Novel tetrapolar single-needle electrode for electrochemotherapy in bone cavities: Modeling, design and validation.

Electrochemotherapy is a cancer treatment in which local pulsed electric fields are delivered through electrodes. The effectiveness of the treatment depends on exposing the tumor to a threshold electric field. Electrode geometry plays an important role in the resulting electric field distribution, especially in hard-to-reach areas and deep-seated tumors. We designed and developed a novel tetrapolar single-needle electrode for proper treatment in bone cavities. In silico and in vitro experiments were performed to evaluate the electric field and electric current produced by the electrode. In addition, tomography images of a real case of nasal cavity tumor were segmented into a 3D simulation to evaluate the electrode performance in a bone cavity. The proposed electrode was validated and its operating range was set up to 650 V. In the nasal cavity tumor, we found that the electrode can produce a circular electric field of 3 mm with an electric current of 14.1 A at 500 V, which is compatible with electrochemotherapy standards and commercial equipment.

The equivalence of different types of electric pulses for electrochemotherapy with cisplatin - an in vitro study.

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.

Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model.

Despite recent advancements in the diagnosis and treatment of uveal melanoma (UM), its metastatic rate remains high and is accompanied by a highly dismal prognosis, constituting an unmet need for the development of novel adjuvant therapeutic strategies. We established an in vivo chick chorioallantoic membrane (CAM)-based UM xenograft model from UPMD2 and UPMM3 cell lines to examine its feasibility for the improvement of selection of drug candidates. The efficacy of calcium electroporation (CaEP) with 5 or 10 mM calcium chloride (Ca) and electrochemotherapy (ECT) with 1 or 2.5 µg/mL bleomycin in comparison to monotherapy with the tested drug or electroporation (EP) alone was investigated on the generated UM tumors. CaEP and ECT showed a similar reduction of proliferation and melanocytic expansion with a dose-dependent effect for bleomycin, whereas CaEP induced a significant increase of the apoptosis and a reduction of vascularization with varying sensitivity for the two xenograft types. Our in vivo results suggest that CaEP and ECT may facilitate the adequate local tumor control and contribute to the preservation of the bulbus, potentially opening new horizons in the adjuvant treatment of advanced UM.

Comparison of bleomycin polidocanol foam vs electrochemotherapy combined with polidocanol foam for treatment of venous malformations.

OBJECTIVE: This study aims to investigate the difference in safety and efficacy between two treatments for venous malformations (VMs), electrochemotherapy combined with polidocanol foam (ECP) and bleomycin polidocanol foam (BPF), providing alternative therapies for VMs. METHODS: We conducted a retrospective review of 152 patients with VMs treated with ECP and BPF. Pre- and post-treatment magnetic resonance images (MRIs) were collected, and clinical follow-up assessments were performed. Imaging results were used to calculate lesion volume changes. Clinical outcomes included changes in pain and improvements in perceived swelling. Patients were followed up at 1 week and 6 months after surgery. All emerging complications were documented in detail. RESULTS: Of the 152 patients, 87 (57.2%) received BPF treatment, and 65 (42.8%) received ECP treatment. The most common location of VMs was the lower extremities (92/152; 60.2%), and the most common symptom was pain (108/152; 71.1%). Forty-three patients had previously undergone therapy in the BPF group (43/87; 49.4%), whereas 30 patients had received prior treatment in the ECP group (30/65; 46.2%). The study found that the percentage of lesion volume reduction in the BPF group was not significantly different from that in the ECP group (75.00% ± 17.85% vs 74.69% ± 8.48%; P = .899). ECP was more effective when the initial lesion volume was greater than 30 mL (67.66% ± 12.34% vs 73.47% ± 8.00%; P = .048). Patients treated with BPF had significantly less posttreatment pain than those treated with ECP, in different baseline lesion size. In the overall sample, pain relief was significantly higher in the BPF group than in the ECP group (4.21 ± 1.19 vs 3.57 ± 0.76; P = .002). However, there was no difference in pain relief between the two groups for the treatment of initially large VMs (4.20 ± 0.94 vs 3.70 ± 0.87; P = .113). The ECP group was significantly more likely to develop hyperpigmentation (5/87; 5.75% vs 11/65; 16.92%; P = .026) and swelling (9/87; 10.34% vs 16/65; 24.62%; P = .019) 1 week after surgery than the BPF group. CONCLUSIONS: Our study demonstrates that both BPF and ECP are effective treatments for VMs, with BPF being a safer option. ECP is a better choice for patients with the initial lesion volume greater than 30 mL, but it is more likely to lead to early swelling and hyperpigmentation.

