Position statement on classification of basal cell carcinomas. Part 1: unsupervised clustering of experts as a way to build an operational classification of advanced basal cell carcinoma based on pattern recognition

Background No simple classification system has emerged for 'advanced basal cell carcinomas', and more generally for all difficult-to-treat BCCs (DTT-BCCs), due to the heterogeneity of situations, TNM inappropriateness to BCCs, and different approaches of different specialists. Objective To generate an operational classification, using the unconscious ability of experts to simplify the great heterogeneity of the clinical situations into a few relevant groups, which drive their treatment decisions. Method Non-supervised independent and blinded clustering of real clinical cases of DTT-BCCs was used. Fourteen international experts from different specialties independently partitioned 199 patient cases considered 'difficult to treat' into as many clusters they want (<= 10), choosing their own criteria for partitioning. Convergences and divergences between the individual partitions were analyzed using the similarity matrix, K-mean approach, and average silhouette method. Results There was a rather consensual clustering of cases, regardless of the specialty and nationality of the experts. Mathematical analysis showed that consensus between experts was best represented by a partition of DTT-BCCs into five clusters, easily recognized a posteriori as five clear-cut patterns of clinical situations. The concept of 'locally advanced' did not appear consistent between experts. Conclusion Although convergence between experts was not granted, this experiment shows that clinicians dealing with BCCs all tend to work by a similar pattern recognition based on the overall analysis of the situation. This study thus provides the first consensual classification of DTT-BCCs. This experimental approach using mathematical analysis of independent and blinded clustering of cases by experts can probably be applied to many other situations in dermatology and oncology

AIDS knowledge and attitudes in a Turkish population: an epidemiological study

BACKGROUND: The aim of this study was to investigate and present some pertinent comments concerning Acquired Immunodeficiency Syndrome (AIDS) knowledge, attitudes and misconceptions among the general population in a city of west Turkey. This study was deemed important and relevant due to the increasing importance of AIDS in Turkey and the other countries. METHODS: Using a multistage area sampling method, a random sample of individuals aged 11–83 years, living in 65 different quarters in the city of Eskisehir, Turkey during September, October and November 2004 were interviewed. RESULTS: In all, 1048 respondents completed the survey. In most items, respondents displayed a fairly good to excellent degree of knowledge about HIV/AIDS. Individuals with higher degrees of education indicated more correct responses in all items relating to knowledge of HIV/AIDS. In general, the respondents' attitudes towards AIDS and people with AIDS were found to be tolerant and positive, with one answer choice showing that the majority of the respondents agreed with the statement that those with HIV/AIDS must be supported, treated and helped (90.7%). Moreover, the proportions of the respondents' misconceptions were found to be significantly low for all the items. However, nearly one fourth of the respondents agreed with the misconceptions 'AIDS is a punishment by God' and 'One is not infected with HIV/AIDS if engaged in sport and well nourished'. CONCLUSION: In general HIV/AIDS related knowledge was high and people showed positive attitudes. However, people continue to hold misconceptions about AIDS and these need to be addressed by health education programs targeting those at higher risk

The evolving field of Dermato-oncology and the role of dermatologists: Position Paper of the EADO, EADV and Task Forces, EDF, IDS, EBDV-UEMS and EORTC Cutaneous Lymphoma Task Force.

BACKGROUND The incidence of skin cancers has been increasing steadily over the last decades. Although there have been significant breakthroughs in the management of skin cancers with the introduction of novel diagnostic tools and innovative therapies, skin cancer mortality, morbidity and costs heavily burden the society. OBJECTIVE Members of the European Association of Dermato-Oncology, European Academy of Dermatology and Venereology, International Dermoscopy Society, European Dermatology Forum, European Board of Dermatovenereology of the European Union of Medical Specialists and EORTC Cutaneous Lymphoma Task Force have joined this effort to emphasize the fundamental role that the specialist in Dermatology-Venereology has in the diagnosis and management of different types of skin cancer. We review the role of dermatologists in the prevention, diagnosis, treatment and follow-up of patients with melanoma, non-melanoma skin cancers and cutaneous lymphomas, and discuss approaches to optimize their involvement in effectively addressing the current needs and priorities of dermato-oncology. DISCUSSION Dermatologists play a crucial role in virtually all aspects of skin cancer management including the implementation of primary and secondary prevention, the formation of standardized pathways of care for patients, the establishment of specialized skin cancer treatment centres, the coordination of an efficient multidisciplinary team and the setting up of specific follow-up plans for patients. CONCLUSION Skin cancers represent an important health issue for modern societies. The role of dermatologists is central to improving patient care and outcomes. In view of the emerging diagnostic methods and treatments for early and advanced skin cancer, and considering the increasingly diverse skills, knowledge and expertise needed for managing this heterogeneous group of diseases, dermato-oncology should be considered as a specific subspecialty of Dermatology-Venereology

Melanocortin-1 Receptor, Skin Cancer and Phenotypic Characteristics (M-SKIP) Project: Study Design and Methods for Pooling Results of Genetic Epidemiological Studies

Background: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods: Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling. Discussion: Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields

Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma.

Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5 × 10(-8)), as did 2 previously reported but unreplicated loci and all 13 established loci. Newly associated SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes in the associated regions, including one involved in telomere biology.[Please see the Supplementary Note for acknowledgments.]This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.337

Interim Analysis of Phase 2 Results for Cemiplimab in Patients with Metastatic Basal Cell Carcinoma (mBCC) who Progressed on or are Intolerant to Hedgehog Inhibitors (HHIs)

Abstract not available

The effect of donors' demographic characteristics in renal function post-living kidney donation. Analysis of a UK single centre cohort

Introduction: There is a great need to increase the organ donor pool, particularly for living donors. This study analyses the difference in post-living donation kidney function according to pre-donation characteristics of age, genetic relationship with the recipient, sex, ethnicity, and Body Mass Index (BMI). Methods: Retrospective single centre analysis of the trajectory of estimated Glomerular Filtration Rate (eGFR) post-living kidney donation, as a measure of kidney function. Mean eGFR of the different groups was compared at 6 months and during the 60 months follow up. Results: Mean age was 46 ± 13 years, 57% were female, and 60% Caucasian. Mean BMI was 27 ± 5 kg/m2, with more than a quarter of the cohort having a BMI > 30 (26%), and the majority of the donors genetically related to their recipients (56%). The higher decline rate in eGFR was at 6 months after donation, with female sex, non-Caucasian ethnicity, and age lower than 60 years being independently associated with higher recovery in kidney function (p < 0.05). In the 60 months follow up, older age, genetic relationship with the recipient, and male sex led to higher percentual difference in eGFR post-donation. Conclusion: In this study, with a high proportion of high BMI living kidney donors, female sex, age lower than 60 years, and non-genetic relationship with recipient were persistently associated with higher increase in post-donation kidney function. Ethnicity and BMI, per se, should not be a barrier to increasing the living donor kidney pool