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Narayanan G, Gentile NT, Eyshi J, Schiro BJ, Gandhi RT, Peña CS, Ucar A, Aparo S, de Zarraga FI, Joseph SN, Asbun HJ, Dijkstra M. Irreversible Electroporation in Treating Colorectal Liver Metastases in Proximity to Critical Structures. J Vasc Interv Radiol 2024; 35:1806-1813. [PMID: 39218213 DOI: 10.1016/j.jvir.2024.08.021] [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: 03/01/2024] [Revised: 08/06/2024] [Accepted: 08/23/2024] [Indexed: 09/04/2024] Open
Abstract
PURPOSE To evaluate the safety, effectiveness, and oncological outcomes of irreversible electroporation (IRE) of unresectable colorectal liver metastases (CRLMs) close to critical structures. MATERIALS AND METHODS This is a single-center, institutional review board (IRB)-approved, retrospective analysis of patients who underwent percutaneous computed tomography (CT)-guided IRE of CRLM. Between August 2018 and October 2023, 26 patients had 46 tumors treated with percutaneous IRE in 30 ablation sessions. Primary end points were tumor response and local progression-free survival analyzed using Kaplan-Meier survival curves. Secondary end points were overall survival (OS), distant progression-free survival (DPFS) analyzed using Kaplan-Meier survival curves, adverse events rated according to the Common Terminology Criteria for Adverse Events (CTCAE), and length of hospital stay. RESULTS All tumors were close to critical structures, including the portal and hepatic veins, inferior vena cava, bile ducts, and gallbladder. All patients received preprocedural systemic therapy (median 10 cycles). Median length of hospital stay was 1 night. Adverse events occurred in 7 (23%) of 30 procedures, with four Grade 1 and two Grade 2 adverse events, including pleural effusions (n = 2), ileus (n = 1), small hematoma (n = 1), and pneumothorax (n = 2) requiring chest tube placements. Following IRE, the 1- and 2-year local tumor progression-free survival rates were 55.0% and 51.3%. The median DPFS was 3.5 months, with 1- and 2-year DPFS rates of 23.3% and 9.7%. Six patients (23.1%) died during follow-up, with a median OS of 40.4 months. The 1- and 2-year OS rates were 90.9% and 83.9%. CONCLUSIONS IRE is a safe and viable option in the treatment of unresectable CRLMs in locations close to critical structures, but carries a risk of local recurrence.
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Affiliation(s)
- Govindarajan Narayanan
- Herbert Wertheim College of Medicine, Florida International University, Miami, Florida; Department of Interventional Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida; Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, Florida
| | - Nicole T Gentile
- Department of Interventional Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida; Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, Florida
| | - Jonathan Eyshi
- Herbert Wertheim College of Medicine, Florida International University, Miami, Florida; Department of Interventional Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida; Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, Florida
| | - Brian J Schiro
- Herbert Wertheim College of Medicine, Florida International University, Miami, Florida; Department of Interventional Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida; Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, Florida
| | - Ripal T Gandhi
- Herbert Wertheim College of Medicine, Florida International University, Miami, Florida; Department of Interventional Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida; Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, Florida
| | - Costantino S Peña
- Herbert Wertheim College of Medicine, Florida International University, Miami, Florida; Department of Interventional Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida; Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, Florida
| | - Antonio Ucar
- Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
| | - Santiago Aparo
- Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
| | - Fernando I de Zarraga
- Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
| | - Sarah N Joseph
- Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
| | - Horacio J Asbun
- Department of Hepatobiliary and Pancreatic Surgery, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
| | - Madelon Dijkstra
- Department of Interventional Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida; Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, Florida; Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, Amsterdam, the Netherlands.
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Narayanan G, Koethe Y, Gentile N. Irreversible Electroporation of the Hepatobiliary System: Current Utilization and Future Avenues. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:251. [PMID: 38399539 PMCID: PMC10890312 DOI: 10.3390/medicina60020251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/23/2024] [Accepted: 01/27/2024] [Indexed: 02/25/2024]
Abstract
Liver cancer remains a leading cause of cancer-related deaths worldwide despite numerous advances in treatment. While surgical resection remains the gold standard for curative treatment, it is only possible for a minority of patients. Thermal ablation is an effective option for the treatment of smaller tumors; however, its use is limited to tumors that are not located in proximity to sensitive structures due to the heat sink effect and the potential of thermal damage. Irreversible electroporation (IRE) is a non-thermal ablative modality that can deliver targeted treatment and the effective destruction of tumors that are in close proximity to or even surrounding vascular or biliary ducts with minimal damage to these structures. IRE produces short pulses of high-frequency energy which opens pores in the lipid bilayer of cells leading to apoptosis and cell death. IRE has been utilized clinically for over a decade in the treatment of liver cancers with multiple studies documenting an acceptable safety profile and high efficacy rates.
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Affiliation(s)
- Govindarajan Narayanan
- Miami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USA;
- Miami Cardiac and Vascular, Baptist Health South Florida, 8900 North Kendall Drive, Miami, FL 33176, USA
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA
| | | | - Nicole Gentile
- Miami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USA;
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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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Hallemeier CL, Sharma N, Anker C, Selfridge JE, Lee P, Jabbour S, Williams V, Liu D, Kennedy T, Jethwa KR, Kim E, Kumar R, Small W, Tchelebi L, Russo S. American Radium Society Appropriate Use Criteria for the use of liver-directed therapies for nonsurgical management of liver metastases: Systematic review and guidelines. Cancer 2023; 129:3193-3212. [PMID: 37409678 DOI: 10.1002/cncr.34931] [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: 03/09/2023] [Revised: 05/09/2023] [Accepted: 05/24/2023] [Indexed: 07/07/2023]
Abstract
The liver is a common site of cancer metastases. Systemic therapy is widely accepted as the standard treatment for liver metastases (LM), although select patients with liver oligometastases may be candidates for potentially curative liver resection. Recent data support the role of nonsurgical local therapies such as ablation, external beam radiotherapy, embolization, and hepatic artery infusion therapy for management of LM. Additionally, for patients with advanced, symptomatic LM, local therapies may provide palliative benefit. The American Radium Society gastrointestinal expert panel, including members representing radiation oncology, interventional radiology, surgical oncology, and medical oncology, performed a systemic review and developed Appropriate Use Criteria for the use of nonsurgical local therapies for LM. Preferred Reporting Items for Systematic reviews and Meta-Analyses methodology was used. These studies were used to inform the expert panel, which then rated the appropriateness of various treatments in seven representative clinical scenarios through a well-established consensus methodology (modified Delphi). A summary of recommendations is outlined to guide practitioners on the use of nonsurgical local therapies for patients with LM.
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Affiliation(s)
| | - Navesh Sharma
- Department of Radiation Oncology, WellSpan Cancer Center, York, Pennsylvania, USA
| | - Christopher Anker
- Division of Radiation Oncology, University of Vermont Larner College of Medicine, Burlington, Vermont, USA
| | - J Eva Selfridge
- Department of Medical Oncology, University Hospitals Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Percy Lee
- Department of Radiation Oncology, City of Hope National Medical Center, Los Angeles, California, USA
| | - Salma Jabbour
- Department of Radiation Oncology, Rutgers Cancer Institute, New Brunswick, New Jersey, USA
| | - Vonetta Williams
- Department of Radiation Oncology, Memorial Sloan Kettering, New York, New York, USA
| | - David Liu
- Department of Radiology, University of British Columbia, Vancouver, Birth Columbia, Canada
| | - Timothy Kennedy
- Department of Surgery, Rutgers Cancer Institute, New Brunswick, New Jersey, USA
| | - Krishan R Jethwa
- Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Ed Kim
- Department of Radiation Oncology, University of Washington, Seattle, Washington, USA
| | - Rachit Kumar
- Department of Radiation Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Sibley Memorial Hospital, Washington, District of Columbia, USA
| | - William Small
- Department of Radiation Oncology, Loyola University Stritch School of Medicine, Maywood, Illinois, USA
| | - Leila Tchelebi
- Department of Radiation Oncology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
| | - Suzanne Russo
- Department of Radiation Oncology, University Hospitals Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
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Campana LG, Daud A, Lancellotti F, Arroyo JP, Davalos RV, Di Prata C, Gehl J. Pulsed Electric Fields in Oncology: A Snapshot of Current Clinical Practices and Research Directions from the 4th World Congress of Electroporation. Cancers (Basel) 2023; 15:3340. [PMID: 37444450 PMCID: PMC10340685 DOI: 10.3390/cancers15133340] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 05/29/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
The 4th World Congress of Electroporation (Copenhagen, 9-13 October 2022) provided a unique opportunity to convene leading experts in pulsed electric fields (PEF). PEF-based therapies harness electric fields to produce therapeutically useful effects on cancers and represent a valuable option for a variety of patients. As such, irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumour-treating fields (TTF) are on the rise. Still, their full therapeutic potential remains underappreciated, and the field faces fragmentation, as shown by parallel maturation and differences in the stages of development and regulatory approval worldwide. This narrative review provides a glimpse of PEF-based techniques, including key mechanisms, clinical indications, and advances in therapy; finally, it offers insights into current research directions. By highlighting a common ground, the authors aim to break silos, strengthen cross-functional collaboration, and pave the way to novel possibilities for intervention. Intriguingly, beyond their peculiar mechanism of action, PEF-based therapies share technical interconnections and multifaceted biological effects (e.g., vascular, immunological) worth exploiting in combinatorial strategies.