Effectiveness and tolerance of electrochemotherapy as palliative therapy for patients with head and neck cancer and malignant melanoma and its relation to early skin reaction.

OBJECTIVES: To evaluate the efficacy and tolerance after the electrochemotherapy treatment for local therapy of cutaneous and subcutaneous metastases of head-and-neck tumors and malignant melanoma refractory to standard therapies, mainly in neck metastasis of squamous cell carcinoma. And, to evaluate the relation of this response according to the skin reaction (healing with ulcer or dry crust). METHODS: prospective pase II, observational clinical study of 56 patients with metastases of head-and-neck squamous cell carcinoma (n=13), papillary thyroid carcinoma (n=4), adenoid cystic carcinoma of parotid gland (n=1) or malignant melanoma (n=37, 5 in head). Patients were treated by electrochemotherapy (application of electrical pulses into the tumor) after the administration of a single intravenous dose of bleomycin. Kaplan-Meier curves were performed. The statistical significance was evaluated using log-rank test; p-value of less than 0.05 was considered as significant. RESULTS: Overall clinical response was observed in 47 patients (84%). Local side effects were mild in all the patients. Ten patients (76.9%) with neck metastasis of squamous cell carcinoma had some degree of response, but only in one was complete. Patients even with only partial response had a higher overall survival than patients without response (p= 0.02). Most of the patients with squamous cell carcinoma had diminution of pain and anxiety. Response rate and overall survival was higher in MM patients (86.5%) than in squamous cell cancer patients (76.9%) (p= 0.043). The healing process (dry crust/ulcer) was not associated with the overall survival (p= 0.86). CONCLUSIONS: Electrochemotherapy is associated a higher overall survival and diminution of pain and anxiety. Therefore, it is an option as palliative treatment for patients with neck metastasis of squamous cell carcinoma refractory to other therapies or even as a concomitant treatment with newer immunotherapies. The type of healing of the surgical wound could not be associated with a higher rate of response or survival. LEVEL OF EVIDENCE: III.

Integrated Time Nanosecond Pulse Irreversible Electroporation (INSPIRE): Assessment of Dose, Temperature, and Voltage on Experimental and Clinical Treatment Outcomes.

OBJECTIVE: This study sought to investigate a novel strategy using temperature-controlled delivery of nanosecond pulsed electric fields as an alternative to the 50-100 microsecond pulses used for irreversible electroporation. METHODS: INSPIRE treatments were carried out at two temperatures in 3D tumor models using doses between 0.001 s and 0.1 s. The resulting treatment zones were quantified using viability staining and lethal electric field intensities were determined numerically. Computational modeling was then used to determine parameters necessary for INSPIRE treatments to achieve equivalent treatment zones to clinical electroporation treatments and evaluate the potential for these treatments to induce deleterious thermal damage. RESULTS: Lethal thresholds between 1109 and 709 V/cm were found for nominal 0.01 s treatments with pulses between 350 ns and 2000 ns at physiological temperatures. Further increases in dose resulted in significant decreases in lethal thresholds. Given these experimental results, treatment zones comparable to clinical electroporation are possible by increasing the dose and voltage used with nanosecond duration pulses. Temperature-controlled simulations indicate minimal thermal cell death while achieving equivalent treatment volumes to clinical electroporation. CONCLUSION: Nanosecond electrical pulses can achieve comparable outcomes to traditional electroporation provided sufficient electrical doses or voltages are applied. The use of temperature-controlled delivery may minimize thermal damage during treatment. SIGNIFICANCE: Intense muscle stimulation and the need for cardiac gating have limited irreversible electroporation. Nanosecond pulses can alleviate these challenges, but traditionally have produced significantly smaller treatment zones. This study suggests that larger ablation volumes may be possible with the INSPIRE approach and that future in vivo studies are warranted.

