1. Bleomycin electrosclerotherapy (BEST) for the treatment of vascular malformations : an International Network for Sharing Practices on Electrochemotherapy (InspECT) study group reportTobian Muir, Giulia Bertino, Aleš Grošelj, Lakshmi Ratnam, Erika Kis, Joy Odili, Ian McCafferty, Walter A Wohlgemuth, Maja Čemažar, Aljoša Krt, Maša Omerzel, Alessandro Zanasi, Michela Battista, Francesca De Terlizzi, Luca Giovanni Campana, Gregor Serša, 2023, pregledni znanstveni članek Povzetek: Biomedical applications of electroporation are expanding out of the field of oncology into vaccination, treatment of arrhythmias and now in the treatment of vascular malformations. Bleomycin is a widely used sclerosing agent in the treatment of various vascular malformations. The application of electric pulses in addition to bleomycin enhances the effectiveness of the drug, as demonstrated by electrochemotherapy, which utilizes bleomycin in the treatment of tumors. The same principle is used in bleomycin electrosclerotherapy (BEST). The approach seems to be effective in the treatment of low-flow (venous and lymphatic) and, potentially, even high-flow (arteriovenous) malformations. Although there are only a few published reports to date, the surgical community is interested, and an increasing number of centers are applying BEST in the treatment of vascular malformations. Within the International Network for Sharing Practices on Electrochemotherapy (InspECT) consortium, a dedicated working group has been constituted to develop standard operating procedures for BEST and foster clinical trials. By treatment standardization and successful completion of clinical trials demonstrating the effectiveness and safety of the approach, higher quality data and better clinical outcomes may be achieved. Ključne besede: vascular malformations, electrosclerotherapy, bleomycin Objavljeno v DiRROS: 25.07.2024; Ogledov: 296; Prenosov: 94 Celotno besedilo (649,88 KB) |
2. Treatment of vulvar cancer recurrences with electrochemotherapy : a detailed analysis of possible causes for unsuccessful treatmentGregor Vivod, Tanja Jesenko, Gorana Gašljević, Nina Kovačević, Maša Omerzel, Gregor Serša, Sebastjan Merlo, Maja Čemažar, 2023, izvirni znanstveni članek Povzetek: Background. Electrochemotherapy has good local effectiveness in the treatment of vulvar cancer. Most studies have reported the safety and effectiveness of electrochemotherapy for palliative treatment of gynecological cancers and mostly vulvar squamous cell carcinoma. Some tumors, however, fail to respond to electrochemotherapy. The biological features/determinants for the nonresponsiveness are not determined yet. Patient and methods. A recurrence of vulvar squamous cell carcinoma was treated by electrochemotherapy using intravenous administration of bleomycin. The treatment was performed by hexagonal electrodes according to standard operating procedures. We analyzed the factors that could determine nonresponsiveness to electrochemotherapy. Results. Based on the presented case of nonresponsive vulvar recurrence to electrochemotherapy, we hypothesize that the vasculature of the tumors prior to treatment may predict the response to electrochemotherapy. The histological analysis showed minimal presence of blood vessels in the tumor. Thus, low perfusion may reduce drug delivery and lead to a lower response rate because of the minor antitumor effectiveness of vascular disruption. In this case, no immune response in the tumor was elicited by electrochemotherapy. Conclusions. In this case, of nonresponsive vulvar recurrence treated by electrochemotherapy, we analyzed possible factors that could predict treatment failure. Based on histological analysis, low vascularization of the tumor was observed, which hampered drug delivery and distribution and resulted in no vascular disrupting action of electrochemotherapy. All these factors could contribute to ineffective treatment with electrochemotherapy. Ključne besede: electrochemotherapy, bleomycin, vulvar cancer Objavljeno v DiRROS: 25.07.2024; Ogledov: 225; Prenosov: 136 Celotno besedilo (1,49 MB) |
