Adjuvant electrochemotherapy after debulking in canine bone osteosarcoma infiltration.

Osteosarcoma is a bone cancer considered rare to humans, but common in dogs. Dogs and humans share genetic homology and environmental risk factors. Improving the treatment of osteosarcoma in dogs could also be relevant to improve procedures in humans. Traditional treatments of osteosarcoma involve surgery and chemotherapy. Such treatments are commonly aggressive and not possible for many patients. Electrochemotherapy emerges as a minimally invasive, effective, and safe treatment alternative. Electrochemotherapy combines applications of high-intensity electric fields during short periods with anti-cancer drugs to improve its medicine cytotoxicity. Analyzing the electric field distribution, as well as electric current density, are essential to electrochemotherapy success. This paper brings the first case of a canine osteosarcoma treatment performed with bleomycin and electrochemotherapy. We performed in silico studies with finite element method software to observe the electric field distribution. In silico experiments help to verify possibilities and limitations of treating bone destruction and macro or micro tumor infiltrations around the primary tumor mass. Results show that both needle or plate electrodes are feasible to remove the tumor even with invasion into the bone. Plate electrodes perform well in treating micro infiltrations when associated with conductive gel and direct contact between electrode and bone (without soft tissues). Needle electrodes are effective in treating tumor infiltration on external cortical bone. Multiple applications are needed to cover all cranium layers with sufficient electric field intensity. Electrochemotherapy protocol with needle or plate electrodes does not present sufficient electric current density capable of affecting brain tissue, even in cases of bone destruction.

Development of an immuno-electrochemical glass carbon electrode sensor based on graphene oxide/gold nanocomposite and antibody for the detection of patulin.

The presence of fungal-produced patulin in foods poses a high health risk to people because it can cause neurologic and gastrointestinal illnesses. A glass carbon electrode (GCE) sensor was developed for the rapid and sensitive detection of patulin. Anti-patulin-BSA IgG of a rabbit was produced and immobilised on a GCE coated with a graphene oxide/gold nanocomposite. The mycotoxin patulin in the samples could be captured by the anti-patulin-BSA IgG on the surface of the GCE sensor. The spatial hindrance effect of IgG on the GCE sensor was reduced by the reaction between IgG and patulin, resulting in a decrease in the electron transfer resistance. The current changes in the immobilised anti-patulin-BSA IgG GCE sensor exhibited a linear relationship with patulin concentration and facilitated the sensitive detection of patulin. This immuno-electrochemical GCE sensor could rapidly detect patulin in less than 1 min with a detection limit of 5 µg/L.

Investigation of safety for electrochemotherapy and irreversible electroporation ablation therapies in patients with cardiac pacemakers.

BACKGROUND: The effectiveness of electrochemotherapy of tumors (ECT) and of irreversible electroporation ablation (IRE) depends on different mechanisms and delivery protocols. Both therapies exploit the phenomenon of electroporation of the cell membrane achieved by the exposure of the cells to a series of high-voltage electric pulses. Electroporation can be fine-tuned to be either reversible or irreversible, causing the cells to either survive the exposure (in ECT) or not (in IRE), respectively. For treatment of tissues located close to the heart (e.g., in the liver), the safety of electroporation-based therapies is ensured by synchronizing the electric pulses with the electrocardiogram. However, the use of ECT and IRE remains contraindicated for patients with implanted cardiac pacemakers if the treated tissues are located close to the heart or the pacemaker. In this study, two questions are addressed: can the electroporation pulses interfere with the pacemaker; and, can the metallic housing of the pacemaker modify the distribution of electric field in the tissue sufficiently to affect the effectiveness and safety of the therapy? RESULTS: The electroporation pulses induced significant changes in the pacemaker ventricular pacing pulse only for the electroporation pulses delivered during the pacing pulse itself. No residual effects were observed on the pacing pulses following the electroporation pulses for all tested experimental conditions. The results of numerical modeling indicate that the presence of metal-encased pacemaker in immediate vicinity of the treatment zone should not impair the intended effectiveness of ECT or IRE even when the casing is in direct contact with one of the active electrodes. Nevertheless, the contact between the casing and the active electrode should be avoided due to significant tissue heating at the site of the other active electrode for the IRE protocol and may cause the pulse generator to fail to deliver the pulses due to excessive current draw. CONCLUSIONS: The observed effects of electroporation pulses delivered in close vicinity of the pacemaker or its electrodes do not indicate adverse consequences for either the function of the pacemaker or the treatment outcome. These findings should contribute to making electroporation-based treatments accessible also to patients with implanted cardiac pacemakers.

