Search

BackgroundDespite the availability of effective systemic therapies, a significant number of advanced melanoma patients develops brain metastases. This study investigated differences in incidence and time to diagnosis of brain metastasis and survival outcomes dependent on the type of first-line therapy.MethodsPatients with metastatic, non-resectable melanoma (AJCCv8 stage IIIC–V) without brain metastasis at start of first-line therapy (1L-therapy) were identified from the prospective multicenter real-world skin cancer registry ADOREG. Study endpoints were incidence of brain metastasis, brain metastasis-free survival (BMFS), progression-free survival (PFS), and overall survival (OS).ResultsOf 1704 patients, 916 were BRAF wild-type (BRAFwt) and 788 were BRAF V600 mutant (BRAFmut). Median follow-up time after start of 1L-therapy was 40.4 months. BRAFwtpatients received 1L-therapy with immune checkpoint inhibitors (ICI) against CTLA-4+PD-1 (n=281) or PD-1 (n=544). In BRAFmutpatients, 1L-therapy was ICI in 415 patients (CTLA-4+PD-1, n=108; PD-1, n=264), and BRAF+MEK targeted therapy (TT) in 373 patients. After 24 months, 1L-therapy with BRAF+MEK resulted in a higher incidence of brain metastasis compared with PD-1±CTLA-4 (BRAF+MEK, 30.3%; CTLA-4+PD-1, 22.2%; PD-1, 14.0%). In multivariate analysis, BRAFmutpatients developed brain metastases earlier on 1L-therapy with BRAF+MEK than with PD-1±CTLA-4 (CTLA-4+PD-1: HR 0.560, 95% CI 0.332 to 0.945, p=0.030; PD-1: HR 0.575, 95% CI 0.372 to 0.888, p=0.013). Type of 1L-therapy, tumor stage, and age were independent prognostic factors for BMFS in BRAFmutpatients. In BRAFwtpatients, tumor stage was independently associated with longer BMFS; ECOG Performance status (ECOG-PS), lactate dehydrogenase (LDH), and tumor stage with OS. CTLA-4+PD-1 did not result in better BMFS, PFS, or OS than PD-1 in BRAFwtpatients. For BRAFmutpatients, multivariate Cox regression revealed ECOG-PS, type of 1L-therapy, tumor stage, and LDH as independent prognostic factors for PFS and OS. 1L-therapy with CTLA-4+PD-1 led to longer OS than PD-1 (HR 1.97, 95% CI 1.122 to 3.455, p=0.018) or BRAF+MEK (HR 2.41, 95% CI 1.432 to 4.054, p=0.001), without PD-1 being superior to BRAF+MEK.ConclusionsIn BRAFmutpatients 1L-therapy with PD-1±CTLA-4 ICI resulted in a delayed and less frequent development of brain metastasis compared with BRAF+MEK TT. 1L-therapy with CTLA-4+PD-1 showed superior OS compared with PD-1 and BRAF+MEK. In BRAFwtpatients, no differences in brain metastasis and survival outcomes were detected for CTLA-4+PD-1 compared with PD-1.

The detection and enrichment of circulating melanoma cells is a challenge, as the cells are very heterogeneous in terms of their biomechanical properties and surface markers. In addition, there is a lack of valid and reliable biomarkers predicting progress and therapeutic response. In this study, we analyze the elasticity of A375 melanoma cells by applying force spectroscopy and a microfluidic method. To identify and eventually separate freely circulating tumor cells, it is crucial to know their physical properties precisely. First, we use standard AFM force spectroscopy, where the elasticity of the cells is calculated from indentation with a pyramidal tip. To extend the limits of the measurements with a tip, we then use cantilevers without a tip to apply force over a larger area of the cells. The resulting Young’s moduli are slightly lower and vary less without the tip, presumably because of the spatial inhomogeneity of the cells. Finally, we implement our microfluidic method: we measure single cell elasticity by analyzing their deformation in high-speed micrographs while passing a stenosis. Combining the force field and the change in shape provides the basis for a stress–strain diagram. The results from the microfluidic deformation analysis were well in accordance with the results from force spectroscopy. The microfluidic method, however, provides advantages over conventional methods, as it is less invasive and less likely to harm the cell during the measurement. The whole cell is measured as one entity without having contact to a stiff substrate, while force spectroscopy is limited to the contact area of the tip, and in some cases dependent of the cell substrate interaction. Consequently, microfluidic deformation analysis allows us to predict the overall elastic behavior of the whole, inhomogeneous cell in three-dimensional force fields. This method may contribute to improve the detection of circulating melanoma cells in the clinical practice.

