China.
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Peng W, Yue Y, Zhang Y, Li H, Zhang C, Wang P, Cao Y, Liu X, Dong S, Wu M, Yao C. Scheduled dosage regimen by irreversible electroporation of loaded erythrocytes for cancer treatment. APL Bioeng 2023; 7:046102. [PMID: 37854061 PMCID: PMC10581719 DOI: 10.1063/5.0174353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 09/27/2023] [Indexed: 10/20/2023] Open
Abstract
Precise control of cargo release is essential but still a great challenge for any drug delivery system. Irreversible electroporation (IRE), utilizing short high-voltage pulsed electric fields to destabilize the biological membrane, has been recently approved as a non-thermal technique for tumor ablation without destroying the integrity of adjacent collagenous structures. Due to the electro-permeating membrane ability, IRE might also have great potential to realize the controlled drug release in response to various input IRE parameters, which were tested in a red blood cell (RBC) model in this work. According to the mathematical simulation model of a round biconcave disc-like cell based on RBC shape and dielectric characteristics, the permeability and the pore density of the RBC membrane were found to quantitatively depend on the pulse parameters. To further provide solid experimental evidence, indocyanine green (ICG) and doxorubicin (DOX) were both loaded inside RBCs (RBC@DOX&ICG) and the drug release rates were found to be tailorable by microsecond pulsed electric field (μsPEF). In addition, μsPEF could effectively modulate the tumor stroma to augment therapy efficacy by increasing micro-vessel density and permeability, softening extracellular matrix, and alleviating tumor hypoxia. Benefiting from these advantages, this IRE-responsive RBC@DOX&ICG achieved a remarkably synergistic anti-cancer effect by the combination of μsPEF and chemotherapy in the tumor-bearing mice model, with the survival time increasing above 90 days without tumor burden. Given that IRE is easily adaptable to different plasma membrane-based vehicles for delivering diverse drugs, this approach could offer a general applicability for cancer treatment.
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Affiliation(s)
- Wencheng Peng
- State Key Laboratory of Power Transmission Equipment and System Security and New Technology, Chongqing University, Chongqing 400044, People's Republic of China
| | - Yaqi Yue
- State Key Laboratory of Power Transmission Equipment and System Security and New Technology, Chongqing University, Chongqing 400044, People's Republic of China
| | - Yuting Zhang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China
| | | | | | | | | | | | - Shoulong Dong
- State Key Laboratory of Power Transmission Equipment and System Security and New Technology, Chongqing University, Chongqing 400044, People's Republic of China
| | - Ming Wu
- Authors to whom correspondence should be addressed: and
| | - Chenguo Yao
- State Key Laboratory of Power Transmission Equipment and System Security and New Technology, Chongqing University, Chongqing 400044, People's Republic of China
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Sotirchos VS, Petre EN, Sofocleous CT. Percutaneous image-guided ablation for hepatic metastases. J Med Imaging Radiat Oncol 2023; 67:832-841. [PMID: 37944085 DOI: 10.1111/1754-9485.13594] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 09/21/2023] [Indexed: 11/12/2023]
Abstract
The presence of hepatic metastases indicates advanced disease and is associated with significant morbidity and mortality, especially when the hepatic disease is not amenable to locoregional treatments. The primary tumour of origin, the distribution and extent of metastatic disease, the underlying liver reserve, the patient performance status and the presence of comorbidities are factors that determine whether a patient will benefit from hepatectomy or local curative-intent treatments. For patients with metastatic colorectal cancer, the most common primary cancer that spreads to the liver, several studies have demonstrated a survival benefit for patients who can be treated with hepatectomy and/or percutaneous ablation, compared to those treated with chemotherapy alone. Despite advances in surgical techniques increasing the percentage of patients eligible for surgery, most patients have unresectable disease or are poor surgical candidates. Percutaneous ablation can be used to provide local disease control and prolong survival for both surgical and non-surgical candidates. This is typically offered to patients with small hepatic metastases that can be ablated with optimal (≥10 mm) or at least adequate minimum ablation margins (≥5 mm), as high local tumour control rates can be achieved for these patients which are comparable to surgical resection. This review summarizes available evidence and outcomes following percutaneous ablation of the most frequently encountered types of hepatic metastases in the clinical practice of interventional oncology. Patient selection, technical considerations, follow-up protocols and oncologic outcomes are presented and discussed.
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Affiliation(s)
- Vlasios S Sotirchos
- Interventional Oncology/Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Elena N Petre
- Interventional Oncology/Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Constantinos T Sofocleous
- Interventional Oncology/Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
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Jacobs EJ, Campelo SN, Aycock KN, Yao D, Davalos RV. Spatiotemporal estimations of temperature rise during electroporation treatments using a deep neural network. Comput Biol Med 2023; 161:107019. [PMID: 37220706 DOI: 10.1016/j.compbiomed.2023.107019] [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: 01/23/2023] [Revised: 04/14/2023] [Accepted: 05/05/2023] [Indexed: 05/25/2023]
Abstract
The nonthermal mechanism for irreversible electroporation has been paramount for treating tumors and cardiac tissue in anatomically sensitive areas, where there is concern about damage to nearby bowels, ducts, blood vessels, or nerves. However, Joule heating still occurs as a secondary effect of applying current through a resistive tissue and must be minimized to maintain the benefits of electroporation at high voltages. Numerous thermal mitigation protocols have been proposed to minimize temperature rise, but intraoperative temperature monitoring is still needed. We show that an accurate and robust temperature prediction AI model can be developed using estimated tissue properties (bulk and dynamic conductivity), known geometric properties (probe spacing), and easily measurable treatment parameters (applied voltage, current, and pulse number). We develop the 2-layer neural network on realistic 2D finite element model simulations with conditions encompassing most electroporation applications. Calculating feature contributions, we found that temperature prediction is mostly dependent on current and pulse number and show that the model remains accurate when incorrect tissue properties are intentionally used as input parameters. Lastly, we show that the model can predict temperature rise within ex vivo perfused porcine livers, with error <0.5 °C. This model, using easily acquired parameters, is shown to predict temperature rise in over 1000 unique test conditions with <1 °C error and no observable outliers. We believe the use of simple, readily available input parameters would allow this model to be incorporated in many already available electroporation systems for real-time temperature estimations.