Electrochemotherapy in 3D Ocular Melanoma Spheroids using a Customized Electrode.

Electrochemotherapy (ECT) is the combination of transient pore formation following electric pulse application with the administration of cytotoxic drugs, which enhances the cytotoxic effect of the applied agent due to membrane changes. In vitro 3D culture systems simulate the in vivo tumor growth and preserve the biological characteristics of tumors more accurately than conventional monolayer cell cultures. We describe a protocol for the development of 3D tumor organoids using conjunctival melanoma (CM) and uveal melanoma (UM) cell lines as well as the use of hand-held customized electrodes, suitable for in vitro ECT in the culture well without destruction of the tumor environment. This protocol analyzes the culture and growth of 3D CM and UM spheroids and their reaction to bleomycin (2.5 µg/mL) alone, electroporation (EP) (750 Volts/cm, 8 pulses, 100 µs, 5 Hz) alone, and ECT as a combination of EP and bleomycin. The drug concentration and the EP settings used in this protocol were established as preferred ECT conditions according to previous experiments. The assay used to determine the spheroid viability was conducted 3-7 days following treatment. The effect on viability and growth of the 3D tumor spheroids was significant only after ECT. The customized electrodes are described in detail in order to facilitate the application of pulses in the culture well. This novel treatment of 3D UM and CM spheroids sets a steppingstone for future clinical application.

Electrochemotherapy in treatment of canine oral malignant melanoma and factors influencing treatment outcome.

Background Oral malignant melanoma is the most common, but aggressive oral cancer in dogs with poor prognosis. Electrochemotherapy (ECT) has therapeutic potential in such tumors as effective local treatment. Therefore, the aim of this prospective clinical study was to evaluate treatment effectiveness of ECT in as first line treatment for canine oral malignant melanoma, and search for factors influencing treatment outcome. Methods Sixty-seven canines with primary oral malignant melanoma, non-candidates for first-line therapy, were enrolled. All dogs received ECT and follow-up exams for the span of two years. Results Based on RECIST criteria, the objective response rate was 100%, 89.5%, 57.7%, and 36.4%, in stage I, II, III and IV, respectively. Only patients in stage I, II and III with partial or complete response improved their quality of life. The median time to progression was 11, 7, 4 and 4 months, and median survival time after the treatment was 16.5, 9.0, 7.5 and 4.5 months, for patients in stage I, II, III and IV, respectively. Significantly better was local response in stage I and II disease (p = 0.0013), without the bone involvement (p = 0.043) Conclusions Electrochemotherapy is effective local treatment of oral canine malignant melanoma when no alternative treatment is available. Better response is expected in stage I and II patients with tumors without bone involvement.

Ablation of soft tissue tumours by long needle variable electrode-geometry electrochemotherapy: final report from a single-arm, single-centre phase-2 study.

