Epiluminiscence or surface microscopy for the diagnosis of melanoma and its precursors

Dermatoskopija je pogosta v rutinskem delu dermatologa. Površinska mikroskopija ali epiluminiscenčna mikroskopija je samo nadgradnja. Njen glavni pomen je pri diferencialni diagnozi pigmentnih sprememb kože. Pomen ABCD kriterijev je osnova epiluminiscenčne mikroskopije. Na osnovi ABCD kriterijev lahko manj izkušeni dermatologi razlikujejo benigne od malignih melanocitnih sprememb, kot tudi melanocitne od nemelanocitnih tumorjev kože.Dermatoscopy has broad application in a daily routine of a dermatologis. With surface microscopy or epiluminiscence microscopy a step ahead was made in the development of this kind of examination. Its main benefits are in diagnosing the changes of the skin pigmentation. The basics of epiluminiscence microscopyare ABCD criteria. Knowing these criteria, even less experienced dermatologists can distinguish between benign and malignant melanocytic changes on the skin as well as between melanocytic and non-melanocytic tumors

Prognostic significance of DNA cytometry in cutaneous malignant lymphomas.

The current classification of cutaneous malignant lymphomas (ML) into low-grade and high-grade lymphomas was found to be of limited reproducibility and permitted only a rough prediction about outcome. With this in mind, the relationship between nuclear DNA content and both prognosis and histologic grading according to the Kiel classification was evaluated on Feulgen-stained imprint specimens. In all, 49 cases of malignant non-Hodgkin's lymphoma, primary of the skin or with an involvement of the skin as one of the first symptoms, were studied using a computerized high-resolution image analysis system. The 2c deviation index (2cDI), which reflects the variation of the nuclear DNA values around the normal diploid peak, was found to be the best prognostically relevant criterion. Using the 2cDI, a significant discrimination (P less than 0.001 in the U test) between low-grade and high-grade ML was achieved. The prognostic benefit of the 2cDI was well documented by a significant inverse correlation between the 2cDI and the period of time until the patients progressed at least into one higher stage or died of lymphoma (r equals -0.63, P less than 0.05). In addition, the 2cDI enabled prognosis of the course of disease. In the group with low 2cDI values (2cDI, less than 0.5), no progression of the disease was observed after 1 year. In the groups presenting with a 2cDI between 0.5 and 1.0 and higher than 1.0, a progression was found in 57% and 64% of the cases studied, respectively. In conclusion, these measurements indicate that the determination of DNA distribution patterns in imprint specimens allows a precise and objective prognostic evaluation of cutaneous ML

Cirulating Sézary Cells in the Diagnosis of Sézary Syndrome (Quantitative and Morphometric Analyses)

Plastic-embedded circulating Sézary cells were examined in semithin and thin sections (assisted by the nuclear contour index-NCI). Eight cases of Sézary syndrome were analyzed as well as 11 controls (3 cases of widespread eczemas and 8 cases of erythroderma), 7 cases of mycosis fungoides, and 3 healthy individuals. Discriminating criteria between Sézary syndrome and benign diseases were sought: in addition to Sézary cells (NCI > 6.5) intermediate lymphocytes (5.0 < NCI ≤ 6.5) proved to be helpful. Cases with Sézary syndrome were clearly differentiated when the following 3 ultrastructural criteria were fulfilled: (1) Sézary cells (SC) > 9%; (2) intermediate lymphocytes (IL) > 20%; (3) the sum of SC and IL > 37%.A good correlation between thin and semithin sections was obtained (correlation coefficient for Sézary cells r = 0.82). Usually the values of SC were slightly higher on thin sections. The diagnosis of SS can be made on semithin sections when the ultrastructural criteria are fulfilled. In this way 8 of 12 samples of Sézary syndrome were correctly classified. Therefore, semithin sections (studied by light microscopy) are recommended as a routine method in the diagnosis of cases suspected of Sézary syndrome, whereas thin sections (studied by electron microscopy) appeared to be necessary in problem cases only

Dermal fillers do not induce upregulation of NLRP3 inflammasomes or expression of inflammatory cytokines in granulomas