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Affiliation(s)
- Luca G. Campana
- Department of Surgery, Manchester University NHS Foundation Trust, Oxford Rd., Manchester M13 9WL, UK;
| | - Adil Daud
- Department of Medicine, University of California, 550 16 Street, San Francisco, CA 94158, USA;
| | - Francesco Lancellotti
- Department of Surgery, Manchester University NHS Foundation Trust, Oxford Rd., Manchester M13 9WL, UK;
| | - Julio P. Arroyo
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA; (J.P.A.); (R.V.D.)
| | - Rafael V. Davalos
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA; (J.P.A.); (R.V.D.)
- Institute for Critical Technology and Applied Sciences, Virginia Tech, Blacksburg, VA 24061, USA
| | - Claudia Di Prata
- Department of Surgery, San Martino Hospital, 32100 Belluno, Italy;
| | - Julie Gehl
- Department of Clinical Oncology and Palliative Care, Zealand University Hospital, 4000 Roskilde, Denmark;
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark
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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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Bakrania A, Joshi N, Zhao X, Zheng G, Bhat M. Artificial intelligence in liver cancers: Decoding the impact of machine learning models in clinical diagnosis of primary liver cancers and liver cancer metastases. Pharmacol Res 2023; 189:106706. [PMID: 36813095 DOI: 10.1016/j.phrs.2023.106706] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 02/17/2023] [Accepted: 02/19/2023] [Indexed: 02/22/2023]
Abstract
Liver cancers are the fourth leading cause of cancer-related mortality worldwide. In the past decade, breakthroughs in the field of artificial intelligence (AI) have inspired development of algorithms in the cancer setting. A growing body of recent studies have evaluated machine learning (ML) and deep learning (DL) algorithms for pre-screening, diagnosis and management of liver cancer patients through diagnostic image analysis, biomarker discovery and predicting personalized clinical outcomes. Despite the promise of these early AI tools, there is a significant need to explain the 'black box' of AI and work towards deployment to enable ultimate clinical translatability. Certain emerging fields such as RNA nanomedicine for targeted liver cancer therapy may also benefit from application of AI, specifically in nano-formulation research and development given that they are still largely reliant on lengthy trial-and-error experiments. In this paper, we put forward the current landscape of AI in liver cancers along with the challenges of AI in liver cancer diagnosis and management. Finally, we have discussed the future perspectives of AI application in liver cancer and how a multidisciplinary approach using AI in nanomedicine could accelerate the transition of personalized liver cancer medicine from bench side to the clinic.
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Affiliation(s)
- Anita Bakrania
- Toronto General Hospital Research Institute, Toronto, ON, Canada; Ajmera Transplant Program, University Health Network, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
| | | | - Xun Zhao
- Toronto General Hospital Research Institute, Toronto, ON, Canada; Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Gang Zheng
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
| | - Mamatha Bhat
- Toronto General Hospital Research Institute, Toronto, ON, Canada; Ajmera Transplant Program, University Health Network, Toronto, ON, Canada; Division of Gastroenterology, Department of Medicine, University Health Network and University of Toronto, Toronto, ON, Canada; Department of Medical Sciences, Toronto, ON, Canada.
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Tasu JP, Tougeron D, Rols MP. Irreversible electroporation and electrochemotherapy in oncology: State of the art. Diagn Interv Imaging 2022; 103:499-509. [PMID: 36266192 DOI: 10.1016/j.diii.2022.09.009] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 09/29/2022] [Accepted: 09/30/2022] [Indexed: 01/10/2023]
Abstract
Thermal tumor ablation techniques including radiofrequency, microwave, LASER, high-intensity focused ultrasound and cryoablation are routinely used to treated liver, kidney, bone, or lung tumors. However, all these techniques are thermal and can therefore be affected by heat sink effect, which can lead to incomplete ablation, and thermal injuries of non-targeted tissues are possible. Under certain conditions, high voltage pulsed electric field can induce formation of pores in the cell membrane. This phenomenon, called electropermeabilization, is also known as "electroporation". Under certain conditions, electroporation can be irreversible, leading to cell death. Irreversible electroporation has demonstrated efficacy for the treatment of liver and prostate cancers, whereas data are scarce regarding pancreatic and renal cancers. During reversible electroporation, transient cell permeability can be used to introduce cytotoxic drugs into tumor cells (commonly bleomycin or cisplatin). Reversible electroporation used in conjunction with cytotoxic drugs shows promise in terms of oncological response, particularly for solid cutaneous and subcutaneous tumors such as melanoma. Irreversible and reversible electroporation are both not thermal ablation techniques and therefore open a new promising horizon for tumor ablation.
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Affiliation(s)
- Jean-Pierre Tasu
- Department of Diagnosis and interventional radiology, University Hospital of Poitiers, 86021 Poitiers, France; LaTim, UBO and INSERM 1101, University of Brest, 29000 Brest, France.
| | - David Tougeron
- Department of Hepatogastroenterology, University Hospital of Poitiers, 86000 Poitiers, France
| | - Marie-Pierre Rols
- Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, 31000 Toulouse, France
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Xu M, Xie LT, Xiao YY, Liang P, Zhao QY, Wang ZM, Chai WL, Wei YT, Xu LF, Hu XK, Kuang M, Niu LZ, Yao CG, Kong HY, Tian G, Xie XY, Cui XW, Xu D, Zhao J, Jiang TA. Chinese clinical practice guidelines for ultrasound-guided irreversible electroporation of liver cancer (version 2022). Hepatobiliary Pancreat Dis Int 2022; 21:462-471. [PMID: 36058782 DOI: 10.1016/j.hbpd.2022.08.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 08/05/2022] [Indexed: 02/05/2023]
Affiliation(s)
- Min Xu
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, Zhejiang 310003, China
| | - Li-Ting Xie
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, Zhejiang 310003, China
| | - Yue-Yong Xiao
- Department of Radiology, The First Medical Center, Chinese PLA General Hospital, Beijing 100000, China
| | - Ping Liang
- Department of Radiology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Qi-Yu Zhao
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, Zhejiang 310003, China
| | - Zhong-Min Wang
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Wei-Lu Chai
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, Zhejiang 310003, China
| | - Ying-Tian Wei
- Department of Radiology, The First Medical Center, Chinese PLA General Hospital, Beijing 100000, China
| | - Lin-Feng Xu
- Department of Interventional Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Xiao-Kun Hu
- Department of the Interventional Medical Center, the Affiliated Hospital of Qingdao University, Qingdao 266000, China
| | - Ming Kuang
- Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
| | - Li-Zhi Niu
- Department of Oncology, Affiliated Fuda Cancer Hospital, Jinan University, Guangzhou 510665, China
| | - Chen-Guo Yao
- School of Electrical Engineering, Chongqing University, Chongqing 400033, China
| | - Hai-Ying Kong
- Department of Anesthesiology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Guo Tian
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, Zhejiang 310003, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
| | - Xin-Wu Cui
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Dong Xu
- Department of Interventional Ultrasound, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China
| | - Jun Zhao
- Department of Anatomy, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Tian-An Jiang
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, Zhejiang 310003, China.