Zielsetzung der Studie war die Charakterisierung der Leistungsdaten der deutschen Hautkliniken.Im Zuge einer versorgungswissenschaftlichen Querschnittsanalyse wurde im Oktober 2019 ein strukturierter Erhebungsbogen an alle Hautkliniken ausgesendet.Von den 115 Kliniken antworteten 95 (82,6 %), davon 34 (35,8 %) Universitätskliniken (UK) und 61 (64,2 %) nicht universitäre Kliniken (NUK), davon 78 % aus dem städtischen (43 % UK, 57 % NUK) und 22 % aus dem ländlichen Raum (10 % UK, 90 % NUK). Die dermatologischen Abteilungen umfassten durchschnittlich 45 stationäre und 11 teilstationäre Betten (UK: 52/13, NUK: 40/9). Versorgt wurden 2018 durchschnittlich 2302 stationäre Patienten (UK: 2874, NUK: 1983), der Case-Mix-Index lag bei 0,76 (UK: 0,74, NUK: 0,77, gesamter Bereich: 0,40-0,96). Die mittlere Liegedauer lag bei den UK mit 5,5 Tagen relevant unter den Daten von 2013 (5,9 Tage) und 2011 (7,1 Tage), bei den NUK mit 5,9 (2018) versus 5,1 Tagen (2013) ebenfalls signifikant niedriger.Die deutschen Hautkliniken weisen nach wie vor ein hohes Aufkommen an stationärer Versorgungsleistung auf, bei dem sich im Vergleich der letzten sechs Jahre nochmals eine Verdichtung mit kürzerer Liegedauer und höherer Belegungsdichte zeigte. Hautkliniken stellen eine essenzielle Säule der dermatologischen Versorgung dar.

Hautkrankheiten werden in Deutschland stationär vorwiegend in den 115 Hautkliniken versorgt.Versorgungswissenschaftliche und gesundheitsökonomische Analyse der dermatologischen stationären Versorgung und Prädiktion des zukünftigen Versorgungsbedarfes auf der Basis von Primär- und Sekundärdaten.Die ambulante und stationäre Versorgung der dermatologischen Behandlungsindikationen wird überwiegend durch Fachärzte für Dermatologie getragen. Stationär wurden 2018 833 491 Fälle behandelt, entsprechend 4,21 % aller stationären Fälle (19 808 687). Häufigste Behandlungsfälle waren: epithelialer Hautkrebs (gesamt 87 386, davon dermatologische Kliniken 52 608), gefolgt von Melanom (23 917/17 774), Psoriasis (19 291/13 352), Erysipel (73 337/11 260), sonstige Dermatitis (12 671/10 842), atopisches Ekzem (11 421/9734) und Herpes zoster (26 249/9652). Mit einer durchschnittlichen Verweildauer von 5,69 Tagen befanden sich die dermatologischen Kliniken im unteren Drittel. Der Anteil der in Hautkliniken versorgten stationären Indikationen war am höchsten bei Prurigo (95,2 %), Pemphigus (94,9 %), Parapsoriasis (94,6 %), Pemphigoid (90,3 %), Dermatitiden (85,6 %) und atopischem Ekzem (85,2 %). Während die Gesamtzahl der stationären Behandlungsfälle in Deutschland zwischen 2000 und 2018 um durchschnittlich 17,5 % gestiegen ist, ist dies bei Hautkrankheiten zu 26,6 % der Fall, bei einzelnen zu über 150 %. Die Projektion der heutigen auf die zukünftige stationäre Versorgung lässt einen weiterhin hohen Bedarf an stationärer Versorgung durch die Hautkliniken erwarten.Die stationäre dermatologische Versorgung ist auch zukünftig ein unerlässlicher Bestandteil der qualifizierten, sozialrechtlich notwendigen Versorgung in Deutschland.

Background In Germany, skin diseases are mainly treated in the 115 dermatological hospitals. Methods Health care and health economic analysis of dermatological inpatient care and prediction of future care needs based on primary and secondary data. Results Outpatient and inpatient care for dermatologic treatment indications is predominantly provided by dermatology specialists. Inpatient treatment was provided for 833,491 cases in 2018, corresponding to 4.21 % of all inpatient cases (19,808,687). Most common treatment cases were: epithelial skin cancer (total 87,386, of which dermatology clinics 52,608), followed by melanoma (23,917/17,774), psoriasis (19,291/13,352), erysipelas (73,337/11,260), other dermatitis (12,671/10,842), atopic dermatitis (AD) (11,421/9,734), and herpes zoster (26,249/9,652). With an average length of stay of 5.69 days, dermatology hospitals were in the bottom third. The proportion of inpatient indications cared for in dermatology hospitals was highest for prurigo (95.2 %), pemphigus (94.9 %), parapsoriasis (94.6 %), pemphigoid (90.3 %), eczema other than AD (85.6 %), and AD (85.2 %). While the total number of inpatient treatment cases in Germany has increased by an average of 17.5 % between 2000 and 2018, this is the case for 26.6 % of skin diseases and over 150 % for individual ones. The projection of current to future inpatient care suggests a continued high demand for inpatient care by dermatology hospitals. Conclusion Inpatient dermatological care will continue to be an indispensable component of qualified, socially necessary care in Germany.