Background: Filling materials have increasingly been used in aesthetics over the last decades. Understanding the pathophysiology of granuloma formation as a very relevant unwanted side effect of filler application may be essential to help avoid these adverse events. Aims: Our aim was to investigate the role of the inflammasome in the formation of filler granuloma, as a central column of the innate immune response. Methods RPMI 1640 medium was used for growth of THP-1 cells and the induction of THP-1 macrophages. Sonication was applied in order to crush the acrylic particles of the filler. ELISA was the method of analysis for the specific cytokines. Biopsy specimens of filler granuloma were analyzed by various immunohistochemical methods. GraphPad Prism 5 software was used for the statistical data analysis. Results: Neither was the sensor NALP3 overexpressed, nor could an elevated expression of cleaved IL-1 beta, IL-18, or IFN-gamma be detected. Furthermore, no increased expression of IL-8 or IL-1 beta was detectable in vitro. Conclusion No increased inflammasome activation could be observed;however, filler granulomas were infiltrated with granulocytes and macrophages. Therefore, we speculate that an unspecific immune response might be the key player in the formation of filler granuloma

Man against machine reloaded : performance of a market-approved convolutional neural network in classifying a broad spectrum of skin lesions in comparison with 96 dermatologists working under less artificial conditions

Copyright © 2019 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.Background: Convolutional neural networks (CNNs) efficiently differentiate skin lesions by image analysis. Studies comparing a market-approved CNN in a broad range of diagnoses to dermatologists working under less artificial conditions are lacking. Materials and methods: One hundred cases of pigmented/non-pigmented skin cancers and benign lesions were used for a two-level reader study in 96 dermatologists (level I: dermoscopy only; level II: clinical close-up images, dermoscopy, and textual information). Additionally, dermoscopic images were classified by a CNN approved for the European market as a medical device (Moleanalyzer Pro, FotoFinder Systems, Bad Birnbach, Germany). Primary endpoints were the sensitivity and specificity of the CNN's dichotomous classification in comparison with the dermatologists’ management decisions. Secondary endpoints included the dermatologists’ diagnostic decisions, their performance according to their level of experience, and the CNN's area under the curve (AUC) of receiver operating characteristics (ROC). Results: The CNN revealed a sensitivity, specificity, and ROC AUC with corresponding 95% confidence intervals (CI) of 95.0% (95% CI 83.5% to 98.6%), 76.7% (95% CI 64.6% to 85.6%), and 0.918 (95% CI 0.866–0.970), respectively. In level I, the dermatologists’ management decisions showed a mean sensitivity and specificity of 89.0% (95% CI 87.4% to 90.6%) and 80.7% (95% CI 78.8% to 82.6%). With level II information, the sensitivity significantly improved to 94.1% (95% CI 93.1% to 95.1%; P < 0.001), while the specificity remained unchanged at 80.4% (95% CI 78.4% to 82.4%; P = 0.97). When fixing the CNN's specificity at the mean specificity of the dermatologists’ management decision in level II (80.4%), the CNN's sensitivity was almost equal to that of human raters, at 95% (95% CI 83.5% to 98.6%) versus 94.1% (95% CI 93.1% to 95.1%); P = 0.1. In contrast, dermatologists were outperformed by the CNN in their level I management decisions and level I and II diagnostic decisions. More experienced dermatologists frequently surpassed the CNN's performance. Conclusions: Under less artificial conditions and in a broader spectrum of diagnoses, the CNN and most dermatologists performed on the same level. Dermatologists are trained to integrate information from a range of sources rendering comparative studies that are solely based on one single case image inadequate.publishersversionPeer reviewe

Validity and reliability of dermoscopic criteria used to differentiate nevi from melanoma aweb-based international dermoscopy society study

