Glioblastoma-Derived IL6 Induces Immunosuppressive Peripheral Myeloid Cell PD-L1 and Promotes Tumor Growth.

Purpose: Upregulation of programmed death-ligand 1 (PD-L1) on circulating and tumor-infiltrating myeloid cells is a critical component of GBM-mediated immunosuppression that has been associated with diminished response to vaccine immunotherapy and poor survival. Although GBM-derived soluble factors have been implicated in myeloid PD-L1 expression, the identity of such factors has remained unknown. This study aimed to identify factors responsible for myeloid PD-L1 upregulation as potential targets for immune modulation.

Autologous Heat Shock Protein Peptide Vaccination for Newly Diagnosed Glioblastoma: Impact of Peripheral PD-L1 Expression on Response to Therapy.

Standard therapy for newly diagnosed glioblastoma (GBM) is surgical resection, followed by concurrent radiotherapy and temozolomide chemotherapy. In this phase II clinical trial, the addition of an autologous heat-shock protein vaccine to standard therapy was evaluated. Tumor-induced immunosuppression, mediated by expression of PD-L1 on tumor and circulating immune cells, may impact the efficacy of vaccination.

Safety and outcomes of preoperative embolization of intracranial hemangioblastomas: A systematic review.

Introduction: While preoperative embolization is often reserved for large and highly vascular tumors in order to minimize blood loss, its safety and efficacy in the treatment of hemangioblastomas (HB) is unclear. We present the largest systematic review focusing on the safety and outcome of preoperative embolization of intracranial HB.

Materials And Methods: To identify all cases of preoperative embolization for HB, a literature search was conducted via Medline (OVID and PubMed), Scopus, Embase, and Web of Science.

Pleomorphic Xanthoastrocytoma with Anaplastic Features: Retrospective Case Series.

Objective: Pleomorphic xanthoastrocytoma (PXA) is a unique meningocerebral glioma with a relatively favorable prognosis. PXA also possesses a variant with anaplastic features (aPXA), which is associated with poor outcomes. To date, few studies have examined the clinicopathologic importance of these anaplastic features.

The limited capacity of malignant glioma-derived exosomes to suppress peripheral immune effectors.

Tumor-derived microvesicular exosomes permit intercellular communication both locally and systemically by delivering a snapshot of the tumor cell's constituents. We thus investigated whether exosomes mediate malignant glioma's facility for inducing peripheral immunosuppression. In Western blot and RT-PCR analyses, glioma-derived exosomes displayed exosome-specific markers, but failed to recapitulate the antigen-presentation machinery, surface co-modulatory signals, or immunosuppressive mediator status of their parent tumor cells.

Immunomonitoring in glioma immunotherapy: current status and future perspectives.

Given the continued poor clinical outcomes and refractory nature of glioblastoma multiforme to traditional interventions, immunotherapy is gaining traction due to its potential for specific tumor-targeting and long-term antitumor protective surveillance. Currently, development of glioma immunotherapy relies on overall survival as an endpoint in clinical trials. However, the identification of surrogate immunologic biomarkers can accelerate the development of successful immunotherapeutic strategies.

Role of preoperative embolization for intradural spinal hemangioblastomas.

Spinal hemangioblastomas (HB) are relatively rare neoplasms with a high degree of vascularity. Therapy for symptomatic tumors involves total resection when possible. Due to the enriched blood supply of these neoplasms, there is a high risk of significant intraoperative blood loss, which can lead to perioperative complications.

Predictors of recurrence in the management of chordoid meningioma.

Management of chordoid meningiomas (CMs) is complicated by high rates of recurrence, particularly following subtotal resection. Optimal management is not established given the paucity of published experience. To identify prognostic factors for recurrence following resection, the authors conducted the largest systematic review of CMs to date.

Prognostic factors for recurrence and complications in the surgical management of primary chordoid gliomas: A systematic review of literature.

Objective: Chordoid gliomas (CG) are rare neoplasms which frequently arise within the third ventricle. Surgery remains the mainstay treatment for CG. The present study comprehensively reviews all reported cases of CG within the literature in order to identify risk factors for surgical complications and tumor recurrence.

The kynurenine to tryptophan ratio as a prognostic tool for glioblastoma patients enrolling in immunotherapy.

We hypothesized that peripheral tryptophan (Trp) and/or kynurenine (Kyn) levels would provide prognostic value for physicians planning to enroll glioblastoma multiforme (GBM) patients in immunotherapy. GBM is the most common form of malignant glioma in adults. Despite aggressive surgical resection, irradiation and chemotherapy, patients with GBM have a median survival of only 14.

Association of tumor location, extent of resection, and neurofibromatosis status with clinical outcomes for 221 spinal nerve sheath tumors.

OBJECT Intradural extramedullary spine tumors represent two-thirds of all primary spine neoplasms. Approximately half of these are peripheral nerve sheath tumors, mainly neurofibromas and schwannomas. Given the rarity of this disease and, thus, the limited analyses of clinical outcomes, the authors examined the association of tumor location, extent of resection, and neurofibromatosis (NF) status with clinical outcomes.

Surgery is cost-effective treatment for young patients with vestibular schwannomas: decision tree modeling of surgery, radiation, and observation.

Object: Vestibular schwannomas (VSs) are managed in 3 ways: observation ("wait and scan"); Gamma Knife surgery (GKS); or microsurgery. Whereas there is considerable literature regarding which management approach is superior, there are only a few studies addressing the cost of treating VSs, and there are no cost-utility analyses in the US to date.

