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1
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Deschamps F, Tselikas L, Cazzato RL, Facchini G, Granata V, Bonnet B, D'Alessio V, Fusco R, Zanasi A, de Terlizzi F, Gangi A, de Baere T, Mir LM. Electrochemotherapy in metastatic epidural spinal cord compression: a review and technical update. Br J Radiol 2025; 98:828-839. [PMID: 39900516 DOI: 10.1093/bjr/tqae219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 08/29/2024] [Accepted: 10/25/2024] [Indexed: 02/05/2025] Open
Abstract
This review aims to analyse the safety and clinical efficacy in terms of pain relief and local tumour control, in patients with metastatic epidural spinal cord compression undergoing electrochemotherapy (ECT). Moreover, a recommendation detailing optimal electrodes insertion is proposed with the intent of improving treatment planning. Clinical studies published between 2015 and 2023 were included since this time window is consistent with recent developments in the field of ECT of spinal metastases. In the whole, 3 articles were included. Results showed that percutaneous image-guided ECT provides effective pain relief with limited procedure-related morbidity, along with local tumour control (complete response 28.5%, 38% partial response, 24% stable disease) at 3-month follow-up in the largest published series so far. In conclusion, ECT should integrate the armamentarium of therapies that are currently being proposed to patients with painful metastatic epidural disease.
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Affiliation(s)
- Frederic Deschamps
- Department of Interventional Radiology, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France
- Université Paris-Saclay, CNRS, Gustave Roussy, Aspects métaboliques et systémiques de l'oncogénèse pour de nouvelles approches thérapeutiques, 94805 Villejuif, France
| | - Lambros Tselikas
- Department of Interventional Radiology, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France
| | - Roberto L Cazzato
- Department of Interventional Radiology, University Hospital of Strasbourg, 1 Pl. de l'Hôpital, 67000 Strasbourg, France
| | - Giancarlo Facchini
- Department of Radiology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
| | - Vincenza Granata
- Division of Radiology, Istituto Nazionale per lo studio e la cura dei Tumori "Fondazione G. Pascale", IRCCS, 80131 Naples, Italy
| | - Baptiste Bonnet
- Department of Interventional Radiology, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France
| | - Valeria D'Alessio
- Clinical Biophysics, IGEA S.p.A, Via Parmenide, 10/A, 41012 Carpi MO, Modena, Italy
| | - Roberta Fusco
- Clinical Biophysics, IGEA S.p.A, Via Parmenide, 10/A, 41012 Carpi MO, Modena, Italy
| | - Alessandro Zanasi
- Clinical Biophysics, IGEA S.p.A, Via Parmenide, 10/A, 41012 Carpi MO, Modena, Italy
| | | | - Afshin Gangi
- Department of Interventional Radiology, University Hospital of Strasbourg, 1 Pl. de l'Hôpital, 67000 Strasbourg, France
| | - Thierry de Baere
- Department of Interventional Radiology, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France
| | - Lluis M Mir
- Université Paris-Saclay, CNRS, Gustave Roussy, Aspects métaboliques et systémiques de l'oncogénèse pour de nouvelles approches thérapeutiques, 94805 Villejuif, France
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Wilke T, Hussain E, Spallek H, de Terlizzi F, Mir LM, Bischoff P, Schäfer A, Bartmuß E, Cadossi M, Zanasi A, Pinkawa M, Kovács A. Comparison of selective intra-arterial to standard intravenous administration in percutaneous electrochemotherapy (pECT) for liver tumors. Radiol Oncol 2025; 59:100-109. [PMID: 40014781 PMCID: PMC11867569 DOI: 10.2478/raon-2025-0017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Accepted: 02/04/2025] [Indexed: 03/01/2025] Open
Abstract
BACKGROUND Electrochemotherapy (ECT) is a local nonsurgical effective tumor treatment in the hand of the clinician for the treatment of patients with liver tumors or metastases. The study aimed to test the technical feasibility and safety of intra-arterial (i.a.) bleomycin administration compared to the established intravenous (i.v.) administration in percutaneous electrochemotherapy (pECT). Furthermore, the equivalence hypothesis was tested between the 2 modalities in terms of local short-term response and progression-free survival. PATIENTS AND METHODS Forty-four patients have been recruited and treated by pECT for hepatocellular carcinoma, cholangiocarcinoma and liver metastatic lesions from cancers of different origin: 18 were treated with standard i.v., 26 with bleomycin i.a. administration. RESULTS The 2 groups were similar for anagraphic and anamnestic data, as well as for most relevant disease specific characteristics. Technical success of the treatment was obtained in 95% and 100% of patients in i.v. and i.a. groups respectively. Short-term local response was similar in the 2 groups with a slightly higher complete remission (CR) rate in the i.a. group. There were 61.9% CR, 23.8% partial remission (PR), 4.8% stable disease (SD) in the i.v. group, and 80.6%, CR 12.9% PR, 3.2% PD (p = 0.3454). One-year progression free survival was 60% (C.I. 33%-88%) in the i.v. group and 67% (C.I. 42%-91%) in the i.a. group (p = 0.5849). CONCLUSIONS The results of this study confirmed the safety and feasibility of super-selective i.a. bleomycin administration. Analysis of local response and progression free survival confirmed the equivalence hypothesis of the new modality compared to standard i.v. administration in the treatment of primary and secondary liver malignancies by pECT.
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Affiliation(s)
- Tim Wilke
- Departement of Gastroenterology, Sinzig Medical Care Center, Linz/Rhein, Germany
| | - Erschad Hussain
- Campus Lübeck, University Schleswig-Holstein, Lübeck, Germany
| | - Hannah Spallek
- Clinic for Gynaecology and Obstetrics, University Hospital Mannheim, Mannheim, Germany
| | | | - Lluis M Mir
- METSY UMR 9018, Université Paris-Saclay, CNRS, Gustave Roussy, Villejuif, France
| | - Peter Bischoff
- Clinic for Diagnostic and Interventional Radiology and Neuroradiology, WEGE Klinik, Bonn, Germany
| | - Andreas Schäfer
- Clinic for Diagnostic and Interventional Radiology and Neuroradiology, WEGE Klinik, Bonn, Germany
| | - Elke Bartmuß
- Clinic for Diagnostic and Interventional Radiology and Neuroradiology, WEGE Klinik, Bonn, Germany
| | - Matteo Cadossi
- IGEA Clinical Biophysics, Laboratory Carpi, Modena, Italy
| | | | - Michael Pinkawa
- Clinic for Radiotherapy and Radiation Oncology, WEGE Klinik, Bonn, Germany
| | - Attila Kovács
- Clinic for Diagnostic and Interventional Radiology and Neuroradiology, WEGE Klinik, Bonn, Germany
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Luerken L, Goetz A, Mayr V, Zhang L, Schlitt A, Haimerl M, Stroszczynski C, Schlitt HJ, Grube M, Kandulski A, Einspieler I. Stereotactic Percutaneous Electrochemotherapy as a New Minimal Invasive Treatment Modality for Primary and Secondary Liver Malignancies. Biomedicines 2024; 12:2870. [PMID: 39767776 PMCID: PMC11673152 DOI: 10.3390/biomedicines12122870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 12/12/2024] [Accepted: 12/16/2024] [Indexed: 01/11/2025] Open
Abstract
Background and Objectives: To report on the first results of safety, efficacy, and outcome of CT-navigated stereotactic percutaneous electrochemotherapy (SpECT) in patients with primary and secondary liver malignancies. Methods: This retrospective study included 23 consecutive lesions in 22 patients who underwent SpECT for primary and secondary malignant liver lesions with locally curative intention. The endpoints were primary technique efficacy (PTE), local tumor progression (LTP), time to progression (TTP), and occurrence of adverse events. Results: The mean maximum diameter of the treated lesions was 42 mm (range: 16 mm-72 mm). Eight lesions were hepatocellular carcinoma (34.8%), five lesions were colorectal liver metastases (21.7%), three lesions were cholangiocellular carcinoma (13.0%), and the other seven lesions were liver metastases from different primary cancers (30.4%). PTE was achieved for 22 lesions (95.7%). The mean follow-up time was 15 months (0-39 months). No LTP was observed. In six patients (27.3%), hepatic tumor progression was observed during follow-up with a mean TTP of 3.8 months (2-8 months). In 10 procedures (43.5%), minor complications (1 CIRSE Grade 2) and side effects occurred, but no major complications were observed. Conclusions: SpECT seems to be a safe and effective new local treatment modality for primary and secondary liver malignancies.