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Affiliation(s)
- Edward J Jacobs
- Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, VA, USA.
| | - Sabrina N Campelo
- Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, VA, USA
| | - Kenneth N Aycock
- Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, VA, USA
| | - Danfeng Yao
- Department of Computer Science, Virginia Tech, Blacksburg, VA, USA
| | - Rafael V Davalos
- Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, VA, USA
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Spiers HVM, Lancellotti F, de Liguori Carino N, Pandanaboyana S, Frampton AE, Jegatheeswaran S, Nadarajah V, Siriwardena AK. Irreversible Electroporation for Liver Metastases from Colorectal Cancer: A Systematic Review. Cancers (Basel) 2023; 15:cancers15092428. [PMID: 37173895 PMCID: PMC10177346 DOI: 10.3390/cancers15092428] [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: 03/17/2023] [Revised: 04/16/2023] [Accepted: 04/20/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND Irreversible electroporation (IRE) is a non-thermal form of ablation based on the delivery of pulsed electrical fields. It has been used to treat liver lesions, particularly those in proximity to major hepatic vasculature. The role of this technique in the portfolio of treatments for colorectal hepatic metastases has not been clearly defined. This study undertakes a systematic review of IRE for treatment of colorectal hepatic metastases. METHODS The study protocol was registered with the PROSPERO register of systematic reviews (CRD42022332866) and reports in compliance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The Ovid MEDLINE®, EMBASE, Web of Science and Cochrane databases were queried in April 2022. The search terms 'irreversible electroporation', 'colon cancer', 'rectum cancer' and 'liver metastases' were used in combinations. Studies were included if they provided information on the use of IRE for patients with colorectal hepatic metastases and reported procedure and disease-specific outcomes. The searches returned 647 unique articles and the exclusions left a total of eight articles. These were assessed for bias using the methodological index for nonrandomized studies (MINORS criteria) and reported using the synthesis without meta-analysis guideline (SWiM). RESULTS One hundred eighty patients underwent treatment for liver metastases from colorectal cancer. The median transverse diameter of tumours treated by IRE was <3 cm. Ninety-four (52%) tumours were adjacent to major hepatic inflow/outflow structures or the vena cava. IRE was undertaken under general anaesthesia with cardiac cycle synchronisation and with the use of either CT or ultrasound for lesion localisation. Probe spacing was less than 3.2 cm for all ablations. There were two (1.1%) procedure-related deaths in 180 patients. There was one (0.5%) post-operative haemorrhage requiring laparotomy, one (0.5%) bile leak, five (2.8%) post-procedure biliary strictures and a zero incidence of post-IRE liver failure. CONCLUSIONS This systematic review shows that IRE for colorectal liver metastases can be accomplished with low procedure-related morbidity and mortality. Further prospective study is required to assess the role of IRE in the portfolio of treatments for patients with liver metastases from colorectal cancer.
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Affiliation(s)
- Harry V M Spiers
- Cambridge Hepato-Pancreato-Biliary Unit, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK
- Department of Surgery, University of Cambridge, Cambridge CB2 0QQ, UK
| | | | | | | | - Adam E Frampton
- Hepato-Pancreato-Biliary Surgery Unit, Royal Surrey NHS Foundation Trust, Guildford GU2 7XX, UK
- Section of Oncology, Deptartment of Clinical & Experimental Medicine, University of Surrey, Guildford GU2 7WG, UK
| | | | - Vinotha Nadarajah
- Department of Radiology, Manchester Royal Infirmary, Manchester M13 9WL, UK
| | - Ajith K Siriwardena
- Hepato-Pancreato-Biliary Unit, Manchester Royal Infirmary, Manchester M13 9WL, UK
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Zhang N, Li Z, Han X, Zhu Z, Li Z, Zhao Y, Liu Z, Lv Y. Irreversible Electroporation: An Emerging Immunomodulatory Therapy on Solid Tumors. Front Immunol 2022; 12:811726. [PMID: 35069599 PMCID: PMC8777104 DOI: 10.3389/fimmu.2021.811726] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 12/13/2021] [Indexed: 01/10/2023] Open
Abstract
Irreversible electroporation (IRE), a novel non-thermal ablation technique, is utilized to ablate unresectable solid tumors and demonstrates favorable safety and efficacy in the clinic. IRE applies electric pulses to alter the cell transmembrane voltage and causes nanometer-sized membrane defects or pores in the cells, which leads to loss of cell homeostasis and ultimately results in cell death. The major drawbacks of IRE are incomplete ablation and susceptibility to recurrence, which limit its clinical application. Recent studies have shown that IRE promotes the massive release of intracellular concealed tumor antigens that become an "in-situ tumor vaccine," inducing a potential antitumor immune response to kill residual tumor cells after ablation and inhibiting local recurrence and distant metastasis. Therefore, IRE can be regarded as a potential immunomodulatory therapy, and combined with immunotherapy, it can exhibit synergistic treatment effects on malignant tumors, which provides broad application prospects for tumor treatment. This work reviewed the current status of the clinical efficacy of IRE in tumor treatment, summarized the characteristics of local and systemic immune responses induced by IRE in tumor-bearing organisms, and analyzed the specific mechanisms of the IRE-induced immune response. Moreover, we reviewed the current research progress of IRE combined with immunotherapy in the treatment of solid tumors. Based on the findings, we present deficiencies of current preclinical studies of animal models and analyze possible reasons and solutions. We also propose possible demands for clinical research. This review aimed to provide theoretical and practical guidance for the combination of IRE with immunotherapy in the treatment of malignant tumors.