3. Treatment of skin tumors with intratumoral interleukin 12 gene electrotransfer in the head and neck region : a first-in-human clinical trial protocolAleš Grošelj, Maša Omerzel, Tanja Jesenko, Maja Čemažar, Boštjan Markelc, Primož Strojan, Gregor Serša, 2022, izvirni znanstveni članek Povzetek: Immune therapies are currently under intensive investigation providing in many cases excellent re-sponses in different tumors. Other possible approach for immunotherapy is a targeted intratumoral delivery of inter-leukin 12 (IL-12), a cytokine with anti-tumor effectiveness. Due to its immunomodulatory action, it can be used as an imunostimulating component to in situ vaccinating effect of local ablative therapies. We have developed a phIL12 plasmid devoid of antibiotic resistance marker with a transgene for human IL-12 p70 protein. The plasmid can be delivered intratumorally by gene electrotransfer (GET). Patients and methods. Here we present a first-in-human clinical trial protocol for phIL12 GET (ISRCTN15479959, ClinicalTrials NCT05077033). The study is aimed at evaluating the safety and tolerability of phIL12 GET in treatment of basal cell carcinomas in patients with operable tumors in the head and neck region. The study is designed as an ex-ploratory, dose escalating study with the aim to determine the safety and tolerability of the treatment and to identify the dose of plasmid phIL12 that is safe and elicits its biological activity. Conclusions. The results of this trail protocol will therefore provide the basis for the use of phIL12 GET as an adjuvant treatment to local ablative therapies, to potentially increase their local and elicit a systemic response. Ključne besede: skin tumors, gene electrotransfer, interleukin 12, clinical trial Objavljeno v DiRROS: 24.07.2024; Ogledov: 235; Prenosov: 82 Celotno besedilo (477,13 KB) |
4. Sunitinib potentiates the cytotoxic effect of electrochemotherapy in pancreatic carcinoma cellsMaša Omerzel, Tanja Jesenko, Boštjan Markelc, Anja Cerovšek, Gregor Serša, Maja Čemažar, 2022, izvirni znanstveni članek Povzetek: One of the new treatment options for unresectable locally advanced pancreatic cancer is electro-chemotherapy (ECT), a local ablative therapy that potentiates the entry of chemotherapeutic drugs into the cells, by the application of an electric field to the tumor. Its feasibility and safety were demonstrated in preclinical and clinical studies; however, there is a lack of preclinical studies assessing the actions of different drugs used in ECT, their mechanisms and interactions with other target drugs that are used in clinical practice. Materials and methods. The aim of the study was to determine the cytotoxicity of two chemotherapeutic drugs usually used in ECT (bleomycin and cisplatin) in the BxPC-3 human pancreatic carcinoma cell line and evaluate the interactions of ECT with the targeted drug sunitinib. First, the cytotoxicity of ECT using both chemotherapeutics was determined. In the next part, the interactions of ECT and sunitinib were evaluated through determination of combined cytotoxicity, sunitinib targets and kinetics of cell death.Results. The results demonstrate that ECT is effective in pancreatic cancer cell line, especially when bleomycin is used, with the onset of cell death in the first hours after the treatment, reaching a plateau at 20 hours after the treat-ment. Furthermore, we provide the rationale for combining ECT with bleomycin and the targeted drug sunitinib to potentiate cytotoxicity. The combined treatment of sunitinib and ECT was synergistic for bleomycin only at the high-est used concentration of bleomycin 0.14 μM, whereas with lower doses of bleomycin, this effect was not observed. The interaction of ECT and treatment with sunitinib was confirmed by course of the cell death, also indicating on synergism Ključne besede: electrochemotherapy, pancreas, sunitinib, pancreatic cancer Objavljeno v DiRROS: 24.07.2024; Ogledov: 227; Prenosov: 137 Celotno besedilo (1,01 MB) Gradivo ima več datotek! Več... |