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Affiliation(s)
- Lukas Luerken
- Department of Radiology, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Andrea Goetz
- Department of Radiology, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Vinzenz Mayr
- Department of Radiology, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Liang Zhang
- Department of Radiology, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Alexandra Schlitt
- Department of Radiology, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Michael Haimerl
- Department of Diagnostic and Interventional Radiology, Klinikum Würzburg Mitte gGmbH, 97070 Würzburg, Germany
| | | | - Hans-Jürgen Schlitt
- Department of Surgery, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Matthias Grube
- Department of Internal Medicine III, Hematology and Oncology, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Arne Kandulski
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Ingo Einspieler
- Department of Radiology, University Hospital Regensburg, 93053 Regensburg, Germany
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Scuderi M, Dermol-Cerne J, Scancar J, Markovic S, Rems L, Miklavcic D. The equivalence of different types of electric pulses for electrochemotherapy with cisplatin - an in vitro study. Radiol Oncol 2024; 58:51-66. [PMID: 38378034 PMCID: PMC10878774 DOI: 10.2478/raon-2024-0005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 12/05/2023] [Indexed: 02/22/2024] Open
Abstract
BACKGROUND Electrochemotherapy (ECT) is a treatment involving the administration of chemotherapeutics drugs followed by the application of 8 square monopolar pulses of 100 μs duration at a repetition frequency of 1 Hz or 5000 Hz. However, there is increasing interest in using alternative types of pulses for ECT. The use of high-frequency short bipolar pulses has been shown to mitigate pain and muscle contractions. Conversely, the use of millisecond pulses is interesting when combining ECT with gene electrotransfer for the uptake of DNA-encoding proteins that stimulate the immune response with the aim of converting ECT from a local to systemic treatment. Therefore, the aim of this study was to investigate how alternative types of pulses affect the efficiency of the ECT. MATERIALS AND METHODS We performed in vitro experiments, exposing Chinese hamster ovary (CHO) cells to conventional ECT pulses, high-frequency bipolar pulses, and millisecond pulses in the presence of different concentrations of cisplatin. We determined cisplatin uptake by inductively coupled plasma mass spectrometry and cisplatin cytotoxicity by the clonogenic assay. RESULTS We observed that the three tested types of pulses potentiate the uptake and cytotoxicity of cisplatin in an equivalent manner, provided that the electric field is properly adjusted for each pulse type. Furthermore, we quantified that the number of cisplatin molecules, resulting in the eradication of most cells, was 2-7 × 107 per cell. CONCLUSIONS High-frequency bipolar pulses and millisecond pulses can potentially be used in ECT to reduce pain and muscle contraction and increase the effect of the immune response in combination with gene electrotransfer, respectively.
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Affiliation(s)
- Maria Scuderi
- Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia
| | - Janja Dermol-Cerne
- Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia
| | - Janez Scancar
- Department of Environmental Sciences, Jožef Stefan Institute, Ljubljana, Slovenia
- Jožef Stefan International Postgraduate School, Ljubljana, Slovenia
| | - Stefan Markovic
- Department of Environmental Sciences, Jožef Stefan Institute, Ljubljana, Slovenia
- Jožef Stefan International Postgraduate School, Ljubljana, Slovenia
| | - Lea Rems
- Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia
| | - Damijan Miklavcic
- Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia
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5
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Martin CH, Martin RCG. Optimal Dosing and Patient Selection for Electrochemotherapy in Solid Abdominal Organ and Bone Tumors. Bioengineering (Basel) 2023; 10:975. [PMID: 37627860 PMCID: PMC10451240 DOI: 10.3390/bioengineering10080975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/15/2023] [Accepted: 08/16/2023] [Indexed: 08/27/2023] Open
Abstract
The primary aim of this study was to analyze studies that use electrochemotherapy (ECT) in "deep-seated" tumors in solid organs (liver, kidney, bone metastasis, pancreas, and abdomen) and understand the similarities between patient selection, oncologic selection, and use of new procedures and technology across the organ systems to assess response rates. A literature search was conducted using the term "Electrochemotherapy" in the title field using publications from 2017 to 2023. After factoring in inclusion and exclusion criteria, 29 studies were analyzed and graded based on quality in full. The authors determined key patient and oncologic selection characteristics and ECT technology employed across organ systems that yielded overall responses, complete responses, and partial responses of the treated tumor. It was determined that key selection factors included: the ability to be administered bleomycin, life expectancy greater than three months, unrespectability of the lesion being treated, and a later stage, more advanced cancer. Regarding oncologic selection, all patient cohorts had received chemotherapy or surgery previously but had disease recurrence, making ECT the only option for further treatment. Lastly, in terms of the use of technology, the authors found that studies with better response rates used the ClinporatorTM and updated procedural guidelines by SOP. Thus, by considering patient, oncologic, and technology selection, ECT can be further improved in treating lesions in solid organs.
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Affiliation(s)
| | - Robert C. G. Martin
- Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40202, USA
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6
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Charalampopoulos G, Iezzi R, Tsitskari M, Mazioti A, Papakonstantinou O, Kelekis A, Kelekis N, Filippiadis D. Role of Percutaneous Ablation in the Management of Intrahepatic Cholangiocarcinoma. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1186. [PMID: 37511998 PMCID: PMC10386331 DOI: 10.3390/medicina59071186] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 06/15/2023] [Accepted: 06/20/2023] [Indexed: 07/30/2023]
Abstract
Cholangiocarcinoma (CCA) is an invasive cancer accounting for <1% of all cancers and 10-15% of primary liver cancers. Intrahepatic CCA (iCCA) is associated with poor survival rates and high post-surgical recurrence rates whilst most diagnosed patients are not surgical candidates. There is a growing literature suggesting percutaneous ablative techniques for the management of patients with iCCA measuring ≤3 cm with contraindications to surgery as well as for recurrent or residual tumors aiming to provide local cancer treatment and control. Most used ablative therapies for iCCA include radiofrequency and microwave ablation with irreversible electroporation, cryoablation and reversible electroporation (electrochemotherapy) being less commonly encountered techniques. Due to the infiltrative margins of the lesion, there is a need for larger safety margins and ablation zone; multi-apparatus ablation or other variations of the technique such as balloon-assisted approaches can be utilized aiming to increase size of the zone of necrosis. The present review paper focuses upon the current role of percutaneous ablative techniques for the therapeutic management of iCCA. The purpose of this review is to present the current minimally invasive ablative techniques in the treatment of iCCA, including local control and survival rates.
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Affiliation(s)
- Georgios Charalampopoulos
- 2nd Department of Radiology, University General Hospital "ATTIKON", Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Roberto Iezzi
- Department of Diagnostic Imaging, Oncologic Radiotherapy and Hematology, A. Gemelli University Hospital Foundation IRCCS, Catholic University of the Sacred Heart, 00168 Rome, Italy
| | - Maria Tsitskari
- Apollonio Private Hospital, 20 Lefkotheou Avenue, 2054 Strovolos, Nicosia, Cyprus
| | - Argyro Mazioti
- 2nd Department of Radiology, University General Hospital "ATTIKON", Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Olympia Papakonstantinou
- 2nd Department of Radiology, University General Hospital "ATTIKON", Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Alexis Kelekis
- 2nd Department of Radiology, University General Hospital "ATTIKON", Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Nikolaos Kelekis
- 2nd Department of Radiology, University General Hospital "ATTIKON", Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Dimitrios Filippiadis
- 2nd Department of Radiology, University General Hospital "ATTIKON", Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
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7
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Robinson TP, Pebror T, Krosin ME, Koniaris LG. Ablative Therapy in Non-HCC Liver Malignancy. Cancers (Basel) 2023; 15:cancers15041200. [PMID: 36831543 PMCID: PMC9954041 DOI: 10.3390/cancers15041200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/07/2023] [Accepted: 02/08/2023] [Indexed: 02/16/2023] Open
Abstract
Surgical extirpation of liver tumors remains a proven approach in the management of metastatic tumors to the liver, particularly those of colorectal origin. Ablative, non-resective therapies are an increasingly attractive primary therapy for liver tumors as they are generally better tolerated and result in far less morbidity and mortality. Ablative therapies preserve greater normal liver parenchyma allowing better post-treatment liver function and are particularly appropriate for treating subsequent liver-specific tumor recurrence. This article reviews the current status of ablative therapies for non-hepatocellular liver tumors with a discussion of many of the clinically available approaches.
