Falk H.a· Vissing M.b,c· Wooler G.d· Gehl J.b,c

Author affiliations

aDepartment of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
bCenter for Experimental Drug and Gene Electrotransfer (C*EDGE), Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Roskilde, Denmark
cDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
dDepartment of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark

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Article / Publication Details

Received: November 23, 2020
Accepted: January 06, 2021
Published online: March 31, 2021

Number of Print Pages: 9

Number of Figures: 5

Number of Tables: 4

ISSN: 1018-8665 (Print)
eISSN: 1421-9832 (Online)

For additional information: www.karger.com/DRM


Background: Keloid scarring is a pathologic proliferation of scar tissue that often causes pruritus, pain, and disfigurement. Keloids can be difficult to treat and have a high risk of recurrence. Recent studies have shown promising results in the treatment of cutaneous metastases with intralesional calcium combined with electroporation (calcium electroporation). As calcium electroporation has shown limited side effects it has advantages when treating benign keloid lesions, and on this indication we performed a phase I study. Methods: Patients with keloids were treated with at least 1 session of calcium electroporation and followed up for 2 years. Calcium was administered intralesionally (220 mM) followed by the application of eight 100-µs pulses (400 V) using linear-array electrodes and Cliniporator (IGEA, Italy). Treatment efficacy was evaluated clinically (size, shape, erythema), by patient self-assessment (pruritus, pain, other) and assessed histologically. Results: Six patients were included in this small proof of concept study. Treatment was well tolerated, with all patients requesting further treatment. Two out of 6 patients experienced a decrease in keloid thickness over 30%. A mean reduction of 11% was observed in volume size, and a mean flattening of 22% was observed (not statistically significant). Five out of 6 patients reported decreased pain and pruritus. No serious adverse effects or recurrences were observed over a mean follow-up period of 338 days. Conclusion: In this first phase I clinical study on calcium electroporation for keloids, treatment was found to be safe with minor side effects. Overall, patients experienced symptom relief, and in some patients keloid thickness was reduced.

© 2021 S. Karger AG, Basel


  1. Naylor MC, Brissett AE. Current concepts in the etiology and treatment of keloids. Facial Plast Surg. 2012 Oct;28(5):504–12.

  2. Monstrey S, Middelkoop E, Vranckx JJ, Bassetto F, Ziegler UE, Meaume S, et al. Updated scar management practical guidelines: non-invasive and invasive measures. J Plast Reconstr Aesthet Surg. 2014 Aug;67(8):1017–25.

  3. Bayat A, McGrouther DA, Ferguson MW. Skin scarring. BMJ. 2003 Jan;326(7380):88–92.

  4. Atiyeh BS. Nonsurgical management of hypertrophic scars: evidence-based therapies, standard practices, and emerging methods. Aesthetic Plast Surg. 2007 Sep-Oct;31(5):468–92.

  5. Rusciani L, Paradisi A, Alfano C, Chiummariello S, Rusciani A. Cryotherapy in the treatment of keloids. J Drugs Dermatol. 2006 Jul-Aug;5(7):591–5.

  6. Hoang D, Reznik R, Orgel M, Li Q, Mirhadi A, Kulber DA. Surgical Excision and Adjuvant Brachytherapy vs External Beam Radiation for the Effective Treatment of Keloids: 10-Year Institutional Retrospective Analysis. Aesthet Surg J. 2017 Feb;37(2):212–25.

  7. Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011 Jan-Feb;17(1-2):113–25.

  8. España A, Solano T, Quintanilla E. Bleomycin in the treatment of keloids and hypertrophic scars by multiple needle punctures. Dermatol Surg. 2001 Jan;27(1):23–7.

  9. Saray Y, Güleç AT. Treatment of keloids and hypertrophic scars with dermojet injections of bleomycin: a preliminary study. Int J Dermatol. 2005 Sep;44(9):777–84.

  10. Naeini FF, Najafian J, Ahmadpour K. Bleomycin tattooing as a promising therapeutic modality in large keloids and hypertrophic scars. Dermatol Surg. 2006 Aug;32(8):1023–9.

  11. Falk H, Lambaa S, Johannesen HH, Wooler G, Venzo A, Gehl J. Electrochemotherapy and calcium electroporation inducing a systemic immune response with local and distant remission of tumors in a patient with malignant melanoma – a case report. Acta Oncol. 2017 Aug;56(8):1126–31.

  12. Falk H, Matthiessen LW, Wooler G, Gehl J. Calcium electroporation for treatment of cutaneous metastases; a randomized double-blinded phase II study, comparing the effect of calcium electroporation with electrochemotherapy. Acta Oncol. 2018 Mar;57(3):311–9.

  13. Plaschke CC, Gehl J, Johannesen HH, Fischer BM, Kjaer A, Lomholt AF, et al. Calcium electroporation for recurrent head and neck cancer: A clinical phase I study. Laryngoscope Investig Otolaryngol. 2019 Jan;4(1):49–56.

