To breathe or not to breathe? Hypoxia after pulsed-electric field treatment reduces the effectiveness of electrochemotherapy in vitro.

Bleomycin, which is the most widely used drugs in electrochemotherapy, requires oxygen to be able to make single- or double-strand brakes in DNA. However, the concentration of oxygen in tumours can be lower than 1%. The aim of this study was to find out whether oxygen concentration in the medium in which cells loaded with bleomycin are incubated, affects the effectiveness of electrochemotherapy in vitro. Experiments were carried out on mouse hepatoma MH-22A cells. Cells were loaded with bleomycin by using a single square-wave electric pulse (2 kV/cm, 100 µs) under normoxic conditions, seeded into Petri dishes, and grown under normoxic and hypoxic conditions. Cell viability was determined by means of a colony-forming assay. We demonstrated that when cells loaded with bleomycin were incubated in hypoxia (0.2% O2), up to 5.3-fold higher concentrations of bleomycin were needed to kill them in comparison with cells grown in normoxia (18.7% O2).

Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases.

Electrochemotherapy is now in routine clinical use to treat cutaneous metastases of any histology, and is listed in national and international guidelines for cutaneous metastases and primary skin cancer. Electrochemotherapy is used by dermatologists, surgeons, and oncologists, and for different degrees and manifestations of metastases to skin and primary skin tumours not amenable to surgery. This treatment utilises electric pulses to permeabilize cell membranes in tumours, thus allowing a dramatic increase of the cytotoxicity of anti-cancer agents. Response rates, often after only one treatment, are very high across all tumour types. The most frequent indications are cutaneous metastases from malignant melanoma and breast cancer. In 2006, standard operating procedures (SOPs) were written for this novel technology, greatly facilitating introduction and dissemination of the therapy. Since then considerable experience has been obtained treating a wider range of tumour histologies and increasing size of tumours which was not originally thought possible. A pan-European expert panel drawn from a range of disciplines from dermatology, general surgery, head and neck surgery, plastic surgery, and oncology met to form a consensus opinion to update the SOPs based on the experience obtained. This paper contains these updated recommendations for indications for electrochemotherapy, pre-treatment information and evaluation, treatment choices, as well as follow-up.

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)

Irreversible electoporation, a new modality in focal therapy for prostate cáncer / Electroporación irreversible: una nueva modalidad en Terapia Focal del cáncer de próstata

The extensive use of prostate-specific antigen (PSA) testing and improved imaging technologies have resulted in an increased diagnosis of prostate cancer. Early diagnosis is often accompanied by an increased number of localized (i.e. unifocal or unilateral), small-volume and low-grade prostate cancers. Focal therapy is an emerging treatment option in prostate cancer, targeting individual cancer areas while sparing important functional and anatomical urological structures. Irreversible electroporation is an innovative treatment modality in focal therapy based on Arch. Esp. Urol. 2016; 69 (6): 337-344 337 the process of cell membrane electroporation limiting damage to adjacent tissue and vital structures. The first phase I-II trials in humans have shown the safety of IRE for focal ablative therapy of prostate cancer and showed encouraging results considering functional preservation. Histological analysis after IRE showed fibrosis without glandular ducts and necrotic tissue with sharp demarcation between unaffected prostatic glandular tissue and the ablation zone. Short-term oncological results are promising; however more data on long-term oncological outcomes are necessary. New studies with IRE and other focal treatment modalities are initiated to explore opportunities for focal therapy in prostate cancer and to optimize current treatment protocols

