Determining venous thromboembolism risk in patients with adult-type diffuse glioma.

Venous thromboembolism (VTE) is a life-threating condition that is common in patients with adult-type diffuse gliomas, yet thromboprophylaxis is controversial because of possible intracerebral hemorrhage. Effective VTE prediction models exist for other cancers, but not glioma. Our objective was to develop a VTE prediction tool to improve glioma patient care, incorporating clinical, blood-based, histologic, and molecular markers. We analyzed preoperative arterial blood, tumor tissue, and clinical-pathologic data (including next-generation sequencing data) from 258 patients with newly diagnosed World Health Organization (WHO) grade 2 to 4 adult-type diffuse gliomas. Forty-six (17.8%) experienced VTE. Tumor expression of tissue factor (TF) and podoplanin (PDPN) each positively correlated with VTE, although only circulating TF and D-dimers, not circulating PDPN, correlated with VTE risk. Gliomas with mutations in isocitrate dehydrogenase 1 (IDH1) or IDH2 (IDHmut) caused fewer VTEs; multivariable analysis suggested that this is due to IDHmut suppression of TF, not PDPN. In a predictive time-to-event model, the following predicted increased VTE risk in newly diagnosed patients with glioma: (1) history of VTE; (2) hypertension; (3) asthma; (4) white blood cell count; (5) WHO tumor grade; (6) patient age; and (7) body mass index. Conversely, IDHmut, hypothyroidism, and MGMT promoter methylation predicted reduced VTE risk. These 10 variables were used to create a web-based VTE prediction tool that was validated in 2 separate cohorts of patients with adult-type diffuse glioma from other institutions. This study extends our understanding of the VTE landscape in these tumors and provides evidence-based guidance for clinicians to mitigate VTE risk in patients with glioma.

Correlation between social media utilization by academic neurosurgery departments and higher online patient ratings.

OBJECTIVE: Patients increasingly utilize online physician review websites (PRWs) and social media to inform healthcare-related decisions. This provides neurosurgeons with opportunities for increased patient engagement. And despite the growing use of social media among neurosurgeons, the relationship between social media utilization and online reviews remains unknown. The goal of this study was to characterize the relationship between social media utilization and PRW ratings across academic neurosurgery departments. METHODS: Social media accounts (Twitter, Facebook, YouTube, Instagram) of academic neurosurgery departments were identified. Online reviews for individual faculty were obtained from Healthgrades, Vitals, WebMD, and Google. Reviews were aggregated to identify the total number of reviews per department, to generate a composite departmental rating, and to calculate a summed departmental score. US News & World Report (USNWR) and Doximity rankings were recorded for each department. Social media utilization by individual neurosurgeons and associated ratings were investigated within the departments with the highest social media utilization. RESULTS: Seventy-eight percent of academic neurosurgery departments utilized social media. The most prevalent platform was YouTube (49.1%), followed by Twitter (46.5%), Facebook (38.6%), and Instagram (16.7%). Higher patient ratings on PRWs were associated with the utilization of YouTube (p = 0.048) or Twitter (p = 0.02). The number of social media platforms utilized demonstrated a significant, positive correlation with patient ratings (p = 0.006) and summed patient ratings (p = 0.048). Although USNWR (p = 0.02) and Doximity (p = 0.0008) rankings correlated with patient ratings, only the number of social media platforms utilized remained a significant predictor of patient ratings on multivariate analysis (p = 0.0001). Thirty-one percent of academic neurosurgeons from departments with high social media utilization were active on social media. The most prevalent social media platform among individual neurosurgeons was Twitter (27.4%), followed by Instagram (8.4%), Facebook (4.9%), and YouTube (2.2%). Higher summed patient scores were associated with individual neurosurgeon utilization of YouTube (p = 0.04), Facebook (p < 0.0001), and Instagram (p = 0.01). Increased social media utilization among neurosurgeons was correlated with a greater number of patient reviews (p = 0.006) and higher summed patient scores (p = 0.003). On multivariate analysis, only Facebook use remained a significant predictor of the number of patient reviews received (p = 0.002) and summed patient satisfaction scores (p < 0.001). CONCLUSIONS: An increased social media presence is associated with higher ratings on PRWs. As neurosurgeons continue to expand their online presence, they should be aware of the possible impact of social media on online patient reviews.