Standard electrochemotherapy (ECT) is effective in many tumour types but is confined to the treatment of small superficial lesions. Variable electrode-geometry ECT (VEG-ECT) may overcome these limitations by using long freely-placeable electrodes. Patients with bulky or deep-seated soft-tissue malignancies not amenable to resection participated in a single-arm phase-2 study (ISRCTN.11667954) and received a single course of VEG-ECT with intravenous bleomycin (15,000 IU/m2) and concomitant electric pulses applied through an adjustable electrode array. The primary outcome was radiologic complete response rate (CRR) per RECIST; secondary endpoints included feasibility, metabolic response, toxicity (CTCAE), local progression-free survival (LPFS) and patient perception (EQ-5D). During 2009-2014, we enrolled 30 patients with trunk/limb sarcomas, melanoma, Merkel-cell carcinoma, and colorectal/lung cancer. Median tumour size was 4.7 cm. Electrode probes were placed under US/TC guidance (28 and 2 patients, respectively). Median procedure duration was 80 minutes. Tumour coverage rate was 97% (29 of 30 patients). Perioperative side-effects were negligible; one patient experienced grade-3 ulceration and infection. One-month 18F-FDG-SUV decreased by 86%; CRR was 63% (95% CI 44-79%). Local control was durable in 24 of 30 patients (two-year LPFS, 62%). Patients reported an improvement in "usual activities", "anxiety/depression", and "overall health" scores. VEG-ECT demonstrated encouraging antitumour activity in soft-tissue malignancies; a single course of treatment produced high and durable responses, with low complications.

Computer simulation of commercial conductive gels and their application to increase the safety of electrochemotherapy treatment.

Electrochemotherapy (ECT) exploits the phenomenon of electroporation, which is the increase of cell permeability through the application of an electrical field. This technique is applied in medical centers in Europe and in veterinary clinics in Europe, Brazil, and Argentina. ECT treatment requires a minimum electric field and anti-cancer drugs (e.g., bleomycin). Irregularly shaped tumors may induce ECT treatment failure because of irregular electric field distribution. Conductive gels have been suggested as a means to increase the homogeneity of the electrical field distribution. The aim of this work was to evaluate if commercial conductive gels could increase the safety of ECT. A veterinary case study of ECT in a dog provided the tumor dimensions for the numerical model. Electrode displacement and commercial conductive gels were simulated to determine if they improved ECT treatments. We conclude that a commercial gel having a conductivity of 0.2 S/m when used in combination with effective treatment planning may improve the outcome of electrochemotherapy procedures.

Application of electrochemotherapy in the management of primary and metastatic cutaneous malignant tumours: a systematic review and meta-analysis.

Electrochemotherapy is becoming a promising technique for the management of malignancies of skin and non-skin origin. The current review aims to clarify current knowledge on administration of electrochemotherapy for the treatment of various skin tumours. A systematic literature search was performed, up to the end of 2016, on studies in which the application of electrochemotherapy for management of primary and metastatic cutaneous malignant tumours was assessed. Having selected appropriate studies, pooled estimates of mean objective (complete) responses, with 95% confidence intervals (CIs), were calculated to assess treatment efficacy. Finally, the main emerging themes from the papers were discussed in more detail. From 465 records identified through database searching, a total of 128 studies were screened, of which 70 were included for review. After a pooled analysis, the estimate for mean objective response following electrochemotherapy was 84.02% (95% CI: 80.08-87.61). Furthermore, the pooled estimate of objective treatment response of evaluated studies was 83.91% (95% CI: 79.15-88.17%) for bleomycin and 80.82% (95% CI: 66.00-92.36%) for cisplatin. Electrochemotherapy is a feasible, inexpensive, fast and easy technique to perform local treatment, regardless of tumour type, with a low level of adverse effects and patient discomfort. This method can be applied alone for patients with primary cutaneous lesions, or local or locoregional metastases, or as an additional treatment modality in patients with distant metastases.

Recommendations and requirements for reporting on applications of electric pulse delivery for electroporation of biological samples.

Electric field-induced membrane changes are an important approach in the life sciences. However, the developments in knowledge and translational applications face problems of reproducibility. Indeed, a quick survey of the literature reveals a lack of transparent and comprehensive reporting of essential technical information in many papers. Too many of the published scientific papers do not contain sufficient information for proper assessment of the presented results. The general rule/guidance in reporting experimental data should require details on exposure conditions such that other researchers are able to evaluate, judge and reproduce the experiments and data obtained. To enhance dissemination of information and reproducibility of protocols, it is important to agree upon nomenclature and reach a consensus on documentation of experimental methods and procedures. This paper offers recommendations and requirements for reporting on applications of electric pulse delivery for electroporation of biological samples in life science.