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10
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Koethe Y, Wilson N, Narayanan G. Irreversible electroporation for colorectal cancer liver metastasis: a review. Int J Hyperthermia 2022; 39:682-687. [PMID: 35469520 DOI: 10.1080/02656736.2021.2008025] [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: 10/18/2022] Open
Abstract
Irreversible electroporation (IRE) ablation is gaining popularity over the last decade as a nonthermal alternative to thermal ablation technologies such as radiofrequency ablation (RFA) and Microwave ablation (MWA). This review serves as a practical guide for applying IRE to colorectal cancer liver metastases (CRLM) for interventional radiologists, oncologists, surgeons, and anesthesiologists. It covers patient selection, procedural technique, anesthesia, imaging, and outcomes.
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Affiliation(s)
- Yilun Koethe
- Department of Interventional Radiology, Oregon Health and Science University, Portland, OR, USA
| | - Nicole Wilson
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Govindarajan Narayanan
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.,Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA.,Miami Cardiac and Vascular, Baptist Health South Florida, Miami, FL, USA
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11
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Thompson SM, Welch BT, Kurup AN. Ablation for oligometastatic colorectal carcinoma in extrahepatic, extrapulmonary sites. Int J Hyperthermia 2022; 39:633-638. [DOI: 10.1080/02656736.2021.1952318] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Affiliation(s)
| | - Brian T. Welch
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - A. Nick Kurup
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
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Lorenzo MF, Campelo SN, Arroyo JP, Aycock KN, Hinckley J, Arena CB, Rossmeisl JH, Davalos RV. An Investigation for Large Volume, Focal Blood-Brain Barrier Disruption with High-Frequency Pulsed Electric Fields. Pharmaceuticals (Basel) 2021; 14:1333. [PMID: 34959733 PMCID: PMC8715747 DOI: 10.3390/ph14121333] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/13/2021] [Accepted: 12/15/2021] [Indexed: 01/28/2023] Open
Abstract
The treatment of CNS disorders suffers from the inability to deliver large therapeutic agents to the brain parenchyma due to protection from the blood-brain barrier (BBB). Herein, we investigated high-frequency pulsed electric field (HF-PEF) therapy of various pulse widths and interphase delays for BBB disruption while selectively minimizing cell ablation. Eighteen male Fisher rats underwent craniectomy procedures and two blunt-tipped electrodes were advanced into the brain for pulsing. BBB disruption was verified with contrast T1W MRI and pathologically with Evans blue dye. High-frequency irreversible electroporation cell death of healthy rodent astrocytes was investigated in vitro using a collagen hydrogel tissue mimic. Numerical analysis was conducted to determine the electric fields in which BBB disruption and cell ablation occur. Differences between the BBB disruption and ablation thresholds for each waveform are as follows: 2-2-2 μs (1028 V/cm), 5-2-5 μs (721 V/cm), 10-1-10 μs (547 V/cm), 2-5-2 μs (1043 V/cm), and 5-5-5 μs (751 V/cm). These data suggest that HF-PEFs can be fine-tuned to modulate the extent of cell death while maximizing peri-ablative BBB disruption. Furthermore, numerical modeling elucidated the diffuse field gradients of a single-needle grounding pad configuration to favor large-volume BBB disruption, while the monopolar probe configuration is more amenable to ablation and reversible electroporation effects.
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Affiliation(s)
- Melvin F. Lorenzo
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA; (S.N.C.); (J.P.A.); (K.N.A.); (C.B.A.); (R.V.D.)
| | - Sabrina N. Campelo
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA; (S.N.C.); (J.P.A.); (K.N.A.); (C.B.A.); (R.V.D.)
| | - Julio P. Arroyo
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA; (S.N.C.); (J.P.A.); (K.N.A.); (C.B.A.); (R.V.D.)
| | - Kenneth N. Aycock
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA; (S.N.C.); (J.P.A.); (K.N.A.); (C.B.A.); (R.V.D.)
| | - Jonathan Hinckley
- Department of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA 24061, USA; (J.H.); (J.H.R.J.)
| | - Christopher B. Arena
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA; (S.N.C.); (J.P.A.); (K.N.A.); (C.B.A.); (R.V.D.)
| | - John H. Rossmeisl
- Department of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA 24061, USA; (J.H.); (J.H.R.J.)
| | - Rafael V. Davalos
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA; (S.N.C.); (J.P.A.); (K.N.A.); (C.B.A.); (R.V.D.)
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13
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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: 8] [Impact Index Per Article: 2.0] [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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14
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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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15
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Tian G, Guan J, Chu Y, Zhao Q, Jiang T. Immunomodulatory Effect of Irreversible Electroporation Alone and Its Cooperating With Immunotherapy in Pancreatic Cancer. Front Oncol 2021; 11:712042. [PMID: 34568040 PMCID: PMC8462269 DOI: 10.3389/fonc.2021.712042] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 08/19/2021] [Indexed: 01/05/2023] Open
Abstract
Emerging studies have showed irreversible electroporation (IRE) focused on pancreatic cancer (PC). However, the effects of IRE treatment on the immune response of PC remain unknown. Moreover, there are few studies on the therapeutic effect of IRE combining with immunotherapy on PC. Thus, we review recent advances in our understanding of IRE alone and its working with immunotherapy towards the immune response of PC, discussing potential opportunities for exploring future treatment strategies.
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Affiliation(s)
- Guo Tian
- Department of Ultrasound Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Department of Biomedicine, Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, China
| | - Jiajia Guan
- Department of Ultrasound Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yanhua Chu
- Department of Ultrasound Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qiyu Zhao
- Department of Ultrasound Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Department of Biomedicine, Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, China
| | - Tian'an Jiang
- Department of Ultrasound Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Department of Biomedicine, Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, China
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16
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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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Lin YM, Paolucci I, Brock KK, Odisio BC. Image-Guided Ablation for Colorectal Liver Metastasis: Principles, Current Evidence, and the Path Forward. Cancers (Basel) 2021; 13:3926. [PMID: 34439081 PMCID: PMC8394430 DOI: 10.3390/cancers13163926] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 07/30/2021] [Accepted: 08/02/2021] [Indexed: 02/07/2023] Open
Abstract
Image-guided ablation can provide effective local tumor control in selected patients with CLM. A randomized controlled trial suggested that radiofrequency ablation combined with systemic chemotherapy resulted in a survival benefit for patients with unresectable CLM, compared to systemic chemotherapy alone. For small tumors, ablation with adequate margins can be considered as an alternative to resection. The improvement of ablation technologies can allow the treatment of tumors close to major vascular structures or bile ducts, on which the applicability of thermal ablation modalities is challenging. Several factors affect the outcomes of ablation, including but not limited to tumor size, number, location, minimal ablation margin, RAS mutation status, prior hepatectomy, and extrahepatic disease. Further understanding of the impact of tumor biology and advanced imaging guidance on overall patient outcomes might help to tailor its application, and improve outcomes of image-guided ablation.
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Affiliation(s)
- Yuan-Mao Lin
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (Y.-M.L.); (I.P.)
| | - Iwan Paolucci
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (Y.-M.L.); (I.P.)
| | - Kristy K. Brock
- Department of Imaging Physics, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Bruno C. Odisio
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (Y.-M.L.); (I.P.)
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18
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Abstract
Liver metastases are commonly detected in a range of malignancies including colorectal cancer (CRC), pancreatic cancer, melanoma, lung cancer and breast cancer, although CRC is the most common primary cancer that metastasizes to the liver. Interactions between tumour cells and the tumour microenvironment play an important part in the engraftment, survival and progression of the metastases. Various cells including liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, parenchymal hepatocytes, dendritic cells, resident natural killer cells as well as other immune cells such as monocytes, macrophages and neutrophils are implicated in promoting and sustaining metastases in the liver. Four key phases (microvascular, pre-angiogenic, angiogenic and growth phases) have been identified in the process of liver metastasis. Imaging modalities such as ultrasonography, CT, MRI and PET scans are typically used for the diagnosis of liver metastases. Surgical resection remains the main potentially curative treatment among patients with resectable liver metastases. The role of liver transplantation in the management of liver metastasis remains controversial. Systemic therapies, newer biologic agents (for example, bevacizumab and cetuximab) and immunotherapeutic agents have revolutionized the treatment options for liver metastases. Moving forward, incorporation of genetic tests can provide more accurate information to guide clinical decision-making and predict prognosis among patients with liver metastases.