Photographic Misrepresentation on Instagram After Facial Cosmetic Surgery: Is Increased Photography Bias Associated With Greater User Engagement?

BACKGROUND: Before-and-after images are commonly used on Instagram (Menlo Park, CA) to advertise aesthetic surgical treatments and are a powerful means of engaging prospective patients. Consistency between before-and-after images accurately demonstrating the postoperative result on Instagram, however, has not been systematically assessed. OBJECTIVES: The aim of this study was to systematically assess facial cosmetic surgery before-and-after photography bias on Instagram. METHODS: The authors queried 19 Instagram facial aesthetic surgery-related hashtags on 3 dates in May 2020. The "top" 9 posts associated with each hashtag (291 posts) were analyzed by 3 plastic surgeons by means of a 5-item rubric quantifying photographic discrepancies between preoperative and postoperative images. Duplicate posts and those that did not include before-and-after images of facial aesthetic surgery procedures were excluded. RESULTS: A total of 3,477,178 posts were queried. Photography conditions were observed to favor visual enhancement of the postoperative result in 282/291 analyzed top posts, with an average bias score of 1.71 [1.01] out of 5. Plastic surgeons accounted for only 27.5% of top posts. Physicians practicing outside their scope of practice accounted for 2.8% of top posts. Accounts with a greater number of followers (P = 0.017) and posts originating from Asia (P = 0.013) were significantly associated with a higher postoperative photography bias score. CONCLUSIONS: Photographic misrepresentation, with photography conditions biased towards enhancing the appearance of the postoperative result, is pervasive on Instagram. This pattern was observed across all physician specialties and raises significant concerns. Accounts with a greater number of followers demonstrated significantly greater postoperative photography bias, suggesting photographic misrepresentation is rewarded by greater user engagement.

Tumor-induced peripheral immunosuppression promotes brain metastasis in patients with non-small cell lung cancer.

INTRODUCTION: Brain metastases are a significant source of morbidity and mortality for patients with lung cancer. Lung cancer can induce local and systemic immunosuppression, promoting tumor growth and dissemination. One mechanism of immunosuppression is tumor-induced expansion of programmed death-ligand 1 (PD-L1) expressing myeloid cells. Here, we investigate peripheral blood immune phenotype in NSCLC patients with or without brain metastasis. METHODS: Peripheral blood was collected from patients with lung metastatic brain tumors and pre-metastatic lung cancer. Immunosuppressive monocytes, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs) were quantified through flow cytometry. T cell reactivity was analyzed via ELISpot. Brain metastasis conditioned media was collected from tumor-derived cell cultures and analyzed for cytokines by ELISA. Naïve monocytes were stimulated with brain metastasis conditioned media to evaluate PD-L1 stimulation. RESULTS: Patients with brain metastatic lung carcinoma demonstrated increased peripheral monocyte PD-L1, MDSC abundance, and Treg percentage compared to early stage pre-metastatic patients and healthy controls. Patients with elevated peripheral monocyte PD-L1 had less reactive T cells and worse survival. Brain metastasis conditioned media stimulation increased monocyte PD-L1, and conditioned media IL-6 levels correlated with PD-L1 induction. Treatment with anti-IL-6 or anti-IL-6 receptor antibodies reduced PD-L1 expression. In summary, patients with lung cancer and brain metastases exhibit multiple markers of peripheral immunosuppression. CONCLUSIONS: The frequency of PD-L1+ myeloid cells correlated with the presence of brain metastases. Tumor-derived IL-6 was capable of inducing PD-L1+ myeloid cells in vitro, suggesting that monitoring of immunosuppressive factors in peripheral blood may identify new targets for therapeutic intervention in selected patients.

Radiosensitization by Histone H3 Demethylase Inhibition in Diffuse Intrinsic Pontine Glioma.