Catheter-based endobronchial electroporation is feasible for the focal treatment of peribronchial tumors.

OBJECTIVE: To evaluate the feasibility of catheter-based endobronchial electroporation for the treatment of peribronchial tumors and assess the incidence of treatment-related adverse events. METHODS: Cytotoxicity of electroporation with or without cisplatin or gefitinib was assessed in vitro with lung cancer and normal cell lines. A novel catheter was designed for endobronchial electroporation, and computer simulations were used to predict in vivo treatment effects. Electroporation with the test catheter was performed (2000 V, 70 pulses) in the main bronchus of 8 pigs at 11 locations. Computed tomography imaging was performed before they were killed at 4 hours (6 animals) or 4 weeks (2 animals) posttreatment. Treated airway and surrounding parenchyma were compared with sham treatment via gross and histopathology. RESULTS: Significant cell death due to electroporation and increased cytotoxicity in combination with cisplatin or gefitinib were observed in cancer cells only (P < .05). Simulations predicted penetrative electroporation of peribronchial parenchyma without tissue heating. Electric pulse delivery in vivo induced transient venous and bronchial spasms that resolved without intervention. Cross-sectional measurement of electroporation effects on computed tomography (14.4 ± 1.4 by 10.5 ± 1.3 mm) and gross pathology (17.2 ± 3.0 by 8.8 ± 0.6 mm) were representative of values predicted by simulation (P < .001). Cell death due to irreversible electroporation was observed in bronchial and parenchymal tissue in acute tissue samples. Treated lung rapidly recovered from the effects of electroporation without change in bronchial patency at 4 weeks posttreatment. CONCLUSIONS: Catheter-based endobronchial electroporation is a reproducible technique that can be used to treat peribronchial tumors in combination with cisplatin, without affecting patency of the treated bronchus.

Oral Mucosa Model for Electrochemotherapy Treatment of Dog Mouth Cancer: Ex Vivo, In Silico, and In Vivo Experiments.

Electrochemotherapy (EQT) is a local cancer treatment well established to cutaneous and subcutaneous tumors. Electric fields are applied to biological tissue in order to improve membrane permeability for cytotoxic drugs. This phenomenon is called electroporation or electropermeabilization. Studies have reported that tissue conductivity is electric field dependent. Electroporation numerical models of biological tissues are essential in treatment planning. Tumors of the mouth are very common in dogs. Inadequate EQT treatment of oral tumor may be caused by significant anatomic variations between dogs and tumor position. Numerical models of oral mucosa and tumor allow the treatment planning and optimization of electrodes for each patient. In this work, oral mucosa conductivity during electroporation was characterized by measuring applied voltage and current of ex vivo rats. This electroporation model was used with a spontaneous canine oral melanoma. The model outcomes of oral tumor EQT is applied in different parts of the oral cavity including near bones and the hard palate. The numerical modeling for treatment planning will help the development of new electrodes and increase the EQT effectiveness.

Irreversible electroporation in the eradication of rabbit VX2 cervical tumors.

The aim of this study was to evaluate the effects of irreversible electroporation (IRE) on the eradication of rabbit VX2 cervical tumors. A VX2 cervical cancer model was first made in 20 New Zealand rabbits. IRE ablation was performed for the cervical cancers of 15 rabbits when the diameter of the tumor was about 1.0-1.5 cm. The control group (n = 5) did not receive IRE ablation. The gross pathology, ultrasound, computed tomography, hematoxylin and eosin, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and proliferating cell nuclear antigen immunohistochemical staining were performed to evaluate the efficacy of IRE on cervical cancer. All the rabbits tolerated the IRE ablation without serious complications. The tumors treated by IRE slightly increased in size during the first two days, but decreased gradually. IRE caused tumor cell death efficiently, mainly through cell apoptosis; however, it did not induce complete tumor ablation in our study. The results suggested that IRE could eradicate rabbit VX2 cervical tumors efficiently. However, the optimal IRE parameters remain to be determined.

