Molecular and environmental aspects of skin cancers

Skin cancers are one of the most common cancers in the Caucasian population. A constantly increasing number of nonmelanoma skin cancers and malignant melanomas is observed. The incidence of skin cancers is associated mainly with exposure to sunlight. Therefore, agricultural workers who work in open spaces are a particularly vulnerable group. Currently, studies on the pathogenesis of skin cancer focus on the molecular basis associated with ultraviolet radiation. This study is an attempt to summarize the current state of knowledge on this issue. There have been demonstrated mutations in different classes of genes associated with carcinogenesis, including protooncogenes, tumour suppressor genes, genes that control apoptosis, genes encoding transcription factors and DNA repair genes in patients with skin cancers. Mutations in the latter result in reducing the effectiveness of DNA repair and fixation of mutations. All changes at the gene level lead to structural changes, quantitative and dysfunction of proteins encoded by these genes. All these factors contribute to the process of carcinogenesis. Due to increasing number of skin cancers, it seems important to increase knowledge of the molecular basis of skin cancers. This knowledge could be crucial for predicting the course of the disease, and for the development of new therapeutic strategies

Fast Track Algorithm: How To Differentiate A “Scleroderma Pattern” From A “Non-Scleroderma Pattern”

Objectives: This study was designed to propose a simple “Fast Track algorithm” for capillaroscopists of any level of experience to differentiate “scleroderma patterns” from “non-scleroderma patterns” on capillaroscopy and to assess its inter-rater reliability. Methods: Based on existing definitions to categorise capillaroscopic images as “scleroderma patterns” and taking into account the real life variability of capillaroscopic images described standardly according to the European League Against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases, a fast track decision tree, the “Fast Track algorithm” was created by the principal expert (VS) to facilitate swift categorisation of an image as “non-scleroderma pattern (category 1)” or “scleroderma pattern (category 2)”. Mean inter-rater reliability between all raters (experts/attendees) of the 8th EULAR course on capillaroscopy in Rheumatic Diseases (Genoa, 2018) and, as external validation, of the 8th European Scleroderma Trials and Research group (EUSTAR) course on systemic sclerosis (SSc) (Nijmegen, 2019) versus the principal expert, as well as reliability between the rater pairs themselves was assessed by mean Cohen's and Light's kappa coefficients. Results: Mean Cohen's kappa was 1/0.96 (95% CI 0.95-0.98) for the 6 experts/135 attendees of the 8th EULAR capillaroscopy course and 1/0.94 (95% CI 0.92-0.96) for the 3 experts/85 attendees of the 8th EUSTAR SSc course. Light's kappa was 1/0.92 at the 8th EULAR capillaroscopy course, and 1/0.87 at the 8th EUSTAR SSc course. C Conclusion: For the first time, a clinical expert based fast track decision algorithm has been developed to differentiate a “non-scleroderma” from a “scleroderma pattern” on capillaroscopic images, demonstrating excellent reliability when applied by capillaroscopists with varying levels of expertise versus the principal expert and corroborated with external validation.Wo