Die stationäre Versorgung in Deutschland ist seit Einführung des DRG-gestützten Entgeltsystems einem Wandel unterworfen. Über wichtige Differenzierungsfaktoren wie das Versorgungsspektrum und die personelle Situation in den Hautkliniken lagen bislang keine Publikationen vor.Versorgungswissenschaftliche Analyse der 115 Hautkliniken im Oktober 2019 mittels eines strukturierten Erhebungsbogens.Das Versorgungsspektrum umfasste durchschnittlich zu 31,0 % allgemeine Dermatologie, 33,6 % operative Dermatologie, 15,6 % Onkologie und 10,1 % Allergologie. Die Kliniken wiesen durchschnittlich 14 Vollzeitstellen und 3 Teilzeitstellen auf (Universitätskliniken: 23/5, nicht universitäre Kliniken: 9/2). Der mittlere Frauenanteil der Ärzteteams betrug: Weiterbildungsärztinnen 73,3 %, Oberärztinnen 53,0 %, Direktorinnen 20,0 %. Die Bewerbersituation der Ober- und Fachärzte wurde überwiegend als schlecht, die der Assistenzärzte als vornehmlich gut bewertet. Schlechtere Bewerbersituationen lagen in den nicht universitären Kliniken sowie in ländlichen Räumen vor. Die Zufriedenheit der ärztlichen Direktoren mit den aktuellen Rahmenbedingungen der stationären Versorgung zeigte unabhängig von Universitätsklinik und nicht universitärer Klinik eine variable Einschätzung. Die Gefährdung der stationären Versorgung wurde jedoch überwiegend als niedrig eingeschätzt (71,6 %).Die Gesamtsituation der stationären dermatologischen Versorgung ist als überwiegend gut einzuordnen. Auch weisen die Hautkliniken weit überwiegend eine große Versorgungsbreite hinsichtlich der Vielfalt an Indikationen auf. Die teilweise als unzureichend bewerteten Rahmenbedingungen erfordern weitergehende Maßnahmen.

Das Pyoderma gangraenosum (PG) ist eine autoinflammatorische Erkrankung, die zur Ulzeration der Haut fuhrt. Sie sollte in der Differenzialdiagnostik von Ulkuserkrankungen berucksichtigt werden. Welche Charakteristika grenzen das PG von anderen ulzerativen Hauterkrankungen ab? Es wurde eine Literaturrecherche durchgefuhrt und die S1-Leitlinie Pyoderma gangraenosum herangezogen. Klinische Manifestationen und Verlaufe werden anhand von Fallbeispielen dargestellt. Das PG ist eine seltene, aber schwerwiegende primar sterile nekrotisierende Hauterkrankung, die im Rahmen von Syndromen und assoziiert mit Komorbiditaten aus dem autoinflammatorischen Spektrum auftreten kann. Die Diagnose wird in der Regel klinisch gestellt. Nicht selten ist das PG eine Ausschlussdiagnose. 70 % der Ulzera treten an den Unterschenkeln auf. Zu den Therapiemoglichkeiten zahlen Immunsuppressiva und Biologika. Das PG ist eine wichtige Differenzialdiagnose von Unterschenkelulzera und sollte in Betracht gezogen werden, wenn entsprechende Komorbiditaten vorliegen und andere Ursachen ausgeschlossen wurden.

Background: Dynamic optical coherence tomography (D-OCT) allows in vivo visualization of blood vessels in the skin and in malignant tumours. Vessel patterns in malignant melanoma may be associated with tumour stage. Objective: The aim of this study was to describe blood vessel patterns in melanomas and to correlate them with stage. Methods: One hundred fifty-nine malignant melanomas were assessed in a multicentre study. Every tumour was imaged using D-OCT prior to surgery and histologic evaluation. The tumour data such as thickness and ulceration as well as the staging at primary diagnosis and a follow-up of at least 40 months resulted in a stage classification. The vessel patterns were assessed according to predefined categories, compared with healthy adjacent skin, and correlated to stage. Results: Melanomas contained more blood vessels in different patterns compared with healthy adjacent skin. In particular, irregular vascular shapes such as blobs, coils, curves and serpiginous vessels were more common in melanomas. In addition, these patterns were significantly more often found in high-risk and metastatic melanomas than in low-risk lesions. Conclusion: In melanomas, the density of the blood vessels is increased, and irregular vascular patterns are more frequent. At higher stages, especially in metastatic melanomas, these atypical vessels are significantly more common.

Purpose Uveal melanoma (UM) is an orphan cancer of high unmet medical need. Current patterns of care and surveillance remain unclear as they are situated in an interdisciplinary setting. Methods A questionnaire addressing the patterns of care and surveillance in the management of patients with uveal melanoma was distributed to 70 skin cancer centers in Austria, Germany and Switzerland. Frequency distributions of responses for each item of the questionnaire were calculated. Results 44 of 70 (62.9%) skin cancer centers completed the questionnaire. Thirty-nine hospitals were located in Germany (88.6%), three in Switzerland (6.8%) and two in Austria (4.5%). The majority (68.2%) represented university hospitals. Most patients with metastatic disease were treated in certified skin cancer centers (70.7%, 29/41). Besides, the majority of patients with UM were referred to the respective skin cancer center by ophthalmologists (87.2%, 34/39). Treatment and organization of follow-up of patients varied across the different centers. 35.1% (14/37) of the centers stated to not perform any screening measures. Conclusion Treatment patterns of patients with uveal melanoma in Germany, Austria and Switzerland remain extremely heterogeneous. A guideline for the treatment and surveillance is urgently needed.