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19
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Bäumler W, Schicho A, Schaible J, Verloh N, Senk K, Wiggermann P, Stroszczynski C, Beyer LP. Changes in gadoxetic-acid-enhanced MR imaging during the first year after irreversible electroporation of malignant hepatic tumors. PLoS One 2020; 15:e0242093. [PMID: 33201902 PMCID: PMC7671553 DOI: 10.1371/journal.pone.0242093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 10/27/2020] [Indexed: 11/19/2022] Open
Abstract
PURPOSE To evaluate the appearance and size of ablation zones in gadoxetic-acid-enhanced magnetic resonance imaging (MRI) during the first year after irreversible electroporation (IRE) of primary or secondary hepatic malignancies and to investigate potential correlations to clinical features. MATERIAL AND METHODS The MRI-appearance of the ablation area was assessed 1-3 days, 6 weeks, 3 months, 6 months, 9 months and 1 year after IRE. The size of the ablation zone and signal intensities of each follow-up control were compared. Moreover, relationships between clinical features and the MRI-appearance of the ablation area 1-3 days after IRE were analyzed. RESULTS The ablation zone size decreased from 5.6 ± 1.4 cm (1-3 days) to 3.7±1.2 cm (1 year). A significant decrease of central hypointensities was observed in T2-blade- (3 months), T2 haste- (6 weeks; 3 months; 6 months; 1 year), T1 arterial phase- (3 months; 1 year), and diffusion-sequences (6 weeks; 3 months; 6 months; 9 months; 1 year). The unenhanced T1-sequences showed significantly increasing central hypointensities (6 weeks; 3 months; 6 months; 9 months; 1 year). Significantly increasing peripheral hypointensities were detected in T1 arterial phase- (3 months; 6 months; 9 months; 1 year) and in T1 portal venous phase-sequences (6 weeks; 3 months; 6 months; 9 months; 1 year). Peripheral hypointensities of unenhanced T1-sequences decreased significantly 1 year after IRE. 1-3 days after IRE central T1 portal venous hypo- or isointensities were detected significantly more often than hyperintensities, if more than 3 IRE electrodes were used. CONCLUSION Hepatic IRE results in continuous reduction of ablation zone size during the first postinterventional year. In addition to centrally decreasing T1-signal and almost steadily increasing signal in the enhanced T2 haste-, diffusion- and T1 arterial phase-sequences, there is a trend toward long-term decreasing T1 arterial- and portal venous MRI-signal intensity of the peripheral ablation area, probably representing a region of reversible electroporation.
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Affiliation(s)
- Wolf Bäumler
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
- * E-mail:
| | - Andreas Schicho
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
| | - Jan Schaible
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
| | - Niklas Verloh
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
| | - Karin Senk
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
| | - Phillip Wiggermann
- Department of Radiology and Nuclear Medicine, Hospital Braunschweig, Braunschweig, Germany
| | | | - Lukas Phillip Beyer
- Department of Diagnostic and Interventional Radiology, Ernst von Bergmann Hospital, Potsdam, Germany
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20
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O'Neill CH, Martin RCG. Cardiac synchronization and arrhythmia during irreversible electroporation. J Surg Oncol 2020; 122:407-411. [PMID: 32483842 DOI: 10.1002/jso.26041] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 05/17/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND OBJECTIVES Irreversible electroporation (IRE) is a nonthermal electrical tumor ablative strategy for unresectable tumors. IRE is relatively safe around critical structures but may induce cardiac arrhythmia when its delivery is not synchronized to the cardiac cycle. We performed a systematic literature review to determine rates of arrhythmia when IRE was utilized with or without cardiac synchronization. METHODS An online literature search was conducted with additional hand selection of articles. Data were extracted and pooled analyses were performed. RESULTS Twelve articles were included in analysis. IRE was performed for 481 patients; 46% hepatic tumors (n = 223), 36% pancreatic lesions (n = 168), and multiple other locations including prostate. Synchronization was performed on 422 patients. Arrhythmias were noted in 3.7% of cases (n = 18/481); cardiac synchronization: 1.2% (n = 5/422) vs unsynchronized: 22.0% (n = 13/59), P < .0001. These events occurred in every organ except the prostate. CONCLUSIONS IRE remains a potent technology for unresectable tumors, but arrhythmia is a clinical concern. This literature review confirms that cardiac gating should be used in all cases outside of prostate to prevent this potentially serious adverse event.
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Affiliation(s)
- Conor H O'Neill
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky
| | - Robert C G Martin
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky
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21
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Geboers B, Scheffer HJ, Graybill PM, Ruarus AH, Nieuwenhuizen S, Puijk RS, van den Tol PM, Davalos RV, Rubinsky B, de Gruijl TD, Miklavčič D, Meijerink MR. High-Voltage Electrical Pulses in Oncology: Irreversible Electroporation, Electrochemotherapy, Gene Electrotransfer, Electrofusion, and Electroimmunotherapy. Radiology 2020; 295:254-272. [PMID: 32208094 DOI: 10.1148/radiol.2020192190] [Citation(s) in RCA: 197] [Impact Index Per Article: 39.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
This review summarizes the use of high-voltage electrical pulses (HVEPs) in clinical oncology to treat solid tumors with irreversible electroporation (IRE) and electrochemotherapy (ECT). HVEPs increase the membrane permeability of cells, a phenomenon known as electroporation. Unlike alternative ablative therapies, electroporation does not affect the structural integrity of surrounding tissue, thereby enabling tumors in the vicinity of vital structures to be treated. IRE uses HVEPs to cause cell death by inducing membrane disruption, and it is primarily used as a radical ablative therapy in the treatment of soft-tissue tumors in the liver, kidney, prostate, and pancreas. ECT uses HVEPs to transiently increase membrane permeability, enhancing cellular cytotoxic drug uptake in tumors. IRE and ECT show immunogenic effects that could be augmented when combined with immunomodulatory drugs, a combination therapy the authors term electroimmunotherapy. Additional electroporation-based technologies that may reach clinical importance, such as gene electrotransfer, electrofusion, and electroimmunotherapy, are concisely reviewed. HVEPs represent a substantial advancement in cancer research, and continued improvement and implementation of these presented technologies will require close collaboration between engineers, interventional radiologists, medical oncologists, and immuno-oncologists.
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Affiliation(s)
- Bart Geboers
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Hester J Scheffer
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Philip M Graybill
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Alette H Ruarus
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Sanne Nieuwenhuizen
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Robbert S Puijk
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Petrousjka M van den Tol
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Rafael V Davalos
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Boris Rubinsky
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Tanja D de Gruijl
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Damijan Miklavčič
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Martijn R Meijerink
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
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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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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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Chow FCL, Chok KSH. Colorectal liver metastases: An update on multidisciplinary approach. World J Hepatol 2019; 11:150-172. [PMID: 30820266 PMCID: PMC6393711 DOI: 10.4254/wjh.v11.i2.150] [Citation(s) in RCA: 142] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 11/24/2018] [Accepted: 12/04/2018] [Indexed: 02/06/2023] Open
Abstract
Liver metastasis is the commonest form of distant metastasis in colorectal cancer. Selection criteria for surgery and liver-directed therapies have recently been extended. However, resectability remains poorly defined. Tumour biology is increasingly recognized as an important prognostic factor; hence molecular profiling has a growing role in risk stratification and management planning. Surgical resection is the only treatment modality for curative intent. The most appropriate surgical approach is yet to be established. The primary cancer and the hepatic metastasis can be removed simultaneously or in a two-step approach; these two strategies have comparable long-term outcomes. For patients with a limited future liver remnant, portal vein embolization, combined ablation and resection, and associating liver partition and portal vein ligation for staged hepatectomy have been advocated, and each has their pros and cons. The role of neoadjuvant and adjuvant chemotherapy is still debated. Targeted biological agents and loco-regional therapies (thermal ablation, intra-arterial chemo- or radio-embolization, and stereotactic radiotherapy) further improve the already favourable results. The recent debate about offering liver transplantation to highly selected patients needs validation from large clinical trials. Evidence-based protocols are missing, and therefore optimal management of hepatic metastasis should be personalized and determined by a multi-disciplinary team.