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Affiliation(s)
- Tyler P. Robinson
- Department of Surgery, Indiana University, Indianapolis, IN 46202, USA
- Correspondence: ; Tel.: +1-312-371-8360
| | - Travis Pebror
- Department of Interventional Radiology, Indiana University, Indianapolis, IN 46202, USA
| | - Matthew E. Krosin
- Department of Interventional Radiology, Indiana University, Indianapolis, IN 46202, USA
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8
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Granata V, Fusco R, D’Alessio V, Simonetti I, Grassi F, Silvestro L, Palaia R, Belli A, Patrone R, Piccirillo M, Izzo F. Percutanous Electrochemotherapy (ECT) in Primary and Secondary Liver Malignancies: A Systematic Review. Diagnostics (Basel) 2023; 13:209. [PMID: 36673019 PMCID: PMC9858594 DOI: 10.3390/diagnostics13020209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/29/2022] [Accepted: 12/31/2022] [Indexed: 01/09/2023] Open
Abstract
The aim of the study was to analyse papers describing the use of Electrochemotherapy (ECT) in local treatment of primary and secondary liver tumours located at different sites and with different histologies. Other Local Ablative Therapies (LAT) are also discussed. Analyses of these papers demonstrate that ECT use is safe and effective in lesions of large size, independently of the histology of the treated lesions. ECT performed better than other thermal ablation techniques in lesions > 6 cm in size and can be safely used to treat lesions distant, close, or adjacent to vital structures. ECT spares vessel and bile ducts, is repeatable, and can be performed between chemotherapeutic cycles. ECT can fill the gap in local ablative therapies due to being lesions too large or localized in highly challenging anatomical sites.
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Affiliation(s)
- Vincenza Granata
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| | - Roberta Fusco
- Oncology Medical and Research & Development Division, Casalnuovo di Napoli, 80013 Naples, Italy
| | - Valeria D’Alessio
- Oncology Medical and Research & Development Division, Casalnuovo di Napoli, 80013 Naples, Italy
| | - Igino Simonetti
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| | - Francesca Grassi
- Division of Radiology, Università degli Studi della Campania Luigi Vanvitelli, 80127 Naples, Italy
| | - Lucrezia Silvestro
- Division of Clinical Experimental Oncology Abdomen, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| | - Raffaele Palaia
- Division of Epatobiliary Surgical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| | - Andrea Belli
- Division of Epatobiliary Surgical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| | - Renato Patrone
- Division of Epatobiliary Surgical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| | - Mauro Piccirillo
- Division of Epatobiliary Surgical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| | - Francesco Izzo
- Division of Epatobiliary Surgical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
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9
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Zhong S, Yao S, Zhao Q, Wang Z, Liu Z, Li L, Wang ZL. Electricity‐Assisted Cancer Therapy: From Traditional Clinic Applications to Emerging Methods Integrated with Nanotechnologies. ADVANCED NANOBIOMED RESEARCH 2022. [DOI: 10.1002/anbr.202200143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Affiliation(s)
- Songjing Zhong
- Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of Sciences Beijing 101400 P.R. China
- School of Nanoscience and Technology University of Chinese Academy of Sciences Beijing 101400 P.R. China
| | - Shuncheng Yao
- Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of Sciences Beijing 101400 P.R. China
- School of Nanoscience and Technology University of Chinese Academy of Sciences Beijing 101400 P.R. China
| | - Qinyu Zhao
- Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of Sciences Beijing 101400 P.R. China
- Center on Nanoenergy Research Guangxi University Nanning 530004 P.R. China
| | - Zhuo Wang
- Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of Sciences Beijing 101400 P.R. China
| | - Zhirong Liu
- Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of Sciences Beijing 101400 P.R. China
- School of Nanoscience and Technology University of Chinese Academy of Sciences Beijing 101400 P.R. China
| | - Linlin Li
- Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of Sciences Beijing 101400 P.R. China
- School of Nanoscience and Technology University of Chinese Academy of Sciences Beijing 101400 P.R. China
- Center on Nanoenergy Research Guangxi University Nanning 530004 P.R. China
| | - Zhong Lin Wang
- Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of Sciences Beijing 101400 P.R. China
- Center on Nanoenergy Research Guangxi University Nanning 530004 P.R. China
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10
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Electrochemotherapy for solid tumors: literature review and presentation of a novel endoscopic approach. Radiol Oncol 2022; 56:285-291. [PMID: 35776844 PMCID: PMC9400449 DOI: 10.2478/raon-2022-0022] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 04/13/2022] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Electrochemotherapy (ECT) is a minimally invasive and safe treatment gaining positive and long-lasting antitumoral results that are receiving the attention of the scientific community. It is a local treatment that combines the use of electroporation and the administration of cytotoxic drugs to induce cell death in the target tissue. ECT is largely used for the treatment of cutaneous and subcutaneous lesions, and good results have been reported for the treatment of deep visceral tumors. The latest literature review is provided. Moreover, in line with its development for the treatment of visceral tumors in this article, we describe a novel approach of ECT: endoscopic treatment of colorectal cancer. Endoscopic ECT application was combined with systemic chemotherapy in the treatment of obstructing rectal cancer without prospective surgery. A good response after ECT was described: concentric involvement of the rectum was reduced, and no stenosing lesions were detected. CONCLUSIONS Clinical studies have demonstrated that ECT is a very effective treatment for tumors of different histologic types and localizations. Endoscopic treatment for gastrointestinal cancer is an innovative application of ECT. The combination of systemic treatment and ECT was safe and highly effective in the treatment of colorectal cancer, especially when obstructive, giving the patient a significant gain in quality of life.
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11
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Granata V, Fusco R, De Muzio F, Cutolo C, Setola SV, Simonetti I, Dell’Aversana F, Grassi F, Bruno F, Belli A, Patrone R, Pilone V, Petrillo A, Izzo F. Complications Risk Assessment and Imaging Findings of Thermal Ablation Treatment in Liver Cancers: What the Radiologist Should Expect. J Clin Med 2022; 11:2766. [PMID: 35628893 PMCID: PMC9147303 DOI: 10.3390/jcm11102766] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Revised: 05/10/2022] [Accepted: 05/12/2022] [Indexed: 02/04/2023] Open
Abstract
One of the major fields of application of ablation treatment is liver tumors. With respect to HCC, ablation treatments are considered as upfront treatments in patients with early-stage disease, while in colorectal liver metastases (CLM), they can be employed as an upfront treatment or in association with surgical resection. The main prognostic feature of ablation is the tumor size, since the goal of the treatment is the necrosis of all viable tumor tissue with an adequate tumor-free margin. Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most employed ablation techniques. Ablation therapies in HCC and liver metastases have presented a challenge to radiologists, who need to assess response to determine complication-related treatment. Complications, defined as any unexpected variation from a procedural course, and adverse events, defined as any actual or potential injury related to the treatment, could occur either during the procedure or afterwards. To date, RFA and MWA have shown no statistically significant differences in mortality rates or major or minor complications. To reduce the rate of major complications, patient selection and risk assessment are essential. To determine the right cost-benefit ratio for the ablation method to be used, it is necessary to identify patients at high risk of infections, coagulation disorders and previous abdominal surgery interventions. Based on risk assessment, during the procedure as part of surveillance, the radiologists should pay attention to several complications, such as vascular, biliary, mechanical and infectious. Multiphase CT is an imaging tool chosen in emergency settings. The radiologist should report technical success, treatment efficacy, and complications. The complications should be assessed according to well-defined classification systems, and these complications should be categorized consistently according to severity and time of occurrence.
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Affiliation(s)
- Vincenza Granata
- Radiology Division, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, Via Mariano Semmola, 80131 Naples, Italy; (S.V.S.); (I.S.); (A.P.)
| | - Roberta Fusco
- Medical Oncology Division, Igea SpA, 80013 Naples, Italy;
| | - Federica De Muzio
- Department of Medicine and Health Sciences V. Tiberio, University of Molise, 86100 Campobasso, Italy;
| | - Carmen Cutolo
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84084 Fisciano, Italy; (C.C.); (V.P.)
| | - Sergio Venanzio Setola
- Radiology Division, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, Via Mariano Semmola, 80131 Naples, Italy; (S.V.S.); (I.S.); (A.P.)
| | - Igino Simonetti
- Radiology Division, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, Via Mariano Semmola, 80131 Naples, Italy; (S.V.S.); (I.S.); (A.P.)
| | - Federica Dell’Aversana
- Division of Radiology, Università degli Studi della Campania Luigi Vanvitelli, 80138 Naples, Italy; (F.D.); (F.G.)
| | - Francesca Grassi
- Division of Radiology, Università degli Studi della Campania Luigi Vanvitelli, 80138 Naples, Italy; (F.D.); (F.G.)
| | - Federico Bruno
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, 20122 Milan, Italy;
- Department of Applied Clinical Sciences and Biotechnology, University of L’Aquila, 67100 L’Aquila, Italy
| | - Andrea Belli
- Hepatobiliary Surgical Oncology Division, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, Via Mariano Semmola, 80131 Naples, Italy; (A.B.); (R.P.); (F.I.)
| | - Renato Patrone
- Hepatobiliary Surgical Oncology Division, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, Via Mariano Semmola, 80131 Naples, Italy; (A.B.); (R.P.); (F.I.)
| | - Vincenzo Pilone
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84084 Fisciano, Italy; (C.C.); (V.P.)
| | - Antonella Petrillo
- Radiology Division, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, Via Mariano Semmola, 80131 Naples, Italy; (S.V.S.); (I.S.); (A.P.)
| | - Francesco Izzo
- Hepatobiliary Surgical Oncology Division, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, Via Mariano Semmola, 80131 Naples, Italy; (A.B.); (R.P.); (F.I.)