PURPOSE: Radiotherapy (RT) has long been and remains the only treatment option for diffuse intrinsic pontine glioma (DIPG). However, all patients show evidence of disease progression within months of completing RT. No further clinical benefit has been achieved using alternative radiation strategies. Here, we tested the hypothesis that histone demethylase inhibition by GSK-J4 enhances radiation-induced DNA damage, making it a potential radiosensitizer in the treatment of DIPG.Experimental Design: We evaluated the effects of GSK-J4 on genes associated with DNA double-strand break (DSB) repair in DIPG cells by RNA sequence, ATAC sequence, and quantitative real-time PCR. Radiation-induced DNA DSB repair was analyzed by immunocytochemistry of DSB markers γH2AX and 53BP1, DNA-repair assay, and cell-cycle distribution. Clonogenic survival assay was used to determine the effect of GSK-J4 on radiation response of DIPG cells. In vivo response to radiation monotherapy and combination therapy of RT and GSK-J4 was evaluated in patient-derived DIPG xenografts. RESULTS: GSK-J4 significantly reduced the expression of DNA DSB repair genes and DNA accessibility in DIPG cells. GSK-J4 sustained high levels of γH2AX and 53BP1 in irradiated DIPG cells, thereby inhibiting DNA DSB repair through homologous recombination pathway. GSK-J4 reduced clonogenic survival and enhanced radiation effect in DIPG cells. In vivo studies revealed increased survival of animals treated with combination therapy of RT and GSK-J4 compared with either monotherapy. CONCLUSIONS: Together, these results highlight GSK-J4 as a potential radiosensitizer and provide a rationale for developing combination therapy with radiation in the treatment of DIPG.

Systemic and local immunosuppression in patients with high-grade meningiomas.

AIM: Despite current treatments, high-grade meningiomas continue to have a poor prognosis. Immunotherapy targeting immune checkpoints, such as PD-L1, has demonstrated significant success in controlling numerous malignancies. In this study, we investigate the extent of systemic and local immunosuppression in meningiomas to assess the potential benefit of immune checkpoint inhibitors for the treatment of high-grade meningiomas. METHODS: Peripheral blood was collected from patients undergoing resection of meningiomas (WHO grade I, n = 18; grade II, n = 25; grade III, n = 10). Immunosuppressive myeloid cells (CD45+CD11b+PD-L1+), myeloid-derived suppressor cells (MDSCs) (CD11b+CD33+HLA-DRlow), and regulatory T cells (Tregs) (CD3+CD4+CD25+FoxP3+) were quantified through flow cytometry. Tissue sections from the same patients were assessed for PD-L1 expression and T cell infiltration via immunohistochemistry. RESULTS: Patients with grade III meningiomas demonstrated increased peripheral monocyte PD-L1 compared to patients with grade I/II meningiomas and healthy controls. Peripheral MDSC abundance was increased in grades II and III meningioma patients. PD-L1 staining of meningioma tissue demonstrated increased positivity in grade III meningiomas. Intratumoral PD-L1 was not associated with progression-free survival. High-grade meningiomas had increased T-cell infiltration. However, a significant proportion of these T cells were exhausted PD1+ T cells and immunosuppressive Tregs. CONCLUSIONS: Patients with meningiomas exhibit signs of peripheral immunosuppression, including increased PD-L1 on myeloid cells and elevated MDSC abundance proportional to tumor grade. Additionally, the tumors express substantial PD-L1 proportional to tumor grade. These results suggest a role for immune checkpoint inhibitors targeting the PD-L1/PD-1 pathway in combination with standard therapies for the treatment of high-grade meningiomas.

Lymphopenia predicts response to stereotactic radiosurgery in lung cancer patients with brain metastases.