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Affiliation(s)
- Nana Zhang
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Zhuoqun Li
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Xuan Han
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Ziyu Zhu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Zhujun Li
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yan Zhao
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Zhijun Liu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yi Lv
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Yu M, Li S. Irreversible electroporation for liver cancer ablation: A meta analysis. Eur J Surg Oncol 2021; 48:1321-1330. [PMID: 35012834 DOI: 10.1016/j.ejso.2021.12.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 11/24/2021] [Accepted: 12/11/2021] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVE To evaluate the efficacy and safety of IRE in the treatment of hepatic malignant tumors, especially the damage to the gastrointestinal tract, bile ducts, and vital vessels. METHODS The relevant literatures published from January 1, 2010 to July 1, 2021 were searched from PubMed and Embase databases. The following keywords were applied: "irreversible electroporation", "IRE", "unresectable Hepa∗ cancer", "ablation" and "ablation therapy". RESULTS Twenty-six studies were identified covering 807 participants and 1115 lesions. The complete ablation rate of liver cancer by IRE was 86% (95% CI: 81%-90%). The incidence of IRE-related complications was 23% (95% CI: 17%-28%), but most of them were minor, major complications such as biliary fistula, intestinal fistula and massive hemorrhage were rare. CONCLUSION Meta-analysis showed that IRE ablation is safe and effective for liver cancer treatment. Bile duct, intestine and blood vessels adjacent to the tumors are rarely damaged by IRE ablation.
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Affiliation(s)
- Maoli Yu
- Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, PR China.
| | - Sheng Li
- Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, PR China.
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Recurrent Colorectal Liver Metastases in the Liver Remnant After Major Liver Surgery-IRE as a Salvage Local Treatment When Resection and Thermal Ablation are Unsuitable. Cardiovasc Intervent Radiol 2021; 45:182-189. [PMID: 34757483 PMCID: PMC8807435 DOI: 10.1007/s00270-021-02981-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 09/18/2021] [Indexed: 11/02/2022]
Abstract
PURPOSE To examine the safety and short-term oncologic outcomes of computer-tomography-guided (CT-guided) irreversible electroporation (IRE) of recurrent, irresectable colorectal liver metastases (CRLM) after major hepatectomy deemed unsuitable for thermal ablation. PATIENTS AND METHODS Twenty-three patients undergoing CT-guided IRE of recurrent CRLM after major hepatectomy were included in this study. All tumors were located adjacent to sole remaining intrahepatic blood vessels and bile ducts, precluding thermal ablation. Patients underwent systematic clinical and imaging follow-up, including magnetic resonance imaging of the liver at 1-month and 3-month intervals thereafter. Time to local and intrahepatic tumor progression within 12 and 36 months and associated risk factors were assessed using Kaplan Meier and Cox regression analysis, respectively. RESULTS Complete ablation with a safety margin of at least 0.5 cm was achieved in 22/23 (95.6%) patients. No vessel injury or thrombosis occurred. Five patients developed moderate biliary stenosis after a median of 4 weeks, without requiring treatment. Local tumor-progression-free rates within 12/36 months were 64%/57.4%, respectively. Intrahepatic-progression-free rate within 12/36 months was 36.4%/19.5%, respectively. Five (23%) patients were tumor-free at the end of follow-up. Multivariate Cox regression analysis did not show any association between local tumor-progression-free rates and patient age, target tumor size, primary tumor side or synchronicity of liver metastases. CONCLUSION In this highly selected patient population with local recurrences of CRLM after major surgery, IRE was shown to be a safe salvage treatment option when thermal ablation is unsuitable.
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11
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Gupta P, Maralakunte M, Sagar S, Kumar-M P, Bhujade H, Chaluvashetty SB, Kalra N. Efficacy and safety of irreversible electroporation for malignant liver tumors: a systematic review and meta-analysis. Eur Radiol 2021; 31:6511-6521. [PMID: 33638687 DOI: 10.1007/s00330-021-07742-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 12/26/2020] [Accepted: 02/03/2021] [Indexed: 01/10/2023]
Abstract
OBJECTIVE The data regarding overall survival (OS) and progression-free survival (PFS) following irreversible electroporation (IRE) is scarce. We performed a systematic review of the safety and efficacy of IRE for liver malignancies. METHODS Searches of MEDLINE, EMBASE, and SCOPUS databases were performed through September 1, 2019. Studies reporting the survival data (OS and PFS) and complications (graded according to the Society of interventional Radiology classification) were included. A generalized linear mixed method with a random-effects model was used for assessing pooled incidence rates and corresponding 95% confidence intervals (CIs). RESULTS A total of 25 studies (n = 776, 15 prospective, 10 retrospective) were included. Metastasis, hepatocellular carcinoma, and cholangiocarcinoma were present in 354, 285, and 100 patients, respectively. The pooled OS at 6, 12, 24, and 36 months was 93.28% (95% CI: 63.23-99.12, I2= 67%), 81.29% (95% CI: 69.80-89.22, I2 = 73%), 61.47% (95% CI: 52.81-69.46, I2 = 0%), and 40.88% (95% CI: 28.43-54.61, I2 = 64%), respectively. The pooled PFS at 6, 12, and 24 months was 79.72% (95% CI: 67.88-87.97, I2 = 70%), 64.19% (95% CI: 56.68-71.06, I2 = 57%), 49.05% (95% CI: 11.47-87.73, I2 = 96%), respectively. Overall complication rate was 23.7%. Major complications (grade C-F) occurred in 6.9% patients. CONCLUSION IRE is associated with favorable OS and PFS. Although the overall complication rate is high, most complications are graded as minor. KEY POINTS • The pooled OS and PFS at 6, 12, and 24 months for all the tumor types was 93.28% and 79.72%, 81.29% and 64.19%, and 61.47% and 49.05%, respectively. • HCC was associated with a better OS at 12 and 36 months. • The overall complication rate was 23.7%, with major complications (SIR grade C-F) comprising 6.9%.