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Affiliation(s)
| | - Kenneth Siu-Ho Chok
- Department of Surgery and State Key Laboratory for Liver Research, the University of Hong Kong, Hong Kong, China.
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25
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Initial experience with irreversible electroporation of liver tumours. Eur J Radiol Open 2019; 6:62-67. [PMID: 30723754 PMCID: PMC6351588 DOI: 10.1016/j.ejro.2019.01.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Revised: 01/14/2019] [Accepted: 01/17/2019] [Indexed: 12/18/2022] Open
Abstract
Introduction Thermal ablation of liver tumours is an established technique used in selected patients with relatively small tumours that can be ablated with margin. Thermal ablation methods are not advisable near larger bile ducts that are sensitive to thermal injury causing strictures and severe morbidity. Irreversible electroporation (IRE) has the possibility to treat these tumours without harming the bile tree. The method is relatively new and has been proven to be feasible and safe with promising oncological results. Methods 50 treatments were performed on 42 patients that were not resectable or treatable by thermal ablation (12 women and 30 men) with 59 tumours in total. 51% were colorectal cancer liver metastases (CRCLM) and 34% were hepatocellular carcinomas (HCC). 70% of the treatments were performed using stereotactic CT-guidance for needle placement. Results 81% of the treatments were performed with initial success. All patients with missed ablations were re-treated. Local recurrence rate at 3 months was 3% and 37% at one year. The complication rate was low with 2 patients having major complications (Clavien-Dindo grade 3b-5) and without 30-day mortality. Conclusion IRE is safe for treating tumours not suitable for thermal ablation with 63% of patients being without local recurrence after one year in a group of patients with tumours deemed unresectable. IRE has a role in the treatment of unresectable liver tumours close to heat-sensitive structures not suitable for thermal ablation. Level of Evidence: Level 4, Case Series.
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Schicho A, Niessen C, Haimerl M, Wiesinger I, Stroszczynski C, Beyer LP, Wiggermann P. Long-term survival after percutaneous irreversible electroporation of inoperable colorectal liver metastases. Cancer Manag Res 2018; 11:317-322. [PMID: 30643457 PMCID: PMC6312065 DOI: 10.2147/cmar.s182091] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Background For colorectal liver metastases (CRLM) that are not amenable to surgery or thermal ablation, irreversible electroporation (IRE) is a novel local treatment modality and additional option. Methods This study is a retrospective long-term follow-up of patients with CRLM who underwent IRE as salvage treatment. Results Of the 24 included patients, 18 (75.0%) were male, and the median age was 57 (range: 28-75) years. The mean time elapsed from diagnosis to IRE was 37.9±37.3 months. Mean overall survival was 26.5 months after IRE (range: 2.5-69.2 months) and 58.1 months after diagnosis (range: 14.8-180.1 months). One-, three-, and five-year survival rates after initial diagnosis were 100.0%, 79.2%, and 41.2%; after IRE, the respective survival rates were 79.1%, 25.0%, and 8.3%. There were no statistically significant differences detected in survival after IRE with respect to gender, age, T- or N-stage at the time of diagnosis, size of metastases subject to IRE, number of hepatic lesions, or time elapsed between IRE and diagnosis. Conclusion For nonresectable CRLM, long-term survival data emphasize the value of IRE as a new minimally invasive local therapeutic approach in multimodal palliative treatment, which is currently limited to systemic or regional therapies in this setting.
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Affiliation(s)
- Andreas Schicho
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany,
| | - Christoph Niessen
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany,
| | - Michael Haimerl
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany,
| | - Isabel Wiesinger
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany,
| | | | - Lukas P Beyer
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany,
| | - Philipp Wiggermann
- Department of Radiology and Nuclear Medicine, Klinikum Braunschweig, Braunschweig, Germany
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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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Alnaggar M, Qaid AM, Chen J, Niu L, Xu K. Irreversible electroporation of malignant liver tumors: Effect on laboratory values. Oncol Lett 2018; 16:3881-3888. [PMID: 30128002 PMCID: PMC6096204 DOI: 10.3892/ol.2018.9058] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 04/25/2018] [Indexed: 12/18/2022] Open
Abstract
Liver cancer is often associated with chronic liver diseases. Treatment with percutaneous irreversible electroporation (IRE) may preserve liver function. In the present study, the clinical data of 29 patients with liver tumors between July 2015 and December 2016, all of whom underwent liver IRE at Fuda Cancer Hospital, Guangzhou, China was retrospectively reviewed. All the patients survived the treatment. Of the 29 patients, 7 were positive for hepatitis B, 15 had hepatocellular carcinoma (HCC) and 7 had pancreatic cancer with liver metastases. All patients survived IRE. Despite liver-protective treatment prior to IRE, the mean alanine transaminase (ALT) and aspartate transaminase (AST) levels were significantly elevated 1-2 days after IRE, to 540 and 712 U/l, respectively; however they had returned to the preoperative values by 2 weeks following IRE. Prior to IRE, the mean total bilirubin and direct bilirubin measurement levels were normal; however, 8-10 days after IRE, they had increased to 24 U/l and 12 µmol/l, respectively, and had returned back to the preoperative levels by 2 weeks after IRE. This first group included all patients. The result of the 4 subgroups of cancer patients demonstrated a variation between different measurement days and recovery with patients positive for the hepatitis B virus taking the longest duration to recover (17±3 days) meanwhile patients with pancreatic cancer with liver metastases took the shortest time to achieve recovery (10.78±2 days). The findings of the present study indicate that hepatic injury caused by IRE is transient and self-limiting in patients with liver tumors.
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Affiliation(s)
- Mohammed Alnaggar
- Biomedical Translational Research Institute and The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510632, P.R. China
- Department of Oncology, Guangzhou Fuda Cancer Hospital, School of Medicine, Jinan University, Guangzhou, Guangdong 510665, P.R. China
| | - Ammar M. Qaid
- Department of Oncology, Affiliated Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
| | - Jibing Chen
- Department of Oncology, Guangzhou Fuda Cancer Hospital, School of Medicine, Jinan University, Guangzhou, Guangdong 510665, P.R. China
| | - Lizhi Niu
- Department of Oncology, Guangzhou Fuda Cancer Hospital, School of Medicine, Jinan University, Guangzhou, Guangdong 510665, P.R. China
- Correspondence to: Dr Lizhi Niu, Department of Oncology, Guangzhou Fuda Cancer Hospital, School of Medicine, Jinan University, 2 Tangdexi Road, Guangzhou, Guangdong 510665, P.R. China, E-mail:
| | - Kecheng Xu
- Department of Oncology, Guangzhou Fuda Cancer Hospital, School of Medicine, Jinan University, Guangzhou, Guangdong 510665, P.R. China
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Conductivity Rise During Irreversible Electroporation: True Permeabilization or Heat? Cardiovasc Intervent Radiol 2018; 41:1257-1266. [PMID: 29687261 PMCID: PMC6021471 DOI: 10.1007/s00270-018-1971-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Accepted: 04/18/2018] [Indexed: 12/18/2022]
Abstract
Purpose Irreversible electroporation (IRE) induces apoptosis with high-voltage electric pulses. Although the working mechanism is non-thermal, development of secondary Joule heating occurs. This study investigated whether the observed conductivity rise during IRE is caused by increased cellular permeabilization or heat development. Methods IRE was performed in a gelatin tissue phantom, in potato tubers, and in 30 patients with unresectable colorectal liver metastases (CRLM). Continuous versus sequential pulsing protocols (10-90 vs. 10-30-30-30) were assessed. Temperature was measured using fiber-optic probes. After temperature had returned to baseline, 100 additional pulses were delivered. The primary technique efficacy of the treated CRLM was compared to the periprocedural current rise. Seven patients received ten additional pulses after a 10-min cool-down period. Results Temperature and current rise was higher for the continuous pulsing protocol (medians, gel: 13.05 vs. 9.55 °C and 9 amperes (A) vs. 7A; potato: 12.70 vs. 10.53 °C and 6.0A vs. 6.5A). After cooling-down, current returned to baseline in the gel phantom and near baseline values (Δ2A with continuous- and Δ5A with sequential pulsing) in the potato tubers. The current declined after cooling-down in all seven patients with CRLM, although baseline values were not reached. There was a positive correlation between current rise and primary technique efficacy (p = 0.02); however, the previously reported current increase threshold of 12–15A was reached in 13%. Conclusion The observed conductivity rise during IRE is caused by both cellular permeabilization and heat development. Although a correlation between current rise and efficacy exists, the current increase threshold seems unfeasible for CRLM. Electronic supplementary material The online version of this article (10.1007/s00270-018-1971-7) contains supplementary material, which is available to authorized users.
