Obese breast cancer patients have worse prognosis than normal weight patients, but the level at which obesity is prognostically unfavorable is unclear. This retrospective analysis was performed using data from the SUCCESS A trial, in which 3754 patients with high-risk early breast cancer were randomized to anthracycline- and taxane-based chemotherapy with or without gemcitabine. Patients were classified as underweight/normal weight (body mass index (BMI) < 25.0), overweight (BMI 25.0–29.9), slightly obese (BMI 30.0–34.9), moderately obese (BMI 35.0–39.9) and severely obese (BMI ≥ 40.0), and the effect of BMI on disease-free survival (DFS) and overall survival (OS) was evaluated (median follow-up 65 months). In addition, subgroup analyses were conducted to assess the effect of BMI in luminal A-like, luminal B-like, HER2 (human epidermal growth factor 2)-positive and triple-negative tumors. Multivariate analyses revealed an independent prognostic effect of BMI on DFS (p = 0.001) and OS (p = 0.005). Compared with underweight/normal weight patients, severely obese patients had worse DFS (hazard ratio (HR) 2.70, 95 % confidence interval (CI) 1.71–4.28, p < 0.001) and OS (HR 2.79, 95 % CI 1.63–4.77, p < 0.001), while moderately obese, slightly obese and overweight patients did not differ from underweight/normal weight patients with regard to DFS or OS. Subgroup analyses showed a similar significant effect of BMI on DFS and OS in patients with triple-negative breast cancer (TNBC), but not in patients with other tumor subtypes. Severe obesity (BMI ≥ 40) significantly worsens prognosis in early breast cancer patients, particularly for triple-negative tumors. Clinicaltrials.gov NCT02181101 . Registered September 2005.

The renin–angiotensin system (RAS) is well known as regulator of electrolytes and blood pressure. Besides this function, there are numerous studies supporting the idea of a local tissue RAS. This system controls the local activity of the different RAS family members, especially of the functional proteins Angiotensin II and Angiotensin (1-7). Those antagonistically acting proteins have been described to be expressed in different organ systems including the human reproductive tract. Therefore, this local RAS has been suspected to be involved in the control and regulation of physiological and pathological conditions in the female reproduction tract. This review of the available literature summarizes the physiological influence of the RAS on the follicular development, ovarian angiogenesis and placental- and uterine function. In addition, in the second part the role of the RAS concerning ovarian- and endometrial cancer becomes elucidated. This section includes possible novel therapeutic strategies via inhibition of RAS-mediated tumor growth and angiogenesis. Looking at a very complex system of agonistic and antagonistic tissue factors, it may be supposed that the RAS in the female reproduction tract will be of rising scientific interest in the upcoming years.

Seventy percent of all breast cancer subtypes are hormone receptor-positive. Adjuvant endocrine therapy in these patients plays a key role. Despite the traditional duration of a 5-year intake, the risk of relapse remains elevated in a substantial proportion of patients. Several trials report that the risk of late recurrence is reduced by the extension of adjuvant endocrine therapy beyond 5 years. However, the optimal duration of endocrine therapy is still a matter of debate. The newer data only show a marginal benefit resulting from extension beyond 7 to 10 years. Furthermore, extension may be associated with more side effects. Thus, the adequate selection of patients qualifying for an extended adjuvant therapy is of importance. Tools/genomic tests, which include the characteristics of the patient and the tumor, may help to better identify patients with a risk of a late relapse. Taken together, the magnitude of benefit for extended adjuvant endocrine therapy is based on the precise estimation of the risk of relapse after 5 years. This must be balanced against the long-term side effects of endocrine treatment and the competing risks. For patients with an intermediate risk, 7 years appears to be the optimal duration, and in those with high-risk features, endocrine therapy up to 10 years may be considered.

Background: Medical education is evolving from "learning by doing" to simulation-based hands-on tutorials. Objective: The aim of this prospective 2-armed study was to evaluate a newly developed augmented reality ultrasound app and its effect on educational training and diagnostic accuracy. Methods: We recruited 66 medical students and, using imaging and measuring a kidney as quality indicators, tested them on the time they needed for these tasks. Both groups used textbooks as preparation; in addition, the study group had access to a virtual ultrasound simulation app for mobile devices. Results: There was no significant difference between the study arms regarding age (P=.97), sex (P=.14), and previous ultrasound experience (P=.66). The time needed to complete the kidney measurements also did not differ significantly (P=.26). However, the results of the longitudinal kidney measurements differed significantly between the study and control groups, with larger, more realistic values in the study group (right kidney: study group median 105.3 mm, range 86.1-127.1 mm, control group median 92 mm, range 50.4-112.2 mm; P<.001; left kidney: study group median 100.3 mm, range 81.7-118.6 mm, control group median 85.3 mm, range 48.3-113.4 mm; P<.001). Furthermore, whereas all students of the study group obtained valid measurements, students of the control group did not obtain valid measurements of 1 or both kidneys in 7 cases. Conclusions: The newly developed augmented reality ultrasound simulator mobile app provides a useful add-on for ultrasound education and training. Our results indicate that medical students’ use of the mobile app for training purposes improved the quality of kidney measurements.