During the development of cosmetic formulations, in vitro and in vivo methods are essential tools used to reliably assess the skin irritation potential of a product or ingredient. Epicutaneous patch testing (single and/or multiple application protocols) has long been used as an initial in vivo method to screen for possible skin irritation properties of a substance or formulation. To confirm the mildness and dermatological and/or consumer acceptance of a product, use tests are often subsequently conducted. A study was therefore initiated to see how well patch test results correlate with use tests with respect to irritation elicited by skincare (leave-on) products.A number of different cosmetic formulations were assessed in both tests. Although the patch test results did not indicate substantial irritation potentials, immediate-type reactions (stinging and redness) were observed in some volunteers which disappeared within approx. 1 h. Although transient, these reactions suggested that consumer acceptance would probably be low and the studies were discontinued. Immediate-type reactions are rare but have been described for some substances used in cosmetics. These unexpected results were nevertheless intriguing and prompted the start of a journey to see if patch test protocols could be modified to assess these reactions. An occlusive short-term patch test protocol with an application period of 20 min was developed. Successful identification of the spontaneous reactions became possible. Furthermore, there was a correlation between the intensity of reactions observed in the short-term patch test and those observed in the controlled in-use studies. Short-term patch testing using the developed protocol can therefore reliably be used as a screening method, for example in the development and optimization of cosmetic formulations containing ingredients that could cause spontaneous reactions, for instance of non-immunological contact urticaria type.The lessons learned from this studies indicate that simple modifications of existing test protocols can lead to important insights into skin reactions. These modifications can then be used to create further building blocks in the development and optimization of test strategies for cosmetic formulations which offer reliable study designs for possible reactions product developers may encounter.Lors du développement de formulations cosmétiques, les méthodes in vitro et in vivo sont des outils essentiels utilisés pour évaluer de manière fiable le potentiel d'irritation cutanée d'un produit ou d'un ingrédient. Le test épicutané (protocoles d'application uniques et / ou multiples) est utilisé depuis longtemps comme méthode initiale in vivo pour dépister les éventuelles propriétés d'irritation cutanée d'une substance ou d'une formulation. Afin de confirmer la douceur et l'acceptation dermatologique et / ou consommateur d'un produit, des tests d'usage sont souvent effectués ultérieurement. Une étude a donc été initiée pour voir dans quelle mesure les résultats des tests épicutanés correspondent aux tests d'usage en ce qui concerne l'irritation provoquée par les produits de soin (sans rinçage). MÉTHODES/RÉSULTATS: Un certain nombre de formulations cosmétiques différentes ont été évaluées dans les deux tests. Bien que les résultats du test épicutané n'indiquent pas de potentiels d'irritation substantiels, des réactions de type immédiat (picotements et rougeurs) ont été observées chez certains volontaires. Celles-ci ont disparu en à peu près 1 heure. Bien que transitoires, ces réactions de type 5 suggéraient que l'acceptation du consommateur serait probablement faible et les études ont été interrompues. Les réactions de type immédiat 6 sont rares mais ont été évoquées en relation avec certaines substances utilisées en cosmétique. Ces résultats inattendus étaient néanmoins intrigants et ont incité le lancement d’un processus pour voir si les protocoles de test épicutané pouvaient être modifiés pour évaluer ces réactions. Un protocole de test épicutané à court terme occlusif avec une période d'application de 20 min a été développé, permettant l'identification réussie des réactions spontanées. Il a été de plus constate une corrélation entre l'intensité des réactions observées dans le test épicutané à court terme et celles observées dans les test d’usage contrôlés. Le test épicutané à court terme utilisant le protocole développé peut donc être utilisé de manière fiable comme méthode de dépistage, par exemple dans le développement et l'optimisation de formulations cosmétiques contenant des ingrédients qui pourraient provoquer des réactions spontanées, par exemple de type urticaire de contact non immunologique.Les leçons tirées de ces études indiquent que de simples modifications des protocoles de test existants peuvent révéler des informations importantes sur les réactions cutanées. Ces modifications peuvent ensuite être utilisées pour créer d'autres blocs de construction dans le développement et l'optimisation de stratégies de test pour des formulations cosmétiques qui offrent des conceptions d'études fiables pour les réactions possibles que les développeurs de produits peuvent rencontrer.

Objectives: Forty to sixty percent of patients with advanced melanoma show primary resistance to PD-1-based immunotherapy, 30–40% of initial responders also progress. Here, we evaluated the outcome of second-line targeted therapy (TT) after progression on PD-1-based immune checkpoint inhibition (ICI) in BRAFV600-mutated melanoma. In addition, we report data on the activity of re-exposure with PD-1-based regimes. Methods: Patients with advanced (non-resectable stage III or IV, AJCC 2017, 8th edition) melanoma progressing on PD-1-based ICI (nivolumab, pembrolizumab or ipilimumab plus nivolumab) and receiving second-line BRAF plus MEK inhibition were identified from the prospective multicenter skin cancer registry ADOREG. Results: We identified 108 patients with unresectable stage III or stage IV melanoma progressing on first-line ICI (nivolumab, pembrolizumab or ipilimumab plus nivolumab) and receiving second-line combined BRAF/MEK inhibition. Seventy-three percent of the cohort presented with primary PD-1 resistant disease. Median progression-free survival (PFS) on ICI was 2.6 (95% CI 2.2–2.9) months. Median PFS on subsequent TT was 6.6 (95% CI 5.4–7.8) months. Median OS from start of second-line TT was 16.0 (95% CI 11.2–20.8) months. The 3-year PFS and OS rates on second-line TT were 16% and 30%. The objective response rate (ORR) and disease control rate (DCR) to TT were 42.6% and 55.6%. In patients with brain metastases, the ORR and DCR were 31.4% and 43.1%. Patients without brain metastases showed an ORR and DCR of 52.6% and 66.7%, respectively. Response to first-line ICI was associated with a numerically higher ORR and DCR to second-line TT and improved OS on TT. Twenty-three patients received third-line ICI of whom two patients showed an objective response. Conclusions: BRAF plus MEK inhibition shows meaningful activity and outcome in patients with advanced melanoma resistant to anti-PD-1-based immunotherapy. Rates of long-term benefit and survival in our study were similar to those reported for treatment-naïve patients receiving first-line MAPKi.