Surgical Bedside Electrochemotherapy for Local Control of a Recurrent Phylloid Malignant Breast Tumor: A Case Report.

BACKGROUND: We present the case of a recurrent malignant phyllodes tumor of the breast, after mastectomy and radiotherapy, in which electrochemotherapy (ECT) was applied to the tumor bed, to achieve better local control. CASE REPORT: A 66-year-old woman with a large malignant phyllodes tumor of the right breast with a size of 40 cm underwent right radical mastectomy and right axillary lymph node sampling. One month after surgery, with histologically clear margins, the woman presented with multiple small oval masses in the upper portion of the chest wall, indicating rapid disease progression. A second radical excision with clear margins was performed, followed by adjuvant radiotherapy. Two months after the end of treatment, a new 3-cm mass was present in the right axillary extension. The patient underwent a third extensive debulking surgery. At the end of the resection, ECT was applied on the tumor bed along the extensive skin flaps and resection margins. After eight months of follow-up, breast magnetic resonance imaging and total body computed tomography showed disease recurrence in the anterior portion of the right serratus muscle and in the lungs bilaterally. The area undergoing previous ECT showed no disease recurrence. The patient received two lines of palliative chemotherapy. She died 28 months after diagnosis. At the time of death, the large area treated with ECT was geometrically spared from local disease progression. CONCLUSION: This case report suggests the potential efficacy of ECT at the operating bedside to increase local control in aggressive malignancies.

Intraoperative electrochemotherapy of the posterior resection surface after pancreaticoduodenectomy: Preliminary results of a hybrid approach treatment of pancreatic cancer.

BACKGROUND: Despite extensive research in recent decades, pancreatic cancer continues to be among the most lethal forms of cancer, with no substantial increase in survival rates. Local recurrences account for approximately 30 per cent of all disease recurrences. With the intent to improve survival, we designed a novel, hybrid treatment strategy consisting of surgical resection and additional intraoperative electrochemotherapy of the posterior resection surface. We present the study protocols and preliminary findings of a prospective pilot study investigating this treatment approach. METHODS: Consenting patients with resectable pancreatic head ductal adenocarcinoma who met the inclusion criteria were enrolled in the study. After surgical resection, electrochemotherapy with bleomycin was performed using plate electrodes to cover the area between anatomical landmarks. RESULTS: Electrochemotherapy of the posterior resection surface was feasible in all 7 patients. We observed pancreatic fistula grade B in only one patient; all other noted complications were Clavien-Dindo grade 2 or less. The hospital mortality was 0%. CONCLUSIONS: Our preliminary results suggest that a hybrid approach combining surgery with intraoperative electrochemotherapy is safe and feasible.

Combination of Electrochemotherapy with Radiotherapy: A Comprehensive, Systematic, PRISMA-Compliant Review of Efficacy and Potential Radiosensitizing Effects in Tumor Control.

Radiotherapy (RT) and electrochemotherapy (ECT) are established local treatments for cancer. While effective, both therapies have limitations, especially in treating bulky and poorly oxygenated tumors. ECT has emerged as a promising palliative treatment, raising interest in exploring its combination with RT to enhance tumor response. However, the potential benefits and challenges of combining these treatments remain unclear. A systematic review was conducted following PRISMA guidelines. PubMed, Scopus, and Cochrane libraries were searched. Studies were screened and selected based on predefined inclusion and exclusion criteria. Ten studies were included, comprising in vitro and in vivo experiments. Different tumor types were treated with ECT alone or in combination with RT. ECT plus RT demonstrated superior tumor response compared to that under single therapies or other combinations, regardless of the cytotoxic agent and RT dose. However, no study demonstrated a clear superadditive effect in cell survival curves, suggesting inconclusive evidence of specific ECT-induced radiosensitization. Toxicity data were limited. In conclusion, the combination of ECT and RT consistently improved tumor response compared to that with individual therapies, supporting the potential benefit of their combination. However, evidence for a specific ECT-induced radiosensitization effect is currently lacking. Additional investigations are necessary to elucidate the potential benefits of this combination therapy.

Negative effects of cancellation during nanosecond range High-Frequency calcium based electrochemotherapy in vitro.

