Prognostic and predictive relevance of CA-125 at primary surgery of ovarian cancer

Introduction  

Despite radical surgery and chemotherapy, most patients with ovarian cancer develop recurrence and die due to progressive disease. To stratify patients for optimal therapy, prognostic and predictive factors are needed. We examined the role of pre- and postoperative CA-125 in this context.     

High platelet reactivity and clinical outcome - fact and fiction

In patients suffering from acute coronary syndromes or undergoing percutaneous coronary intervention, oral antiplatelet treatment is routinely administered with the primary aim of inhibiting platelet-mediated thrombus formation and subsequent abrupt vessel occlusion. Simultaneous inhibition of blood platelet cyclooxygenase-1 by aspirin and of the P2Y12 receptor by clopidogrel or prasugrel is currently recommended in this setting. Inter-individual response variability to aspirin and especially to clopidogrel is the subject of much debate as evidence has grown over the years linking an attenuated response to treatment with the occurrence of ischaemic events. Consequently, the clinical entity of high (on-treatment) platelet reactivity (HPR) was born and subsequently characterised in numerous studies over the last decade. Until recently, alternative treatment options were limited in patients exhibiting HPR. At present the antiplatelet therapy landscape is changing with the advent of prasugrel and ticagrelor as alternative and more potent treatment options. Different tests for monitoring platelet function are available and are being increasingly employed in research projects and clinical routine. These tests may prove useful for achieving optimal platelet inhibition for the individual patient, and several centres now incorporate such testing in day-to-day practice. Widespread adoption of this practice and incorporation into clinical guidelines awaits the results of ongoing trials in which treatment is changed based on platelet function monitoring. This review aims to summarise available facts and fiction in relation to platelet function testing and reactivity with a particular focus on P2Y12 receptor inhibition in patients undergoing coronary stent placement.     

Spatial relation between a rigid (digital) intraoral X-ray receptor and longitudinal axes of maxillary teeth

The purpose of this study was to quantify the existing (inevitable) angle which in intraoral radiology appears between tooth length axis and receptor caused by the anatomical situation. Especially in the upper jaw, due to its arched anatomy, a true “paralleling technique” is not achievable. The angulation necessarily causes distortion and a foreshortening of the image; hence, the foreshortened image leads to misinterpretations in diagnostics. We investigated the effects of the realistic angulation on these image deteriorating factors. Two hundred ninety-four plaster models of the upper jaw were collected, and the angles between a dummy receptor and the axes of the central incisor or the first molar were measured. For evaluation, a rigid dummy of an intraoral charge-coupled device (CCD) receptor (30 mm × 40 mm) was used. The mean angulation evaluated for central incisors was 36.7° (range 19–56°) and for first molars 42.5° (range 26–56°). This leads to a foreshortening of the tooth ranging from 5.4% to 44.1% in the image, when magnification is neglected. Large angles of up to 56°, in both incisor and molar region, result in a relevant underestimation of true tooth length up to 44%. It is important to note that this error cannot be simply corrected by means of local magnification correction. Techniques should be developed that allow for automated assessment of the effective angle to provide information for distortion correction.     

Exome-based gene panel analysis in a cohort of acute juvenile ischemic stroke patients:relevance of NOTCH3 and GLA variants

Journal of Neurology - Genetic variants are considered to have a crucial impact on the occurrence of ischemic stroke. In clinical routine, the diagnostic value of next-generation sequencing (NGS)...     

Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients

Breast cancer brain metastases (BCBM) are detected with increasing incidence. In order to detect potential genes involved in BCBM, we first screened for genes down-regulated by methylation in cell lines with site-specific metastatic ability. The expression of five genes, CADM1, SPARC, RECK, TNFAIP3 and CXCL14, which were also found down-regulated in gene expression profiling analyses of BCBM tissue samples, was verified by qRT-PCR in a larger patient cohort. CADM1 was chosen for further down-stream analyses. A higher incidence of CADM1 methylation, correlating with lower expression levels, was found in BCBM as compared to primary BC. Loss of CADM1 protein expression was detected most commonly among BCBM samples as well as among primary tumors with subsequent brain relapse. The prognostic role of CADM1 expression was finally verified in four large independent breast cancer cohorts (n=2136). Loss of CADM1 protein expression was associated with disease stage, lymph node status, and tumor size in primary BC. Furthermore, all analyses revealed a significant association between loss of CADM1 and shorter survival. In multivariate analyses, survival was significantly shorter among patients with CADM1-negative tumors. Loss of CADM1 expression is an independent prognostic factor especially associated with the development of brain metastases in breast cancer patients.     

