"Your Skin Tells You" Campaign for Keratinocyte Cancers: When Individuals' Selection Makes the Difference.

BACKGROUND: Prevention campaigns for skin cancers have focused primarily on melanoma, and over time there has been increasing awareness of the need to select the population to be screened to maximize program effectiveness. OBJECTIVES: The objective of the study was to report the results of a free dermatological initiative, as part of an awareness campaign dedicated to keratinocyte cancers, targeting individuals pre-selected through a short questionnaire. METHODS: One day of dermatological consultations was held at 15 dermato-oncology referral centers during May 22-June 30, 2021. For selection, individuals answered a telephone interview consisting of 7 yes/no questions on risk factors. Demographics, clinical characteristics of suspicious tumors, and histopathologic diagnosis of excised lesions were collected. Suspicion rate, detection rate, and positive predictive values (PPVs) for any skin cancer, basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma were calculated. RESULTS: A total of 320 individuals (56.9% males; 43.1% females) with a median age of 69.6 (range 21-91) years qualified for the screening initiative. Overall, skin cancers and precancerous lesions were diagnosed in 65.9% of the patients. Suspicion rate was 28.7% for any skin cancer (92/320), 22.8% for BCC (73/320), 4.7% for cSCC (15/320), and 1.2% for melanoma (4/320). Detection rate was 23.4% for any skin cancer (PPV 93.7%), 18.1% for BCC (PPV 95.1%), 4.4% for cSCC (PPV 93.3%), and 0.9% for melanoma (PPV 75%). CONCLUSIONS: Selection of individuals at high risk is a cost-effective approach for early detection campaigns for keratinocyte cancers.

Searching Novel Therapeutic Targets for Scleroderma: P2X7-Receptor Is Up-regulated and Promotes a Fibrogenic Phenotype in Systemic Sclerosis Fibroblasts.

Objectives: Systemic sclerosis (SSc) is a connective tissue disorder presenting fibrosis of the skin and internal organs, for which no effective treatments are currently available. Increasing evidence indicates that the P2X7 receptor (P2X7R), a nucleotide-gated ionotropic channel primarily involved in the inflammatory response, may also have a key role in the development of tissue fibrosis in different body districts. This study was aimed at investigating P2X7R expression and function in promoting a fibrogenic phenotype in dermal fibroblasts from SSc patients, also analyzing putative underlying mechanistic pathways. Methods: Fibroblasts were isolated by skin biopsy from 9 SSc patients and 8 healthy controls. P2X7R expression, and function (cytosolic free Ca2+ fluxes, α-smooth muscle actin [α-SMA] expression, cell migration, and collagen release) were studied. Moreover, the role of cytokine (interleukin-1ß, interleukin-6) and connective tissue growth factor (CTGF) production, and extracellular signal-regulated kinases (ERK) activation in mediating P2X7R-dependent pro-fibrotic effects in SSc fibroblasts was evaluated. Results: P2X7R expression and Ca2+ permeability induced by the selective P2X7R agonist 2'-3'-O-(4-benzoylbenzoyl)ATP (BzATP) were markedly higher in SSc than control fibroblasts. Moreover, increased αSMA expression, cell migration, CTGF, and collagen release were observed in lipopolysaccharides-primed SSc fibroblasts after BzATP stimulation. While P2X7-induced cytokine changes did not affect collagen production, it was completely abrogated by inhibition of the ERK pathway. Conclusion: In SSc fibroblasts, P2X7R is overexpressed and its stimulation induces Ca2+-signaling activation and a fibrogenic phenotype characterized by increased migration and collagen production. These data point to the P2X7R as a potential, novel therapeutic target for controlling exaggerated collagen deposition and tissue fibrosis in patients with SSc.

Computer-assisted melanoma diagnosis: a new integrated system.

In dermatology, attempts at synergy between man and machine have mainly been made to improve melanoma diagnosis. The aim of the present study was to test an 'integrated digital dermoscopy analysis' (i-DDA) system with a series of melanocytic lesions that were benign and malignant in nature, and to evaluate its discriminating power with respect to histological diagnosis. In a retrospective study we used an i-DDA system to evaluate a series of 856 excised, clinically atypical pigmented skin lesions (584 benign and 272 malignant). The system evaluated 48 parameters to be studied as possible discriminant variables, grouped into four categories (geometries, colours, textures and islands of colour) integrated with three personal metadata items (sex, age and site of lesion) and presence/absence of three dermoscopic patterns (regression structures, blue-white veil and polymorphic vascular structures). Stepwise multivariate logistic regression of i-DDA data selected nine variables with the highest possible discriminant power. At the end of the stepwise procedure the percentage of cases correctly classified by i-DDA was 89.2% (100% sensitivity and 40.8% specificity). The limitations of the study included those associated with a retrospective design and the 'a priori' exclusion of nonmelanocytic skin lesions. By incorporating numerical digital features with personal data and some dermoscopic patterns into the learning process, the proposed i-DDA improved the performance of assisted melanoma diagnosis, with the advantage that our results can be objectively repeated in any other clinical setting.

Autologous epidermal cultures and narrow-band ultraviolet B in the surgical treatment of vitiligo.

BACKGROUND: Vitiligo is an acquired skin disorder with a great social impact. It can be successfully treated with autologous epidermal grafting. OBJECTIVE: To evaluate the possibility of treating vitiligo by autologous grafting of epidermal cells and narrow-band ultraviolet B (UVB). METHODS: Autologous epidermal cultures were prepared starting from small biopsies of normally pigmented skin. Cells were cultured on hyaluronic acid membranes using medium supplemented with patient's serum. Cell cultures were grafted onto laser-abraded depigmented areas. Patients underwent narrow-band UVB therapy 3 weeks after grafting. RESULTS: Repigmentation of the grafted areas started 1 month after transplant and continued until 4 months after grafting. All patients were evaluated 3, 6, 12, and 18 months after grafting. At the 18-month follow-up, repigmentation was observed in 75% of patients with focal and segmental vitiligo and in 30% of patients with generalized vitiligo. CONCLUSIONS: This therapy can be considered for the treatment of stable vitiligo (especially focal and segmental) resistant to standard therapies. Their results are encouraging from the clinical and esthetic point of view, although the treatment is costly and highly specialized.

Skin allograft in the treatment of toxic epidermal necrolysis (TEN).

BACKGROUND: TEN is a severe form of exfoliative dermatitis. Its course is acute and its outcome fatal in 40% of cases. Wound cover to prevent fluid/protein loss and infections and to control pain, is the first step, as for burns. Skin allograft can be successfully used for this purpose. OBJECTIVE: We report two cases of TEN with de-epithelialization of 50 and 70% of the total body surface area. The patients were given support therapy and treated with human glycerol-preserved skin allografts for wound cover. METHODS: Patients were grafted with glycerol-preserved donor skin, obtained from a skin bank. RESULTS: Re-epithelization of treated areas was complete in 8 days; pain relief was obtained soon after the graft. CONCLUSIONS: Glycerol-preserved skin allograft is an effective treatment in extensive skin loss, for its barrier and analgesic effect. Quality standards of this product ensure safety and simplicity of use at limited cost.