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Affiliation(s)
- Pankaj Gupta
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
| | - Muniraju Maralakunte
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Sathya Sagar
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Praveen Kumar-M
- Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Harish Bhujade
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Sreedhara B Chaluvashetty
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Naveen Kalra
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
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12
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Eresen A, Yang J, Scotti A, Cai K, Yaghmai V, Zhang Z. Combination of natural killer cell-based immunotherapy and irreversible electroporation for the treatment of hepatocellular carcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1089. [PMID: 34423001 PMCID: PMC8339821 DOI: 10.21037/atm-21-539] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 04/05/2021] [Indexed: 01/10/2023]
Abstract
Hepatocellular carcinoma (HCC) is among the most lethal cancer types despite great advancement in overall survival of the patients over the last decades. Surgical resection or partial hepatectomy has been approved as the curative treatment for early-stage HCC patients however only up to 30% of them are eligible for the procedures. Natural killer (NK) cells are cytotoxic lymphocytes recognized for killing virally infected cells and improving immune functions for defending the body against malignant cells. Although autologous NK cells failed to demonstrate significant clinical benefit, transfer of allogeneic adoptive NK cells arises as a promising approach for the treatment of solid tumors. The immunosuppressive tumor microenvironment and inadequate homing efficiency of NK cells to tumors can inhibit adoptive transfer immunotherapy (ATI) efficacy. However, potential of the NK cells is challenged by the transfection efficiency. The local ablation techniques that employ thermal or chemical energy have been investigated for the destruction of solid tumors for three decades and demonstrated promising benefits for individuals not eligible for surgical resection or partial hepatectomy. Irreversible electroporation (IRE) is one of the most recent minimally invasive ablation methods that destruct the cell within the targeted region through non-thermal energy. IRE destroys the tumor cell membrane by delivering high-frequency electrical energy in short pulses and overcomes tumor immunosuppression. The previous studies demonstrated that IRE can induce immune changes which can facilitate activation of specific immune responses and improve transfection efficiency. In this review paper, we have discussed the mechanism of NK cell immunotherapy and IRE ablation methods for the treatment of HCC patients and the combinatorial benefits of NK cell immunotherapy and IRE ablation.
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Affiliation(s)
- Aydin Eresen
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,Department of Radiological Sciences, University of California Irvine, Irvine, CA, USA
| | - Jia Yang
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Alessandro Scotti
- Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA.,Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA
| | - Kejia Cai
- Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA.,Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA
| | - Vahid Yaghmai
- Department of Radiological Sciences, University of California Irvine, Irvine, CA, USA.,Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA
| | - Zhuoli Zhang
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,Department of Radiological Sciences, University of California Irvine, Irvine, CA, USA.,Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA.,Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA
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13
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Rohan T, Andrasina T, Juza T, Matkulcik P, Červinka D, Svobodova I, Novotná V, Bernard V, Valek V, Goldberg SN. Experimental model of occluded biliary metal stent recanalization using irreversible electroporation via a tubular catheter. Int J Hyperthermia 2021; 38:393-401. [PMID: 33682581 DOI: 10.1080/02656736.2021.1875061] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
PURPOSE To demonstrate the feasibility of irreversible electroporation (IRE) for treating biliary metal stent occlusion in an experimental liver model. METHODS AND MATERIALS IRE was performed using an expandable tubular IRE-catheter placed in nitinol stents in the porcine liver. A 3-electrode IRE-catheter was connected to an IRE-generator and one hundred 100μs pulses of constant voltage (300, 650, 1000, and 1300 V) were applied. Stent occlusion was simulated by insertion of liver tissue both ex vivo (n = 94) and in vivo in 3 pigs (n = 14). Three scenarios of the relationship between the stent, electrodes, and inserted tissue (double contact, single contact, and stent mesh contact) were studied. Electric current was measured and resistance and power calculated. Pigs were sacrificed 72 h post-procedure. Harvested samples (14 experimental, 13 controls) underwent histopathological analysis. RESULTS IRE application was feasible at 300 and 650 V for the single and double contact setup in both ex vivo and in vivo studies. Significant differences in calculated resistance between double contact and single contact settings were observed (ex-vivo p ˂ 0.0001, in-vivo p = 0.02; Mann-Whitney). A mild temperature increase of the surrounding liver parenchyma was noted with increasing voltage (0.9-5.9 °C for 300-1000 V). The extent of necrotic changes in experimental samples in vivo correlated with the measured electric current (r2 = 0.39, p = 0.01). No complications were observed during or after the in-vivo procedure. CONCLUSION Endoluminal IRE using an expandable tubular catheter in simulated metal stent occlusion is feasible. The relationship of active catheter electrodes to stent ingrowth tissue can be estimated based on resistance values.