5. Radiotherapy-associated angiosarcoma in the breast reconstructed by autologous free-flap and treated with electrochemotherapyRomi Cencelj-Arnež, Jerica Novak, Andreja Klevišar Ivančič, Maša Omerzel, Maja Čemažar, Marko Snoj, 2021, izvirni znanstveni članek Povzetek: Radiotherapy-associated angiosarcoma (RAA) of the breast is a rare complication of radiotherapy, which is often difficult to identify and has poor prognosis. It usually presents as violaceous skin, erythema or rapidly growing palpable firm mass that can be confused with other benign skin lesions. Patients and methods After reviewing the literature, we found only four cases with RAA after mastectomy and autologous breast reconstruction. The presented case is the first that was treated by electrochemotherapy. The patient presented with secondary angiosarcoma of the breast five years after mastectomy, immediate breast reconstruction with deep inferior epigastric artery perforator free flap and adjuvant radiotherapy. Results Electrochemotherapy was feasible, safe and effective in treatment of radiation induced sarcoma. Most of the treated lesions in several consecutive electrochemotherapy sessions responded with complete response, but multiple recurrences occurred in non-treated areas. Conclusions Patients with breast cancer after skin-sparing mastectomy and immediate breast reconstruction, who receive radiotherapy, need regular long-term follow up and low threshold for biopsy of any suspicious lesions is mandatory. Electrochemotherapy proved as one of feasible modalities of treatment for RAA. Ključne besede: angiosarcoma, breast reconstruction, breast cancer, electrochemotherapy Objavljeno v DiRROS: 22.07.2024; Ogledov: 340; Prenosov: 102 Celotno besedilo (797,06 KB) |
6. Percutaneous image guided electrochemotherapy of hepatocellular carcinoma : technological advancementMihajlo Djokić, Rok Dežman, Maja Čemažar, Miha Štabuc, Miha Petrič, Lojze Šmid, Rado Janša, Boštjan Plešnik, Maša Omerzel, Urša Lampreht Tratar, Blaž Trotovšek, Bor Kos, Damijan Miklavčič, Gregor Serša, Peter Popović, 2020, izvirni znanstveni članek Povzetek: 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. Ključne besede: electrochemotherapy, hepatocellular carcinoma, percutaneous, minimally invasive Objavljeno v DiRROS: 12.07.2024; Ogledov: 278; Prenosov: 142 Celotno besedilo (1,52 MB) |
7. Long term response of electrochemotherapy with reduced dose of bleomycin in elderly patients with head and neck non-melanoma skin cancerČrt Jamšek, Gregor Serša, Maša Omerzel, Aleš Grošelj, 2020, izvirni znanstveni članek Povzetek: . Electrochemotherapy (ECT) is a local cancer treatment based on electroporation where the electric field is used to enhance cell membrane permeability and thereby facilitating the transition of chemotherapeutic agents into the cell. For the treatment of non-melanoma skin cancer, a standard dosage of 15,000 IU/m2 bleomycin (BLM) is used. The aim of the present study was to evaluate the long-term ECT response in the group of elderly patients with non-melanoma skin cancer treated with a reduced dose of BLM in comparison to the outcome in the patients treated with the standard dose of BLM. Patients and methods. Twenty-eight patients older than 65 years, with a total of 52 non-melanoma skin lesions were included in the study. Twelve patients (24 lesions) in the experimental group received a reduced dose of BLM (10,000 IU/m2), 16 patients (28 lesions) were treated with a standard dose of BLM (15,000 IU/m2). Results. No statistically significant difference in tumor control was observed between both groups. In the experimental group, tumors recurred in 39.0% of treated lesions in a median follow-up time of 28 months. In the control group, the recurrence rate of treated lesions was 15.4% in a median follow-up time of 40 months. Conclusions. ECT with a reduced dose of BLM is a feasible treatment option for elderly patients with equal efficacy to standard dose treatment and should be considered as a treatment modality in advanced aged patients with comorbidities, where overall life expectancy is poor Ključne besede: electrochemotherapy, bleomycin, non-melanoma skin cancer Objavljeno v DiRROS: 12.07.2024; Ogledov: 286; Prenosov: 62 Celotno besedilo (269,64 KB) |
8. Radiological findings of porcine liver after electrochemotherapy with bleomycinMaja Brložnik, Nina Boc, Gregor Serša, Jan Žmuc, Gorana Gašljević, Alenka Seliškar, Rok Dežman, Ibrahim Edhemović, Nina Milevoj, Tanja Plavec, Vladimira Erjavec, Darja Pavlin, Maša Omerzel, Erik Brecelj, Urša Lampreht Tratar, Bor Kos, Jani Izlakar, Marina Štukelj, Damijan Miklavčič, Maja Čemažar, 2019, izvirni znanstveni članek Objavljeno v DiRROS: 05.07.2024; Ogledov: 284; Prenosov: 131 Celotno besedilo (1,17 MB) Gradivo ima več datotek! Več... |