Soluble MUC1 has been discussed as a biomarker for predicting prognosis, treatment efficacy, and monitoring disease activity in breast cancer (BC) patients. Most studies in adjuvant settings have used preoperative assessment. This study, part of the SUCCESS-A trial (NCT02181101), assessed the prognostic value of soluble MUC1 before and after standard adjuvant chemotherapy. Patients with high-risk BC were treated within the SUCCESS-A trial with either three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide followed by three cycles of docetaxel or three cycles of FEC followed by three cycles of docetaxel and gemcitabine. Cox regression analyses were performed to investigate the prognostic value of CA27.29 before and after chemotherapy relative to disease-free survival (DFS), along with established BC prognostic factors such as age, body mass index, tumor size, nodal status, estrogen receptor, progesterone receptor, HER2 status, and grading. Pre-chemotherapy and post-chemotherapy CA27.29 assessments were available for 2687 patients of 3754 randomized patients. Pre-chemotherapy CA27.29 assessment was associated with DFS in addition to established prognostic factors. It had no prognostic value in node-negative patients, but there was a clear association in node-positive patients. Post-chemotherapy CA27.29 assessment did not add any prognostic value, either on its own or in addition to pre-chemotherapy CA27.29 assessment.

Introduction The corpus luteum (CL) is dependent on luteal vascular permeability, which is controlled by human chorionic gonadotropin (hCG) via vascular endothelial growth factor (VEGF). In this study we investigated the role of a potential VEGF antagonist pathway – Slit2/Robo4 – and its influence on endothelial cell adhesion. Materials and Methods Luteinized granulosa cells (LGCs) were stimulated with hCG in the absence or presence of a VEGF inhibitor. The expression of VEGF and Slit2 were measured. Human umbilical vein endothelial cells (HUVECs) were stimulated with Slit2 or VEGF, and gene expressions of cadherin 5 (CDH5) and claudin 5 (CLDN5) were measured. Following Robo4 knockdown, CDH5, CLDN5 and endothelial permeability were measured. Results Stimulation of human LGCs with hCG significantly increased VEGF while Slit2 expression was significantly suppressed. Inhibition of VEGF action after hCG stimulation did not change Slit2 suppression. Slit2 knockdown did not affect VEGF expression. While VEGF stimulation of HUVECs significantly suppressed CDH5 and CLDN5 gene expression, stimulation of HUVECs with Slit2 resulted in a significant increase in CDH5 and CLDN5. Robo4 knockdown was done, leading to downregulation of CDH5 and CLDN5 which resulted in significantly increased permeability. Conclusions Our results indicate the existence of a VEGF-antagonist pathway in the CL that decreases vascular permeability. During the functional life of the CL the pathway is suppressed by hCG. It is possible that stimulation of this pathway could be used to treat ovarian hyperstimulation syndrome. Einleitung Voraussetzung für die regelrechte Funktion des Corpus luteum ist ein durchlässiges Gefäßsystem. Diese vaskuläre Durchlässigkeit wird durch die Einwirkung des humanen Choriogonadotropins (hCG) auf den Vascular Endothelial Growth Factor (VEGF) kontrolliert. In dieser Studie untersuchten wir ein potenzielles VEGF-antagonistisches System – das Slit2/Robo4-System – und dessen Auswirkung auf die endotheliale Zelladhäsion. Material und Methoden Luteinisierte Granulosazellen (LGC) wurden mit hCG stimuliert mit oder ohne Beigabe eines VEGF-Hemmers. Es wurde die VEGF- und Slit2-Expression gemessen. Aus der menschlichen Nabelschnur gewonnene venöse Endothelzellen (HUVECs) wurden mit Slit2 oder VEGF stimuliert. Danach wurde die Genexpression von Cadherin 5 (CDH5) und Claudin 5 (CLDN5) gemessen. Es wurden ein Robo4-Knockdown durchgeführt und die nachfolgende CDH5- und CLDN5-Expression sowie die endotheliale Durchlässigkeit gemessen. Ergebnisse Die Stimulation von menschlichen LGCs mit dem hCG führte zu einer wesentlichen Steigerung von VEGF, während die Slit2-Expression signifikant unterdrückt wurde. Die Hemmung der VEGF-Aktivität nach der hCG-Stimulation wirkte sich nicht auf die Unterdrückung der Slit2-Expression aus. Der Slit2-Knockdown hatte keine Auswirkungen auf die VEGF-Expression. Während die VEGF-Stimulation von HUVECs die Genexpression von CDH5 und CLDN5 signifikant unterdrückte, führte die Slit2-Stimulation von HUVECs zu einer signifikanten Steigerung der CDH5- und CLDN5-Expression. Es wurde ein Robo4-Knockdown durchgeführt, was zu einer Herabregulation von CDH5 und CLDN5 führte und die Durchlässigkeit signifikant steigerte. Schlussfolgerung Unsere Ergebnisse weisen auf das Vorhandensein eines VEGF-antagonistischen Systems im Corpus luteum hin, das die vaskuläre Gefäßdurchlässigkeit mindert. Dieses System wird während der Funktionsdauer des Corpus luteum durch das hCG unterdrückt. Es kann daher angenommen werden, dass eine Stimulation dieses Systems zur Behandlung beispielsweise des ovariellen Hyperstimulationssyndroms eingesetzt werden könnte.