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Affiliation(s)
- T Rohan
- Department of Radiology and Nuclear Medicine, University Hospital Brno and Masaryk University Brno, Brno, Czech Republic
| | - T Andrasina
- Department of Radiology and Nuclear Medicine, University Hospital Brno and Masaryk University Brno, Brno, Czech Republic
| | - T Juza
- Department of Radiology and Nuclear Medicine, University Hospital Brno and Masaryk University Brno, Brno, Czech Republic
| | - P Matkulcik
- Department of Radiology and Nuclear Medicine, University Hospital Brno and Masaryk University Brno, Brno, Czech Republic
| | - D Červinka
- Faculty of Electrical Engineering and Communication, Department of Power Electrical and Electronic Engineering, Brno University of Technology, Brno, Czech Republic
| | - I Svobodova
- Department of Pathology, St. Anne's University Hospital Brno, Brno, Czech Republic
| | - V Novotná
- Faculty of Electrical Engineering and Communication, Department of Power Electrical and Electronic Engineering, Brno University of Technology, Brno, Czech Republic
| | - V Bernard
- Faculty of Medicine, Department of Biophysics, Masaryk University, Brno, Czech Republic
| | - V Valek
- Department of Radiology and Nuclear Medicine, University Hospital Brno and Masaryk University Brno, Brno, Czech Republic
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14
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Beitel-White N, Lorenzo MF, Zhao Y, Brock RM, Coutermarsh-Ott S, Allen IC, Manuchehrabadi N, Davalos RV. Multi-Tissue Analysis on the Impact of Electroporation on Electrical and Thermal Properties. IEEE Trans Biomed Eng 2021; 68:771-782. [PMID: 32746081 PMCID: PMC8048145 DOI: 10.1109/tbme.2020.3013572] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Tissue electroporation is achieved by applying a series of electric pulses to destabilize cell membranes within the target tissue. The treatment volume is dictated by the electric field distribution, which depends on the pulse parameters and tissue type and can be readily predicted using numerical methods. These models require the relevant tissue properties to be known beforehand. This study aims to quantify electrical and thermal properties for three different tissue types relevant to current clinical electroporation. METHODS Pancreatic, brain, and liver tissue were harvested from pigs, then treated with IRE pulses in a parallel-plate configuration. Resulting current and temperature readings were used to calculate the conductivity and its temperature dependence for each tissue type. Finally, a computational model was constructed to examine the impact of differences between tissue types. RESULTS Baseline conductivity values (mean 0.11, 0.14, and 0.12 S/m) and temperature coefficients of conductivity (mean 2.0, 2.3, and 1.2 % per degree Celsius) were calculated for pancreas, brain, and liver, respectively. The accompanying computational models suggest field distribution and thermal damage volumes are dependent on tissue type. CONCLUSION The three tissue types show similar electrical and thermal responses to IRE, though brain tissue exhibits the greatest differences. The results also show that tissue type plays a role in the expected ablation and thermal damage volumes. SIGNIFICANCE The conductivity and its changes due to heating are expected to have a marked impact on the ablation volume. Incorporating these tissue properties aids in the prediction and optimization of electroporation-based therapies.
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15
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Mathy RM, Tinoush P, da Florencia RD, Braun A, Ghamarnejad O, Radeleff B, Kauczor HU, Chang DH. Impact of needle positioning on ablation success of irreversible electroporation: a unicentric retrospective analysis. Sci Rep 2020; 10:21902. [PMID: 33318515 PMCID: PMC7736875 DOI: 10.1038/s41598-020-78660-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Accepted: 11/27/2020] [Indexed: 12/18/2022] Open
Abstract
Irreversible electroporation (IRE) is an ablation procedure in which cell death is induced by ultrashort electrical pulses. In this unicentric retrospective study we investigated the influence of needle positioning on ablation success. 15 IREs with residual tumor after ablation, detected in the first follow-up MRI, were included, and compared with 30 successful ablations. Evaluation of needle geometry revealed significantly higher values for needle divergence (NDiv, 7.0° vs. 3.7°, p = 0.02), tumor-center-to-ablation-center distance (TACD, 11.6 vs. 3.2 mm, p < 0.001), tumor-to-needle distance (4.7 vs. 1.9 mm, p = 0.04), and tumor diameter per needle (7.5 vs. 5.9 mm/needle, p = 0.01) in patients with residual tumor. The average number of needles used was higher in the group without residual tumor after ablation (3.1 vs. 2.4, p = 0.04). In many cases with residual tumor, needle depth was too short (2.1 vs. 6.8 mm tumor overlap beyond the most proximal needle tip, p < 0.01). The use of a stereotactic navigation system in 10 cases resulted in a lower NDiv value (2.1° vs. 5.6°, p < 0.01). Thus, correct needle placement seems to be a crucial factor for success and the assistance of a stereotactic navigation system might be helpful. As most important geometrical parameter TACD could be identified. Main reasons for high TACD were insufficient needle depth and a lesion location out of the needle plane.
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Affiliation(s)
- René Michael Mathy
- Clinic for Diagnostic and Interventional Radiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany.
| | - Parham Tinoush
- Clinic for Diagnostic and Interventional Radiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Ricardo Daniel da Florencia
- Clinic for Diagnostic and Interventional Radiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Alexander Braun
- Clinic for Diagnostic and Interventional Radiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Omid Ghamarnejad
- Clinic for Diagnostic and Interventional Radiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Boris Radeleff
- Clinic for Diagnostic and Interventional Radiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Hans-Ulrich Kauczor
- Clinic for Diagnostic and Interventional Radiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - De-Hua Chang
- Clinic for Diagnostic and Interventional Radiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
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16
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Freeman E, Cheung W, Kavnoudias H, Majeed A, Kemp W, Roberts SK. Irreversible Electroporation For Hepatocellular Carcinoma: Longer-Term Outcomes At A Single Centre. Cardiovasc Intervent Radiol 2020; 44:247-253. [PMID: 33051707 DOI: 10.1007/s00270-020-02666-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 09/22/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS Irreversible electroporation (IRE) is a non-thermal ablation technique for unresectable hepatocellular carcinoma (HCC) not amenable to standard thermal ablation. The aim of this study was to report our longer-term outcomes using this treatment modality. METHOD We identified all patients at our institution who underwent IRE for HCC between December 2008 and October 2019 as recommended after multi-disciplinary team review. Demographic, clinical, tumour response and survival data up until 1 March, 2020 were analysed. The primary outcome was local recurrence-free survival (LRFS) in patients who had a complete response (CR). Secondary outcomes included CR rates, procedure-related complications and the incidence of death or liver transplantation. RESULTS A total of 23 patients (78% males, median age 65.2 years) received IRE therapy to 33 HCC lesions during the study period with the median tumour size being 2.0 cm (range 1.0-5.0 cm). Twenty-nine (87.9%) lesions were successfully ablated after one (n = 26) or two (n = 3) procedures. The median follow-up time for these lesions was 20.4 months. The median overall LRFS was 34.5 (95% CI 24.8 -) months with a 6- and 12-month LRFS of 87.9% (95% CI 75.8-100) and 83.6% (95% CI 70.2-99.7), respectively. Tumours < 2 cm had a 12-month LRFS of 100% (95% CI 100-100). CONCLUSION IRE appears to be an efficacious local ablative method for early stage HCC not amenable to standard ablative techniques, with very good CR rates and longer-term LRFS, particularly for smaller lesions. Further studies comparing this technique to more widely accepted ablative methods such as radiofrequency and microwave ablation are warranted.