Electroquimioterapia para el tratamiento del melanoma cutáneo locorregionalmente avanzado irresecable. Revisión sistemática / Electrochemotherapy for the treatment of unresectable locoregionally advanced cutaneous melanoma: a systematic review

La electroquimioterapia (EQT) es una modalidad de tratamiento de lesiones cutáneas y subcutáneas originadas por melanoma u otros tumores. El procedimiento consiste en la administración de agentes antineoplásicos, seguido de impulsos eléctricos locales, para conseguir un efecto conocido como electroporación, que permite la entrada al citosol de medicamentos que no difunden a través de la membrana celular. El objetivo de esta revisión es establecer la evidencia que sustenta la incorporación de la EQT como estrategia terapéutica en el melanoma. Además, se ha llevado a cabo una revisión sistemática de la literatura con síntesis cualitativa. Se ha realizado una búsqueda cualificada de la literatura en bases de datos referenciales y a texto completo. Fueron seleccionados 7 estudios: 3 revisiones sistemáticas y 4 series de casos. La calidad de la evidencia encontrada no es buena, pero la coincidencia de sus resultados en algunas las variables le da consistencia. Los metaanálisis muestran resultados a favor de la EQT frente a la quimioterapia. La EQT parece un procedimiento efectivo en el tratamiento local de nódulos tumorales malignos (nivel medio o bajo de calidad de la evidencia). Es un tratamiento fácil de administrar, económico y bien tolerado con el que se consigue respuesta objetiva en circunstancias determinadas. No hay evidencia de que pueda afectar el curso natural de la enfermedad, por lo que debe considerarse un tratamiento paliativo. Con un nivel de la evidencia 1- (1 menos), puede recomendarse la incorporación de la EQT para el tratamiento paliativo del melanoma locorregionalmente avanzado irresecable (fuerza de la recomendación: B)

Electrochemotherapy is a therapeutic option for the treatment of cutaneous and subcutaneous metastases from melanoma and other tumors. The procedure consists of the administration of anticancer drugs followed by locally applied electrical impulses to achieve an effect known as electroporation, which facilitates entry into the cytosol of drugs that cannot cross the cell membrane. The aim of this review is to evaluate the evidence that supports the use of electrochemotherapy as a therapeutic strategy in melanoma. We conducted a qualitative systematic review of the literature using advanced searches of bibliographic databases and full text reviews. Seven studies (3 systematic reviews and 4 cases series) were selected. The quality of the evidence was not good, but the coincidence of results for certain variables supports their consistency. Results of the meta-analyses favored electrochemotherapy over chemotherapy. Electrochemotherapy appears to be an effective procedure for the local treatment of malignant tumor nodules (evidence of intermediate or low quality). This inexpensive method is simple to apply, well tolerated, and achieves objective responses under certain circumstances. There is no evidence that electrochemotherapy alters the natural course of the disease and it should therefore be considered a palliative treatment. With an evidence level of 1- (minus), electrochemotherapy can be recommended for the palliative treatment of unresectable, locoregionally advanced melanoma (grade B recommendation)

Electrochemotherapy in the treatment of metastatic malignant melanoma: a prospective cohort study by InspECT.