El uso extensivo de la prueba del antígeno prostático específico (PSA) y la mejoría de las técnicas de imagen han dado como resultado un aumento del diagnóstico del cáncer de próstata. El diagnóstico precoz se acompaña con frecuencia de un número aumentado de tumores localizados (unifocales o unilaterales), de pequeño volumen y bajo grado. La terapia focal es una opción de tratamiento emergente en cáncer de próstata, dirigida a tratar áreas de cáncer individuales conservando importantes estructuras funcionales y anatómicas. La electroporación irreversible es una modalidad de tratamiento innovadora en terapia focal basada en el proceso de electroporación de membrana celular que limita el daño a los tejidos y estructuras vitales adyacentes. Los primeros ensayos clínicos de fase I-II en humanos han demostrado la seguridad de la electroporación irreversible para terapia ablativa focal del cáncer de próstata y mostraron resultados alentadores considerando la preservación funcional. Los análisis histológicos después de la electroporación mostraron fibrosis sin ductos glandulares y tejido necrótico con clara demarcación entre el tejido glandular prostático no afecto y la zona de ablación. Los resultados oncológicos a corto plazo son prometedores; sin embargo son necesarios más datos y resultados oncológicos a largo plazo. Se están iniciando nuevos estudios con electroporación irreversible y otras modalidades de tratamiento focal para explorar las oportunidades de terapia focal en cáncer de próstata y para optimizar los protocolos de tratamiento actuales

An Overview of the Efficacy of a Next Generation Electroceutical Wound Care Device.

Novel approaches including nonpharmacological methodologies for prevention and control of microbial pathogens and emerging antibiotic resistance are urgently needed. Procellera is a wound care device consisting of a matrix of alternating silver (Ag) and zinc (Zn) dots held in position on a polyester substrate with a biocompatible binder. This electroceutical medical device is capable of generating a direct current voltage (0.5-0.9 Volts). Wound dressings containing metals such as Ag and/or Zn as active ingredients are being used for control of colonized and infected wounds. Reports on the presence of electric potential field across epithelium and wound current on wounding have shown that wound healing is enhanced in the presence of an external electrical field. However, majority of the electrical devices require an external power source for delivering pulsed or continuous electric power at the wound site. A microelectric potential-generating system without an external power source is an ideal treatment modality for application in both clinical and field settings. The research presented herein describes efficacy evaluation of a wireless bioelectric dressing against both planktonic and biofilm forms of wound pathogens including multidrug resistant organisms.

Electrochemotherapy: from the drawing board into medical practice.

Electrochemotherapy is a local treatment of cancer employing electric pulses to improve transmembrane transfer of cytotoxic drugs. In this paper we discuss electrochemotherapy from the perspective of biomedical engineering and review the steps needed to move such a treatment from initial prototypes into clinical practice. In the paper also basic theory of electrochemotherapy and preclinical studies in vitro and in vivo are briefly reviewed. Following this we present a short review of recent clinical publications and discuss implementation of electrochemotherapy into standard of care for treatment of skin tumors, and use of electrochemotherapy for other targets such as head and neck cancer, deep-seated tumors in the liver and intestinal tract, and brain metastases. Electrodes used in these specific cases are presented with their typical voltage amplitudes used in electrochemotherapy. Finally, key points on what should be investigated in the future are presented and discussed.

Preclinical validation of electrochemotherapy as an effective treatment for brain tumors.

Electrochemotherapy represents a strategy to enhance chemotherapeutic drug uptake by delivering electrical pulses which exceed the dielectric strength of the cell membrane, causing transient formation of structures that enhance permeabilization. Here we show that brain tumors in a rat model can be eliminated by electrochemotherapy with a novel electrode device developed for use in the brain. By using this method, the cytotoxicity of bleomycin can be augmented more than 300-fold because of increased permeabilization and more direct passage of drug to the cytosol, enabling highly efficient local tumor treatment. Bleomycin was injected intracranially into male rats inoculated with rat glia-derived tumor cells 2 weeks before the application of the electrical field (32 pulses, 100 V, 0.1 ms, and 1 Hz). In this model, where presence of tumor was confirmed by magnetic resonance imaging (MRI) before treatment, we found that 9 of 13 rats (69%) receiving electrochemotherapy displayed a complete elimination of tumor, in contrast to control rats treated with bleomycin only, pulses only, or untreated where tumor progression occurred in each case. Necrosis induced by electrochemotherapy was restricted to the treated area, which MRI and histology showed to contain a fluid-filled cavity. In a long-range survival study, treatment side effects seemed to be minimal, with normal rat behavior observed after electrochemotherapy. Our findings suggest that electrochemotherapy may offer a safe and effective new tool to treat primary brain tumors and brain metastases.