BACKGROUND: Stereotactic radiosurgery (SRS) can enhance immune activation and improve disease control through stimulation of anti-tumor immunity. However, patients with cancer receiving chemotherapy are often immunosuppressed, which may impact the efficacy of SRS. Here we investigate the relationship between systemic lymphopenia and response to SRS in patients with brain-metastatic lung cancer. METHODS: We reviewed 125 patients with lung cancer brain metastases treated with SRS between January 2014 and May 2017. Complete blood counts from the time of SRS were reviewed, and lymphopenia was defined as absolute lymphocyte count < 1×109 cells/L. Kaplan-Meier survival analysis and cox proportional-hazards models were used to evaluate risks of progression and death. RESULTS: The median age was 65 years (range 43-86), with 54% female patients. Lymphopenia was present in 60 patients. In univariate analysis, lymphopenic patients had significantly shorter PFS (HR = 2.995, p < 0.0001) and OS (HR = 3.928, p < 0.0001). When accounting for age, gender, smoking history, ECOG score, surgery, and tumor histology in a multivariate model, lymphopenia remained significantly predictive of worse PFS (HR = 1.912, p = 0.002) and OS (HR = 2.257, p < 0.001). Patients who received immunotherapy within 3 months of SRS demonstrated significantly shorter PFS (HR = 3.578, p = 0.006) and OS (HR = 6.409, p = 0.001) if lymphopenic. CONCLUSIONS: Brain-metastatic lung cancer patients with lymphopenia treated with SRS had significantly worse PFS and OS. The effect of lymphopenia was even more pronounced in patients receiving immunotherapy. These data demonstrate the significant impact of deficient immunity on disease control and survival. Lymphopenic patients may benefit from interventions to improve immune function prior to SRS for brain metastases.

Long-term glioblastoma survival following recovery from cytomegalovirus colitis: A case report.

Survival outcomes for patients with glioblastoma (GBM) are universally poor with only a small percentage of patients surviving five years beyond initial diagnosis. Activation of the immune system against tumor cells is the basis of immunotherapy and aims to facilitate long-term immune surveillance and tumor suppression. Cytomegalovirus (CMV) has emerged as an immunologic target in GBM given that tumor cells have been shown to express the CMV-associated proteins IE1 and pp65. Moreover, vaccine therapy targeting CMV antigens has promoted improved survival outcomes with long-term survivors. In this report, we present the case of a 69 year-old woman with GBM who survived seven years post-diagnosis. Following tumor resection, the patient underwent concomitant radiation and temozolomide therapy that was complicated by CMV colitis and abdominal abscesses. Despite not receiving adjuvant temozolomide, the patient demonstrated a five year progression-free survival before requiring re-resection for radiation necrosis. Following re-resection, the patient survived for two additional years. As the patient's tumor stained positive for CMV antigens IE1 and pp65, it is hypothesized that she developed an immune response against CMV during recovery that contributed to anti-tumor surveillance and prolonged survival. Overall, this case supports further investigation into the role of CMV and immunotherapy in GBM.

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. EXPERIMENTAL DESIGN: Conditioned media from patient-derived GBM explant cell cultures was assessed for cytokine expression and utilized to stimulate naïve myeloid cells. Myeloid PD-L1 induction was quantified by flow cytometry. Candidate cytokines correlated with PD-L1 induction were evaluated in tumor sections and plasma for relationships with survival and myeloid PD-L1 expression. The role of identified cytokines on immunosuppression and survival was investigated in vivo utilizing immunocompetent C57BL/6 mice bearing syngeneic GL261 and CT-2A tumors. RESULTS: GBM-derived IL6 was identified as a cytokine that is necessary and sufficient for myeloid PD-L1 induction in GBM through a STAT3-dependent mechanism. Inhibition of IL6 signaling in orthotopic murine glioma models was associated with reduced myeloid PD-L1 expression, diminished tumor growth, and increased survival. The therapeutic benefit of anti-IL6 therapy proved to be CD8+ T-cell dependent, and the antitumor activity was additive with that provided by programmed death-1 (PD-1)-targeted immunotherapy. CONCLUSIONS: Our findings suggest that disruption of IL6 signaling in GBM reduces local and systemic myeloid-driven immunosuppression and enhances immune-mediated antitumor responses against GBM.

Methylation-dependent Tissue Factor Suppression Contributes to the Reduced Malignancy of IDH1-mutant Gliomas.

