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Electroporation in Vascular Malformations

Electroporation in Vascular Malformations

Vascular malformations are congenital anomalies of the vasculature that persist and grow throughout life, encompassing slow-flow venous and lymphatic lesions as well as fast-flow arteriovenous malformations. Despite their benign histology, they can cause pain, disfigurement, functional impairment and bleeding, and are frequently located in anatomically challenging sites of the head, neck and extremities. Conventional management, such as surgery, percutaneous sclerotherapy, and embolization is often incomplete, carries a substantial recurrence rate, and is difficult to apply to diffuse or infiltrative lesions. This persistent unmet need has driven the search for more targeted, tissue-sparing approaches.

Electroporation entered this field as a direct extension of electrochemotherapy in oncology. It had long been recognized that electrochemotherapy exerts pronounced vascular effects: an immediate transient vasoconstriction, the so-called “vascular lock”, followed by damaging endothelial cells, known as vascular-disrupting effect. Reframing these vascular effects as a therapeutic goal opened the door to treating vascular anomalies. The result is bleomycin electrosclerotherapy (BEST), in which electric pulses dramatically enhance the intracellular uptake of bleomycin by the endothelial cells lining the malformation.

Mechanistically, bleomycin is a potent sclerosant whose action is limited by poor cellular entry. Electroporation overcomes this barrier by delivering a large intracellular dose that triggers endothelial cell death, vessel wall damage, thrombosis, and subsequent fibrosis with shrinkage of the lesion. Because permeabilization is confined to the pulsed volume, the sclerosing effect is spatially targeted and achieved at markedly lower bleomycin doses than those required for conventional sclerotherapy, reducing systemic exposure. However, key aspects of this mechanism, including the precise endothelial response to BEST and how vessel architecture and hemodynamics influence bleomycin distribution within the lesion, remain incompletely understood.

Clinically, BEST has been used most successfully for slow-flow venous and lymphatic malformations, including lesions that proved refractory to standard therapy or were considered inoperable. Both percutaneous and intraoperative treatment are feasible, and the procedure can be repeated. Early multicenter experience has shown high rates of symptomatic improvement and lesion regression with a favorable safety profile, and work is ongoing to extend the approach to more complex and fast-flow anomalies.

This progress builds on tools first developed for oncological electroporation, including pulse generators, adaptable electrode designs, and image-guided planning. Multidisciplinary teams have worked together to bring the method into practice. An emerging international consensus is now consolidating terminology, indications and protocols.

Electroporation-based treatment of vascular malformations exemplifies how a principle established in oncology can be redirected to a distinct clinical problem: minimally invasive, targeted, repeatable and dose-sparing. Continued refinement of hardware, standardized protocols and patient selection promises to widen its role — a development that ISEBTT and its community are helping to shape.

— Contributed by Gregor Serša

References

  1. Markelc B, Serša G, Čemažar M. Differential mechanisms associated with vascular disrupting action of electrochemotherapy: intravital microscopy on the level of single normal and tumor blood vessels. PLoS One. 2013;8(3):e59557. doi:10.1371/journal.pone.0059557
  2. McMorrow L, Shaikh M, Kessell G, Muir T. Bleomycin electrosclerotherapy: new treatment to manage vascular malformations. Br J Oral Maxillofac Surg. 2017 Nov;55(9):977-979. doi: 10.1016/j.bjoms.2017.10.002. Epub 2017 Oct 18.
  3. Wohlgemuth WA, Müller-Wille R, Meyer L, et al. Bleomycin electrosclerotherapy in therapy-resistant venous malformations of the body. J Vasc Surg Venous Lymphat Disord. 2021;9(3):731–739. doi:10.1016/j.jvsv.2020.09.009
  4. Kostusiak M, Murugan S, Muir T. Bleomycin electrosclerotherapy treatment in the management of vascular malformations. Dermatol Surg. 2022;48(1):67–71. doi:10.1097/DSS.0000000000003220
  5. Krt A, Čemažar M, Lovrič D, Serša G, Jamšek Č, Grošelj A. Combining superselective catheterization and electrochemotherapy: a new technological approach to the treatment of high-flow head and neck vascular malformations. Front Oncol. 2022;12:1025270. doi:10.3389/fonc.2022.1025270
  6. Muir T, Bertino G, Grošelj A, et al. Bleomycin electrosclerotherapy (BEST) for the treatment of vascular malformations. An InspECT study group report. Radiol Oncol. 2023;57(2):141–149. doi:10.2478/raon-2023-0029
  7. Muir T, Wohlgemuth WA, Čemažar M, et al. Current Operating Procedure (COP) for Bleomycin ElectroScleroTherapy (BEST) of low-flow vascular malformations. Radiol Oncol. 2024. doi:10.2478/raon-2024-0061
  8. Lisec B, Cemazar M, Muir T, Omerzel M, Jesenko T, Markelc B, Groselj A, Dezman R, Stabuc M, Kuhelj D, Sersa G. Bleomycin ElectroScleroTherapy (BEST): mechanistic parallels to electrochemotherapy, experimental models, and unresolved questions. Radiol Oncol. 2026; 60(1):1-14. doi: 10.2478/raon-2026-0017

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