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Affiliation(s)
- E Freeman
- Department of Gastroenterology, Alfred Hospital, The Alfred55 Commercial Rd, Melbourne, 3004, Australia
| | - W Cheung
- Department of Radiology, Alfred Hospital, Melbourne, Australia
| | - H Kavnoudias
- Department of Radiology, Alfred Hospital, Melbourne, Australia
| | - A Majeed
- Department of Gastroenterology, Alfred Hospital, The Alfred55 Commercial Rd, Melbourne, 3004, Australia.,Department of Medicine, Central Clinical School, Monash University, Melbourne, Australia
| | - W Kemp
- Department of Gastroenterology, Alfred Hospital, The Alfred55 Commercial Rd, Melbourne, 3004, Australia.,Department of Medicine, Central Clinical School, Monash University, Melbourne, Australia
| | - S K Roberts
- Department of Gastroenterology, Alfred Hospital, The Alfred55 Commercial Rd, Melbourne, 3004, Australia. .,Department of Medicine, Central Clinical School, Monash University, Melbourne, Australia.
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17
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Liu ZG, Chen XH, Yu ZJ, Lv J, Ren ZG. Recent progress in pulsed electric field ablation for liver cancer. World J Gastroenterol 2020; 26:3421-3431. [PMID: 32655266 PMCID: PMC7327785 DOI: 10.3748/wjg.v26.i24.3421] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 05/06/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
Abstract
The number of liver cancer patients is likely to continue to increase in the coming decades due to the aging of the population and changing risk factors. Traditional treatments cannot meet the needs of all patients. New treatment methods evolved from pulsed electric field ablation are expected to lead to breakthroughs in the treatment of liver cancer. This paper reviews the safety and efficacy of irreversible electroporation in clinical studies, the methods to detect and evaluate its ablation effect, the improvements in equipment and its antitumor effect, and animal and clinical trials on electrochemotherapy. We also summarize studies on the most novel nanosecond pulsed electric field ablation techniques in vitro and in vivo. These research results are certain to promote the progress of pulsed electric field in the treatment of liver cancer.
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Affiliation(s)
- Zhen-Guo Liu
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
- Gene Hospital of Henan Province, Zhengzhou 450052, Henan Province, China
- Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Xin-Hua Chen
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China
| | - Zu-Jiang Yu
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
- Gene Hospital of Henan Province, Zhengzhou 450052, Henan Province, China
- Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Jun Lv
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
- Gene Hospital of Henan Province, Zhengzhou 450052, Henan Province, China
- Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Zhi-Gang Ren
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
- Gene Hospital of Henan Province, Zhengzhou 450052, Henan Province, China
- Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
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18
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Aycock KN, Davalos RV. Irreversible Electroporation: Background, Theory, and Review of Recent Developments in Clinical Oncology. Bioelectricity 2019; 1:214-234. [PMID: 34471825 PMCID: PMC8370296 DOI: 10.1089/bioe.2019.0029] [Citation(s) in RCA: 93] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Irreversible electroporation (IRE) has established a clinical niche as an alternative to thermal ablation for the eradication of unresectable tumors, particularly those near critical vascular structures. IRE has been used in over 50 independent clinical trials and has shown clinical success when used as a standalone treatment and as a single component within combinatorial treatment paradigms. Recently, many studies evaluating IRE in larger patient cohorts and alongside other novel therapies have been reported. Here, we present the basic principles of reversible electroporation and IRE followed by a review of preclinical and clinical data with a focus on tumors in three organ systems in which IRE has shown great promise: the prostate, pancreas, and liver. Finally, we discuss alternative and future developments, which will likely further advance the use of IRE in the clinic.
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Affiliation(s)
- Kenneth N Aycock
- Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Virginia
| | - Rafael V Davalos
- Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Virginia
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19
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Is irreversible electroporation safe and effective in the treatment of hepatobiliary and pancreatic cancers? Hepatobiliary Pancreat Dis Int 2019; 18:117-124. [PMID: 30655073 DOI: 10.1016/j.hbpd.2019.01.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 12/21/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND Irreversible electroporation (IRE) is a novel ablative technique for hepatobiliary and pancreatic cancers. This review summarizes the data regarding the safety and efficacy of IRE in the treatment of hepatobiliary and pancreatic cancers. DATA SOURCES Studies were identified by searching PubMed and Embase for articles published in English from database inception through July 31, 2017. For inclusion, each clinical study had to report morbidity and survival data on hepatobiliary and pancreatic cancers treated with IRE and contain at least 10 patients. Studies that met these criteria were included for analysis. Two authors assessed each clinical study for data extraction. The controversial parts were resolved through discussion with seniors. RESULTS A total of 24 clinical studies were included. Fourteen focused on hepatic ablation with IRE comprising 437 patients with 666 lesions of different tumor types. Two patients (0.5%) died after the IRE procedure. Morbidity of hepatic ablation with IRE ranged from 7% to 35%. Most complications were mild. Complete response for hepatic tumors was reported as 57%-97%. Ten studies with 455 patients focused on pancreatic IRE. The overall mortality of IRE in pancreatic cancer was 2%. Overall severe morbidity of IRE in pancreatic cancer ranged from 0 to 20%. The median overall survival after IRE ranged from 7 to 23 months. Patients treated with IRE combined with surgical resection showed a longer overall survival. CONCLUSIONS IRE significantly improves the prognosis of advanced hepatobiliary and pancreatic malignances, and companied with less complications. Hence, IRE is a relatively safe and effective non-thermal ablation strategy and potentially recommended as an option for therapy of patients with hepatobiliary and pancreatic malignances.