IMPORTANCE The comparative diagnostic performance of dermoscopic algorithms and their individual criteria are not well studied. OBJECTIVES To analyze the discriminatory power and reliability of dermoscopic criteria used in melanoma detection and compare the diagnostic accuracy of existing algorithms. DESIGN, SETTING, AND PARTICIPANTS Thiswas a retrospective, observational study of 477 lesions (119 melanomas [24.9%] and 358 nevi [75.1%]), which were divided into 12 image sets that consisted of 39 or 40 images per set. A link on the International Dermoscopy Society website from January 1, 2011, through December 31, 2011, directed participants to the study website. Data analysis was performed from June 1, 2013, through May 31, 2015. Participants included physicians, residents, and medical students, and there were no specialty-Type or experience-level restrictions. Participants were randomly assigned to evaluate 1 of the 12 image sets. MAIN OUTCOMES AND MEASURES Associations with melanoma and intraclass correlation coefficients (ICCs) were evaluated for the presence of dermoscopic criteria. Diagnostic accuracy measures were estimated for the following algorithms: The ABCD rule, the Menzies method, the 7-point checklist, the 3-point checklist, chaos and clues, and CASH (color, architecture, symmetry, and homogeneity). RESULTS A total of 240 participants registered, and 103 (42.9%) evaluated all images. The 110 participants (45.8%) who evaluated fewer than 20 lesions were excluded, resulting in data from 130 participants (54.2%), 121 (93.1%) of whom were regular dermoscopy users. Criteria associated with melanoma included marked architectural disorder (odds ratio [OR], 6.6; 95%CI, 5.6-7.8), pattern asymmetry (OR, 4.9; 95%CI, 4.1-5.8), nonorganized pattern (OR, 3.3; 95%CI, 2.9-3.7), border score of 6 (OR, 3.3; 95%CI, 2.5-4.3), and contour asymmetry (OR, 3.2; 95%CI, 2.7-3.7) (P &lt; .001 for all). Most dermoscopic criteria had poor to fair interobserver agreement. Criteria that reached moderate levels of agreement included comma vessels (ICC, 0.44; 95%CI, 0.40-0.49), absence of vessels (ICC, 0.46; 95%CI, 0.42-0.51), dark brown color (ICC, 0.40; 95%CI, 0.35-0.44), and architectural disorder (ICC, 0.43; 95%CI, 0.39-0.48). The Menziesmethod had the highest sensitivity for melanoma diagnosis (95.1%) but the lowest specificity (24.8%) compared with any other method (P &lt; .001). The ABCD rule had the highest specificity (59.4%). All methods had similar areas under the receiver operating characteristic curves. CONCLUSIONS AND RELEVANCE Important dermoscopic criteria for melanoma recognition were revalidated by participants with varied experience. Six algorithms tested had similar but modest levels of diagnostic accuracy, and the interobserver agreement of most individual criteria was poor

Growth optimization and device integration of narrow-bandgap graphene nanoribbons

The electronic, optical and magnetic properties of graphene nanoribbons (GNRs) can be engineered by controlling their edge structure and width with atomic precision through bottom-up fabrication based on molecular precursors. This approach offers a unique platform for all-carbon electronic devices but requires careful optimization of the growth conditions to match structural requirements for successful device integration, with GNR length being the most critical parameter. In this work, we study the growth, characterization, and device integration of 5-atom wide armchair GNRs (5-AGNRs), which are expected to have an optimal band gap as active material in switching devices. 5-AGNRs are obtained via on-surface synthesis under ultra-high vacuum conditions from Br- and I-substituted precursors. We show that the use of I-substituted precursors and the optimization of the initial precursor coverage quintupled the average 5-AGNR length. This significant length increase allowed us to integrate 5-AGNRs into devices and to realize the first field-effect transistor based on narrow bandgap AGNRs that shows switching behavior at room temperature. Our study highlights that optimized growth protocols can successfully bridge between the sub-nanometer scale, where atomic precision is needed to control the electronic properties, and the scale of tens of nanometers relevant for successful device integration of GNRs

Delphi Consensus Among International Experts on the Diagnosis, Management, and Surveillance for Lentigo Maligna

Introduction: Melanoma of the lentigo maligna (LM) type is challenging. There is lack of consensus on the optimal diagnosis, treatment, and follow-up. Objectives: To obtain general consensus on the diagnosis, treatment, and follow-up for LM. Methods: A modified Delphi method was used. The invited participants were either members of the International Dermoscopy Society, academic experts, or authors of published articles relating to skin cancer and melanoma. Participants were required to respond across three rounds using a 4-point Likert scale). Consensus was defined as >75% of participants agreeing/strongly agreeing or disagreeing/strongly disagreeing. Results: Of the 31 experts invited to participate in this Delphi study, 29 participants completed Round 1 (89.9% response rate), 25/31 completed Round 2 (77.5% response rate), and 25/31 completed Round 3 (77.5% response rate). Experts agreed that LM diagnosis should be based on a clinical and dermatoscopic approach (92%) followed by a biopsy. The most appropriate primary treatment of LM was deemed to be margin-controlled surgery (83.3%), although non-surgical modalities, especially imiquimod, were commonly used either as alternative off-label primary treatment in selected patients or as adjuvant therapy following surgery; 62% participants responded life-long clinical follow-up was needed for LM. Conclusions: Clinical and histological diagnosis of LM is challenging and should be based on macroscopic, dermatoscopic, and RCM examination followed by a biopsy. Different treatment modalities and follow-up should be carefully discussed with the patient

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)