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12
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Electrochemotherapy of Primary Colon Rectum Cancer and Local Recurrence: Case Report and Prospective Analysis. J Clin Med 2022; 11:jcm11102745. [PMID: 35628872 PMCID: PMC9143872 DOI: 10.3390/jcm11102745] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/05/2022] [Accepted: 05/09/2022] [Indexed: 12/21/2022] Open
Abstract
Purpose: Surgery, radiotherapy, and oncological treatment (chemotherapy and antineoplastic antibodies) are standard treatments of rectal cancer. ECT has shown its effectiveness and suitability in deep solid tumors conducted in both preclinical and clinical studies. We show here an update and preliminary results with locally advanced rectum cancer (LARC) treated with ECT. Methods: Two patients with major clinical response to restaging after neoadjuvant treatment for LARC were subjected to ECT 12 weeks after completing chemo-radiation therapy. One patient was subjected to ECT on a colorectal local recurrence formed after neoadjuvant treatment for LARC and surgery. Computed Tomography and Magnetic Resonance Imaging were used to assess ECT response. Results: The results showed stable disease in two of the three patients treated, while one patient achieved a complete response. The local control of disease is maintained in the patient follow-up. For each patient, a reduction in pain was observed and for the patient with local recurrence, a reduction in bleeding present before ECT was also achieved. Conclusion: Preliminary results showed that ECT is a safe and effective treatment in patients with a major clinical response or local recurrence after neoadjuvant therapy for LARC and allows a reduction in pain and bleeding with a consequent improvement to quality of life.
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13
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Percutaneous electrochemotherapy in primary and secondary liver malignancies - local tumor control and impact on overall survival. Radiol Oncol 2022; 56:102-110. [PMID: 35148468 PMCID: PMC8884851 DOI: 10.2478/raon-2022-0003] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 12/24/2021] [Indexed: 12/12/2022] Open
Abstract
Background Local nonsurgical tumor ablation currently represents a further option for the treatment of patients with liver tumors or metastases. Electrochemotherapy (ECT) is a welcome addition to the portfolio of local therapies. A retrospective analysis of patients with liver tumors or metastases treated with ECT is reported. Attention is given to the safety and efficacy of the treatment over time. Patients and methods Eighteen consecutive patients were recruited with measurable liver tumors of different histopatologic origins, mainly colorectal cancer, breast cancer, and hepatocellular cancer. They were treated with percutaneous ECT following the standard operating procedures (SOP) for ECT under general anaesthesia and muscle relaxation. Treatment planning was performed based on MRI preoperative images. The follow-up assessment included contrast-enhanced MR within at least 1–3 months after treatment and then after 5, 7, 9, 12, and 18 months until progression of the disease or death. Results Only mild or moderate side effects were observed after ECT. The objective response rate was 85.7% (complete response 61.9%, partial 23.8%), the mean progression-free survival (PFS) was 9.0 ± 8.2 months, and the overall survival (OS) was 11.3 ± 8.6 months. ECT performed best (PFS and OS) in lesions within 3 and 6 cm diameters (p = 0.0242, p = 0.0297). The effectiveness of ECT was independent of the localization of the lesions: distant, close or adjacent to vital structures. Progression-free survival and overall survival were independent of the primary histology considered. Conclusions Electrochemotherapy provides an effective valuable option for the treatment of unresectable liver metastases not amenable to other ablative techniques.
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Trotovšek B, Djokić M, Čemažar M, Serša G. New era of electrochemotherapy in treatment of liver tumors in conjunction with immunotherapies. World J Gastroenterol 2021; 27:8216-8226. [PMID: 35068866 PMCID: PMC8717013 DOI: 10.3748/wjg.v27.i48.8216] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 10/28/2021] [Accepted: 12/16/2021] [Indexed: 02/06/2023] Open
Abstract
Electrochemotherapy is a local ablative therapy that increases the cytotoxicity of either bleomycin or cisplatin by applying electric pulses (electroporation) to tumors. It has already been widely used throughout Europe for the treatment of various types of human and veterinary cutaneous tumors, with an objective response rate ranging from 70%-90%, depending on the tumor histotype. Recently, electrochemotherapy was introduced for the treatment of primary liver tumors, such as hepatocellular carcinoma (HCC). The complete response rate was 85% per treated lesion, with a durable response. Therefore, electrochemotherapy could become a treatment of choice for HCC, especially after achieving a transition from an open surgery approach to a percutaneous approach that uses dedicated electrodes. Electrochemotherapy elicits a local immune response and can be considered an in situ vaccination. HCC, among others, is a potentially immunogenic tumor; thus, electrochemotherapy could boost adjuvant immunotherapy to achieve a better and longer-lasting antitumor response. Therefore, therapeutic strategies that combine electrochemotherapy with immune checkpoint inhibitors or adjuvant treatment with cytokines are indicated for HCC. Immunogene therapy using electroporation as a delivery system for plasmid DNA coding for interleukin-12 is a highly promising approach. This electroporation approach has shown efficacy in preclinical settings and veterinary oncology and is awaiting translation for the treatment of liver tumors, i.e., HCC.
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Affiliation(s)
- Blaž Trotovšek
- Department of Abdominal Surgery, University Medical Centre Ljubljana, Ljubljana 1000, Slovenia
- Medical Faculty Ljubljana, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Mihajlo Djokić
- Department of Abdominal Surgery, University Medical Centre Ljubljana, Ljubljana 1000, Slovenia
- Medical Faculty Ljubljana, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Maja Čemažar
- Department of Experimental Oncology, Institute of Oncology, Ljubljana 1000, Slovenia
- Faculty of Health Sciences, University of Primorska, Izola 6310, Slovenia
| | - Gregor Serša
- Department of Experimental Oncology, Institute of Oncology, Ljubljana 1000, Slovenia
- Faculty of Health Sciences, University of Ljubljana, Ljubljana 1000, Slovenia
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15
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Electrochemotherapy of Deep-Seated Tumors: State of Art and Perspectives as Possible "EPR Effect Enhancer" to Improve Cancer Nanomedicine Efficacy. Cancers (Basel) 2021; 13:cancers13174437. [PMID: 34503247 PMCID: PMC8431574 DOI: 10.3390/cancers13174437] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 08/29/2021] [Accepted: 08/30/2021] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Electroporation-based therapies (reversible electroporation, irreversible electroporation, electrochemotherapy) are used for the selective treatment of deep-seated tumors. The combination of the structural modifications of the lipid bilayer of cell membranes, due to the application of electrical pulses in the targeted tissue, with the concomitant systemic (intravenous) administration of drugs can be considered as a sort of bridge between local-regional and systemic treatments. A possible further application of these techniques can be envisaged in their use as enhancers of the so-called “enhanced permeability and retention” effect. The intratumoral uptake of drug-loaded nanocarriers concomitant with the application of electric pulses in the target tumor is a new scenario worthy of attention and can represent a potential new frontier for drug delivery in oncology. Abstract Surgical resection is the gold standard for the treatment of many kinds of tumor, but its success depends on the early diagnosis and the absence of metastases. However, many deep-seated tumors (liver, pancreas, for example) are often unresectable at the time of diagnosis. Chemotherapies and radiotherapies are a second line for cancer treatment. The “enhanced permeability and retention” (EPR) effect is believed to play a fundamental role in the passive uptake of drug-loaded nanocarriers, for example polymeric nanoparticles, in deep-seated tumors. However, criticisms of the EPR effect were recently raised, particularly in advanced human cancers: obstructed blood vessels and suppressed blood flow determine a heterogeneity of the EPR effect, with negative consequences on nanocarrier accumulation, retention, and intratumoral distribution. Therefore, to improve the nanomedicine uptake, there is a strong need for “EPR enhancers”. Electrochemotherapy represents an important tool for the treatment of deep-seated tumors, usually combined with the systemic (intravenous) administration of anticancer drugs, such as bleomycin or cisplatin. A possible new strategy, worthy of investigation, could be the use of this technique as an “EPR enhancer” of a target tumor, combined with the intratumoral administration of drug-loaded nanoparticles. This is a general overview of the rational basis for which EP could be envisaged as an “EPR enhancer” in nanomedicine.
