Repetitive Daylight Photodynamic Therapy versus Cryosurgery for Prevention of Actinic Keratoses in Photodamaged Facial Skin: A Prospective, Randomized Controlled Multicentre Two-armed Study.

Actinic keratoses are a chronic condition in ultraviolet-damaged skin, with a risk of progressing to invasive skin cancer. The aim of this study was to investigate the preventive potential of field-directed repetitive daylight photodynamic therapy for actinic keratoses. A randomized trial was performed, including 58 patients with ≥5 actinic keratoses on photodamaged facial skin, who received either 5 full-face sessions of daylight photodynamic therapy within a period of 2 years or lesion-directed cryosurgery. Primary outcome was the mean cumulative number of new actinic keratoses developed between visits 2 and 6 (visit 6 being a follow-up). This outcome was lower after daylight photo-dynamic therapy (7.7) compared with cryosurgery (10.2), but the difference did not reach significance (-2.5, 95% confidence interval -6.2 to 1.2; p=0.18). Several signs of photoageing (fine lines, pigmentation, roughness, erythema, sebaceous gland hyperplasia) were significantly reduced after daylight photodynamic therapy, but not after cryosurgery. Significantly less pain and fewer side-effects were reported during daylight photodynamic therapy than during cryosurgery. This study found that repetitive daylight photodynamic therapy had photo-rejuvenating effects. However, the prevention of actinic keratoses by this therapy could not be proven in a statistically reliable manner.

Topical Diclofenac Reprograms Metabolism and Immune Cell Infiltration in Actinic Keratosis.

Background: Melanoma and squamous cell carcinoma of the skin are characterized by an altered glucose metabolism, but little is known about metabolic changes in precancerous skin lesions such as actinic keratosis (AK). Here, we studied the central carbon metabolism and immune cell infiltrate of actinic keratosis lesions before, under, and 4 weeks after treatment with topical diclofenac (Solaraze®). Methods: This study was designed as a prospective, randomized, controlled, monocentric investigation (ClinicalTrials.gov Identifier: NCT01935531). Myeloid and T cell infiltration was analyzed in skin biopsies from 28 patients by immunohistochemistry. Furthermore, immune cell activation was determined via quantitative real-time PCR (IFN-γ, IL-10, CSF1, TGF-ß, IL-6). Glucose, amino acid and Krebs' cycle metabolism was studied by mass spectrometry prior, during and after treatment with topical diclofenac. Biopsies from sun-exposed, untreated, healthy skin served as controls. Results: Increased lactate and decreased glucose levels suggested accelerated glycolysis in pre-treatment AK. Further, levels of Krebs' cycle intermediates other than citrate and amino acids were elevated. Analysis of the immune infiltrate revealed less epidermal CD1a+ cells but increased frequencies of dermal CD8+ T cells in AK. Treatment with diclofenac reduced lactate and amino acid levels in AK, especially in responding lesions, and induced an infiltration of dermal CD8+ T cells accompanied by high IFN-γ mRNA expression, suggesting improved T cell function. Discussion: Our study clearly demonstrated that not only cancers but also pre-malignant skin lesions, like AK, exhibit profound changes in metabolism, correlating with an altered immune infiltrate. Diclofenac normalizes metabolism, immune cell infiltration and function in AK lesions, suggesting a novel mechanism of action.

Phototherapy-induced elevation of serum level of melanoma inhibitory activity.

BACKGROUND: Phototherapy is a frequently used treatment modality for a variety of dermatologic diseases. UV radiation has different effects on the skin, for example increased production and release of cytokines and other proteins, and is involved in the initiation and progression of skin cancer. Objective of this clinical trial was to investigate potential systemic effects of UV phototherapy on cytokine profiles in blood. METHODS: In a prospective, mono-centric, one-armed study, the serum levels of the melanoma tumour marker "melanoma inhibitory activity" (MIA), Il-1α, Il-4, Il-6, Il-10, TNF-α and IFN-γ of 115 patients with different skin diseases were compared before and 24-48 hours as well as 2-4 weeks after the first phototherapy with PUVA (psoralen and ultraviolet A), UVA or UVB, or both. Data were analysed using linear mixed models. RESULTS: Estimated marginal means of MIA levels were 6.05 ng/mL (95%-CI: 5.37-6.72, range: 2.83-14.49) before the first treatment, which had significantly increased to 6.79 ng/mL 2-4 weeks after the first phototherapy (CI 95%: 6.12-7.47, range: 3.09-15.45; P = 0.0042). MIA levels 2-4 weeks after the first phototherapy were significantly higher than 24-48 hours after the first phototherapy (P = 0.0083). 2-4 weeks after the first treatment, TNF-α levels had decreased significantly (P = 0.033) more in patients with psoriasis who had responded well to phototherapy than in patients unresponsive to treatment. Serum levels of the other cytokines had not changed significantly. CONCLUSIONS: Short-term phototherapy significantly increased the serum levels of the melanoma tumour marker MIA. The potential clinical relevance of these findings (ie an increased risk of melanoma) is unclear and should be further investigated.

Fractional carbon dioxide laser resurfacing of skin grafts: long-term results of a prospective, randomized, split-scar, evaluator-blinded study.

BACKGROUND: Fractional ablative resurfacing is frequently used for treating atrophic and acne scars as well as for the early improvement of scars after surgery. No evidence-based clinical data on improving the appearance of skin grafts by fractional CO2 -laser resurfacing have been available so far. OBJECTIVES: The primary outcome parameter was the adaptation of the skin graft to the surrounding skin 2, 6, and 12 months after the second laser treatment. Secondary outcome parameters were melanin variation, skin roughness, resizing of the skin graft, and patient satisfaction with cosmetic results. METHODS: The randomized half of the skin graft was treated with the fractional CO2 -laser two times in a 4-week interval, whereby the first laser treatment was conducted 3-8 weeks after surgery. Two independent dermatologists assessed the adaptation of the treated area and the untreated control of the skin graft to the surrounding skin using follow-up pictures and an 11-point scale (0 representing no adaptation at all and 10 complete adaptation). RESULTS: Adaptation to the surrounding skin was significantly improved after laser therapy. The mean investigator ratings showed poor adaptation to the surrounding skin before the first treatment (treatment: 2.24 ± 1.00; control group: 1.95 ± 1.27; P < .001; n = 26) but significant improvement at the follow-up visits (8 weeks: treatment: 6.38 ± 1.47; control group 5.29 ± 1.27; P < .001; 6 months: treatment: 7.31 ± 1.24; control group 6.04 ± 0.91; 12 months: treatment: 7.6 ± 1.26; control group: 6.57 ± 1.02; n = 26). After fractional ablative laser treatment, appearance of the skin grafts was significantly improved for all time points. Profilometric analysis showed significantly reduced skin roughness 1 year after laser treatment compared to control (P = .003). Pigmentary irregularities were improved. Melanin distribution was significantly more uniform 1 year after laser treatment compared to control (P = .034). Patients were reasonably satisfied with both sides of the skin graft before treatment but more satisfied with the laser-treated side at the other time points (P < .001). CONCLUSIONS: Adaptation of the skin graft to the surrounding skin was significantly improved after ablative fractional skin resurfacing. Skin roughness and melanin variation were also improved. Patient satisfaction with the appearance of the skin graft was significantly higher after graft resurfacing. Thus, this treatment modality can be recommended for patients wishing to improve the appearance of their skin graft. Lasers Surg. Med. 50:1010-1016, 2018. © 2018 Wiley Periodicals, Inc.