8. General discussion 203 8. Two studies, a prospective- and retrospective cohort study, were identified that investigated the effectiveness and tolerability of intralesional jet injections to treat keloids with respectively bleomycin, and jet injections with a combination of 5-FU, triamcinolone and lidocaine.11,12 Both cohort studies showed high effectiveness and tolerability with NFI-assisted jet injections to treat keloids. However, the study of Saray et al. in which NFIassisted treatment with bleomycin was given, methodological quality lacked.12 Moreover, a SLI was used in this study, while our previous ex vivo studies show that EPI result in a more favorable biodistribution (consistent and accurate dermal drug delivery) compared to SLI in normal skin. No RCTs that investigated the efficacy, safety and patient satisfaction of NFI-assisted jetinjections in keloids were found. We concluded that high-quality RCTs are warranted to support evidence-based recommendations concerning the usage of NFI-assisted treatment of keloids in clinical practice. The efficacy and safety of intralesional EPI-assisted bleomycin to treat severe keloids Bleomycin owes its working mechanism to cell apoptosis and its anti-angiogenic effect. It binds to DNA strands via electrochemical attraction and cleaves these DNA strands by oxidizing metal ions which creates free radicals.13 In the dermis, bleomycin specifically induces cell apoptosis of keratinocytes and fibroblasts, and thereby suppresses the synthesis of collagen.14 The efficacy and safety of intralesional bleomycin in dermatological indications including keloid was investigated prior to our clinical studies in a previous systematic review that was outside the scope of this thesis.15 This review showed that the intralesional drug delivery of bleomycin was efficacious and safe to treat keloidal scars. Intralesional bleomycin for keloids was investigated in three studies. Importantly, in the study of Neini et al. no recurrences were observed at 3 months followup.16 Other studies that were outside the scope of this review, also found low recurrence rates with intralesional bleomycin treatment in keloids.5 The adverse events were all mild to moderate and included transient symptoms of erythema, hyperpigmentation, pain, superficial necrosis and superficial ulceration. Contraindications of bleomycin are
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