Until now, the clinical differentiation between a nevus and a melanoma is still challenging in some cases. Line-field confocal optical coherence tomography (LC-OCT) is a new tool with the aim to change that. The aim of the study was to evaluate LC-OCT for the discrimination between nevi and melanomas. A total of 84 melanocytic lesions were examined with LC-OCT and 36 were also imaged with RCM. The observers recorded the diagnoses, and the presence or absence of the 18 most common imaging parameters for melanocytic lesions, nevi, and melanomas in the LC-OCT images. Their confidence in diagnosis and the image quality of LC-OCT and RCM were evaluated. The most useful criteria, the sensitivity and specificity of LC-OCT vs. RCM vs. histology, to differentiate a (dysplastic) nevus from a melanoma were analyzed. Good image quality correlated with better diagnostic performance (Spearman correlation: 0.4). LC-OCT had a 93% sensitivity and 100% specificity compared to RCM (93% sensitivity, 95% specificity) for diagnosing a melanoma (vs. all types of nevi). No difference in performance between RCM and LC-OCT was observed (McNemar’s p value = 1). Both devices falsely diagnosed dysplastic nevi as non-dysplastic (43% sensitivity for dysplastic nevus diagnosis). The most significant criteria for diagnosing a melanoma with LC-OCT were irregular honeycombed patterns (92% occurrence rate; 31.7 odds ratio (OR)), the presence of pagetoid spread (89% occurrence rate; 23.6 OR) and the absence of dermal nests (23% occurrence rate, 0.02 OR). In conclusion LC-OCT is useful for the discrimination between melanomas and nevi.

In der taglichen Praxis konnen Nagelpigmentierungen eine diagnostische Herausforderung darstellen, insbesondere wenn sie dermatoskopisch unspezifische Veranderungen zeigen. Wir stellen exemplarische Falle vor, bei denen die optische Koharenztomographie als schnelle, nichtinvasive bildgebende Methode typische Veranderungen zeigte, die hinweisend fur die Diagnose waren.

BackgroundDespite of various therapeutic strategies, treatment of patients with melanoma brain metastasis (MBM) still is a major challenge. This study aimed at investigating the impact of type and sequence of immune checkpoint blockade (ICB) and targeted therapy (TT), radiotherapy, and surgery on the survival outcome of patients with MBM.MethodWe assessed data of 450 patients collected within the prospective multicenter real-world skin cancer registry ADOREG who were diagnosed with MBM before start of the first non-adjuvant systemic therapy. Study endpoints were progression-free survival (PFS) and overall survival (OS).ResultsOf 450 MBM patients, 175 (38.9%) received CTLA-4+PD-1 ICB, 161 (35.8%) PD-1 ICB, and 114 (25.3%) BRAF+MEK TT as first-line treatment. Additional to systemic therapy, 67.3% of the patients received radiotherapy (stereotactic radiosurgery (SRS); conventional radiotherapy (CRT)) and 24.4% had surgery of MBM. 199 patients (42.2%) received a second-line systemic therapy. Multivariate Cox regression analysis revealed the application of radiotherapy (HR for SRS: 0.213, 95% CI 0.094 to 0.485, p1 cm: 1.977, 95% CI 1.117 to 3.500, p=0.019), age (HR for age >65 years: 1.802, 95% CI 1.016 to 3.197, p=0.044), and ECOG performance status (HR for ECOG ≥2: HR: 2.615, 95% CI 1.024 to 6.676, p=0.044) as independent prognostic factors of OS on first-line therapy. The type of first-line therapy (ICB vs TT) was not independently prognostic. As second-line therapy BRAF+MEK showed the best survival outcome compared with ICB and other therapies (HR for CTLA-4+PD-1 compared with BRAF+MEK: 13.964, 95% CI 3.6 to 54.4, pConclusionsIn patients with MBM, the addition of radiotherapy resulted in a favorable OS on systemic therapy. In BRAF-mutated MBM patients, ICB as first-line therapy and BRAF+MEK as second-line therapy were associated with a significantly prolonged OS.

Along with the rising melanoma incidence in recent decades and bad prognoses resulting from late diagnoses, distinguishing between benign and malignant melanocytic lesions has become essential. Unclear cases may require the aid of non-invasive imaging to reduce unnecessary biopsies. This multicentric, case-control study evaluated the potential of dynamic optical coherence tomography (D-OCT) to identify distinguishing microvascular features in nevi. A total of 167 nevi, including dysplastic ones, on 130 participants of all ages and sexes were examined by D-OCT and dermoscopy with a histological reference. Three blinded analyzers evaluated the lesions. Then, we compared the features to those in 159 melanomas of a prior D-OCT study and determined if a differential diagnosis was possible. We identified specific microvascular features in nevi and a differential diagnosis of melanomas and nevi was achieved with excellent predictive values. We conclude that D-OCT overcomes OCT´s inability to distinguish melanocytic lesions based on its focus on microvascularization. To determine if an addition to the gold standard of a clinical-dermoscopic examination improves the diagnosis of unclear lesions, further studies, including a larger sample of dysplastic nevi and artificial intelligence, should be conducted.