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Rega D, Granata V, Petrillo A, Pace U, Sassaroli C, Di Marzo M, Cervone C, Fusco R, D’Alessio V, Nasti G, Romano C, Avallone A, Pecori B, Botti G, Tatangelo F, Maiolino P, Delrio P. Organ Sparing for Locally Advanced Rectal Cancer after Neoadjuvant Treatment Followed by Electrochemotherapy. Cancers (Basel) 2021; 13:cancers13133199. [PMID: 34206858 PMCID: PMC8267997 DOI: 10.3390/cancers13133199] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/23/2021] [Accepted: 06/23/2021] [Indexed: 12/21/2022] Open
Abstract
Simple Summary This is a Phase II randomized controlled trial conducted with the aim of investigating whether the use of Electrochemotherapy after neoadjuvant therapy (ECT) and before surgery in patients with major clinical response allows for a more conservative surgical approach in patients with Locally Advanced Rectal Cancer (LARC) in comparison with the control group that will not receive ECT. The treatment response, in both the control arm and in the treatment arm, will be assessed using the histopathological tumor regression grade on tissue specimens after local excision. Abstract Background: Currently, 45–55% of rectal cancer patients receive preoperative chemo- radio-therapy for Locally Advanced Rectal Cancer (LARC). The idea of our study is to use Electrochemotherapy (ECT) before surgery, in patients with major clinical response after neoadjuvant therapy, to allow for a more conservative surgical approach. Objective: To evaluate the increase of the complete response rate after neoadjuvant treatment in LARC and to spare organ function due to total mesorectal excision (TME). Patients and Methods: This is a Phase II randomized controlled trial enrolling 70 patients that will be developed in two stages. In the first step, 28 patients will be enrolled: 14 of these will receive ECT for four weeks after neo-adjuvant treatment and then local excision (treatment group) and 14 patients will receive neo-adjuvant treatment and then local excision (control group). If an increase of response rate is observed in the first stage, and/or feasibility/safety is demonstrated, the second stage of the trial will be performed, enrolling an additional 42 patients. The treatment response. in both the control arm and the treatment arm, will be assessed using the histopathological tumor regression grade on tissue specimens after local excision.
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Affiliation(s)
- Daniela Rega
- Division of Colorectal Surgery, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy; (D.R.); (U.P.); (C.S.); (M.D.M.); (C.C.); (P.D.)
| | - Vincenza Granata
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy;
- Correspondence:
| | - Antonella Petrillo
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy;
| | - Ugo Pace
- Division of Colorectal Surgery, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy; (D.R.); (U.P.); (C.S.); (M.D.M.); (C.C.); (P.D.)
| | - Cinzia Sassaroli
- Division of Colorectal Surgery, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy; (D.R.); (U.P.); (C.S.); (M.D.M.); (C.C.); (P.D.)
| | - Massimiliano Di Marzo
- Division of Colorectal Surgery, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy; (D.R.); (U.P.); (C.S.); (M.D.M.); (C.C.); (P.D.)
| | - Carmela Cervone
- Division of Colorectal Surgery, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy; (D.R.); (U.P.); (C.S.); (M.D.M.); (C.C.); (P.D.)
| | - Roberta Fusco
- IGEA SpA Medical Division-Oncology, Via Casarea 65, Casalnuovo di Napoli, I-80013 Napoli, Italy; (R.F.); (V.D.)
| | - Valeria D’Alessio
- IGEA SpA Medical Division-Oncology, Via Casarea 65, Casalnuovo di Napoli, I-80013 Napoli, Italy; (R.F.); (V.D.)
| | - Guglielmo Nasti
- Division of Abdominal Medical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy; (G.N.); (C.R.); (A.A.)
| | - Carmela Romano
- Division of Abdominal Medical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy; (G.N.); (C.R.); (A.A.)
| | - Antonio Avallone
- Division of Abdominal Medical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy; (G.N.); (C.R.); (A.A.)
| | - Biagio Pecori
- Division of Abdominal Radiotherapy, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy;
| | - Gerardo Botti
- Division of Pathological Anatomy, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy; (G.B.); (F.T.)
| | - Fabiana Tatangelo
- Division of Pathological Anatomy, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy; (G.B.); (F.T.)
| | - Piera Maiolino
- Division of Pharmacy, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy;
| | - Paolo Delrio
- Division of Colorectal Surgery, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy; (D.R.); (U.P.); (C.S.); (M.D.M.); (C.C.); (P.D.)
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Fusco R, Di Bernardo E, D'Alessio V, Salati S, Cadossi M. Reduction of muscle contraction and pain in electroporation-based treatments: An overview. World J Clin Oncol 2021; 12:367-381. [PMID: 34131568 PMCID: PMC8173331 DOI: 10.5306/wjco.v12.i5.367] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 03/17/2021] [Accepted: 04/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In the first studies of electrochemotherapy (ECT), small cutaneous metastases were treated and only mild or moderate pain was observed; therefore, pain was not considered a significant issue. As the procedure began to be applied to larger cutaneous metastases, pain was reported more frequently. For that reason, reduction of both muscle contractions and pain have been investigated over the years.
AIM To present an overview of different protocols described in literature that aim to reduce muscle contractions and pain caused by the electroporation (EP) effect in both ECT and irreversible EP treatments.
METHODS Thirty-three studies published between January 1999 and November 2020 were included. Different protocol designs and electrode geometries that reduce patient pain and the number of muscle contractions and their intensity were analysed.
RESULTS The analysis showed that both high frequency and bipolar/biphasic pulses can be used to reduce pain and muscle contractions in patients who undergo EP treatments. Moreover, adequate electrode design can decrease EP-related morbidity. Particularly, needle length, diameter and configuration of the distance between the needles can be optimised so that the muscle volume crossed by the current is reduced as much as possible. Bipolar/biphasic pulses with an inadequate pulse length seem to have a less evident effect on the membrane permeability compared with the standard pulse protocol. For that reason, the number of pulses and the voltage amplitude, as well as the pulse duration and frequency, must be chosen so that the dose of delivered energy guarantees EP efficacy.
CONCLUSION Pain reduction in EP-based treatments can be achieved by appropriately defining the protocol parameters and electrode design. Most results can be achieved with high frequency and/or bipolar/biphasic pulses. However, the efficacy of these alternative protocols remains a crucial point to be assessed further.
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Affiliation(s)
- Roberta Fusco
- Department of Medical Oncology, IGEA SpA, Carpi 41012, Modena, Italy
| | - Elio Di Bernardo
- Department of Medical Oncology, IGEA SpA, Carpi 41012, Modena, Italy
| | - Valeria D'Alessio
- Department of Medical Oncology, IGEA SpA, Carpi 41012, Modena, Italy
| | - Simona Salati
- Department of Medical Oncology, IGEA SpA, Carpi 41012, Modena, Italy
| | - Matteo Cadossi
- Department of Medical Oncology, IGEA SpA, Carpi 41012, Modena, Italy
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18
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Granata V, Fusco R, Salati S, Petrillo A, Di Bernardo E, Grassi R, Palaia R, Danti G, La Porta M, Cadossi M, Gašljević G, Sersa G, Izzo F. A Systematic Review about Imaging and Histopathological Findings for Detecting and Evaluating Electroporation Based Treatments Response. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18115592. [PMID: 34073865 PMCID: PMC8197272 DOI: 10.3390/ijerph18115592] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 05/16/2021] [Accepted: 05/19/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND Imaging methods and the most appropriate criteria to be used for detecting and evaluating response to oncological treatments depend on the pathology and anatomical site to be treated and on the treatment to be performed. This document provides a general overview of the main imaging and histopathological findings of electroporation-based treatments (Electrochemotherapy-ECT and Irreversible electroporation-IRE) compared to thermal approach, such as radiofrequency ablation (RFA), in deep-seated cancers with a particular attention to pancreatic and liver cancer. METHODS Numerous electronic datasets were examined: PubMed, Scopus, Web of Science and Google Scholar. The research covered the years from January 1990 to April 2021. All titles and abstracts were analyzed. The inclusion criteria were the following: studies that report imaging or histopathological findings after ablative thermal and not thermal loco-regional treatments (ECT, IRE, RFA) in deep-seated cancers including pancreatic and liver cancer and articles published in the English language. Exclusion criteria were unavailability of full text and congress abstracts or posters and different topic respect to inclusion criteria. RESULTS 558 potentially relevant references through electronic searches were identified. A total of 38 articles met the inclusion criteria: 20 studies report imaging findings after RFA or ECT or IRE in pancreatic and liver cancer; 17 studies report histopathological findings after RFA or ECT or IRE; 1 study reports both imaging and histopathological findings after RFA or ECT or IRE. CONCLUSIONS Imaging features are related to the type of therapy administrated, to the timing of re-assessment post therapy and to the imaging technique being used to observe the effects. Histological findings after both ECT and IRE show that the treated area becomes necrotic and encapsulated in fibrous tissue, suggesting that the size of the treated lesion cannot be measured as an endpoint to detect response. Moreover, histology frequently reported signs of apoptosis and reduced vital tissue, implying that imaging criteria, which take into account the viability and not the size of the lesion, are more appropriate to evaluate response to treatment.