9. Ultrasonographic changes in the liver tumors as indicators of adequate tumor coverage with electric field for effective electrochemotherapyNina Boc, Ibrahim Edhemović, Bor Kos, Maja Marolt-Mušič, Erik Brecelj, Blaž Trotovšek, Maša Omerzel, Mihajlo Djokić, Damijan Miklavčič, Maja Čemažar, Gregor Serša, 2018, izvirni znanstveni članek Povzetek: The aim of the study was to characterize ultrasonographic (US) findings during and after electrochemotherapy of liver tumors to determine the actual ablation zone and to verify the coverage of the treated tumor with a sufficiently strong electric field for effective electrochemotherapy. Patients and methods. US findings from two representative patients that describe immediate and delayed tumor changes after electrochemotherapy of colorectal liver metastases are presented. Results. The US findings were interrelated with magnetic resonance imaging (MRI). Electrochemotherapy-treated tumors were exposed to electric pulses based on computational treatment planning. The US findings indicate immediate appearance of hyperechogenic microbubbles along the electrode tracks. Within minutes, the tumors became evenly hyperechogenic, and simultaneously, an oedematous rim was formed presenting as a hypoechogenic formation which persisted for several hours after treatment. The US findings overlapped with computed electric field distribution in the treated tissue, indicating adequate coverage of tumors with sufficiently strong electric field, which may predict an effective treatment outcome. Conclusions. US provides a tool for assessment of appropriate electrode insertion for intraoperative electrochemotherapy of liver tumors and assessment of the appropriate coverage of a tumor with a sufficiently strong electric field and can serve as predictor of the response of tumors. Ključne besede: elctrochemotherapy, ultrasound, treatment plan, liver Objavljeno v DiRROS: 11.06.2024; Ogledov: 303; Prenosov: 96 Celotno besedilo (1,07 MB) |
10. Effectiveness of electrochemotherapy after IFN-[alpha] adjuvant therapy of melanoma patientsAndrejc Hribernik, Maja Čemažar, Gregor Serša, Maša Omerzel, Marko Snoj, 2016, izvirni znanstveni članek Povzetek: The combination of electrochemotherapy with immuno-modulatory treatments has already been explored and proven effective. However, the role of interferon alpha (IFN-alpha) adjuvant therapy of melanoma patients and implication on electrochemotherapy effectiveness has not been explored yet. Therefore, the aim of the study was to retrospectively evaluate the effectiveness and safety of electrochemotherapy after the previous adjuvant treatment with IFN-alpha in melanoma patients. Patients and methods. The study was a retrospective single-center observational analysis of the patients with advanced melanoma, treated with electrochemotherapy after previous IFN-alpha adjuvant therapy. Five patients, treated between January 2008 and December 2014, were included into the study, regardless of the time point of IFN-alpha adjuvant therapy. Results. Electrochemotherapy of recurrent melanoma after the IFN-alpha adjuvant therapy proved to be a safe and effective treatment. Patients with one or two metastases responded completely. Among patients with multiple metastases, there was a variable response rate. In one patient all 23 metastases responded completely, in second patient more than 85% of all together 80 metastases responded completely and in third patient all 5 metastases had partial response. Taking into account all metastases from all patients together there was an 85% complete response rate. Conclusions. The study showed that electrochemotherapy of recurrent melanoma after the IFN-alpha adjuvant therapy is a safe and effective treatment modality, which results in a high complete response rate, not only in single metastasis, but also in multiple metastases. The high complete response rate might be due to an IFN-alpha immune-editing effect, however, further studies with a larger number of patients are needed to support this presumption. Ključne besede: electrochemotherapy, IFN-alpha, melanoma Objavljeno v DiRROS: 30.04.2024; Ogledov: 401; Prenosov: 122 Celotno besedilo (898,63 KB) |