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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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Cohen EI, Field D, Lynskey GE, Kim AY. Technology of irreversible electroporation and review of its clinical data on liver cancers. Expert Rev Med Devices 2018; 15:99-106. [PMID: 29307242 DOI: 10.1080/17434440.2018.1425612] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Irreversible electroporation (IRE) has developed as a novel percutaneous ablative technique over the past decade and its utility in the treatment of primary and metastatic liver disease has progressed rapidly. AREAS COVERED After discussing the principles behind the technology and the practical steps in its use, this article offers a detailed analysis of the recent published work that evaluates its safety and efficacy. The strengths and weaknesses of other ablative techniques, including radiofrequency ablation, microwave ablation and cryoablation, are discussed in detail. Other aspects of IRE, including post-treatment clinical follow-up, expected imaging findings, and the most frequently encountered complications, are covered. Finally, the future of IRE is examined as it pertains to advancements in the treatment of hepatic malignancy. EXPERT COMMENTARY The characteristics of IRE that make this technology uniquely suited for the treatment of liver tumors have allowed it to gain a significant foothold in interventional oncology. Continued development of IRE will lead to further advances in the management of previously untreatable liver cancers.
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Affiliation(s)
- Emil I Cohen
- a Division of Interventional Radiology, Department of Radiology , Medstar Georgetown University Hospital , Washington , DC , USA
| | - David Field
- a Division of Interventional Radiology, Department of Radiology , Medstar Georgetown University Hospital , Washington , DC , USA
| | - George Emmett Lynskey
- a Division of Interventional Radiology, Department of Radiology , Medstar Georgetown University Hospital , Washington , DC , USA
| | - Alexander Y Kim
- a Division of Interventional Radiology, Department of Radiology , Medstar Georgetown University Hospital , Washington , DC , USA
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Langan RC, Goldman DA, D'Angelica MI, DeMatteo RP, Allen PJ, Balachandran VP, Jarnagin WR, Kingham TP. Recurrence patterns following irreversible electroporation for hepatic malignancies. J Surg Oncol 2017; 115:704-710. [PMID: 28493544 DOI: 10.1002/jso.24570] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Accepted: 01/05/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Irreversible electroporation (IRE) has emerged as a novel, safe ablative therapy for peri-vascular lesions. However, there remains a paucity of data on long-term outcomes. METHODS We identified patients who underwent open IRE (1/2011-6/2015) for primary and secondary hepatic malignancies. Local ablation-zone recurrence (LR) was determined by cross-sectional imaging. Cumulative incidence (CumI) of LR was calculated and a competing risks regression assessed factors associated with LR. RESULTS Forty patients had 77 lesions treated. The majority of lesions were of colorectal origin (74%). Median tumor size was 1.3 cm (range 0.5-6). Most patients (86%) had prior systemic therapy and 29% received systemic therapy following IRE. With a median follow-up of 25.7 months (range 4.5-58.8 months), 10 lesions in 9 patients recurred locally (CumI: 13.4%, 95%CI: 7.8-22.2%). Median estimated time to LR was not reached and no LR occurred after 19 months. Factors significantly associated with LR included ablation zone size (HR 1.58; 95%CI 1.12-2.23; P = 0.0093) and body mass index (HR 1.21 95%CI 1.10-1.34; P = 0.0001). CONCLUSION IRE LR rates were low after the treatment of well selected, small tumors. This technique is useful for lesions in anatomic locations precluding resection or thermal ablation.
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Affiliation(s)
- Russell C Langan
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Debra A Goldman
- Department of Epidemiology and Biostatistics, Biostatistics Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Michael I D'Angelica
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Ronald P DeMatteo
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Peter J Allen
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Vinod P Balachandran
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - William R Jarnagin
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - T Peter Kingham
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, New York
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Lyu T, Wang X, Su Z, Shangguan J, Sun C, Figini M, Wang J, Yaghmai V, Larson AC, Zhang Z. Irreversible electroporation in primary and metastatic hepatic malignancies: A review. Medicine (Baltimore) 2017; 96:e6386. [PMID: 28445252 PMCID: PMC5413217 DOI: 10.1097/md.0000000000006386] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Liver cancer makes up a huge percentage of cancer mortality worldwide. Irreversible electroporation (IRE) is a relatively new minimally invasive nonthermal ablation technique for tumors that applies short pulses of high frequency electrical energy to irreversibly destabilize cell membrane to induce tumor cell apoptosis. METHODS This review aims to investigate the studies regarding the use of IRE treatment in liver tumors and metastases to liver. We searched PubMed for all of IRE relevant English language articles published up to September 2016. They included clinical trials, experimental studies, observational studies, and reviews. This review manuscript is nothing with ethics issues and ethical approval is not provided. RESULTS In recent years, increasingly more studies in both preclinical and clinical settings have been conducted to examine the safety and efficacy of this new technique, shedding light on the crucial advantages and disadvantages that IRE possesses. Unlike the current leading thermal ablation techniques, such as radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation, IRE requires shorter ablation time without damaging adjacent important vital structures. CONCLUSION Although IRE has successfully claimed its valuable status in the field of hepatic cancer treatment both preclinical and clinical settings. In order to systemically test and establish its safety and efficacy for clinical applications, more studies still need to be conducted.
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Affiliation(s)
- Tianchu Lyu
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Xifu Wang
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Zhanliang Su
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Junjie Shangguan
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Chong Sun
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Matteo Figini
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Jian Wang
- Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Vahid Yaghmai
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA
| | - Andrew C. Larson
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA
| | - Zhuoli Zhang
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Tianjin, China
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Petre EN, Sofocleous C. Thermal Ablation in the Management of Colorectal Cancer Patients with Oligometastatic Liver Disease. Visc Med 2017; 33:62-68. [PMID: 28612019 DOI: 10.1159/000454697] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Surgical resection of limited colorectal liver disease improves long-term survival and can be curative in a subset of selected cases. Image-guided percutaneous ablation therapies have emerged as safe and effective alternative options for selected patients with unresectable colorectal liver metastases (CLM) that can be ablated with margins. Ablation causes focal destruction of tissue and has increasingly been shown to provide durable eradication of tumors. METHODS A selective review of literature was conducted in PubMed, focusing on recent studies reporting on the safety, efficacy, and long-term outcomes of percutaneous ablation modalities in the treatment of CLM. The present work gives an overview of the different ablation techniques, their current clinical indications, and reported outcomes from most recently published studies. The 'test of time' concept for using ablation as a first local therapy is also described. RESULTS There are several thermal ablative tools currently available, including radiofrequency ablation (RFA), microwave ablation, and cryoablation. Most data to date originated from the application of RFA. Adjuvant thermal ablation in the treatment of oligometastatic colon cancer liver disease offers improved oncologic outcomes. The ideal CLM amenable to percutaneous ablation is a solitary tumor with the largest diameter up to 3 cm that can be completely ablated with a sufficient margin. 5-year overall survival rates up to 70% after ablation of unresectable CLM have been reported. Pathologic confirmation of complete tumor necrosis with margins over 5 mm provides best long-term local tumor control by thermal ablation. CONCLUSION Current evidence suggests that percutaneous ablation as adjuvant to chemotherapy improves oncologic outcomes of patients with CLM. For small tumors that can be ablated completely with clear margins, percutaneous ablation may offer outcomes similar to those of surgery.