BACKGROUND Actinic keratoses (AKs) can histologically be classified by the extent of atypical keratinocytes throughout the epidermis or their pattern of basal proliferation. Currently, no data on the inter-rater reliability of both scores is available. OBJECTIVE To evaluate the inter-rater reliability of the two classification schemes; histological grade (AK I-III) and basal proliferation (PRO I-III). METHODS Histological images of 54 AKs were classified by 21 independent dermatopathologists with regard to basal proliferation (PRO I-III), histological grade (AK I-III) and assumed risk of progression into invasive carcinoma. RESULTS Overall, of the 54 AKs 16.7% (9/54) were classified as AK I, 66.7% (36/54) as AK II, and 16.7% (9/54) as AK III. With regards to basal growth pattern, 25.9% (14/54) were classified as PRO I, 42.6% (23/54) as PRO II, and 31.5% (17/54) as PRO III. We observed a highly significant inter-rater reliability for PRO-grading (P < 0.001) which was higher than for AK-grading (Kendall's W coefficient: AK = 0.488 vs. PRO = 0.793). We found substantial agreement for assumed progression risk for AKs with worsening basal proliferation (k = 0.759) compared to moderate agreement (k = 0.563) for different AK-gradings. CONCLUSIONS Histological classification of basal growth pattern (PRO) showed higher inter-rater reliability compared to the established classification of atypical keratinocytes throughout epidermal layers. Moreover, experienced dermatopathologists considered basal proliferation to be more important in terms of progression risk than upwards directed growth patterns. It should be considered to classify AKs according to their basal proliferation pattern (PRO I-III).

Basal cell carcinoma (BCC) is the most common malignant tumor among fair-skinned individuals, and its incidence had been steadily rising in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 2 addresses issues such as proper risk stratification, the various therapeutic approaches, and prevention as well as follow-up of patients with basal cell carcinoma.

BACKGROUND Basal cell carcinoma (BCC) is the most common skin cancer in the general population. Treatments vary from Mohs surgery to topical therapy, depending on the subtype. Dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) have gained a foothold in daily clinical practice to optimize diagnosis and subtype-oriented treatment. The new technique of line-field confocal OCT (LC-OCT) allows imaging at high resolution and depth, but its use has not yet been investigated in larger studies. AIM To evaluate the main LC-OCT criteria for the diagnosis and subtyping of BCC compared with histopathology, OCT and RCM. METHODS In total, 52 histopathologically confirmed BCCs were evaluated for imaging criteria. Their frequency, predictive values and ROC curves were calculated. A multinominal regression with stepwise variables selection to distinguish BCC subtypes was performed. RESULTS Nodular BCCs were mainly characterized by atypical keratinocytes, altered dermoepidermal junction (DEJ), tumour nests in the dermis, dark clefting, prominent vascularization and white hyper-reflective stroma. Superficial BCCs showed a thickening of the epidermis due to a series of tumour lobules with clear connection to the DEJ (string of pearls pattern). Infiltrative BCCs were characterized by elongated hyporeflective tumour strands, surrounded by bright collagen (shoal of fish pattern). The overall BCC subtype agreement between LC-OCT and conventional histology was 90.4% (95% CI 79.0-96.8). CONCLUSION LC-OCT allows noninvasive, real-time identification of BCCs and their subtypes in vertical, horizontal and three-dimension mode compared with histology, RCM and OCT. Further larger studies are needed to better explore the clinical applications of this promising device.

Die neue M‑WBO (Musterweiterbildungsordnung) wurde 6 Jahre lang entwickelt und zum 01.07.2020 von den meisten LAK (Landesarztekammern) in Kraft gesetzt. Die kunftige Weiterbildung zum Hautarzt ist kompetenzorientiert. Dies soll beobachtbare, erfolgreiche Problemlosungen in der Praxis ermoglichen. Damit ist der Kompetenzerwerb nur davon abhangig, ob das Ziel erreicht wurde. Zur Feststellung des Erreichens der jeweiligen Kompetenzen sind neue Verfahren notig, u.a. jahrliche Weiterbildungsgesprache, arbeitsplatzbasierte Prufungen und ein eLogbuch (elektronisches Logbuch). Stationare Mindestzeiten entfallen kunftig. Die Weiterbildung kann prinzipiell komplett ambulant erfolgen. Die M‑WBO Dermatologie umfasst 14 thematische Blocke mit differenzierter Beschreibung von kognitiven und Methoden- bzw. Handlungskompetenzen. Die Richtzahlen dermatologischer Zusatzweiterbildungen wurden erheblich in die Zeit der Grundweiterbildung verschoben. Zusatzweiterbildungen konnen berufsbegleitend erworben werden. Fachlich empfohlene Weiterbildungsplane (FEWP) sind die konkreten Ausfuhrungsbestimmungen der M‑WBO. Sie sind kein Teil der WBO und konnen angepasst werden. Im Zusammenhang mit diesem neuen Ansatz sind derzeit noch zahlreiche Fragen offen, wie Dokumentation in der Praxis oder Finanzierung.