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20
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Zhang K, Xu G, Qiu R, Wang L, Li J, Qian F. The effects of irreversible electroporation on the stomach wall after ablating hepatic tissues. Biomed Microdevices 2018; 20:97. [PMID: 30406862 DOI: 10.1007/s10544-018-0345-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
This study aimed to evaluate the effect of irreversible electroporation (IRE) on the stomach wall after IRE was applied on liver tissues adjacent to the anterior wall of the stomach. IRE ablation was performed in eight Tibet mini-pigs with three lesions per pig. The IRE electrodes were inserted into the liver tissues situated close to the anterior wall of the stomach. As for the control group, the IRE electrodes were also inserted into the liver tissues for three lesions in four Tibet mini-pigs but did not turn on the current. Serum aminotransferase and WBC levels clearly increased in all the IRE ablated animals by Day 1 and decreased gradually thereafter. The gross postmortem examination at 7 days post-IRE revealed a whitish lesion with sharp demarcation on the serosal surface of the stomach, but we could not find any signs of ablation or just find a small, slightly reddish lesion at the Day-28 examination. On the Day-7 histopathological examination, inflammation and fibrosis were observed in the serosal layer of the stomach in each animal and mild inflammation of the myofibers was found in only two pigs. All the stomach layers returned to normalcy by 28 days post-IRE. Thus, IRE ablation of hepatic tissues situated close to the stomach wall cannot lead to stomach perforation. IRE is therefore a safe procedure for ablating hepatic tumors that are adjacent to the stomach.
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Affiliation(s)
- Kai Zhang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, 130041, Jilin, China
| | - Guangmeng Xu
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, 130041, Jilin, China
| | - Renna Qiu
- Department of Anesthesia, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China
| | - Lizhe Wang
- The First Hospital of Jilin University, Changchun, 130021, Jilin, China
| | - Jiannan Li
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, 130041, Jilin, China.
| | - Feng Qian
- Department of Anesthesia, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China.
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21
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Stewart CL, Warner S, Ito K, Raoof M, Wu GX, Kessler J, Kim JY, Fong Y. Cytoreduction for colorectal metastases: liver, lung, peritoneum, lymph nodes, bone, brain. When does it palliate, prolong survival, and potentially cure? Curr Probl Surg 2018; 55:330-379. [PMID: 30526930 DOI: 10.1067/j.cpsurg.2018.08.004] [Citation(s) in RCA: 167] [Impact Index Per Article: 23.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 08/28/2018] [Indexed: 12/19/2022]
Affiliation(s)
- Camille L Stewart
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA
| | - Susanne Warner
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA
| | - Kaori Ito
- Department of Surgery, Michigan State University, Lansing, MI
| | - Mustafa Raoof
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA
| | - Geena X Wu
- Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, CA
| | - Jonathan Kessler
- Department of Diagnostic Radiology, City of Hope National Medical Center, Duarte, CA
| | - Jae Y Kim
- Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, CA
| | - Yuman Fong
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA.
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22
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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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23
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Distelmaier M, Barabasch A, Heil P, Kraemer NA, Isfort P, Keil S, Kuhl CK, Bruners P. Midterm Safety and Efficacy of Irreversible Electroporation of Malignant Liver Tumors Located Close to Major Portal or Hepatic Veins. Radiology 2017; 285:1023-1031. [PMID: 28799842 DOI: 10.1148/radiol.2017161561] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Purpose To investigate the efficacy and safety of irreversible electroporation (IRE) in the treatment of hepatic tumors not suitable for thermal ablation (radiofrequency ablation [RFA] or microwave ablation). Materials and Methods This was an institutional review board-approved prospective study in 29 patients (15 men, 14 women; mean age, 63 years ± 12 [standard deviation]) with 43 primary (n = 8) or secondary (n = 35) malignant liver tumors who underwent computed tomography (CT)-guided IRE. All target tumors were located immediately adjacent to major hepatic veins, portal veins, or both; thus, they were not considered suitable for RFA or microwave ablation. Patients underwent postinterventional CT and magnetic resonance (MR) imaging. Systematic follow-up MR imaging was performed for 24 months on average to assess complete ablation, intrahepatic tumor recurrence, and complications. The 95% confidence intervals (CIs) were determined for the rate of bile duct strictures, incomplete ablation, and tumor recurrence. Results Complete ablation was achieved in 40 (93%; 95% CI: 85, 100) of 43 target tumors, with a safety margin of 5-10 mm, and was confirmed at immediate postinterventional CT and MR imaging. In 13 (33%; 95% CI: 18, 47) of 40 completely ablated tumors, intrahepatic tumor recurrence was observed at 2-18 months. However, only two (15%; 95% CI: 0, 35) of these 13 tumors were observed within the ablation zone. In the remaining 11 (85%; 95% CI: 65, 100), tumor growth was observed alongside the needle tract. None of the two true local recurrences occurred at the site of the vessel. All adjacent vessels remained perfused at follow-up. Five (24%; 95% CI: 5, 39) of 21 patients with target tumors adjacent to portal veins developed mild to moderate cholestasis 2-6 weeks after IRE. Conclusion IRE is useful to avoid incomplete ablation secondary to heat-sink effects and damage to major blood vessels; however, needle tract seeding is observed in 26% of treated tumors, and IRE induces sufficient local heating to bile ducts in 24% of ablations. © RSNA, 2017.
