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Electroporation-Based Treatments in Urology.

ABSTRACT: The observation that an application of a pulsed electric field (PEF) resulted in an increased permeability of the cell membrane has led to the discovery of the phenomenon called electroporation (EP). Depending on the parameters of the electric current and cell features, electroporation can be either reversible or irreversible. The irreversible electroporation (IRE) found its use in urology as a non-thermal ablative method of prostate and renal cancer. As its mechanism is based on the permeabilization of cell membrane phospholipids, IRE (as well as other treatments based on EP) provides selectivity sparing extracellular proteins and matrix. Reversible EP enables the transfer of genes, drugs, and small exogenous proteins. In clinical practice, reversible EP can locally increase the uptake of cytotoxic drugs such as cisplatin and bleomycin. This approach is known as electrochemotherapy (ECT). Few in vivo and in vitro trials of ECT have been performed on urological cancers. EP provides the possibility of transmission of genes across the cell membrane. As the protocols of gene electrotransfer (GET) over the last few years have improved, EP has become a well-known technique for non-viral cell transfection. GET involves DNA transfection directly to the cancer or the host skin and muscle tissue. Among urological cancers, the GET of several plasmids encoding prostate cancer antigens has been investigated in clinical trials. This review brings into discussion the underlying mechanism of EP and an overview of the latest progress and development perspectives of EP-based treatments in urology.

SUBMITTER: Kielbik A

PROVIDER: S-EPMC7465806 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Electroporation-Based Treatments in Urology.

Kiełbik Aleksander A Szlasa Wojciech W Saczko Jolanta J Kulbacka Julita J

Cancers 20200807 8

The observation that an application of a pulsed electric field (PEF) resulted in an increased permeability of the cell membrane has led to the discovery of the phenomenon called electroporation (EP). Depending on the parameters of the electric current and cell features, electroporation can be either reversible or irreversible. The irreversible electroporation (IRE) found its use in urology as a non-thermal ablative method of prostate and renal cancer. As its mechanism is based on the permeabiliz ...[more]

PMID: 32784598

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Project description:BackgroundIrreversible Electroporation (IRE) is a novel image-guided tissue ablation technology that induces cell death via very short but strong pulsed electric fields. IRE has been shown to have preserving properties towards vessels and nerves and the extracellular matrix. This makes IRE an ideal candidate to treat prostate cancer (PCa) where other treatment modalities frequently unselectively destroy surrounding structures inducing severe side effects like incontinence or impotence. We report the retrospective assessment of 471 IRE treatments in 429 patients of all grades and stages of PCa with 6-year maximum follow-up time.Material and findingsThe patient cohort consisted of low (25), intermediate (88) and high-risk cancers (312). All had multi-parametric magnetic resonance imaging, and 199 men had additional 3D-mapping biopsy for diagnostic work-up prior to IRE. Patients were treated either focally (123), sub-whole-gland (154), whole-gland (134) or for recurrent disease (63) after previous radical prostatectomy, radiation therapy, etc. Adverse effects were mild (19.7%), moderate (3.7%) and severe (1.4%), never life-threatening. Urinary continence was preserved in all cases. IRE-induced erectile dysfunction persisted in 3% of the evaluated cases 12 months post treatment. Mean transient IIEF-5-Score reduction was 33% within 12-month post IRE follow-up and 15% after 12 months. Recurrences within the follow-up period occurred in 10% of the treated men, 23 in or adjacent to the treatment field and 18 outside the treatment field (residuals). Including residuals for worst case analysis, Kaplan Maier estimation on recurrence rate at 5 years resulted in 5.6% (CI95: 1.8-16.93) for Gleason 6, 14.6% (CI95: 8.8-23.7) for Gleason 7 and 39.5% (CI95: 23.5-61.4) for Gleason 8-10.ConclusionThe results indicate comparable efficacy of IRE to standard radical prostatectomy in terms of 5-year recurrence rates and better preservation of urogenital function, proving the safety and suitability of IRE for PCa treatment. The data also shows that IRE, besides focal therapy of early PCa, can also be used for whole-gland ablations, in patients with recurrent PCa, and as a problem-solver for local tumor control in T4-cancers not amenable to surgery and radiation therapy anymore.

Project description:AimThe management of urology patient is currently disrupted by the COVID-19 epidemic. In the field of functional urology, there are clinical situations with a high risk of complication if management is delayed and a great heterogeneity of advisable reprogramming times after cancellation. A prioritization of functional urology procedures is necessary to adapt management during the COVID-19 crisis and to better organize post-epidemic recovery.Material and methodsThe advice of AFU scientific committees in the field of functional urology (neuro-urology, female and perineology, male LUTS) was requested and supplemented by a review of the currently available recommendations on the subject of urology and COVID-19. These opinions were combined to draw up temporary recommendations to help reorganize practices during the epidemic and prepare the post-critical phase.ResultsMost of the recommendations available on career-oriented social networks (Twitter, LinkedIn) or in literature concern cancer or general urology. Eight out of ten propose a cancellation of all functional urology procedures without distinction. But the 3 AFU committees covering the field of functional urology have identified three clinical situations in which surgical procedures that can be maintained during the COVID-19 epidemic (priority level A): conclusion of a neuromodulation test in progress (implantation or explantation), botulinum toxin A bladder injections for unbalanced neurologic bladder, cystectomy and ileal conduit for urinary fistula in perineal bedsore or refractory unbalanced neurologic bladder with acute renal failure and vesico-enteric or prostato-pubic fistulas. Management adaptation of the other pathologies are proposed, as well as the application of 3 priority levels (B, C, D) for rescheduled procedures for a better management of the post-crisis activity resumption.ConclusionThe joint functional urology committees indicate that there are specific clinical situations in this field that demand non-delayed care during COVID crisis. They underline the need to establish a hierarchy for the cancelled surgeries, in order to reduce the arm of long reschedule delays and to optimize post-lockdown activity resumption.

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Electroporation-Based Treatments in Urology.

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Electroporation-Based Treatments in Urology.

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