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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.
Background: No simple staging system has emerged for basal cell carcinomas (BCCs), since they do not follow the TNM process, and practitioners failed to agree on simple clinical or pathological criteria as a basis for a classification. Operational classification of BCCs is required for decision-making, trials and guidelines. Unsupervised clustering of real cases of difficult-to-treat BCCs (DTT-BCCs; part 1) has demonstrated that experts could blindly agree on a five groups classification of DTT-BCCs based on five patterns of clinical situations. Objective: Using this five patterns to generate an operational and comprehensive classification of BCCs. Method: Testing practitioner's agreement, when using the five patterns classification to ensure that it is robust enough to be used in the practice. Generating the first version of a staging system of BCCs based on pattern recognition. Results: Sixty-two physicians, including 48 practitioners and the 14 experts who participated in the generation of the five different patterns of DTT-BCCs, agreed on 90% of cases when classifying 199 DTT-BCCs cases using the five patterns classification (part 1) attesting that this classification is understandable and usable in practice. In order to cover the whole field of BCCs, these five groups of DTT-BCCs were added a group representing the huge number of easy-to-treat BCCs, for which sub-classification has little interest, and a group of very rare metastatic cases, resulting in a four-stage and seven-substage staging system of BCCs. Conclusion: A practical classification adapted to the specificities of BCCs is proposed. It is the first tumour classification based on pattern recognition of clinical situations, which proves to be consistent and usable. This EADO staging system version 1 will be improved step by step and tested as a decision tool and a prognostic instrument.
Cutaneous T cell lymphomas (CTCLs) represent a heterogeneous group of T cell lymphomas that primarily affect the skin. The most frequent forms of CTCL are mycosis fungoides and Sézary syndrome. Both are characterized by frequent recurrence, developing chronic conditions and high mortality with a lack of a curative treatment. In this study, we evaluated the effect of short-chain, cell-permeable C6 Ceramide (C6Cer) on CTCL cell lines and keratinocytes. C6Cer significantly reduced cell viability of CTCL cell lines and induced cell death via apoptosis and necrosis. In contrast, primary human keratinocytes and HaCaT keratinocytes were less affected by C6Cer. Both keratinocyte cell lines showed higher expressions of ceramide catabolizing enzymes and HaCaT keratinocytes were able to metabolize C6Cer faster and more efficiently than CTCL cell lines, which might explain the observed protective effects. Along with other existing skin-directed therapies, C6Cer could be a novel well-tolerated drug for the topical treatment of CTCL.
Background: An experienced life-threating anaphylactic reaction to hymenoptera venom can sustainably impair patients’ quality of life (QoL). Besides carrying emergency medication, venom-specific immunotherapy (VIT) exists as a causal treatment of allergy.
Objective: This study aimed to examine QoL, anxiety, depression, and physical and mental health in patients allergic to hymenoptera venom before and during VIT and the impact of a tolerated sting challenge (SC).
Methods: Between July 2017 and August 2017, 142 patients with venom allergy were analyzed using validated questionnaires as the: Vespid Allergy Quality for Life Questionnaire" (VQLQ-d), the "Hospital Anxiety and Depression Scale" (HADS-D) and the "Short Form 36" (SF-36). To evaluate the impact of VIT and SC on the QoL, patients were divided into 3 groups: (A) VIT and tolerated SC (n = 45), (B) VIT before carrying out SC (n = 73), and (C) therapy-naïve before VIT (n = 20). Further parameters like gender, age, insect species, and severity of the anaphylactic reaction were assessed.
Results: A significant correlation between the health-related QoL and the parameters of gender and state of treatment was seen. Especially male patients, as well as patients allergic to yellow jacket venom, benefit from a SC in terms of a significant increase in their QoL. In the total study cohort, a clear trend was observed towards a higher QoL in patients under VIT who tolerated a SC. Overall, neither the patients’ age nor the insect species exerted a relevant influence on QoL, depression or anxiety. However, women showed a lower QoL combined with higher anxiety and depression scores than men.
Conclusion: Immunotherapy leads to an improved QoL, which can be further increased by a SC. A tolerated SC conceivably reassures the patients by objectifying the treatment success. Female patients appear to have a stronger impaired QoL per se. Taken together, a SC can be performed during VIT to strengthen the patients’ QoL.
Evaluation of 2‑methoxyestradiol serum levels as a potential prognostic marker in malignant melanoma
(2021)
Experimental findings indicated that 2‑methoxyestradiol (2‑ME), an endogenous metabolite of 17β‑estradiol, may exhibit anti‑tumorigenic properties in various types of tumour, such as melanoma and endometrial carcinoma. In patients with endometrial cancer, the serum levels of 2‑ME are decreased compared with those in healthy controls, and this finding has been associated with a poor outcome. The aim of the present study was to examine whether the serum levels of 2‑ME are decreased in patients with melanoma, and whether this decrease may be correlated with disease stage and, therefore, serve as a prognostic indicator. ELISA was used to detect serum levels of 2‑ME in patients with stage I‑IV malignant melanoma (MM). A cohort of 78 patients with MM was analysed, along with 25 healthy controls, among whom 15 were women in the second trimester of pregnancy (positive control). As expected, significantly elevated levels of serum 2‑ME were observed in pregnant control patients compared with those in patients with MM and healthy controls. There was no observed correlation between 2‑ME serum levels in patients with MM and disease stage, tumour thickness, lactate dehydrogenase or S100 calcium‑binding protein B levels. In addition, the 2‑ME levels of patients with MM did not differ significantly from those of normal healthy controls. Overall, the findings of the present study indicated that the 2‑ME serum levels in patients with MM were not decreased, and there was no correlation with early‑ or advanced‑stage disease. Therefore, in contrast to published results on endometrial cancer, endogenous serum 2‑ME levels in MM were not found to be correlated with tumour stage and did not appear to be a suitable prognostic factor in MM.