Drug delivery using nanosecond pulsed electric fields is a new branch of electroporation-based treatments, which potentially can substitute European standard operating procedures for electrochemotherapy. In this work, for the first time, we characterize the effects of ultra-fast repetition frequency (1-2.5 MHz) nanosecond pulses (5-9 kV/cm, 200 and 400 ns) in the context of nano-electrochemotherapy with calcium. Additionally, we investigate the feasibility of bipolar symmetric (↑200 ns + ↓200 ns) and asymmetric (↑200 ns + ↓400 ns) nanosecond protocols for calcium delivery. The effects of bipolar cancellation and the influence of interphase delay (200 ns) are overviewed. Human lung cancer cell lines A549 and H69AR were used as a model. It was shown that unipolar pulses delivered at high frequency are effective for electrochemotherapy with a significant improvement in efficiency when the delay between separate pulses is reduced. Bipolar symmetric pulses trigger the cancellation phenomenon limiting applications for drug delivery and can be compensated by the asymmetry of the pulse (↑200 ns + ↓400 ns or ↑400 ns + ↓200 ns). The results of this study can be successfully used to derive a new generation of nsPEF protocols for successful electrochemotherapy treatments.

Evaluation of the safety and feasibility of electrochemotherapy with intravenous bleomycin as local treatment of bladder cancer in dogs.

Local treatment of canine urothelial carcinoma (UC) of the bladder is a challenge. More than 90% of the cases invade the muscular layer, more than 50% develop on bladder sites with a difficult surgical approach and often requiring radical surgical procedures. This study aims to evaluate the safety and feasibility of electrochemotherapy (ECT) with intravenous bleomycin (BLM) as a local therapy for bladder UC. This prospective study included 21 dogs with spontaneous bladder UC. Regional/distant metastases and neoplastic infiltration of the serosa was considered the main exclusion criteria. We had no deaths during ECT or in the immediate postoperative period, and no suture dehiscence. Most dogs (19/21) developed mild adverse effects, whereas two dogs developed ureteral stenosis. Complete response (CR) was achieved in 62% of the cases (13/21), while partial response (PR) was achieved in 24% (5/21). The median survival and disease-free survival times were 284 and 270 days, respectively. Overall survival was significantly better in the dogs who achieved a CR. In conclusion, ECT was well-tolerated in dogs with UC, demonstrating its safety and feasibility. These data pave the way for new studies aimed at evaluating the effectiveness of ECT in canine bladder UC as a translational model for human disease.

[Electrochemotherapy in metastatic melanoma]. / Elektrokemoterápia áttétes melanomában.

INTRODUCTION: In metastatic melanoma, despite the increased survival rates with new innovative therapies, therapeutic response is still quite heterogenous, not always durable. In the case of oligoprogression, several additional therapeutic modalities are available such as electrochemotherapy in the local treatment of cutaneous or subcutaneous metastases. OBJECTIVE: Analysis of our experiences with electrochemotherapy in patients with metastatic melanoma. METHOD AND RESULTS: 23 patients with metastatic melanoma (10 male and 13 female) were treated with electrochemotherapy, between 2016 and 2021 in our Institute. Median age was 74.5 years. The location of metastases varied. 13 of our patients (57%) had metastases on the lower limbs, in 5 cases (22%) metastases were located in the head and neck region, in 4 cases (17%) on the upper limbs, and one (4%) patient received electrochemotherapy for metastases located on the chest. Prior to electrochemotherapy, 7 patients (30%) received chemotherapy, 6 patients (26%) were treated with immunotherapy and 2 patients (9%) received targeted therapy, while electrochemotherapy was first-line treatment for 8 patients (35%). Complete remission was achieved in 12 cases (52%), and partial remission in 6 cases (26%). In 1 case (4%) stable disease was observed, and in 4 patients (35%) progression was detected. We continued the previous systemic therapy which was effective in other localizations after the electrochemotherapy in 8 patients (35%) and in the case of 4 patients (17%) no further systemic therapy was needed. Side effects were observed in 8 patients (35%), 1 had severity of G3. CONCLUSION: Electrochemotherapy in melanoma results in effective local tumor control, improved quality of life, and survival advantage in most of the patients, with tolerable side effects. Orv Hetil. 2023; 164(35): 1381-1386.