BACKGROUND: (ECT) is an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour. OBJECTIVES: To investigate the effectiveness of ECT in cutaneous metastases of melanoma and to identify factors that affect (beneficially or adversely) the outcome. METHODS: Thirteen cancer centres in the International Network for Sharing Practices on Electrochemotherapy consecutively and prospectively uploaded data to a common database. ECT consisted of intratumoral or intravenous injection of bleomycin, followed by application of electric pulses under local or general anaesthesia. RESULTS: In total, 151 patients with metastatic melanoma were identified from the database, 114 of whom had follow-up data of 60 days or more. Eighty-four of these patients (74%) experienced an overall response (OR = complete response + partial response). Overall, 394 lesions were treated, of which 306 (78%) showed OR, with 229 showing complete response (58%). In multivariate analysis, factors positively associated with overall response were coverage of deep margins, absence of visceral metastases, presence of lymphoedema and treatment of nonirradiated areas. Factors significantly associated with complete response to ECT treatment were coverage of deep margins, previous irradiation of the treated area and tumour size (< 3 cm). One-year overall survival in this cohort of patients was 67% (95% confidence interval 57-77%), while melanoma-specific survival was 74% (95% confidence interval 64-84%). No serious adverse events were reported, and the treatment was in general very well tolerated. CONCLUSIONS: ECT is a highly effective local treatment for melanoma metastases in the skin, with no severe adverse effects noted in this study. In the presence of certain clinical factors, ECT may be considered for local tumour control as an alternative to established local treatments, or as an adjunct to systemic treatments.

Electroporación percutánea irreversible de un tumor renal: manejo anestésico / Percutaneous irreversible electroporation of a renal tumor: anesthetic management

La electroporación percutánea irreversible (EPI) es un novedoso método de ablación tumoral. Mediante la aplicación al tumor y tejidos adyacentes de breves pulsos eléctricos de alto voltaje se generan alteraciones en la permeabilidad de la membrana de sus células, lo cual termina provocando su muerte. Este alto voltaje aplicado precisa la actuación del anestesiólogo, ya que existe riesgo de desarrollar importantes complicaciones, como arritmias cardíacas o convulsiones. Presentamos el caso de un varón de 66 años diagnosticado de adenocarcinoma renal y sometido a EPI para su ablación con intención curativa bajo anestesia general. Se trata del primer caso en el que se realiza esta técnica en España (AU)

Percutaneous irreversible electroporation (IRE) is a novel tumour ablation method. The application of short and high-voltage electrical pulses to the target lesion induces alterations in cell membrane permeability, finally causing tumour cell death. The extremely high-voltage that is needed in this technique requires the surveillance and management of an experienced anaesthesiologist, as it involves a significant risk of complications, such as cardiac arrhythmias or seizures. The case is presented of a 66 year-old patient diagnosed with a renal adenocarcinoma, and who received without intention-to-cure IRE under general anaesthesia. This case represents the first time this type of technique is used in Spain (AU)

Tissue Ablation by a Synergistic Combination of Electroporation and Electrolysis Delivered by a Single Pulse.

A synergistic combination of electroporation and electrolysis (SEE) has been found with distinct advantages over tissue ablation by electrolysis or electroporation alone. Minimally invasive tissue ablation by electrolysis uses a low magnitude direct electric current to produce a lesion due to the creation of chemical products that result in cell death. Electroporation creates permeabilizations in the cell membrane which may lead to loss of cell homeostasis and cell death. When these two modes of tissue ablation are combined, a more effective method of cell death is achieved, likely due to the ability of electrolytic products to access the cell interior through the permeabilized cell membrane. Here, a new method of achieving SEE tissue ablation is obtained through the application of a single exponential decay pulse. This parametric study explores the mechanisms of damage as a function of the initial electric field and amount of delivered charge. It is seen that treatment parameters can dictate the mode of tissue ablation, either by SEE or by irreversible electroporation alone.

Conductive Gel Increases the Small Tumor Treatment With Electrochemotherapy Using Needle Electrodes.

The combination of chemotherapy drugs and high electric field treatment in local cancer is named electrochemotherapy. The European Standard Operation Procedure of Electrochemotherapy (ESOPE) provides guidelines for treatment of cutaneous and subcutaneous tumors. The electrochemotherapy of numerous tumors varying in sizes is more convenient using needle electrodes. However, ESOPE recommends that needle electrodes are applied to deeper tumors. The application of needle electrodes to treatment of superficial small tumors seems to be practical in electrochemotherapy. Plate electrodes and gel improve the electrochemotherapy efficacy. This technique provides electric field homogeneity in irregularly shaped tissue structures (bulk tumors). We propose an investigation of needle electrode and gel in electrochemotherapy of superficial tumors. In vivo experiment with squamous cell carcinoma (SCC) spontaneous nodules in dog was used to validate the mathematical tissue model. The numerical model considers the tissue conductivity dependent on local electric field. Our studies demonstrated that conductive gel is important for effective treatment of superficial tumors with needle electrodes. The needle electrodes and gel presented reduction of medium current, increased the tumor-free margin, and improved the practical application in relation to plate electrode.