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Affiliation(s)
- Vincenza Granata
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy; (V.G.); (A.P.)
| | - Roberta Fusco
- Oncology Medical and Research & Development Division, IGEA SpA, I-41012 Carpi, Italy; (S.S.); (E.D.B.); (M.C.)
- Correspondence:
| | - Simona Salati
- Oncology Medical and Research & Development Division, IGEA SpA, I-41012 Carpi, Italy; (S.S.); (E.D.B.); (M.C.)
| | - Antonella Petrillo
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy; (V.G.); (A.P.)
| | - Elio Di Bernardo
- Oncology Medical and Research & Development Division, IGEA SpA, I-41012 Carpi, Italy; (S.S.); (E.D.B.); (M.C.)
| | - Roberta Grassi
- Radiology Division, Università Degli Studi Della Campania Luigi Vanvitelli, I-80143 Naples, Italy;
- Italian Society of Medical and Interventional Radiology SIRM, SIRM Foundation, Via della Signora 2, 20122 Milan, Italy
| | - Raffaele Palaia
- Hepatobiliary Surgical Oncology Division, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy; (R.P.); (F.I.)
| | - Ginevra Danti
- Radiology Division, Azienda Ospedaliero-Universitaria Careggi, I-50139 Florence, Italy;
| | | | - Matteo Cadossi
- Oncology Medical and Research & Development Division, IGEA SpA, I-41012 Carpi, Italy; (S.S.); (E.D.B.); (M.C.)
| | - Gorana Gašljević
- Department of Pathology, Institute of Oncology Ljubljana, Zaloska cesta 2, SI-1000 Ljubljana, Slovenia;
| | - Gregor Sersa
- Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska cesta 2, SI-1000 Ljubljana, Slovenia;
- Faculty of Health Sciences, University of Ljubljana, Zdravstvena pot 5, SI-1000 Ljubljana, Slovenia
| | - Francesco Izzo
- Hepatobiliary Surgical Oncology Division, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, I-80131 Naples, Italy; (R.P.); (F.I.)
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Stefano M, Prosperi E, Fugazzola P, Benini B, Bisulli M, Coccolini F, Mastronardi C, Palladino A, Tomasoni M, Agnoletti V, Giampalma E, Ansaloni L. Case Report: Cytoreductive Surgery and HIPEC Associated With Liver Electrochemotherapy in a Cholangiocarcinoma Patient With Peritoneal Carcinomatosis and Liver Metastasis Case Report. Front Surg 2021; 8:624817. [PMID: 33816544 PMCID: PMC8018578 DOI: 10.3389/fsurg.2021.624817] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Accepted: 01/18/2021] [Indexed: 01/10/2023] Open
Abstract
Introduction: Cholangiocarcinoma (CCA) is the second most common primary tumor of the liver, and the recurrence after hepatic resection (HR), the only curative therapy, is linked with a worse prognosis. Systemic chemotherapy (SC) and liver loco-regional treatments, like trans-arterial chemoembolization (TACE) or radio embolization (TARE), have been employed for the treatment of unresectable intrahepatic metastasis (IM) with benefit on overall survival (OS), but SC has a limited effect on peritoneal metastasis (PM). In the last years, novel treatments like electrochemotherapy (ECT) with bleomycine (BLM) for IM and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) for PM have been applied in small series but with encouraging results. We hereby describe the first synchronous application of ECT and CRS and HIPEC for the treatment of a patient with IM and PM from CCA. Case Description: A 47-year-old male patient with CCA underwent HR followed by adjuvant SC. After 14 months, for the occurrence of IM, the patient underwent a second HR and SC. Nonetheless, a new recurrence occurred and a third attempt of HR was proposed. Due to the intraoperative finding of unresectable IM with PM, no resective procedure was performed and the patient was referred to our center. CRS and HIPEC with cisplatin and mitomycin for PM and ECT with BLM on a bulky metastasis of the hepatic hilum were performed after 38 months from the first HR. The length of hospital stay was 19 days. At the computed tomography (CT) performed 11 days after treatment complete necrosis of the treated IM was detected. Results: CT scan after 3 and 6 months and magnetic resonance after 9 months were performed. Necrosis of the treated IM nor PM but progression of the residual liver lesions was observed. After 3 months, the patient received SC and underwent TACE after 8 months and TARE after 9 months for the residual liver metastases. At 14 months from CRS and HIPEC, the patient is alive, in good condition, and with stability of the disease. Conclusions: The association of ECT and CRS and HIPEC could be safe and effective for the treatment of unresectable recurrent intrahepatic CCA with PM.
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Affiliation(s)
- Mauro Stefano
- General and Emergency Surgery Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Enrico Prosperi
- General and Emergency Surgery Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Paola Fugazzola
- General and Emergency Surgery Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Beatrice Benini
- Anesthesia and Intensive Care Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Marcello Bisulli
- Interventional Radiology Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Federico Coccolini
- General Emergency and Trauma Surgery Department, Pisa University Hospital, Pisa, Italy
| | - Costantino Mastronardi
- Anesthesia and Intensive Care Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Alessandro Palladino
- General and Emergency Surgery Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Matteo Tomasoni
- General and Emergency Surgery Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Vanni Agnoletti
- Anesthesia and Intensive Care Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Emanuela Giampalma
- Interventional Radiology Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
| | - Luca Ansaloni
- General and Emergency Surgery Department, Azienda Unità Sanitaria Locale Romagna Trauma Center “Maurizio Bufalini” Hospital, Cesena, Italy
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20
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Merola G, Fusco R, Di Bernardo E, D’Alessio V, Izzo F, Granata V, Contartese D, Cadossi M, Audenino A, Perazzolo Gallo G. Design and Characterization of a Minimally Invasive Bipolar Electrode for Electroporation. BIOLOGY 2020; 9:biology9090303. [PMID: 32967343 PMCID: PMC7563710 DOI: 10.3390/biology9090303] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 09/18/2020] [Accepted: 09/18/2020] [Indexed: 12/21/2022]
Abstract
OBJECTIVE To test a new bipolar electrode for electroporation consisting of a single minimally invasive needle. METHODS A theoretical study was performed by using Comsol Multiphysics® software. The prototypes of electrode have been tested on potatoes and pigs, adopting an irreversible electroporation protocol. Different applied voltages and different geometries of bipolar electrode prototype have been evaluated. RESULTS Simulations and pre-clinical tests have shown that the volume of ablated area is mainly influenced by applied voltage, while the diameter of the electrode had a lesser impact, making the goal of minimal-invasiveness possible. The conductive pole's length determined an increase of electroporated volume, while the insulated pole length inversely affects the electroporated volume size and shape; when the insulated pole length decreases, a more regular shape of the electric field is obtained. Moreover, the geometry of the electrode determined a different shape of the electroporated volume. A parenchymal damage in the liver of pigs due to irreversible electroporation protocol was observed. CONCLUSION The minimally invasive bipolar electrode is able to treat an electroporated volume of about 10 mm in diameter by using a single-needle electrode. Moreover, the geometry and the electric characteristics can be selected to produce ellipsoidal ablation volumes.
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Affiliation(s)
- Giulia Merola
- Oncology Medical and Research & Development Division, Igea SpA, 41012 Carpi, Italy; (G.M.); (E.D.B.); (V.D.); (M.C.); (G.P.G.)
| | - Roberta Fusco
- Oncology Medical and Research & Development Division, Igea SpA, 41012 Carpi, Italy; (G.M.); (E.D.B.); (V.D.); (M.C.); (G.P.G.)
- Correspondence:
| | - Elio Di Bernardo
- Oncology Medical and Research & Development Division, Igea SpA, 41012 Carpi, Italy; (G.M.); (E.D.B.); (V.D.); (M.C.); (G.P.G.)
| | - Valeria D’Alessio
- Oncology Medical and Research & Development Division, Igea SpA, 41012 Carpi, Italy; (G.M.); (E.D.B.); (V.D.); (M.C.); (G.P.G.)
| | - Francesco Izzo
- Hepatobiliary Surgical Oncology Unit, “Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli”, 80131 Naples, Italy;
| | - Vincenza Granata
- Radiology Unit, “Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli”, 80131 Naples, Italy;
| | - Deyanira Contartese
- Complex Structure of Surgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy;
| | - Matteo Cadossi
- Oncology Medical and Research & Development Division, Igea SpA, 41012 Carpi, Italy; (G.M.); (E.D.B.); (V.D.); (M.C.); (G.P.G.)
| | - Alberto Audenino
- Department of Mechanical and Aerospace Engineering, Politecnico di Torino, 10138 Turin, Italy;
| | - Giacomo Perazzolo Gallo
- Oncology Medical and Research & Development Division, Igea SpA, 41012 Carpi, Italy; (G.M.); (E.D.B.); (V.D.); (M.C.); (G.P.G.)