PURPOSE: Gliomas with isocitrate dehydrogenase 1 mutations (IDH1mut) are less aggressive than IDH1 wild-type (IDH1wt) gliomas and have global genomic hypermethylation. Yet it is unclear how specific hypermethylation events contribute to the IDH1mut phenotype. Previously, we showed that the gene encoding the procoagulant tissue factor (TF), F3, is among the most hypermethylated and downregulated genes in IDH1mut gliomas, correlating with greatly reduced thrombosis in patients with IDH1mut glioma. Because TF also increases the aggressiveness of many cancers, the current study explored the contribution of TF suppression to the reduced malignancy of IDH1mut gliomas.Experimental Design: TF expression was manipulated in patient-derived IDH1mut and IDH1wt glioma cells, followed by evaluation of in vitro and in vivo behavior and analyses of cell signaling pathways. RESULTS: A demethylating agent, decitabine, increased F3 transcription and TF-dependent coagulative activity in IDH1mut cells, but not in IDH1wt cells. TF induction enhanced the proliferation, invasion, and colony formation of IDH1mut cells, and increased the intracranial engraftment of IDH1mut GBM164 from 0% to 100% (P = 0.0001). Conversely, TF knockdown doubled the median survival of mice engrafted with IDH1wt/EGFRvIIIamp GBM6, and caused complete regression of IDH1wt/EGFRamp GBM12 (P = 0.001). In vitro and in vivo effects were linked to activation of receptor tyrosine kinases (RTK) by TF through a Src-dependent intracellular pathway, even when extracellular RTK stimulation was blocked. TF stimulated invasion predominately through upregulation of ß-catenin. CONCLUSIONS: These data show that TF suppression is a component of IDH1mut glioma behavior, and that it may therefore be an attractive target against IDH1wt gliomas.

The immune checkpoint protein PD-L1 induces and maintains regulatory T cells in glioblastoma.

Glioblastoma (GBM) promotes immunosuppression through upregulation of PD-L1 and regulatory T cell (Treg) expansion, but the association of these suppressive factors has not been well elucidated. Here, we investigate a role of PD-L1 in expanding Tregs and the value of targeting the PD-1 receptor to inhibit Treg expansion. Quantitative RNA sequencing data from The Cancer Genome Atlas were evaluated for an association between CD274 and FOXP3 transcript expressions and impact of FOXP3 on clinical outcomes. Peripheral leukocytes from patients with newly diagnosed GBM were profiled for PD-L1+ myeloid expressions and Treg abundance. Healthy lymphocytes were assessed for impact of recombinant PD-L1 on expansion of the inducible Treg (iTreg) population. iTreg function was evaluated by the capacity to suppress effector T cell proliferation. Specificity of responses were confirmed by pharmacologic inhibition of the PD-1 receptor. Increased PD-L1 mRNA expression in GBM corresponded to increased FOXP3 mRNA (p = 0.028). FOXP3 elevation had a negative impact on overall survival (HR = 2.0; p < 0.001). Peripheral PD-L1 positivity was associated with an increased Treg fraction (p = 0.008). Lymphocyte activation with PD-L1 co-stimulation resulted in greater iTreg expansion compared to activation alone (18.3% vs. 6.5%; p < 0.001) and improved preservation of the Treg phenotype. Suppressive capacity on naïve T cell proliferation was sustained. Nivolumab inhibited PD-L1-induced Treg expansion (p < 0.001). These results suggest that PD-L1 may expand and maintain immunosuppressive Tregs, which are associated with decreased survival in glioma patients. Blockade of the PD-L1/PD-1 axis may reduce Treg expansion and further improve T cell function beyond the direct impact on effector cells.

Sellar plasmacytomas masquerading as pituitary adenomas: A systematic review.

Given the rarity of intracranial plasmacytomas, these lesions are frequently misdiagnosed as pituitary adenomas. We report on the distinguishing characteristics of sellar plasmacytomas from cases in the literature and our experience. A literature search was conducted to collect all documented cases of a plasmacytoma originating in the sellar region. Patient characteristics, medical history, presentation, tumor characteristics, and survival data were collected. An additional case from our institution not previously reported was included. Thirty-one patients with sellar plasmacytomas were studied. Presenting symptoms were most commonly headache (68%), diplopia (65%) and visual field disturbances (10%). Fifteen patients (48%) were initially suspected of having a pituitary adenoma. Pathologic diagnosis of plasmacytoma preceded a finding of multiple myeloma in 14 cases (45%). Thirty patients (90%) had surgical intervention. Adjuvant therapy consisted of radiotherapy for twenty-five patients (81%) and chemotherapy for sixteen (52%). Tumor recurrence was reported for 7 cases (23%). Nine deaths were reported (23%). We demonstrate that cranial nerve involvement is far more common in sellar plasmacytomas than conventional pituitary adenomas. Given the successful management of these tumors with radiotherapy, such deficits, particularly in patients with known multiple myeloma, should impact the diagnostic workup and treatment considerations.