[Electrochemotherapy for multiple cutaneous tumors in immunosuppressed patients]. / Immunszupprimált betegek multiplex bordaganatainak elektrokemoterápiás kezelése.

INTRODUCTION: The risk of cutaneous malignancies is significantly higher in immunosuppressed patients compared to the general population. These high-risk skin tumors tend to be aggressive, multiplex, rapidly growing lesions. It is common to see local recurrence after surgical excision. Multiplex tumors are difficult to treat, especially in the head/neck region. OBJECTIVE: Amongst the standard treatment options, electrochemotherapy can be a suitable option. Our aim was to evaluate the efficacy of electrochemotherapy in immunocompromised patients. METHOD: In 9 immunosuppressed patients, 118 (average: 13, n = 5-27) non-melanoma skin tumors were treated with electrochemotherapy with intravenous administration of bleomycin, according to the ESOPE criteria. RESULTS: The median follow-up was 15 months. 6 months after the treatment, the objective response rate was 96%. We observed complete response in 88%, partial response in 8% and progressive disease in 2% of the treated lesions. In 2%, the response was not evaluable. CONCLUSION: In immunocompromised patients, electrochemotherapy is an effective and safe therapeutic option for non-melanoma skin tumors. In order to provide more ideal management for this special sub-group, prevention, multidisciplinary approach and optimized immunosuppressive therapy is essential. Orv Hetil. 2023; 164(37): 1462-1468.

Musa acuminata as electroporation model.

Electrochemotherapy (ECT) and Irreversible electroporation (IRE) are cancer treatments based on electric field distribution in tissues. Solanum tuberosum (potato tissue) phantom is known to mimic changes in the electrical conductivity that occur in animal tissues during electroporation (EP). Electric field distribution is assessed through enzymatic staining. However, the 24-h wait for this assessment could slow agile response scenarios. We developed and validated the Musa acuminata (cavendish banana) conductivity model, which quickly evaluates EP by tissue staining. We investigated the frequency response of the tissue using impedance spectroscopy analysis, conductivity changes, and enzymatic staining. We optimized three usual EP models: adapted Gompertz, smoothed Heaviside, and the sigmoid or logistic function. We found dielectric parameters in banana tissue similar to those in potato (electrical conductivity of 0.035 S/m and relative permittivity of 4.1×104). The coefficients of determination R2 were 99.94% (Gompertz), 99.85% (Heaviside), and 99.58% (sigmoid). The sigmoid and Heaviside functions described the calibration and validation electric currents with 95% confidence. We observed the electroporated areas in bananas 3h30m after EP. Staining was significant after 450 V/cm. The conductivity model of Musa acuminata suits treatment planning, hardware development, and training scenarios. Banana phantom supports the 3Rs practice and is a reliable alternative for potato in EP studies.

Electrochemotherapy vs radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies: A systematic review and narrative synthesis.

BACKGROUND: Electrochemotherapy has gained international traction and commendation in national guidelines as an effective tool in the management of cutaneous malignancies not amenable to surgical resection. Despite this, no level 5 evidence exists comparing it to radiotherapy in the treatment of cutaneous malignancies. This systematic review aimed to examine the literature directly and indirectly comparing electrochemotherapy and radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies. MATERIALS & METHODS: The protocol for this review was registered on the PROSPERO International Prospective Register of Systematic Reviews with the protocol ID CRD42021285415. Searches of MEDLINE, Embase, CINAHL, CENTRAL and ClinicalTrials.gov databases were undertaken from database inception to 28 December 2021. Studies in humans comparing treatment with electrochemotherapy to radiotherapy and reporting tumour response with a minimum four week follow-up were eligible. Risk of bias was assessed using the ROBINS-I tool. Results are provided as a narrative synthesis. RESULTS: Two case series with a total of 92 patients were identified as relevant to this study. Both case series examined patients with cutaneous squamous cell carcinoma. One case series examined elderly patients with predominantly head/neck lesions. The other examined younger patients with predominantly limb lesions who had cutaneous squamous cell carcinoma directly attributable to a rare skin condition. CONCLUSION: There is little literature presenting comparative data for electrochemotherapy and radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases. Included studies were marred by serious risk of bias particularly due to confounding. The inherent bias and heterogeneity of the included studies precluded synthesis of a consolidated comparison of clinical outcomes between the two therapies. Further research is required in this domain in the form of clinical trials and observational studies to inform guidelines for electrochemotherapy treatment.