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Affiliation(s)
- Martina Distelmaier
- From the Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
| | - Alexandra Barabasch
- From the Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
| | - Philipp Heil
- From the Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
| | - Nils A Kraemer
- From the Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
| | - Peter Isfort
- From the Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
| | - Sebastian Keil
- From the Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
| | - Christiane K Kuhl
- From the Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
| | - Philipp Bruners
- From the Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
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Zimmerman A, Grand D, Charpentier KP. Irreversible electroporation of hepatocellular carcinoma: patient selection and perspectives. J Hepatocell Carcinoma 2017; 4:49-58. [PMID: 28331845 PMCID: PMC5357069 DOI: 10.2147/jhc.s129063] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Irreversible electroporation (IRE) is a novel form of tissue ablation that uses high-current electrical pulses to induce pore formation of the cell lipid bilayer, leading to cell death. The safety of IRE for ablation of hepatocellular carcinoma (HCC) has been established. Outcome data for ablation of HCC by IRE are limited, but early results are encouraging and suggest equivalency to the outcomes obtained for thermal ablation for appropriately selected, small (<3 cm) tumors. Long-term oncologic efficacy and histopathologic response data have not been published, and therefore, application of IRE for the treatment of HCC should still be viewed with caution.
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Affiliation(s)
| | - David Grand
- Department of Radiology, Rhode Island Hospital, Brown University, Providence, RI, USA
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Thillai K, Repana D, Korantzis I, Kane P, Prachalias A, Ross P. Clinical outcomes for patients with liver-limited metastatic colorectal cancer: Arguing the case for specialist hepatobiliary multidisciplinary assessment. Eur J Surg Oncol 2016; 42:1331-6. [PMID: 27174600 DOI: 10.1016/j.ejso.2016.03.031] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Revised: 03/22/2016] [Accepted: 03/31/2016] [Indexed: 12/18/2022] Open
Abstract
In patients with liver-limited metastatic colorectal cancer, hepatic resection can offer a significant survival benefit over systemic therapy alone. Specialist hepatobiliary multidisciplinary meetings are currently believed to provide the best forum to discuss the management for these patients. A retrospective analysis was undertaken of patients diagnosed with liver-limited metastatic colorectal cancer over 6 months within a cancer network in the United Kingdom. In addition, patients who were diagnosed but not referred to the hepatobiliary meeting were discussed within a virtual multi-disciplinary setting. Contributors were blinded and proposed management recorded. 159 newly diagnosed patients with liver-limited metastatic colorectal cancer were identified. 68 (43%) were referred at initial diagnosis and 38 (24%) referred following systemic treatment. 35 (51%) who were discussed at baseline underwent a subsequent hepatectomy or radiofrequency ablation, as did 18 (47%) patients referred after chemotherapy. Of the remaining 53 (33%) patients not referred, imaging was available for 31 (58%). Decisions regarding potential liver-directed therapy were discussed within a multi-disciplinary setting. 13 (42%) were identified as resectable or potentially resectable and 11 (36%) may have been suitable for a clinical trial. In reality, none of these 31 patients (100%) underwent surgery or ablation. Whilst the majority of patients with liver-limited metastatic colorectal cancer were referred appropriately, this study demonstrates that a significant number with potentially resectable disease are not being discussed at specialist meetings. A review of all diagnosed cases would ensure that an increased number of patients are offered hepatic resection or ablation.
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Affiliation(s)
- K Thillai
- Department of Medical Oncology, Guy's and St Thomas' NHS Trust, London, United Kingdom
| | - D Repana
- Department of Medical Oncology, Guy's and St Thomas' NHS Trust, London, United Kingdom
| | - I Korantzis
- Department of Medical Oncology, Guy's and St Thomas' NHS Trust, London, United Kingdom
| | - P Kane
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - A Prachalias
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - P Ross
- Department of Medical Oncology, Guy's and St Thomas' NHS Trust, London, United Kingdom; Institute of Liver Studies, King's College Hospital, London, United Kingdom.
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26
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Ultrasound validation of mathematically modeled irreversible electroporation ablation areas. Surgery 2016; 159:1032-40. [DOI: 10.1016/j.surg.2015.10.030] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Revised: 10/06/2015] [Accepted: 10/28/2015] [Indexed: 12/18/2022]
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Eisele RM, Chopra SS, Glanemann M, Gebauer B. Risk of local failure after ultrasound guided irreversible electroporation of malignant liver tumors. Interv Med Appl Sci 2014; 6:147-53. [PMID: 25598987 DOI: 10.1556/imas.6.2014.4.2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2014] [Revised: 07/29/2014] [Accepted: 09/03/2014] [Indexed: 12/18/2022] Open
Abstract
INTRODUCTION Irreversible electroporation (IRE) is considered superior to thermoablations for tumors in the vicinity of larger vessels and the liver hilum. We report on an initial clinical experience of IRE. MATERIALS AND METHODS Indications included focal liver lesions <3 cm, irresectability due to contraindications and expected complications and/or irradicality following radiofrequency ablation (RFA). Ultrasound was chosen for guidance and needle placement. RESULTS IRE was intended to perform in 14 patients with 1 procedure aborted due to technical failure. Among the 13 successfully treated were 7 percutaneous, 4 laparoscopic, and 2 open surgical procedures. The average age was 63 ± 10 years. Twelve solitary nodules and one bifocal disease were treated with an average size of 1.5 cm ± 0.5 cm. Median follow-up was 6 months. Three incomplete ablations account for 21% (3/14), 2 of them occurring in 2 metastases larger than 2 cm percutaneously treated with 5 needles instead of 4 used for smaller tumor sizes. CONCLUSION IRE was introduced without difficulties into clinical practice. As a main obstacle emerged in visualization of the needles, computed tomography may offer advantages in the guidance of percutaneous IRE of liver metastases larger than 2 cm. Local failure occurred in 21%.
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