Simple Summary Actinic keratoses (AKs) are extremely common in the elderly population; they are universally recognized as precursors of invasive squamous cell carcinoma, and their risk of progression relates to the basal growth pattern of keratinocytes in the histological slides, based on a model called “PRO” classification. Since AKs can be investigated at bedside with non-invasive devices such the new line-field confocal optical coherence tomography (LC-OCT), we hypothesized that it was also possible to use such devices for reproducing the PRO classification and assessing the progression risk of AK without an invasive biopsy. In this pilot study, we demonstrated the feasibility of the LC-OCT severity grading of AKs based on the histological PRO classification, obtaining a good correlation between the two models and strong interobserver agreement. Abstract It is known that actinic keratoses (AKs) can progress to invasive squamous cell carcinoma (SCC). The histological PRO grading of AKs is based on the growth pattern of basal keratinocytes and relates to their progression risk. AKs can be non-invasively characterized by line-field confocal optical coherence tomography (LC-OCT). The aim of the study was to define criteria for an LC-OCT grading of AKs based on the PRO classification and to correlate it with its histological counterpart. To evaluate the interobserver agreement for the LC-OCT PRO classification, fifty AKs were imaged by LC-OCT and biopsied for histopathology. PRO histological grading was assessed by an expert consensus, while two evaluator groups separately performed LC-OCT grading on vertical sections. The agreement between LC-OCT and histological PRO grading was 75% for all lesions (weighted kappa 0.66, 95% CI 0.48–0.83, p ≤ 0.001) and 85.4% when comparing the subgroups PRO I vs. PRO II/III (weighted kappa 0.64, 95% CI 0.40–0.88, p ≤ 0.001). The interobserver agreement for LC-OCT was 90% (Cohen’s kappa 0.84, 95% CI 0.71–0.91, p ≤ 0.001). In this pilot study, we demonstrated that LC-OCT is potentially able to classify AKs based on the basal growth pattern of keratinocytes, in-vivo reproducing the PRO classification, with strong interobserver agreement and a good correlation with histopathology.

BACKGROUND Inpatient care in Germany has been subject to change since the introduction of the DRG-based payment system. There have been no publications on important differentiating factors such as the spectrum of care and the staffing situation in dermatology. METHODS Health care analysis of 115 dermatology hospitals in October 2019 using a structured survey questionnaire. RESULTS On average, the spectrum of care included 31.0 % general dermatology, 33.6 % surgical dermatology, 15.6 % oncology, and 10.1 % allergology. The clinics had an average of 14 full-time positions and 3 part-time positions (university clinics: 23/5, non-university clinics: 9/2). The mean nationwide proportion of women in the physician teams showed the following distribution: postgraduate physicians 73.3 %, senior physicians 53.0 %, directors 20.0 %. The applicant situation of senior physicians and specialists was assessed as predominantly poor, that of residents as predominantly good. Worse applicant situations were present in non-university hospitals and in rural areas. The satisfaction of the medical directors with the current conditions of inpatient care showed a variable assessment independent of university hospital and non-university hospital status. However, the threat to inpatient care was predominantly assessed as low (71.6 %). CONCLUSIONS The overall situation of inpatient dermatological care can be classified as predominantly good. In addition, the majority of dermatology clinics provide a wide range of care with regard to the variety of indications. The general conditions, which in some cases are rated as inadequate, require further measures.

Optical coherence tomography (OCT) has been able to establish itself in recent years not only in academic-scientific, but also in everyday dermatological practice. Its focus lies on epithelial tumors of the skin, which can be diagnosed intuitively and within a few seconds. Thus, basal cell carcinomas, actinic keratoses, and different stages of field cancerization can be diagnosed and monitored for response to therapy or possible recurrence. This often helps to avoid invasive sample extraction. Recently, the field of OCT and its latest advancement, dynamic OCT (D-OCT), has been expanded to include non-oncologic dermatological diseases. This encompasses inflammatory dermatoses and the analysis of physiological skin parameters such as hydration. Thanks to automated vascular imaging and the measurement of objective parameters such as epidermal thickness, blood flow at depth, optical attenuation coefficient, and skin roughness, more and more characteristics of the skin can be studied in a noninvasive and standardized way. New potential areas of application are eczema, contact allergic dermatitis, psoriasis, rosacea, telangiectasia, acute and chronic wounds, melasma and nevus flammeus but also melanocytic lesions.

Optical coherence tomography (OCT) and confocal laser microscopy (CLSM) are established non-invasive methods in clinical dermatological routine diagnosis. Whereas CLSM is especially useful to distinguish between nevi and melanoma, OCT is suitable for the diagnosis and differentiation of non-melanoma skin cancer. Line-field confocal optical coherence tomography (LC-OCT) is a new innovative device, which has better cellular resolution than OCT and a higher penetration depth than CLSM. Similar to CLSM, LC-OCT also allows 3D images in real time to be taken. Therefore LC-OCT is very useful for the examination of skin lesions of all kinds, since it unites the features of CLSM and OCT.

