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Objective Transclival endoscopic endonasal approaches to the skull base are novel with few published cases. We report our institution's experience with this technique and discuss outcomes according to the clival region involved. Design Retrospective case series. Setting Tertiary care academic medical center Participants All patients who underwent endoscopic endonasal transclival approaches for skull base lesions from 2008 to 2012. Main Outcome Measures Pathologies encountered, mean intraoperative time, intraoperative complications, gross total resection, intraoperative cerebrospinal fluid (CSF) leak, postoperative CSF leak, postoperative complications, and postoperative clinical course. Results A total of 49 patients underwent 55 endoscopic endonasal transclival approaches. Pathology included 43 benign and 12 malignant lesions. Mean follow-up was 15.4 months. Mean operative time was 167.9 minutes, with one patient experiencing an intraoperative internal carotid artery injury. Of the 15 cases with intraoperative cerebrospinal fluid (CSF) leaks, 1 developed postoperative CSF leak (6.7%). There were six other postoperative complications: four systemic complications, one case of meningitis, and one retropharyngeal abscess. Gross total resection was achieved for all malignancies approached with curative intent. Conclusions This study provides evidence that endoscopic endonasal transclival approaches are a safe and effective strategy for the surgical management of a variety of benign and malignant lesions. Level of Evidence 4. [ABSTRACT FROM AUTHOR]

Background: Tumor metastases pose the greatest threat to a patient's survival, and thus, understanding the biology of disseminated cancer cells is critical for developing effective therapies. Methods: Microarrays and immunohistochemistry were used to analyze primary breast tumors, regional (lymph node) metastases, and distant metastases in order to identify biological features associated with distant metastases. Results: When compared with each other, primary tumors and regional metastases showed statistically indistinguishable gene expression patterns. Supervised analyses comparing patients with distant metastases versus primary tumors or regional metastases showed that the distant metastases were distinct and distinguished by the lack of expression of fibroblast/mesenchymal genes, and by the high expression of a 13-gene profile (that is, the 'vascular endothelial growth factor (VEGF) profile') that included VEGF, ANGPTL4, ADM and the monocarboxylic acid transporter SLC16A3. At least 8 out of 13 of these genes contained HIF1α binding sites, many are known to be HIF1α-regulated, and expression of the VEGF profile correlated with HIF1α IHC positivity. The VEGF profile also showed prognostic significance on tests of sets of patients with breast and lung cancer and glioblastomas, and was an independent predictor of outcomes in primary breast cancers when tested in models that contained other prognostic gene expression profiles and clinical variables. Conclusion: These data identify a compact in vivo hypoxia signature that tends to be present in distant metastasis samples, and which portends a poor outcome in multiple tumor types. This signature suggests that the response to hypoxia includes the ability to promote new blood and lymphatic vessel formation, and that the dual targeting of multiple cell types and pathways will be needed to prevent metastatic spread. [ABSTRACT FROM AUTHOR]

The article reports that recent technical advances enabling the precise delivery of cranial stereotactic radiation (SRT), and the increased recognition of the neurocognitive effects for whole brain radiation (WBRT), have led to a strong trend away from the use of WBRT in favor of SRT. In the current study, we assessed predictive factors for development of symptomatic leptomeningeal disease (LMD) in women with breast cancer brain metastases (BCBM) who received SRT.

An abstract of a study which compared vascularity visualised on gadolinium-enhanced magnetic resonance imaging between the immediate postoperative and late postoperative periods is presented.

Background: Glioma-associated macrophages and microglia (GAMs) are components of the glioblastoma (GBM) microenvironment that express MerTK, a receptor tyrosine kinase that triggers efferocytosis and can suppress innate immune responses. The aim of the study was to define MerTK as a therapeutic target using an orally bioavailable inhibitor, UNC2025., Methods: We examined MerTK expression in tumor cells and macrophages in matched patient GBM samples by double-label immunohistochemistry. UNC2025-induced MerTK inhibition was studied in vitro and in vivo., Results: MerTK/CD68+ macrophages increased in recurrent tumors while MerTK/glial fibrillary acidic protein-positive tumor cells did not. Pharmacokinetic studies showed high tumor exposures of UNC2025 in a syngeneic orthotopic allograft mouse GBM model. The same model mice were randomized to receive vehicle, daily UNC2025, fractionated external beam radiotherapy (XRT), or UNC2025/XRT. Although median survival (21, 22, 35, and 35 days, respectively) was equivalent with or without UNC2025, bioluminescence imaging (BLI) showed significant growth delay with XRT/UNC2025 treatment and complete responses in 19%. The responders remained alive for 60 days and showed regression to 1%-10% of pretreatment BLI tumor burden; 5 of 6 were tumor free by histology. In contrast, only 2% of 98 GBM mice of the same model treated with XRT survived 50 days and none survived 60 days. UNC2025 also reduced CD206+ macrophages in mouse tumor samples., Conclusions: These results suggest that MerTK inhibition combined with XRT has a therapeutic effect in a subset of GBM. Further mechanistic studies are warranted., (Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)