Chemogenomic Screening in a Patient-Derived 3D Fatty Liver Disease Model Reveals the CHRM1-TRPM8 Axis as a Novel Module for Targeted Intervention.

Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of chronic liver disease with few therapeutic options. To narrow the translational gap in the development of pharmacological MASH treatments, a 3D liver model from primary human hepatocytes and non-parenchymal cells derived from patients with histologically confirmed MASH was established. The model closely mirrors disease-relevant endpoints, such as steatosis, inflammation and fibrosis, and multi-omics analyses show excellent alignment with biopsy data from 306 MASH patients and 77 controls.

S2k guideline basal cell carcinoma of the skin (update 2023).

Basal cell carcinoma is the most common malignant tumor in the fair-skinned population and its incidence continues to rise. An update of the S2k guideline with the participation of all specialist societies familiar with the clinical picture and previous literature research is of great importance for the quality of care for affected patients. In addition to epidemiology, diagnostics and histology are discussed.

Baseline metastatic growth rate is an independent prognostic marker in patients with advanced BRAF V600 mutated melanoma receiving targeted therapy.

Background: Targeted therapy (TT) of BRAF V600 mutated unresectable melanoma with inhibitors of the MAPK pathway achieves response rates of up to 76%, but most patients develop secondary resistance. Albeit TT is strikingly efficacious during the first days of treatment, even in advanced cases, long-term survival is highly unlikely, especially in patients with unfavorable baseline characteristics like elevated lactate dehydrogenase (LDH). In patients treated with anti-PD-1 immune checkpoint inhibitors, elevated baseline metastatic growth rate (MGR) was the most important prognostic factor.

S2k Guideline - Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) - Update 2022.

Merkel cell carcinoma (MCC, ICD-O M8247/3) is a rare, malignant, primary skin tumor with epithelial and neuroendocrine differentiation. The tumor cells share many morphologic, immunohistochemical, and ultrastructural features with cutaneous Merkel cells. Nevertheless, the cell of origin of MCC is unclear.

Early Tumor Size Reduction of at least 10% at the First Follow-Up Computed Tomography Can Predict Survival in the Setting of Advanced Melanoma and Immunotherapy.

Rationale And Objectives: Early tumor size reduction (TSR) has been explored as a prognostic factor for survival in patients with advanced melanoma in clinical trials. The purpose of this analysis is to validate, in a routine clinical milieu, the predictive capacity of TSR by 10% for overall survival (OS) and progression-free survival (PFS) and to compare its predictive performance with the RECIST 1.1 criteria.

Pretreatment metastatic growth rate determines clinical outcome of advanced melanoma patients treated with anti-PD-1 antibodies: a multicenter cohort study.

Background: Checkpoint inhibitors revolutionized the treatment of metastatic melanoma patients. Although tumor burden and lactate dehydrogenase (LDH) are associated with overall survival (OS), the impact of tumor growth kinetics remains elusive and in part contradictory. The aims of this study were to develop a novel simple and rapid method that estimates pretreatment metastatic growth rate (MGR) and to investigate its prognostic impact in melanoma patients treated with antiprogrammed death receptor-1 (PD-1) antibodies.

CT texture analysis compared to Positron Emission Tomography (PET) and mutational status in resected melanoma metastases.

Purpose: To evaluate the potential of CT texture analysis parameters and metabolic characteristics of melanoma metastases in F- FDG PET/CT to predict relevant mutations of tumour cells for targeted therapy in metastatic melanoma patients in correlation with histopathologic specimen.

Material And Methods: 66 melanoma patients, examined with contrast-enhanced F-FDG PET/CT before scheduled metastasectomy without any prior systemic therapy, were included in this single-centre retrospective analysis under IRB waiver. The largest, resected metastasis in each patient was assessed with CT texture analysis and semiquantitative F-FDG PET parameters.

MDM2, MDM4 and EGFR Amplifications and Hyperprogression in Metastatic Acral and Mucosal Melanoma.

Background: Mucosal and acral melanoma respond worse to immune checkpoint inhibitors (ICI) than cutaneous melanoma. as well as amplifications are supposed to be associated with hyperprogression on ICI in diverse cancers. We therefore investigated the response of metastatic acral and mucosal melanoma to ICI in regard to or amplifications and melanoma type.