Methods: In this study, the authors used the University of California at San Francisco medical record and hospital accounting databases to determine total hospital charges and costs for 33 patients who underwent open surgery, 42 patients who had GKS, and 12 patients who were observed between 2010 and 2013.

Heat shock protein vaccines against glioblastoma: from bench to bedside.

Current adjuvant treatment regimens available for the treatment of glioblastoma are widely ineffective and offer a dismal prognosis. Advancements in conventional treatment strategies have only yielded modest improvements in overall survival. Immunotherapy remains a promising adjuvant in the treatment of GBM through eliciting tumor specific immune responses capable of producing sustained antitumor response while minimizing systemic toxicity.

Survival impact of time to initiation of chemoradiotherapy after resection of newly diagnosed glioblastoma.

OBJECT There are few and conflicting reports on the effects of delayed initiation of chemoradiotherapy on the survival of patients with glioblastoma. The standard of care for newly diagnosed glioblastoma is concurrent radiotherapy and temozolomide chemotherapy after maximal safe resection; however, the optimal timing of such therapy is poorly defined. Given the lack of consensus in the literature, the authors performed a retrospective analysis of The Cancer Genome Atlas (TCGA) database to investigate the effect of time from surgery to initiation of therapy on survival in newly diagnosed glioblastoma.

Proportional upregulation of CD97 isoforms in glioblastoma and glioblastoma-derived brain tumor initiating cells.

CD97 is a novel glioma antigen that confers an invasive phenotype and poor survival in patients with glioblastoma (GBM), the most aggressive primary malignant brain tumor. The short isoform of CD97, known as EGF(1,2,5), has been shown to promote invasion and metastasis, but its role in gliomas and GBM-derived brain tumor initiating cells (BTICs) has not been studied. We sought to characterize CD97 expression among gliomas and identify the specific isoforms expressed.

Impact of resident involvement in neurosurgery: an analysis of 8748 patients from the 2011 American College of Surgeons National Surgical Quality Improvement Program database.

Object: This study evaluates the impact of resident presence in the operating room on postoperative outcomes in neurosurgery.

Methods: The authors retrospectively reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) and identified all cases treated in a neurosurgery service in 2011. Propensity scoring analysis and multiple logistic regression models were used to reduce patient bias and to assess independent effect of resident involvement.

Factors predicting recurrence after resection of clival chordoma using variable surgical approaches and radiation modalities.

Background: Clival chordomas frequently recur because of their location and invasiveness.

Objective: To investigate clinical, operative, and anatomic factors associated with clival chordoma recurrence.

Methods: Retrospective review of clival chordomas treated at our center from 1993 to 2013.

Protein kinase A-dependent phosphorylation of Dock180 at serine residue 1250 is important for glioma growth and invasion stimulated by platelet derived-growth factor receptor α.

Background: Dedicator of cytokinesis 1 (Dock1 or Dock180), a bipartite guanine nucleotide exchange factor for Rac1, plays critical roles in receptor tyrosine kinase-stimulated cancer growth and invasion. Dock180 activity is required in cell migration cancer tumorigenesis promoted by platelet derived growth factor receptor (PDGFR) and epidermal growth factor receptor.

Methods: To demonstrate whether PDGFRα promotes tumor malignant behavior through protein kinase A (PKA)-dependent serine phosphorylation of Dock180, we performed cell proliferation, viability, migration, immunoprecipitation, immunoblotting, colony formation, and in vivo tumorigenesis assays using established and short-term explant cultures of glioblastoma cell lines.

Stable luciferase expression does not alter immunologic or in vivo growth properties of GL261 murine glioma cells.

Background: GL261 cells are murine glioma cells that demonstrate proliferation, invasion, and angiogenesis when implanted in syngeneic C57BL/6 mice, providing a highly useful immunocompetent animal model of glioblastoma. Modification of tumor cells for luciferase expression enables non-invasive monitoring of orthotopic tumor growth, and has proven useful for studying glioblastoma response to novel therapeutics. However, tumor modification for luciferase has the potential for evoking host immune response against otherwise syngeneic tumor cells, thereby mitigating the tumor cells' value for tumor immunology and immunotherapy studies.

Risk factors for postoperative cerebrospinal fluid leak and meningitis after expanded endoscopic endonasal surgery.

Postoperative cerebrospinal fluid (CSF) leak is a serious complication of transsphenoidal surgery, which can lead to meningitis and often requires reparative surgery. We sought to identify preoperative risk factors for CSF leaks and meningitis. We reviewed 98 consecutive expanded endoscopic endonasal surgeries performed from 2008-2012 and analyzed preoperative comorbidities, intraoperative techniques, and postoperative care.

Vaccine therapies in malignant glioma.

Glioblastoma is a grade IV astrocytoma that is widely accepted in clinical neurosurgery as being an extremely lethal diagnosis. Long-term survival rates remain dismal, and even when tumors undergo gross resection with confirmation of total removal on neuroimaging, they invariably recur with even greater virulence. Standard therapeutic modalities as well as more contemporary treatments have largely resulted in disappointing improvements.

Medical errors in neurosurgery.

Background: Medical errors cause nearly 100,000 deaths per year and cost billions of dollars annually. In order to rationally develop and institute programs to mitigate errors, the relative frequency and costs of different errors must be documented. This analysis will permit the judicious allocation of scarce healthcare resources to address the most costly errors as they are identified.