  14. Bong AH, Monteith GR. Calcium signaling and the therapeutic targeting of cancer cells. Biochim Biophys Acta Mol Cell Res. 2018 Nov;1865(11 11 Pt B):1786–94.

  15. Gehl J, Skovsgaard T, Mir LM. Enhancement of cytotoxicity by electropermeabilization: an improved method for screening drugs. Anticancer Drugs. 1998 Apr;9(4):319–25.

  16. Frandsen SK, Gissel H, Hojman P, Tramm T, Eriksen J, Gehl J. Direct therapeutic applications of calcium electroporation to effectively induce tumor necrosis. Cancer Res. 2012 Mar;72(6):1336–41.

  17. Kunte C, Letulé V, Gehl J, Dahlstroem K, Curatolo P, Rotunno R, et al.; InspECT (the International Network for Sharing Practices on Electrochemotherapy). Electrochemotherapy in the treatment of metastatic malignant melanoma: a prospective cohort study by InspECT. Br J Dermatol. 2017 Jun;176(6):1475–85.

  18. Gehl J, Sersa G, Matthiessen LW, Muir T, Soden D, Occhini A, et al. Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases. Acta Oncol. 2018 Jul;57(7):874–82.

  19. Matthiessen LW, Keshtgar M, Curatolo P, Kunte C, Grischke EM, Odili J, et al. Electrochemotherapy for Breast Cancer-Results From the INSPECT Database. Clin Breast Cancer. 2018 Oct;18(5):e909–17.

  20. Sainsbury DC, Allison KP, Muir T. Electrochemotherapy treatment of a recalcitrant earlobe keloid scar with chronic lymphocytic leukaemia infiltration. J Plast Reconstr Aesthet Surg. 2010 Oct;63(10):e733–6.

  21. Manca G, Pandolfi P, Gregorelli C, Cadossi M, de Terlizzi F. Treatment of keloids and hypertrophic scars with bleomycin and electroporation. Plast Reconstr Surg. 2013 Oct;132(4):621e–30e.

  22. Frandsen SK, Gissel H, Hojman P, Eriksen J, Gehl J. Calcium electroporation in three cell lines: a comparison of bleomycin and calcium, calcium compounds, and pulsing conditions. Biochim Biophys Acta. 2014 Mar;1840(3):1204–8.

  23. Hansen EL, Sozer EB, Romeo S, Frandsen SK, Vernier PT, Gehl J. Dose-dependent ATP depletion and cancer cell death following calcium electroporation, relative effect of calcium concentration and electric field strength. PLoS One. 2015 Apr;10(4):e0122973.

  24. Gargiulo M, Papa A, Capasso P, Moio M, Cubicciotti E, Parascandolo S. Electrochemotherapy for non-melanoma head and neck cancers: clinical outcomes in 25 patients. Ann Surg. 2012 Jun;255(6):1158–64.

  25. Matthiessen LW, Johannesen HH, Hendel HW, Moss T, Kamby C, Gehl J. Electrochemotherapy for large cutaneous recurrence of breast cancer: a phase II clinical trial. Acta Oncol. 2012 Jul;51(6):713–21.

  26. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228–47.

  27. Draaijers LJ, Tempelman FR, Botman YA, Tuinebreijer WE, Middelkoop E, Kreis RW, et al. The patient and observer scar assessment scale: a reliable and feasible tool for scar evaluation. Plast Reconstr Surg. 2004 Jun;113(7):1960–5.

  28. Edhemovic I, Brecelj E, Gasljevic G, Marolt Music M, Gorjup V, Mali B, et al. Intraoperative electrochemotherapy of colorectal liver metastases. J Surg Oncol. 2014 Sep;110(3):320–7.

  29. Egeland C, Baeksgaard L, Johannesen HH, Löfgren J, Plaschke CC, Svendsen LB, et al. Endoscopic electrochemotherapy for esophageal cancer: a phase I clinical study. Endosc Int Open. 2018 Jun;6(6):E727–34.

  30. Vitfell-Rasmussen J, Sandvik RM, Dahlstrøm K, Al-Farra G, Krarup-Hansen A, Gehl J. Tumor reduction and symptom relief after electrochemotherapy in a patient with aggressive fibromatosis – a case report. Acta Oncol. 2018 Mar;57(3):431–4.

  31. Frandsen SK, Krüger MB, Mangalanathan UM, Tramm T, Mahmood F, Novak I, et al. Normal and Malignant Cells Exhibit Differential Responses to Calcium Electroporation. Cancer Res. 2017 Aug;77(16):4389–401.

  32. Frandsen SK, Gibot L, Madi M, Gehl J, Rols MP. Calcium Electroporation: Evidence for Differential Effects in Normal and Malignant Cell Lines, Evaluated in a 3D Spheroid Model. PLoS One. 2015 Dec;10(12):e0144028.

Article / Publication Details

Received: November 23, 2020
Accepted: January 06, 2021
Published online: March 31, 2021

Number of Print Pages: 9

Number of Figures: 5

Number of Tables: 4

ISSN: 1018-8665 (Print)
eISSN: 1421-9832 (Online)

For additional information: www.karger.com/DRM

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