Fachklinik Hornheide

ObjectivesSmall cell lung cancer (SCLC) accounts for approximately 15% of lung tumors and is marked by aggressive growth and early metastatic spread. In this study, we used two SCLC mouse models with differing tumor mutation burdens (TMB). To investigate tumor composition, spatial architecture, and interactions with the surrounding microenvironment, we acquired multiplexed images of mouse lung tumors using imaging mass cytometry (IMC). These data build upon a previously published characterization of the mouse model.Data descriptionAfter tumor detection, mice were assigned to one of five treatment groups. Lung tumor tissues were imaged with a 37-marker IMC panel designed to identify major cell types—tumor, immune, and structural—as well as their functional states. When possible, each tumor was sampled both at its center and border regions. Tumor masks in the form of binary images are provided to delineate tumor areas. Additional metadata include tumor onset and endpoint dates to support downstream correlation or predictive analyses based on the image data. This dataset offers a valuable resource for studying the histological and cellular complexity of SCLC in a genetically controlled mouse model across multiple therapeutic conditions.

ZusammenfassungIn der konservativen Dermatologie treten relevante Schmerzen als begleitendes Symptom komplexer und schwerwiegender Erkrankungen auf und beeinträchtigen die Lebensqualität maßgeblich. Zwei typischerweise mit Schmerzen einhergehende Erkrankungen sind der Herpes zoster und das Pyoderma gangraenosum. Die supportive Therapie umfasst Maßnahmen, die zusätzlich zur krankheitsspezifischen Therapie eingesetzt werden, um krankheitsbegleitende Symptome wie Schmerzen zu lindern und das Wohlbefinden der Patienten zu verbessern. Inhalt dieser Übersichtsarbeit ist die spezifische pharmakologische Schmerztherapie unter Berücksichtigung von Kontraindikationen und Anwendungsbeschränkungen einschließlich Dosierung, Dosisanpassung und Wechselwirkungen. Neben Nichtopioidanalgetika finden auch gezielt ausgewählte Opioide in der Schmerztherapie Anwendung, können jedoch durch Nebenwirkungen wie Übelkeit und Obstipation das Wohlbefinden und die Therapieadhärenz der Behandelten vermindern. Eine supportive Begleittherapie dieser Nebenwirkungen ist daher essenziell. In diesem Artikel werden Prinzipien für die gezielte pharmakologische Schmerztherapie, basierend auf den aktuellen Leitlinien und Empfehlungen der Fachgesellschaften, speziell für den dermatologischen Einsatz aufgearbeitet.

Enhancer of zeste homolog 2 (EZH2) is a transcriptional enzyme implicated in tumor development and is often correlated to poor patient outcomes in various malignancies. The study evaluated various methods for EZH2 expression in lip and ear squamous cell carcinomas (LSCC, ESCC) by matching patients with and without lymph node metastasis (LNM) and further analysis of clinical outcome parameters. EZH2 inhibition therapy has shown promising results in multiple cancer entities, with ongoing research exploring its potential in other malignancies. This approach may also be applicable to high-risk LSCC and ESCC. A total of 122 patients who had been surgically treated for LSCC and ESCC were selected to form LNM-positive and LNM-negative matched pairs. EZH2 expression has been examined after immunostaining of the tumor tissue with EZH2-antibodies and quantified as extent, intensity, and score. Pursuing the clinical benefit, we analyzed three different EZH2-score approaches to determine aberrations in EZH2 expression. While the overall EZH2 extent did not correlate with clinical outcome, the EZH2-intensity and -score was lower in patients who developed a local relapse or distant metastasis (DM). High EZH2-scores correlated with increasing grading, pN-, and American Joint Committee on Cancer-stage. Overall, the carcinoma tissue samples showed a high expression of EZH2 (mean expression > 60%). The hypothesis of the predictive prognostic contribution of EZH2 in clinical decisions regarding the occurrence of LNM was not substantiated by our data. Nevertheless, the elevated expression of EZH2 we have observed in our findings could be utilized as a pretherapeutic assessment prior to targeted therapies with tazemetostat. Subsequent research should substantiate this hypothesis.