Baseline clinical and imaging predictors of treatment response and overall survival of patients with metastatic melanoma undergoing immunotherapy.

Purpose: We aimed to identify predictive clinical and CT imaging biomarkers and assess their predictive capacity regarding overall survival (OS) and treatment response in patients with metastatic melanoma undergoing immunotherapy.

Methods: The local institutional ethics committee approved this retrospective study and waived informed patient consent. 103 patients with immunotherapy for metastatic melanoma were randomly divided into training (n = 69) and validation cohort (n = 34).

Tumor mutation burden and circulating tumor DNA in combined CTLA-4 and PD-1 antibody therapy in metastatic melanoma - results of a prospective biomarker study.

Background: Metastasized or unresectable melanoma has been the first malignant tumor to be successfully treated with checkpoint inhibitors. Nevertheless, about 40-50% of the patients do not respond to these treatments and severe side effects are observed in up to 60%. Therefore, there is a high need to identify reliable biomarkers predicting response.

S2k guidelines for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) - update 2018.

Merkel cell carcinoma (MCC, ICD-O M8247 / 3) is a rare malignant primary skin tumor with epithelial and neuroendocrine differentiation. The neoplastic cells share many morphological, immunohistochemical and ultrastructural characteristics with Merkel cells of the skin. The diagnosis of MCC is rarely made on clinical grounds.

Meningeal enhancement depicted by magnetic resonance imaging in tumor patients: neoplastic meningitis or therapy-related enhancement?

Purpose: To assess the prevalence of false-positive meningeal contrast enhancement in patients with solid tumors who were undergoing chemotherapy.

Methods: A total of 2572 magnetic resonance imaging (MRI) examinations of the brain were retrospectively evaluated by two readers for the presence of pathological meningeal contrast enhancement conspicuous for neoplastic meningitis. These patients either had malignant melanoma, breast or lung cancer, or lymphoma.

Radiation Pneumonitis after Intensity-Modulated Radiotherapy for Esophageal Cancer: Institutional Data and a Systematic Review.

Radiation pneumonitis (RP) is a serious complication that can occur after thoracic radiotherapy. The goal of this study is to investigate the incidence of RP after radiochemotherapy with intensity modulated radiotherapy (IMRT) in patients with esophageal cancer and correlate this with dose volume histogram (DVH) related parameters. For this purpose, the clinical course of 73 patients was evaluated and irradiation doses to the lungs were extracted from radiotherapy treatment plans.

S2k Guidelines for Cutaneous Basal Cell Carcinoma - Part 2: Treatment, Prevention and Follow-up.

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.

Immunotherapy plus surgery/radiosurgery is associated with favorable survival in patients with melanoma brain metastasis.

Aim: Melanoma brain metastases (MBM) are associated with a dismal prognosis. Few clinical trials evaluated the impact of immunotherapy (IT) and targeted therapy (TT) alone or in combination with surgery and radiotherapy in this population.

Patients & Methods: Retrospective analysis of data from 163 patients diagnosed with MBM between January 2014 and December 2016.

S2k Guidelines for Cutaneous Basal Cell Carcinoma - Part 1: Epidemiology, Genetics and Diagnosis.

Basal cell carcinoma is the most common malignant tumor among fair-skinned individuals, and its incidence has been rising steadily 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 1 highlights new developments in genetics in particular as well as aspects regarding epidemiology, diagnosis, and histology.

Mid-term development of the right ventricle in competitive athletes.

Background: Long-term intensive training induces physiological, morphological, and functional adaption of the athlete's heart.

Purpose: To evaluate the development of athlete's heart during a mid-term follow-up of competitive athletes using cardiac magnetic resonance (CMR).

Material And Methods: Eighteen competitive long-distance runners and triathletes (age 43 ± 13 years, 3 women) were prospectively examined in a longitudinal follow-up study 5.

Breast tomosynthesis for the clarification of mammographic BI-RADS 3 lesions can decrease follow-up examinations and enables immediate cancer diagnosis.

Background The limited sensitivity of mammography in case of a high breast density often produces unclear or false-positive findings, so-called BI-RADS 3 lesions, which have to be followed up to prove benignity. Digital breast tomosynthesis (DBT) was developed to reduce such summation effects. Purpose To evaluate the influence of an additional DBT on the management of mammographic BI-RADS 3 findings and whether DBT can decrease the time to definitive diagnosis or not.