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Affiliation(s)
- Elena Nadia Petre
- Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Constantinos Sofocleous
- Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Wong J, Cooper A. Local Ablation for Solid Tumor Liver Metastases: Techniques and Treatment Efficacy. Cancer Control 2016; 23:30-5. [PMID: 27009454 DOI: 10.1177/107327481602300106] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Treatment options for liver metastases from solid tumors, such as colon cancer, breast cancer, neuroendocrine tumors, and sarcomas, have expanded in recent years and now include nonresection methods. METHODS The literature focused on the treatment of liver metastases was reviewed for technique, perioperative, and long-term outcomes specifically related to local ablation techniques for liver metastases. RESULTS Ablation modalities have become popular as therapies for patients who are not appropriate candidates for surgical resection. Use of these techniques, alone or in combination with other liver-directed therapies (and often systemic therapy), has extended the rate of survival for patients with liver metastases and, at times, offers nearly equivalent disease-free survival rates to surgical resection. CONCLUSIONS Although surgical resection remains the optimal treatment for liver metastasis, local options, including microwave ablation and radiofrequency ablation, can offer similar long-term local control in appropriately selected patients.
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Affiliation(s)
- Joyce Wong
- Department of Surgical Oncology, Penn State Hershey Medical Center, Hershey, PA 17033, USA.
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Vollherbst D, Bertheau RC, Fritz S, Mogler C, Kauczor HU, Ryschich E, Radeleff BA, Pereira PL, Sommer CM. Electrochemical Effects after Transarterial Chemoembolization in Combination with Percutaneous Irreversible Electroporation: Observations in an Acute Porcine Liver Model. J Vasc Interv Radiol 2016; 27:913-921.e2. [PMID: 27103147 DOI: 10.1016/j.jvir.2016.02.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Revised: 01/30/2016] [Accepted: 02/01/2016] [Indexed: 12/18/2022] Open
Abstract
PURPOSE To evaluate the effects of combined use of transarterial chemoembolization and irreversible electroporation (IRE) for focal tissue ablation in an acute porcine liver model. MATERIALS AND METHODS Two established interventional techniques were combined: IRE with zones of irreversible and reversible electroporation and chemoembolization with microspheres, iodized oil, and doxorubicin. IRE was performed before chemoembolization in two pigs (pigs 1 and 2; IRE/chemoembolization group), chemoembolization was performed before IRE in two pigs (pigs 3 and 4; chemoembolization/IRE group), and only IRE was performed in two pigs (pigs 5 and 6). Five study groups were defined: IRE/chemoembolization (pigs 1 and 2), chemoembolization/IRE (pigs 3 and 4), IRE only (pigs 5 and 6), chemoembolization only (tissue outside the IRE zones in pigs 1-4), and control (untreated liver tissue outside the IRE zones in pigs 5 and 6). Animals were euthanized 2 hours after intervention. Size and shape of IRE zones on contrast-enhanced computed tomography, cell death on light microscopy, and doxorubicin tissue concentrations on chromatography and fluorescence microscopy were analyzed. RESULTS Size and shape of IRE zones were not significantly different (eg, P = .067 for volume). A histologic marker for irreversible cell death was positive in IRE/chemoembolization, chemoembolization/IRE, and IRE groups only in the macroscopically visible IRE zones. Doxorubicin tissue concentrations were not significantly different (P = .873). However, in the reversible electroporation (RE) zones, broad areas with intense intranuclear doxorubicin accumulation were observed in IRE/chemoembolization but not in chemoembolization/IRE and chemoembolization groups. CONCLUSIONS IRE before chemoembolization enhances the intranuclear accumulation of doxorubicin in the RE zone.
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Affiliation(s)
- Dominik Vollherbst
- Clinic for Diagnostic and Interventional Radiology, Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany; Clinic for Radiology, Minimally-Invasive Therapies and Nuclear Medicine, Cancer Center Heilbronn-Franken, SLK Kliniken Heilbronn, Heilbronn, Germany
| | - Robert C Bertheau
- Clinic for Diagnostic and Interventional Radiology, Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany
| | - Stefan Fritz
- Department of General Visceral and Transplantation Surgery, Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany
| | - Carolin Mogler
- Department of General Pathology, Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany
| | - Hans-Ulrich Kauczor
- Clinic for Diagnostic and Interventional Radiology, Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany
| | - Eduard Ryschich
- Department of General Visceral and Transplantation Surgery, Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany
| | - Boris A Radeleff
- Clinic for Diagnostic and Interventional Radiology, Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany
| | - Philippe L Pereira
- Clinic for Radiology, Minimally-Invasive Therapies and Nuclear Medicine, Cancer Center Heilbronn-Franken, SLK Kliniken Heilbronn, Heilbronn, Germany
| | - Christof M Sommer
- Clinic for Diagnostic and Interventional Radiology, Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany; Clinic for Diagnostic and Interventional Radiology, Stuttgart Cancer Center, European Siemens Reference Site for Interventional Oncology and Radiology, Klinikum Stuttgart, Stuttgart, Germany.
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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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Padia SA, Johnson GE, Yeung RS, Park JO, Hippe DS, Kogut MJ. Irreversible Electroporation in Patients with Hepatocellular Carcinoma: Immediate versus Delayed Findings at MR Imaging. Radiology 2015; 278:285-94. [PMID: 26523493 DOI: 10.1148/radiol.2015150031] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE To assess the postprocedure findings of irreversible electroporation (IRE) in patients with hepatocellular carcinoma (HCC) at magnetic resonance (MR) imaging. MATERIALS AND METHODS This retrospective study was Institutional Review Board approved, and informed consent was waived. Twenty patients with HCC were treated with IRE over a 2.5-year period. The median patient age was 62 years, and 75% of patients had cirrhosis with a Child-Pugh score of A. The median tumor diameter was 2.0 cm (range, 1.0-3.3 cm). Contrast material-enhanced multiphase MR imaging was performed on postprocedure days 1 and 30 and every 90 days thereafter. Ablation zone sizes and signal intensities were compared between each time point for both T1- and T2-weighted images. Trends in signal intensity and tumor dimensions over time were quantified by using generalized linear models. RESULTS MR imaging appearances of treated tumors include a zone of peripheral enhancement with centripetal filling on delayed contrast-enhanced images. Compared with postprocedure day 1, every 90 days there is a decrease of 28.9% (mean, axis) in the size of the enhancing ablation zone. Over time, there is a trend toward decreasing signal intensity in the peripheral ablation zone on both T2-weighted (P = .01) and contrast-enhanced T1-weighted (P < .08) images. Conversely, the tumor itself typically has increased signal intensity on the same sequences. CONCLUSION IRE of HCC results in a large region of enhancement on immediate postprocedure MR images that, over time, involutes and is associated with decreasing signal intensity of the peripheral ablation zone. This phenomenon may represent resolution of the reversible penumbra.
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Affiliation(s)
- Siddharth A Padia
- From the Section of Interventional Radiology (S.A.P., G.E.J., M.J.K.), Department of Surgery (R.S.Y.), and Department of Radiology (D.S.H.), University of Washington, Box 357115, 1959 NE Pacific St, Seattle, WA 98119
| | - Guy E Johnson
- From the Section of Interventional Radiology (S.A.P., G.E.J., M.J.K.), Department of Surgery (R.S.Y.), and Department of Radiology (D.S.H.), University of Washington, Box 357115, 1959 NE Pacific St, Seattle, WA 98119
| | - Raymond S Yeung
- From the Section of Interventional Radiology (S.A.P., G.E.J., M.J.K.), Department of Surgery (R.S.Y.), and Department of Radiology (D.S.H.), University of Washington, Box 357115, 1959 NE Pacific St, Seattle, WA 98119
| | - James O Park
- From the Section of Interventional Radiology (S.A.P., G.E.J., M.J.K.), Department of Surgery (R.S.Y.), and Department of Radiology (D.S.H.), University of Washington, Box 357115, 1959 NE Pacific St, Seattle, WA 98119
| | - Daniel S Hippe
- From the Section of Interventional Radiology (S.A.P., G.E.J., M.J.K.), Department of Surgery (R.S.Y.), and Department of Radiology (D.S.H.), University of Washington, Box 357115, 1959 NE Pacific St, Seattle, WA 98119
| | - Matthew J Kogut
- From the Section of Interventional Radiology (S.A.P., G.E.J., M.J.K.), Department of Surgery (R.S.Y.), and Department of Radiology (D.S.H.), University of Washington, Box 357115, 1959 NE Pacific St, Seattle, WA 98119
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Scheffer HJ, Vroomen LGPH, Nielsen K, van Tilborg AAJM, Comans EFI, van Kuijk C, van der Meijs BB, van den Bergh J, van den Tol PMP, Meijerink MR. Colorectal liver metastatic disease: efficacy of irreversible electroporation--a single-arm phase II clinical trial (COLDFIRE-2 trial). BMC Cancer 2015; 15:772. [PMID: 26497813 PMCID: PMC4619419 DOI: 10.1186/s12885-015-1736-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Accepted: 10/08/2015] [Indexed: 12/18/2022] Open
Abstract
Background Irreversible electroporation (IRE) is a novel image-guided tumor ablation technique that has shown promise for the ablation of lesions in proximity to vital structures such as blood vessels and bile ducts. The primary aim of the COLDFIRE-2 trial is to investigate the efficacy of IRE for unresectable, centrally located colorectal liver metastases (CRLM). Secondary outcomes are safety, technical success, and the accuracy of contrast-enhanced (ce)CT and 18F-FDG PET-CT in the detection of local tumor progression (LTP). Methods/design In this single-arm, multicenter phase II clinical trial, twenty-nine patients with 18F-FDG PET-avid CRLM ≤ 3,5 cm will be prospectively included to undergo IRE of the respective lesion. All lesions must be unresectable and unsuitable for thermal ablation due to vicinity of vital structures. Technical success is based on ceMRI one day post-IRE. All complications related to the IRE procedure are registered. Follow-up consists of 18F-FDG PET-CT and 4-phase liver CT at 3-monthly intervals during the first year of follow-up. Treatment efficacy is defined as the percentage of tumors successfully eradicated 12 months after the initial IRE procedure based on clinical follow-up using both imaging modalities, tumor marker and (if available) histopathology. To determine the accuracy of 18F-FDG PET-CT and ceCT, both imaging modalities will be individually scored by two reviewers that are blinded for the final oncologic outcome. Discussion To date, patients with a central CRLM unsuitable for resection or thermal ablation have no curative treatment option and are given palliative chemotherapy. For these patients, IRE may prove a life-saving treatment option. The results of the proposed trial may represent an important step towards the implementation of IRE for central liver tumors in the clinical setting. Trial registration Trial registration number: NCT02082782.