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21
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Hsiao CY, Yang PC, Li X, Huang KW. Clinical impact of irreversible electroporation ablation for unresectable hilar cholangiocarcinoma. Sci Rep 2020; 10:10883. [PMID: 32616770 PMCID: PMC7331634 DOI: 10.1038/s41598-020-67772-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 06/08/2020] [Indexed: 02/08/2023] Open
Abstract
Irreversible electroporation (IRE) is a non-thermal ablation modality that has been shown to be safe and effective in its application to tumors that are close to risky areas. This study aims to assess the safety and efficacy of IRE for unresectable hilar cholangiocarcinoma. Nine patients from two medical centers in Asia received IRE treatment between June 2015 and July 2017. Before IRE treatment, percutaneous biliary decompressions had been performed on eight patients, and internal stenting had been performed on one patient. All patients tolerated the procedure well without high-grade complications. The ablated tumors had constant size without contrast enhancement for more than three months in eight patients and the level of CA19-9 decreased significantly in all patients. The percutaneous biliary drainage tube was removed from two patients with recanalization of the bile duct. The internal stent in one patient was removed without further stenting. The median overall survival period was 26 months, and the progression-free survival was 18 months. Bile ducts remained narrow in the majority (2/3) of the treated patients. Nevertheless, IRE ablation of unresectable hilar cholangiocarcinoma involving vital structures is a safe and feasible primary treatment for local tumor control and is effective in prolonging survival.
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Affiliation(s)
- Chih-Yang Hsiao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei City, 10002, Taiwan
- Department of Surgery, National Taiwan University Hospital, 7 Chung-Shan South Rd, Taipei, 10002, Taiwan, ROC
- Department of Traumatology, National Taiwan University Hospital, Taipei City, 10002, Taiwan
| | - Po-Chih Yang
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei City, 10002, Taiwan
- Center for Organ Transplantation and Liver Disease Treatment, Fu Jen Catholic University Hospital, New Taipei City, 24352, Taiwan
| | - Xiaoyong Li
- Department of Hepatopancreatobiliary Surgery, The Fifth Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, China
| | - Kai-Wen Huang
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei City, 10002, Taiwan.
- Department of Surgery, National Taiwan University Hospital, 7 Chung-Shan South Rd, Taipei, 10002, Taiwan, ROC.
- Hepatitis Research Center, National Taiwan University Hospital, Taipei City, 10002, Taiwan.
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22
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Djokic M, Dezman R, Cemazar M, Stabuc M, Petric M, Smid LM, Jansa R, Plesnik B, Bosnjak M, Tratar UL, Trotovsek B, Kos B, Miklavcic D, Sersa G, Popovic P. Percutaneous image guided electrochemotherapy of hepatocellular carcinoma: technological advancement. Radiol Oncol 2020; 54:347-352. [PMID: 32562533 PMCID: PMC7409604 DOI: 10.2478/raon-2020-0038] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 06/01/2020] [Indexed: 12/17/2022] Open
Abstract
Background Electrochemotherapy is an effective treatment of colorectal liver metastases and hepatocellular carcinoma (HCC) during open surgery. The minimally invasive percutaneous approach of electrochemotherapy has already been performed but not on HCC. The aim of this study was to demonstrate the feasibility, safety and effectiveness of electrochemotherapy with percutaneous approach on HCC. Patient and methods The patient had undergone the transarterial chemoembolization and microwave ablation of multifocal HCC in segments III, V and VI. In follow-up a new lesion was identified in segment III, and recognized by multidisciplinary team to be suitable for minimally invasive percutaneous electrochemotherapy. The treatment was performed with long needle electrodes inserted by the aid of image guidance. Results The insertion of electrodes was feasible, and the treatment proved safe and effective, as demonstrated by control magnetic resonance imaging. Conclusions Minimally invasive, image guided percutaneous electrochemotherapy is feasible, safe and effective in treatment of HCC.
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Affiliation(s)
- Mihajlo Djokic
- University Medical Centre Ljubljana, Clinical Department of Abdominal Surgery, Ljubljana, Slovenia
| | - Rok Dezman
- University Medical Centre Ljubljana, Clinical Institute of Radiology, Ljubljana, Slovenia
| | - Maja Cemazar
- Institute of Oncology Ljubljana, Department of Experimental Oncology, Ljubljana, Slovenia
- University of Primorska, Faculty of Health Sciences, Izola, Slovenia
| | - Miha Stabuc
- University Medical Centre Ljubljana, Clinical Institute of Radiology, Ljubljana, Slovenia
| | - Miha Petric
- University Medical Centre Ljubljana, Clinical Department of Abdominal Surgery, Ljubljana, Slovenia
| | - Lojze M. Smid
- University Medical Centre Ljubljana, Clinical Department of Gastroenterology, Ljubljana, Slovenia
| | - Rado Jansa
- University Medical Centre Ljubljana, Clinical Department of Gastroenterology, Ljubljana, Slovenia
| | - Bostjan Plesnik
- University Medical Centre Ljubljana, Clinical Department of Abdominal Surgery, Ljubljana, Slovenia
| | - Masa Bosnjak
- Institute of Oncology Ljubljana, Department of Experimental Oncology, Ljubljana, Slovenia
| | - Ursa Lampreht Tratar
- Institute of Oncology Ljubljana, Department of Experimental Oncology, Ljubljana, Slovenia
| | - Blaz Trotovsek
- University Medical Centre Ljubljana, Clinical Department of Abdominal Surgery, Ljubljana, Slovenia
| | - Bor Kos
- University of Ljubljana, Faculty of Electrical Engineering, Ljubljana, Slovenia
| | - Damijan Miklavcic
- University of Ljubljana, Faculty of Electrical Engineering, Ljubljana, Slovenia
| | - Gregor Sersa
- Institute of Oncology Ljubljana, Department of Experimental Oncology, Ljubljana, Slovenia
- University of Ljubljana, Faculty of Health Sciences, Ljubljana, Slovenia
| | - Peter Popovic
- University Medical Centre Ljubljana, Clinical Institute of Radiology, Ljubljana, Slovenia
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23
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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: 199] [Impact Index Per Article: 39.8] [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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24
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Single-needle electroporation and interstitial electrochemotherapy: in vivo safety and efficacy evaluation of a new system. Eur Radiol 2019; 29:6300-6308. [DOI: 10.1007/s00330-019-06251-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 04/12/2019] [Accepted: 04/24/2019] [Indexed: 12/18/2022]
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25
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Hoejholt KL, Mužić T, Jensen SD, Dalgaard LT, Bilgin M, Nylandsted J, Heimburg T, Frandsen SK, Gehl J. Calcium electroporation and electrochemotherapy for cancer treatment: Importance of cell membrane composition investigated by lipidomics, calorimetry and in vitro efficacy. Sci Rep 2019; 9:4758. [PMID: 30894594 PMCID: PMC6427041 DOI: 10.1038/s41598-019-41188-z] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Accepted: 02/20/2019] [Indexed: 12/21/2022] Open
Abstract
Calcium electroporation is a novel anti-cancer treatment investigated in clinical trials. We explored cell sensitivity to calcium electroporation and electroporation with bleomycin, using viability assays at different time and temperature points, as well as heat calorimetry, lipidomics, and flow cytometry. Three cell lines: HT29 (colon cancer), MDA-MB231 (breast cancer), and HDF-n (normal fibroblasts) were investigated for; (a) cell survival dependent on time of addition of drug relative to electroporation (1.2 kV/cm, 8 pulses, 99 µs, 1 Hz), at different temperatures (37 °C, 27 °C, 17 °C); (b) heat capacity profiles obtained by differential scanning calorimetry without added calcium; (c) lipid composition by mass spectrometry; (d) phosphatidylserine in the plasma membrane outer leaflet using flow cytometry. Temperature as well as time of drug administration affected treatment efficacy in HT29 and HDF-n cells, but not MDA-MB231 cells. Interestingly the HT29 cell line displayed a higher phase transition temperature (approximately 20 °C) versus 14 °C (HDF-n) and 15 °C (MDA-MB231). Furthermore the HT29 cell membranes had a higher ratio of ethers to esters, and a higher expression of phosphatidylserine in the outer leaflet. In conclusion, lipid composition and heat capacity of the membrane might influence permeabilisation of cells and thereby the effect of calcium electroporation and electrochemotherapy.