Long-term motor and cognitive outcome in children with congenital diaphragmatic hernia

Aims: To determine the motor and cognitive outcome in a regional cohort of survivors of surgically corrected congenital diaphragmatic hernia. Methods: Thirty‐three children (85% of survivors) were examined at a mean age of 8.6 years (3.3–15.7 years), seven had a genetic comorbidity. Outcome was assessed with the Wechsler Preschool and Primary Scale of Intelligence 3rd version and the Wechsler Intelligence Scale 4th version. Motor performance was tested with the Movement Assessment Battery for Children 2nd edition in children younger than 5 years and thereafter with the Zurich Neuromotor Assessment. Results: Children without a genetic comorbidity had a normal cognitive outcome (median IQ 103, 70–121), but fine motor (p = 0.008) and gross motor outcome (p = 0.001) were poorer than the norm. Medical variables were not predictive of adverse outcome, whereas genetic comorbidity was the strongest predictor of low IQ (p < 0.001) and of poor motor performance (p = 0.04). Conclusions: In the absence of a genetic comorbidity, children with congenital diaphragmatic hernia have a favourable cognitive outcome, but motor outcome may be affected. This needs to be taken into account for parental counselling. Further, long‐term neurodevelopmental assessment in children with congenital diaphragmatic hernia is important to provide early therapeutic interventions.     

Management of patients with brain metastases receiving trastuzumab treatment for metastatic breast cancer

Background: With the more effective control of visceral metastases in patients with metastatic breast cancer (MBC), an increasing number of patients face brain metastases (BM). The aim of this retrospective analysis was to investigate the incidence and factors affecting the prognosis of patients with BM under trastuzumab treatment for MBC. Patients and Methods: A total of 75 HER2positive patients treated with trastuzumab for MBC were included. Results are discussed in the context of the current literature. Results: Patients who developed BM (n = 29) had longer median progression-free survival (PFS) during first-line chemotherapy and longer overall survival (OS) after diagnosis of MBC than 46 patients without BM (PFS: 27 vs. 14 months, p = 0.039; OS: 46 vs. 18 months, p = 0.067). Median survival of patients with continuation of trastuzumab after diagnosis of BM was longer than survival of patients with discontinuation of trastuzumab treatment after BM (18 vs. 3 months, p = 0.006). Survival of patients who were treated with surgery and radiotherapy for BM was better compared with radiotherapy alone (9 vs. 5 months, p = not significant) or best supportive care (9 vs. 2 months, p = 0.049). Conclusions: Continuation of trastuzumab treatment as well as resection of BM seem to give further benefit in the treatment of patients with HER2-overexpressing MBC.     

ERG oncogene modulates prostaglandin signaling in prostate cancer cells

Androgen dependent induction of the ETS related gene (ERG) expression in more than half of all prostate cancers results from gene fusions involving regulatory sequence of androgen regulated genes (i.e. TMPRSS2, SLC45A3 and NDRG1) and protein coding sequence of the ERG. Emerging studies in experimental models underscore the functions of ERG in prostate tumorigenesis. However, biological and biochemical functions of ERG in prostate cancer (CaP) remain to be elucidated. This study suggests that ERG activation plays a role in prostaglandin signaling because knockdown of ERG expression in TMPRSS2-ERG fusion containing CaP cells leads to altered levels of the 15-hydroxy-prostaglandin dehydrogenase (HPGD), a tumor suppressor and prostaglandin catabolizing enzyme, and prostaglandin E2 (PGE2) . We demonstrate that HPGD expression is regulated by the binding of the ERG protein to the core promoter of this gene. Moreover, prostaglandin E2 dependent cell growth and urokinase-type plasminogen activator (uPA) expression are also affected by ERG knockdown. Together, these data imply that the ERG oncoprotein in CaP cells positively influence prostaglandin mediated signaling, which may contribute to tumor progression.