Merkel cell carcinoma (MCC) is a rare and frequently fatal form of skin cancer. Apart from Programmed Cell Death Protein 1 (PD-1)/Programmed Death-Ligand 1 (PD-L1) signaling, there is a lack of knowledge regarding other immune checkpoint molecules. Recent studies have observed elevated glycoprotein CD200 (also known as OX-2) mRNA expression in in different types of tumors, with CD200R-expressing myeloid cells present in the tumor microenvironment. However, the potential role of the CD200/CD200 axis as an additional checkpoint modulator remains widely unexplored. The aim of this study was to determine the intratumoral protein expression of CD200 as well as CD200R in a larger cohort of MCC patients and to correlate the expression levels with patients' outcomes. In this multicenter study, we investigated 68 patients with MCC (68 primary tumors and 15 corresponding metastases). Immunohistochemistry (IHC) was performed for CD200 as well as CD200R. Digital quantification and analysis of IHC were performed using QuPath-0.2.3. CD200 and CD200R expression was observed in 100% of cases. Univariate analysis revealed that low CD200 expression in primary tumors (p = 0.0007, HR 9.35), male sex (p = 0.045, HR 2.41), and immunosuppression (p = 0.0031, HR 6.36) were significantly associated with MCC relapse. Low CD200 expression was also linked to prior immune checkpoint inhibitors (ICI) and/or chemotherapy treatment (p = 0.037). Multivariable analysis confirmed that low CD200 expression (p = 0.0012, HR 5.25) and immunosuppression (p = 0.0056, HR 4.11) were independent predictors of MCC relapse. Expression of CD200/CD200R proteins is very high in MCC and may thus be of diagnostic value. More importantly, low intratumoral CD200 protein expression in primary MCC represents a robust independent predictor of MCC relapse.

This study aims to analyze microvascular reconstruction in Oral and Maxillofacial Surgery (OMFS) in Europe. Based on previous studies, a dynamic online questionnaire was developed and subjected to internal and external evaluation. The questionnaire comprised multiple-choice, rating, and open-ended questions, addressing general and specific aspects and the impacts of the COVID-19 pandemic on microvascular reconstruction in OMFS in Europe. It was implemented into SurveyMonkey's® online survey software and emailed to OMFS departments registered with the European Association for Cranio-Maxillofacial Surgery (EACMFS). Seventy-five participants from 23 European countries participated. Among them, 89% perform between 1 and 70 microvascular free flaps (MFF) annually. 38% of the participants reported a reduction in MFF due to the COVID-19 pandemic. The radial forearm (41% of participants) and fibula free flap (31%) are the most reported MFF. In most cases (59%), MFF procedures are exclusively performed by OMFS for OMFS patients, while 43% of participants reported cooperations with plastic surgeons to perform MFF for OMFS patients. Many participants prefer arterial end-to-end anastomoses (54%) using the facial artery (54%) and, if available, two venous anastomoses (68%). Low molecular weight heparin is the most used postoperative anticoagulant, reported by 67% of participants. For flap monitoring, clinical assessment and Doppler ultrasound are preferred by most participants (95% and 78%, respectively). Many participants (66%) indicated that tracheotomy is only performed when necessary. Differences were observed in relation to CAD/CAM (Computer-Aided Design/Computer-Aided Manufacturing) techniques, types of osteosynthesis, and dental implant treatment. This study highlighted variability in microvascular reconstruction in OMFS in Europe. Further studies are needed to assess these aspects in detail.

ZusammenfassungDas korrekte Vorgehen bei der Totenbeschau nach einem vollzogenen assistierten Suizid (AS) sorgte in Österreich nach Inkrafttreten des Sterbeverfügungsgesetzes am 01.01.2022 für Verwirrung. Da die Gesetzgebung zur Totenbeschau in den Bundesländern unterschiedlich geregelt ist, wird das Hinzuziehen der Polizei, die darauffolgende Meldung bei der Staatsanwaltschaft und eine evtl. notwendige gerichtliche Obduktion unterschiedlich gehandhabt. Da der AS in den meisten „Todesart-Dokumentationen“ noch keine eigene Entität mit einer nachfolgend klar definierten Handlungsanweisung ist, ist vor allem in Bundesländern, wo gesetzlich zwischen einer natürlichen und unnatürlichen Todesart unterschieden wird, die Verständigung der Polizei bei einem AS gefordert, obwohl der AS nicht illegal (=straffrei gestellt), aber eben eine unnatürliche Todesart ist. Es wird von den politischen Akteur:innen eine bundesländerübergreifende einheitliche Regelung in Österreich angestrebt. Um die korrekte Dokumentation eines AS zu verbessern, müssen Arbeitgeber:innen medizinischer Einrichtungen aller Art jedenfalls dringlich für ihre Todesfalldokumentation die Dokumentation eines stattgehabten „AS als eigene Todesart“ einräumen.