Evaluation of the Electroporation Efficiency of a Grid Electrode for Electrochemotherapy: From Numerical Model to In Vitro Tests.

Electrochemotherapy (ECT) is a local anticancer treatment based on the combination of chemotherapy and short, tumor-permeabilizing, voltage pulses delivered using needle electrodes or plate electrodes. The application of ECT to large skin surface tumors is time consuming due to technical limitations of currently available voltage applicators. The availability of large pulse applicators with few and more spaced needle electrodes could be useful in the clinic, since they could allow managing large and spread tumors while limiting the duration and the invasiveness of the procedure. In this article, a grid electrode with 2-cm spaced needles has been studied by means of numerical models. The electroporation efficiency has been assessed on human osteosarcoma cell line MG63 cultured in monolayer. The computational results show the distribution of the electric field in a model of the treated tissue. These results are helpful to evaluate the effect of the needle distance on the electric field distribution. Furthermore, the in vitro tests showed that the grid electrode proposed is suitable to electropore, by a single application, a cell culture covering an area of 55 cm(2). In conclusion, our data might represent substantial improvement in ECT in order to achieve a more homogeneous and time-saving treatment, with benefits for patients with cancer.

[Electroporation: characteristics and therapeutic application of the method (a review)]. / Élektroporatsiia: kharakteristika i lechebnoe ispol'zovanie metoda (obzor).

The article briefly summarizes the currently available information on electroporation and electroporation-based therapy. We consider the definition and the biophysical basis of the method as well as the possible mechanisms underlying the formation of pores under the influence of the application of a pulsed electric field. The characteristics of the devices for electroporation are described and the most typical examples of the use of electroporation and electrochemotherapy in experimental and clinical oncology, dermatology, cosmetology, and other fields of medicine are provided.

Modeling the positioning of single needle electrodes for the treatment of breast cancer in a clinical case.

BACKGROUND: Breast cancer is the most common cancer in women worldwide and is the second most common cause of cancer death in women. Electrochemotherapy (ECT) used in early-phase clinical trials for the treatment of primary breast cancer resulted in a not complete tumor necrosis in most cases. The present study was undertaken to analyze the feasibility to use ECT to treat patients with histologically proven unifocal ductal breast cancer. In particular, results of ECT treatment in a clinical case are compared with the ones of a simplified 3D dosimetric model. METHODS: This clinical study was conducted with the pulse generator Cliniporator Vitae (IGEA, Carpi, Italy). ECT procedures were performed according to ESOPE standard operating procedures. Five single needle electrodes were used with one positioned in the center of the tumor, and the other four distributed around the nodule. Histological images of the resected tumor are compared with the maps of the electric field obtained with a simplified 3D model in Comsol Multiphysics v 4.3. RESULTS: The results of the clinical case demonstrated a reduced efficacy of the ECT treatment described. The proposed simple numerical model of the breast tumor located in a low conductive tissue suggests that this is due to the reduced electric field induced inside the tumor with such 5 electrodes placement. However, where the electric field is predicted higher than the reversible electroporation threshold (E>400 V/cm), also the histological images confirm the necrosis of the target with a good agreement between the modeled and clinical results. CONCLUSIONS: The results suggest the dependence of the effectiveness of the treatment on the careful placement of the electrodes. A detailed planned procedure for the tumor analysis after the treatment is also needed in order to better correlate the single electrode positions and the histological images. Simulation models could be used to identify better electrodes configuration in planning the experimental protocol for ECT treatment of breast tumors.