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. Studies that were in English, included intracranial hemangioblastomas treated with preoperative embolization and provided sufficient disaggregated clinical data for each patient were included. Historical control patients with non-embolized intracranial HB undergoing resection were similarly identified. RESULTS: A total of 111 patients that underwent preoperative embolization of HB prior to planned resection were identified. Patient age ranged from 12 to 72 years, with a cohort of 63% males and 36% females. Nine studies comprising 392 non-embolized patients were included as controls. Gross total resection was achieved in 83.7% of embolized and 95.6% of non-embolized patients. Intraoperative blood transfusion was required in 15.3% of embolized and 0.51% of non-embolized controls, while rates of post-operative hemorrhage were 8.4% and 1.6%, respectively. Complication rates from embolization were 11.7% and following consequent surgery were 20.7%. DISCUSSION: Embolization did not increase rates of gross total resection, decrease estimated blood loss, or decrease incidence of complications. Not only does embolization fail to mitigate surgical risks, the embolization procedure itself carries significant risk for complications. Embolization should not be standard of care for intracranial HB.

Semi-automated counting of axon regeneration in poly(lactide co-glycolide) spinal cord bridges.

BACKGROUND: Spinal cord injury (SCI) is a debilitating event with multiple mechanisms of degeneration leading to life-long paralysis. Biomaterial strategies, including bridges that span the injury and provide a pathway to reconnect severed regions of the spinal cord, can promote partial restoration of motor function following SCI. Axon growth through the bridge is essential to characterizing regeneration, as recovery can occur via other mechanisms such as plasticity. Quantitative analysis of axons by manual counting of histological sections can be slow, which can limit the number of bridge designs evaluated. In this study, we report a semi-automated process to resolve axon numbers in histological sections, which allows for efficient analysis of large data sets. NEW METHOD: Axon numbers were estimated in SCI cross-sections from animals implanted with poly(lactide co-glycolide) (PLG) bridges with multiple channels for guiding axons. Immunofluorescence images of histological sections were filtered using a Hessian-based approach prior to threshold detection to improve the signal-to-noise ratio and filter out background staining associated with PLG polymer. RESULTS: Semi-automated counting successfully recapitulated average axon densities and myelination in a blinded PLG bridge implantation study. COMPARISON WITH EXISTING METHODS: Axon counts obtained with the semi-automated technique correlated well with manual axon counts from blinded independent observers across sections with a wide range of total axons. CONCLUSIONS: This semi-automated detection of Hessian-filtered axons provides an accurate and significantly faster alternative to manual counting of axons for quantitative analysis of regeneration following SCI.

Clinical attributes and surgical outcomes of angiocentric gliomas.

Angiocentric gliomas (AG) are exceedingly rare low-grade neoplasms which often present in the form of intractable epilepsy within younger patients. The current study extensively reviews all reported cases which were pathologically verified as AG in the literature to analyze clinical attributes and surgical outcomes of this neoplasm. There were 88 patients with AG reported in the literature consisting mostly of pediatric cases. The sex distribution consisted of 45 males and 36 females with the remaining seven cases not documenting sex. The average age of initial diagnosis was 16years with almost half of all diagnosed patients being within the first decade of life. In cases where extent of resection was reported, gross total resection (GTR) was achieved in 54 patients, subtotal resection (STR) in 16, and biopsy only in three. Post-operative complications were transient and only occurred in three patients with no reports of death following surgery. Only five cases reported tumor recurrence on follow-up. Eight patients had seizure recurrence post-operatively and GTR offered improved rates of seizure control when compared to STR (p=0.0005). Nearly half of the cases of AG are diagnosed within the first decade of life and they usually manifest with intractable seizures. GTR appears to offer better seizure control in the post-operative period. Surgical resection is the mainstay therapy for AG as post-operative complications and tumor recurrence remain uncommon. Since the number of reported cases is limited, future studies with longer follow-up periods will help elaborate more long-term outcomes.