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Affiliation(s)
- Hester J Scheffer
- Department of Radiology and Nuclear Medicine, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
| | - Laurien G P H Vroomen
- Department of Radiology and Nuclear Medicine, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
| | - Karin Nielsen
- Department of Surgery, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
| | - Aukje A J M van Tilborg
- Department of Radiology and Nuclear Medicine, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
| | - Emile F I Comans
- Department of Radiology and Nuclear Medicine, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
| | - Cornelis van Kuijk
- Department of Radiology and Nuclear Medicine, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
| | - Bram B van der Meijs
- Department of Radiology and Nuclear Medicine, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
| | - Janneke van den Bergh
- Department of Radiology and Nuclear Medicine, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
| | - Petrousjka M P van den Tol
- Department of Surgery, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
| | - Martijn R Meijerink
- Department of Radiology and Nuclear Medicine, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
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Sugimoto K, Moriyasu F, Kobayashi Y, Kasuya K, Nagakawa Y, Tsuchida A, Hara T, Iobe H, Oshiro H. Assessment of various types of US findings after irreversible electroporation in porcine liver: comparison with radiofrequency ablation. J Vasc Interv Radiol 2015; 26:279-87.e3. [PMID: 25645416 DOI: 10.1016/j.jvir.2014.11.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 10/04/2014] [Accepted: 11/04/2014] [Indexed: 12/18/2022] Open
Abstract
PURPOSE To assess various ultrasound (US) findings, including B-mode, shear-wave elastography (SWE), and contrast-enhanced US, in accurately assessing ablation margins after irreversible electroporation (IRE) based on radiologic-pathologic correlation, and to compare these findings between IRE and radiofrequency (RF) ablation. MATERIALS AND METHODS IRE (n = 9) and RF ablation (n = 3) were performed in vivo in three pig livers. Each ablation zone was imaged by each method immediately after the procedure and 90 minutes later. Ablation zones were evaluated based on gross pathologic and histopathologic findings in samples from animals euthanized 2 hours after the last ablation. The characteristics and dimensions of the histologic ablation zones were qualitatively and quantitatively compared against each US finding. RESULTS In B-mode US at 90 minutes after IRE, the ablation zones appeared as hyperechoic areas with a peripheral hyperechoic rim, showing excellent correlation (r(2) = 0.905, P < .0001) with gross pathologic findings. SWE showed that tissue stiffness in the IRE ablation zones increased over time. Contrast-enhanced US depicted the IRE ablation zones as hypovascular areas in the portal phase, and showed the highest correlation (r(2) = 0.923, P < .0001) with gross pathologic findings. The RF ablation zones were clearly visualized by B-mode US. SWE showed that tissue stiffness after RF ablation was higher than after IRE. Contrast-enhanced US depicted the RF ablation zones as avascular areas. CONCLUSIONS IRE and RF ablation zones can be most accurately predicted by portal-phase contrast-enhanced US measurements obtained immediately after ablation.
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Affiliation(s)
- Katsutoshi Sugimoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
| | - Fuminori Moriyasu
- Department of Gastroenterology and Hepatology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Yoshiyuki Kobayashi
- Department of Gastroenterology and Hepatology, Tokyo Medical University Hachioji Medical Center, Tokyo
| | - Kazuhiko Kasuya
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Yuichi Nagakawa
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Akihiko Tsuchida
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Takeshi Hara
- Department of Intelligent Image Information, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Hiroaki Iobe
- Department of Anatomic Pathology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Hisashi Oshiro
- Department of Anatomic Pathology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan
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Lencioni R, Crocetti L, Narayanan G. Irreversible Electroporation in the Treatment of Hepatocellular Carcinoma. Tech Vasc Interv Radiol 2015; 18:135-9. [DOI: 10.1053/j.tvir.2015.06.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Scheffer HJ, Melenhorst MC, Echenique AM, Nielsen K, van Tilborg AA, van den Bos W, Vroomen LG, van den Tol PM, Meijerink MR. Irreversible Electroporation for Colorectal Liver Metastases. Tech Vasc Interv Radiol 2015; 18:159-69. [DOI: 10.1053/j.tvir.2015.06.007] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Gonzalez-Beicos A, Venkat S, Songrug T, Poveda J, Garcia-Buitrago M, Poozhikunnath Mohan P, Narayanan G. Irreversible Electroporation of Hepatic and Pancreatic Malignancies: Radiologic-Pathologic Correlation. Tech Vasc Interv Radiol 2015; 18:176-82. [PMID: 26365548 DOI: 10.1053/j.tvir.2015.06.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Irreversible electroporation (IRE) is a novel therapy that has shown to be a feasible and promising alternative to conventional ablative techniques when treating tumors near vital structures or blood vessels. The clinical efficacy of IRE has been evaluated using established imaging criteria. This study evaluates the histologic and imaging response of hepatic and pancreatic malignancies that were surgically resected after IRE. In total, 12 lesions ablated with IRE were included, including 3 pancreatic carcinomas, 5 primary tumors of the liver, and 4 metastatic tumors of the liver. The rate of complete response to IRE was 25% based on the histologic evaluation of the resected tumors. Although treatment-related vessel wall changes were noted in several cases in histologic findings, there was no evidence of vascular luminal narrowing or obliteration in any of the specimens. The imaging response to IRE before surgical resection usually resulted in underestimation of disease burden when compared with the histologic response seen on the resected specimens.
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Affiliation(s)
- Aldo Gonzalez-Beicos
- Interventional Radiology, Department of Radiology, University of Miami, Miller School of Medicine, Miami, FL.
| | - Shree Venkat
- Interventional Radiology, Department of Radiology, University of Miami, Miller School of Medicine, Miami, FL
| | - Tanakorn Songrug
- Interventional Radiology, Department of Radiology, University of Miami, Miller School of Medicine, Miami, FL
| | - Julio Poveda
- Gastrointestinal Pathology, Department of Pathology, University of Miami, Miller School of Medicine, Miami, FL
| | - Monica Garcia-Buitrago
- Gastrointestinal Pathology, Department of Pathology, University of Miami, Miller School of Medicine, Miami, FL
| | - Prasoon Poozhikunnath Mohan
- Interventional Radiology, Department of Radiology, University of Miami, Miller School of Medicine, Miami, FL
| | - Govindarajan Narayanan
- Interventional Radiology, Department of Radiology, University of Miami, Miller School of Medicine, Miami, FL
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