Histologic changes of porcine portal vein anastomosis after electrochemotherapy with bleomycin.

Electrochemotherapy (ECT1) is used for treatment of unresectable abdominal malignancies. This study aims to show that ECT of porcine portal vein anastomosis is safe and feasible in order to extend the indications for margin attenuation after resection of locally advanced pancreatic carcinoma. No marked differences were found between the control group and ECT treated groups. Electroporation thus caused irreversible damage to the vascular smooth muscle cells in tunica media that could bedue to the narrow irreversible electroporation zone that may occur near the electrodes, or due to vasa vasorum thrombosis in the tunica externa. Based on the absence of vascular complications, and similar histological changes in lienal veinanastomosis, we can conclude that ECT of portal vein anastomosis is safe and feasible.

Influence of electric field, blood velocity, and pharmacokinetics on electrochemotherapy efficiency.

The convective delivery of chemotherapeutic drugs in cancerous tissues is directly proportional to the blood perfusion rate, which in turns can be transiently reduced by the application of high-voltage and short-duration electric pulses due to vessel vasoconstriction. However, electric pulses can also increase vessel wall and cell membrane permeabilities, boosting the extravasation and cell internalization of drug. These opposite effects, as well as possible adverse impacts on the viability of tissues and endothelial cells, suggest the importance of conducting in silico studies about the influence of physical parameters involved in electric-mediated drug transport. In the present work, the global method of approximate particular solutions for axisymmetric domains, together with two solution schemes (Gauss-Seidel iterative and linearization+successive over-relaxation), is applied for the simulation of drug transport in electroporated cancer tissues, using a continuum tumor cord approach and considering both the electropermeabilization and vasoconstriction phenomena. The developed global method of approximate particular solutions algorithm is validated with numerical and experimental results previously published, obtaining a satisfactory accuracy and convergence. Then, a parametric study about the influence of electric field magnitude and inlet blood velocity on the internalization efficacy, drug distribution uniformity, and cell-kill capacity of the treatment, as expressed by the number of internalized moles into viable cells, homogeneity of exposure to bound intracellular drug, and cell survival fraction, respectively, is analyzed for three pharmacokinetic profiles, namely one-short tri-exponential, mono-exponential, and uniform. According to numerical results, the trade-off between vasoconstriction and electropermeabilization effects and, consequently, the influence of electric field magnitude and inlet blood velocity on the assessment parameters considered here (efficacy, uniformity, and cell-kill capacity) is different for each pharmacokinetic profile deemed.

Effects of pulse repetition rate in static electrochemotherapy models.

Electroporation alters cell membrane structure and tissue electrical properties by short and intense pulsed electric fields (PEF). Static mathematical models are often used to explain the change in electrical properties of tissues caused by electroporation. Electric pulse repetition rate may play an important role, as tissue dielectric dispersion, electroporation dynamics, and Joule heating may affect the electrical properties. In this work, we investigate the effects on the magnitude of the electric current when the repetition rate of the standard electrochemotherapy protocol is increased. Liver, oral mucosa, and muscle tissues were studied. Ex vivo animal experiments show that the magnitude of the electric current increases when the repetition rate is changed from 1 Hz to 5 kHz (10.8% for liver, 5.8% for oral mucosa, and 4.7% for muscle). Although a correction factor could reduce the error to less than 1%, dynamic models seem to be necessary to analyze different protocol signatures. Authors should be aware that static models and experimental results can only be compared if they use exactly the same PEF signature. The repetition rate is a key information to consider in the pretreatment computer study because the current at 1 Hz PEF differs from a 5 kHz PEF.

Bleomycin electrosclerotherapy (BEST) for the treatment of vascular malformations. An International Network for Sharing Practices on Electrochemotherapy (InspECT) study group report.

BACKGROUND: 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. CONCLUSIONS: 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.