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. Immunomonitoring techniques possess the potential to elucidate immunological mechanisms of antitumor responses, monitor disease progression, evaluate therapeutic effect, identify candidates for immunotherapy, and serve as prognostic markers of clinical outcome. Current immunomonitoring assays assess delayed-type hypersensitivity, T cell proliferation, cytotoxic T-lymphocyte function, cytokine secretion profiles, antibody titers, and lymphocyte phenotypes. Yet, no single immunomonitoring technique can reliably predict outcomes, relegating immunological markers to exploratory endpoints. In response, the most recent immunomonitoring assays are incorporating emerging technologies and novel analysis techniques to approach the goal of identifying a competent immunological biomarker which predicts therapy responsiveness and clinical outcome. This review addresses the current status of immunomonitoring in glioma vaccine clinical trials with emphasis on correlations with clinical response.

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. A comprehensive search on MEDLINE (OVID and Pubmed), Scopus, Embase, and Web of Science utilizing the search terms "chordoid" AND "meningioma" was performed to identify all reports of pathologically confirmed intracranial CMs. A total of 221 patients were included, comprising 120 females and 101 males. Mean age, MIB-1/Ki67, and tumor size was 45.5 years, 4.3% (range 0.1-26.6%), and 4.1 cm (range 0.8-10 cm), respectively. 5-, and 10- year progression free survival was 67.5 and 54.4%, respectively. Gross total resection (GTR) and subtotal resection was achieved in 172 and 48 patients, respectively. Adjuvant radiotherapy (RT) was given to 30 patients. Multivariate analysis found GTR was strongly correlated with decreased recurrence rates (HR 0.04, p = <0.0001), while higher MIB-1 labeling index (≥5 vs <5%) was associated with increased recurrence (HR 7.08; p = 0.016). Adjuvant RT, age, gender, and tumor location were not associated with recurrence. GTR resection is the strongest predictor of tumor control, and should be the goal to minimize local progression. Additionally, higher MIB-1 labeling was associated with increased rates of tumor recurrence. Tumors that are subtotally resected or demonstrate higher MIB-1 are at greater recurrence and warrant consideration for RT and close long term follow up.

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. METHODS: A comprehensive search on MEDLINE (OVID and PubMed), Scopus, Embase, and Web of Science was conducted following PRISMA guidelines to identify all reported cases of CG. RESULTS: A total of 81 patients met the study criteria which comprised of 33 males and 48 females. Median age at diagnosis was 48 years with a range from 5 to 72 years, and mean tumor size was 3.1cm. Biopsy, subtotal resection (STR), and gross total resection (GTR) were achieved in 8, 34, and 33 patients, respectively, with six cases not reporting extent of resection (EOR). Thirteen patients underwent adjuvant radiotherapy. Postoperative complications were noted in 30 cases (37%), with new onset diabetes insipidus being the most common. Postoperative morbidity was not associated with age, tumor size, or extent of resection. A trans-lamina terminalis approach demonstrated a strong trend towards decreased overall rates of postoperative morbidity compared to other approaches (p=0.051). GTR was associated with improved progression-free survival (PFS; p=0.028), while adjuvant radiotherapy, age, tumor size and proliferative index were not predictive of patient outcomes. CONCLUSION: GTR should be the primary goal for the management of CG, as it is associated with improved rates of tumor control without an increased rate of postoperative complications. Surgical approach was a stronger predictor of complication rates than extent of resection. Morbidity remains high, and future studies to further elaborate on factors predictive of postoperative complications are critical.

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. Heat shock proteins (HSP) function as intracellular chaperones and have been implicated in the activation of both innate and adaptive immune systems. Vaccines formulated from HSP-peptide complexes, derived from autologous tumor, have been applied to the field of immunotherapy for glioblastoma. The results from the phase I and II clinical trials have been promising. Here we review the role of HSP in cellular function and immunity, and its application in the treatment of glioblastoma.