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Affiliation(s)
- K L Hoejholt
- Center for Experimental Drug and Gene Electrotransfer, Department of Oncology, Copenhagen University Hospital Herlev, Herlev, Denmark
| | - T Mužić
- Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
| | - S D Jensen
- Center for Experimental Drug and Gene Electrotransfer, Department of Oncology, Copenhagen University Hospital Herlev, Herlev, Denmark
| | - L T Dalgaard
- Department of Science and Environment, Roskilde University, Roskilde, Denmark
| | - M Bilgin
- Danish Cancer Society Research Center (DCRC), Copenhagen, Denmark
| | - J Nylandsted
- Danish Cancer Society Research Center (DCRC), Copenhagen, Denmark
| | - T Heimburg
- Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
| | - S K Frandsen
- Center for Experimental Drug and Gene Electrotransfer, Department of Oncology, Copenhagen University Hospital Herlev, Herlev, Denmark.
- Center for Experimental Drug and Gene Electrotransfer, Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Roskilde, Denmark.
| | - J Gehl
- Center for Experimental Drug and Gene Electrotransfer, Department of Oncology, Copenhagen University Hospital Herlev, Herlev, Denmark.
- Center for Experimental Drug and Gene Electrotransfer, Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Roskilde, Denmark.
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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26
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Irreversible electroporation for hepatic tumors. J Ultrasound 2019; 22:1-3. [PMID: 30840216 DOI: 10.1007/s40477-019-00367-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 02/21/2019] [Indexed: 01/04/2023] Open
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27
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Large Liver Blood Vessels and Bile Ducts Are Not Damaged by Electrochemotherapy with Bleomycin in Pigs. Sci Rep 2019; 9:3649. [PMID: 30842517 PMCID: PMC6403381 DOI: 10.1038/s41598-019-40395-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 02/15/2019] [Indexed: 12/13/2022] Open
Abstract
The first clinical studies on the use of electrochemotherapy to treat liver tumours that were not amenable to surgery or thermal ablation techniques have recently been published. However, there is still a lack of data on the effects of electrochemotherapy on normal liver tissue. Therefore, we designed a translational animal model study to test whether electrochemotherapy with bleomycin causes clinically significant damage to normal liver tissue, with emphasis on large blood vessels and bile ducts. We performed electrochemotherapy with bleomycin or delivered electric pulses alone using a potentially risky treatment strategy in eight pigs. Two and seven days after treatment, livers were explanted, and histological analysis was performed. Blood samples were collected before treatment and again before euthanasia to evaluate blood biomarkers of liver function and systemic inflammatory response. We found no thrombosis or other clinically significant damage to large blood vessels and bile ducts in the liver. No clinical or laboratory findings suggested impaired liver function or systemic inflammatory response. Electrochemotherapy with bleomycin does not cause clinically significant damage to normal liver tissue. Our study provides further evidence that electrochemotherapy with bleomycin is safe for treatment of patients with tumours near large blood vessels in the liver.
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Granata V, Fusco R, Setola SV, Palaia R, Albino V, Piccirillo M, Grimm R, Petrillo A, Izzo F. Diffusion kurtosis imaging and conventional diffusion weighted imaging to assess electrochemotherapy response in locally advanced pancreatic cancer. Radiol Oncol 2019; 53:15-24. [PMID: 30681974 PMCID: PMC6411027 DOI: 10.2478/raon-2019-0004] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Accepted: 11/18/2018] [Indexed: 02/06/2023] Open
Abstract
Background The aim of the study was to evaluate diagnostic performance of functional parameters derived by conventional mono-exponential approach of diffusion weighted imaging (DWI) and by diffusion kurtosis imaging (DKI) in the assessment of pancreatic tumours treated with electrochemotherapy (ECT). Patients and methods Twenty-one consecutive patients with locally advanced pancreatic adenocarcinoma subjected to ECT were enrolled in a clinical approved trial. Among twenty-one enrolled patients, 13/21 (61.9%) patients were subjected to MRI before and after ECT. DWI was performed with a 1.5 T scanner; a free breathing axial single shot echo planar DWI pulse sequence parameters were acquired using seven b value = 0, 50, 100, 150, 400, 800, 1000 s/mm2. Apparent diffusion coefficient by conventional mono-exponential approach and mean of diffusion coefficient (MD) and mean of diffusional kurtosis (MK) by DKI approach were derived from DWI. Receiver operating characteristic (ROC) analysis was performed and sensitivity, specificity, positive and negative predictive value were calculated. Results Among investigated diffusion parameters, only the MD derived by DKI showed a significant variation of values between pre and post treatment (p = 0.02 at Wilcoxon test) and a significant statistically difference for percentage change between responders and not responders (p = 0.01 at Kruskal Wallis test). MD had a good diagnostic performance with a sensitivity of 80%, a specificity of 100% and area under ROC of 0.933. Conclusions MD derived by DKI allows identifying responders and not responders patients subject to ECT treatment. MD had higher diagnostic performance to assess ECT response compared to conventional DWI derived parameters.
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Affiliation(s)
- Vincenza Granata
- Division of Radiology, Instituto Nazionale Tumori – IRCCS – Fondazione G. Pascale, Napoli, Italia
- Vincenza Granata, Division of Radiology, Instituto Nazionale Tumori – IRCCS – Fondazione G. Pascale, Napoli, Italia. Phone: +39 081 5903 714; Fax:+39 0815903825;
| | | | - Sergio Venanzio Setola
- Division of Radiology, Instituto Nazionale Tumori – IRCCS – Fondazione G. Pascale, Napoli, Italia
| | - Raffaele Palaia
- Division of Hepatobiliary Surgical Oncology, Unit, Instituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Napoli, Italia
| | - Vittorio Albino
- Division of Hepatobiliary Surgical Oncology, Unit, Instituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Napoli, Italia
| | - Mauro Piccirillo
- Division of Hepatobiliary Surgical Oncology, Unit, Instituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Napoli, Italia
| | | | - Antonella Petrillo
- Division of Radiology, Instituto Nazionale Tumori – IRCCS – Fondazione G. Pascale, Napoli, Italia
| | - Francesco Izzo
- Division of Hepatobiliary Surgical Oncology, Unit, Instituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Napoli, Italia
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Campana LG, Edhemovic I, Soden D, Perrone AM, Scarpa M, Campanacci L, Cemazar M, Valpione S, Miklavčič D, Mocellin S, Sieni E, Sersa G. Electrochemotherapy - Emerging applications technical advances, new indications, combined approaches, and multi-institutional collaboration. Eur J Surg Oncol 2018; 45:92-102. [PMID: 30528893 DOI: 10.1016/j.ejso.2018.11.023] [Citation(s) in RCA: 121] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Accepted: 11/30/2018] [Indexed: 12/18/2022] Open
Abstract
The treatment of tumors with electrochemotherapy (ECT) has surged over the past decade. Thanks to the transient cell membrane permeabilization induced by the short electric pulses used by ECT, cancer cells are exposed to otherwise poorly permeant chemotherapy agents, with consequent increased cytotoxicity. The codification of the procedure in 2006 led to a broad diffusion of the procedure, mainly in Europe, and since then, the progressive clinical experience, together with the emerging technologies, have extended the range of its application. Herein, we review the key advances in the ECT field since the European Standard Operating Procedures on ECT (ESOPE) 2006 guidelines and discuss the emerging clinical data on the new ECT indications. First, technical developments have improved ECT equipment, with custom electrode probes and dedicated tools supporting individual treatment planning in anatomically challenging tumors. Second, the feasibility and short-term efficacy of ECT has been established in deep-seated tumors, including bone metastases, liver malignancies, and pancreatic and prostate cancers (long-needle variable electrode geometry ECT), and gastrointestinal tumors (endoscopic ECT). Moreover, pioneering studies indicate lung and brain tumors as suitable future targets. A further advance relates to new combination strategies with immunotherapy, gene electro transfer (GET), calcium EP, and radiotherapy. Finally and fourth, cross-institutional collaborative groups have been established to refine procedural guidelines, promote clinical research, and explore new indications.
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Affiliation(s)
- Luca G Campana
- Department of Surgery Oncology and Gastroenterology (DISCOG), University of Padua, Italy; Surgical Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
| | - Ibrahim Edhemovic
- Department of Surgical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia
| | | | - Anna M Perrone
- Oncologic Gynecology Unit, Sant'Orsola-Malpighi Hospital, Bologna, Italy
| | - Marco Scarpa
- Surgical Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Laura Campanacci
- 3rd Orthopaedic and Traumatologic Clinic Prevalently Oncologic, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Maja Cemazar
- Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia
| | - Sara Valpione
- Christie NHS Foundation Trust, CRUK Manchester Institute, The University of Manchester, Manchester, M20 4GJ, UK
| | - Damijan Miklavčič
- University of Ljubljana, Faculty of Electrical Engineering, Ljubljana, Slovenia
| | - Simone Mocellin
- Department of Surgery Oncology and Gastroenterology (DISCOG), University of Padua, Italy; Surgical Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Elisabetta Sieni
- Department of Industrial Engineering, University of Padua, Italy
| | - Gregor Sersa
- Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia
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