Die optische Koharenztomographie (OCT) und die konfokale Lasermikroskopie (KLM) ermoglichen eine nichtinvasive bildgebende Diagnostik der Haut. Gerade weil bei Kindern die Indikation fur eine Hautbiopsie eher zuruckhaltend gestellt wird, konnen OCT und KLM fur die Abklarung von kindlichen Hautveranderungen hilfreich sein. Auserdem stellen Biopsien immer nur eine Momentaufnahme eines kleinen Bezirkes der Haut dar, wahrend die nichtinvasiven Methoden ermoglichen, mehrere Lokalisationen im Zeitverlauf zu untersuchen, sodass auch dynamische Veranderungen und Therapieverlaufe sichtbar gemacht werden konnen. In der padiatrischen Dermatologie eignen sie sich insbesondere zur Abklarung atypischer Pigmentlasionen, bei infektiosen Dermatosen wie Skabies oder Tinea und zur Diagnostik entzundlicher und degenerativer Dermatosen.

Background The treatment of keratinocyte cancers (KC) strictly depends on their differentiation and invasiveness. Non-invasive diagnostic techniques can support the diagnosis in real time, avoiding unnecessary biopsies. This study aimed to preliminarily define main imaging criteria and histological correlations of actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) using the novel device line-field confocal optical coherence tomography (LC-OCT). Methods Dermoscopy and LC-OCT images of 73 histopathologically confirmed lesions (46 AKs, 11 BD and 16 SCCs) were included in the study. Exemplary lesions (10 AKs, 5 BD and 5 SCCs) were additionally investigated with optical coherence tomography and reflectance confocal microscopy. Results Most common LC-OCT findings of KC in the descriptive statistics were hyperkeratosis/parakeratosis, disruption of stratum corneum, broadened epidermis, basal and suprabasal keratinocyte atypia, dilated vessels/neoangiogenesis and elastosis/collagen alterations. In the univariate multinomial logistic regression, a preserved DEJ was less common in SCC compared with AK and BD, BD displayed marked keratinocyte atypia involving all epidermal layers (bowenoid pattern), while SCC showed ulceration, increased epidermal thickness, keratin plugs, acantholysis, not visible/interrupted DEJ and epidermal bright particles. LC-OCT increased the diagnostic confidence by 24.7% compared with dermoscopy alone. Conclusions Our study describes for the first time specific LC-OCT features of different stages of KC and their histopathological correlates, focusing on keratinocyte morphology and architecture of the epidermis and DEJ. LC-OCT may open new scenarios in the bedside diagnosis, treatment planning and follow-up of KC.

Background Considerable parts of the global population are affected by androgenetic alopecia (AGA). Aims The efficacy of a foam containing nicotinic acid hexyl ester, polyphenols, zinc, glycine, and caffeine in comparison with a vehicle control foam was assessed in a double-blind vehicle-controlled study in men with AGA over 6 months. Patients/methods Sixty-two men with AGA were assigned either to the active ingredients (verum) or the vehicle group. They applied the products twice daily on affected scalp areas over 6 months. Automated phototrichograms were obtained at baseline, after 3 and 6 months. In addition, a clinical rating by a dermatologist and by the subjects themselves was documented using standardized questionnaires. Results The reduction of the telogen rate from T0 to T6 was significantly stronger in the verum group compared to the vehicle group. The reduction was significant from T0 to T3 and T6 in the verum group, but in the vehicle group only from T0 to T3, not to T6. Significantly increased hair density was noticed in both groups at all time points, but the change from T0 to T6 did not differ significantly between the groups. Cosmetic acceptance of the foam and its application regimen was generally good in both groups. Slight reddening and burning after application of verum in six cases was probably due to the presence of hexyl nicotinate. Conclusion The study demonstrated a reduction of the telogen rate by a cosmetic foam in men affected by AGA, indicating a benefit for cosmetic intervention against male pattern hair loss.

The amount of training needed to correctly interpret optical coherence tomography scans of the skin is undefined. The aim of this study was to illustrate how cumulative sum charts can be used to determine how many optical coherence tomography scans novice assessors should evaluate in order to obtain competence in diagnosing basal cell carcinoma. Four hundred lesions suspected for non-melanoma skin cancer were evaluated by optical coherence tomography in combination with clinical photographs, using a 5-point confidence scale. The diagnostic error rate (sum of false-negative and false-positive optical coherence tomography results/total number of cases) was used to evaluate performance, with histopathological diagnosis as the reference standard. Acceptable and unacceptable error rates were set at 16% and 25%, respectively. Adequate performance was reached after assessing 183-311 scans, dependent on the cut-off for a positive test result. In conclusion, cumulative sum analysis is useful to monitor the progress of optical coherence tomography trainees. The caseload necessary for training is substantial.

Actinic keratoses (AKs) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guidelines for actinic keratosis and cutaneous squamous cell carcinoma were developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guidelines are aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AKs and cSCC. The guidelines are also aimed at affected patients, their relatives, policy makers and insurance funds. In the second part, we will address aspects relating to epidemiology, etiology, surgical and systemic treatment of cSCC, follow-up and disease prevention, and discuss AKs and cSCC in the context of occupational disease regulations.

Actinic keratoses (AK) are common lesions in light‐skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence‐based framework for clinical decision making, the guideline “actinic keratosis and cutaneous squamous cell carcinoma” was developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guideline is aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office‐based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AK and cSCC. The guideline is also aimed at affected patients, their relatives, policy makers and insurance funds. In the first part, we will address aspects relating to diagnosis, interventions for AK, care structures and quality‐of‐care indicators.