Phosphatase and Tensin Homologue on chromosome Ten (PTEN) is a tumor suppressor and an antagonist of the phosphoinositide-3 kinase (PI3K) pathway. We identified a 576-amino acid translational variant of PTEN, termed PTEN-Long, that arises from an alternative translation start site 519 bp upstream of the ATG initiation sequence, adding 173 N-terminal amino acids to the normal PTEN open reading frame. PTEN-Long is a membrane permeable lipid phosphatase that is secreted from cells and can enter other cells. As an exogenous agent, PTEN-Long antagonized PI3K signaling and induced tumor cell death in vitro and in vivo. By providing a means to restore a functional tumor suppressor protein to tumor cells, PTEN-Long may have therapeutic uses.

Carotid-cavernous fistulas (CCFs) are vascular shunts allowing blood to flow from the carotid artery into the cavernous sinus. The characteristic clinical features seen in patients with CCFs are the sequelae of hemodynamic dysfunction within the cavernous sinus. Once routinely treated with open surgical procedures, including carotid ligation or trapping and cavernous sinus exploration, endovascular therapy is now the treatment modality of choice in many cases. The authors provide a review of CCFs, detailing the current classification and clinical management of these lesions. Therapeutic options including conservative management, open surgery, endovascular intervention, and radiosurgical therapy are presented. The complications and treatment results as reported in the contemporary literature are also reviewed.

Glioblastomas (GBMs) diffusely infiltrate the brain, making complete removal by surgical resection impossible. The mixture of neoplastic and nonneoplastic cells that remain after surgery form the biological context for adjuvant therapeutic intervention and recurrence. We performed RNA-sequencing (RNA-seq) and histological analysis on radiographically guided biopsies taken from different regions of GBM and showed that the tissue contained within the contrast-enhancing (CE) core of tumors have different cellular and molecular compositions compared with tissue from the nonenhancing (NE) margins of tumors. Comparisons with the The Cancer Genome Atlas dataset showed that the samples from CE regions resembled the proneural, classical, or mesenchymal subtypes of GBM, whereas the samples from the NE regions predominantly resembled the neural subtype. Computational deconvolution of the RNA-seq data revealed that contributions from nonneoplastic brain cells significantly influence the expression pattern in the NE samples. Gene ontology analysis showed that the cell type-specific expression patterns were functionally distinct and highly enriched in genes associated with the corresponding cell phenotypes. Comparing the RNA-seq data from the GBM samples to that of nonneoplastic brain revealed that the differentially expressed genes are distributed across multiple cell types. Notably, the patterns of cell type-specific alterations varied between the different GBM subtypes: the NE regions of proneural tumors were enriched in oligodendrocyte progenitor genes, whereas the NE regions of mesenchymal GBM were enriched in astrocytic and microglial genes. These subtypespecific patterns provide new insights into molecular and cellular composition of the infiltrative margins of GBM.glioma | tumor heterogeneity | microenvironment

Craniopharyngioma is a rare primary central nervous system neoplasm. Our objective was to determine factors associated with incidence, treatment, and survival of craniopharyngiomas in the United States. We used the surveillance, epidemiology and end results program (SEER) database to identify patients who received a diagnosis of craniopharyngioma during 2004-2008. We analyzed clinical and demographic information, including age, race, sex, tumor histology, and treatment. Age-adjusted incidence rates and age, sex, and race-adjusted expected survival rates were calculated. We used Cox proportional hazards models to determine the association between covariates and overall survival. We identified 644 patients with a diagnosis of craniopharyngioma. Black race was associated with an age-adjusted relative risk for craniopharyngioma of 1.26 (95% confidence interval [CI], 0.98-1.59), compared with white race. One- and 3-year survival rates of 91.5% (95% CI, 88.9%-93.5%), and 86.2% (95% CI, 82.7%-89.0%) were observed for the cohort; relative survival rates were 92.1% (95% CI, 89.5%-94.0%) and 87.6% (95% CI, 84.1%-90.4%) for 1- and 3-years, respectively. In the multivariable model, factors associated with prolonged survival included younger age, smaller tumor size, subtotal resection, and radiation therapy. Black race, on the other hand, was associated with worse overall survival in the final model. We demonstrated that >85% of patients survived 3 years after diagnosis and that subtotal resection and radiation therapy were associated with prolonged survival. We also noted a higher incidence rate and worse 1- and 3-year survival rates in the black population. Future investigations should examine these racial disparities and focus on evaluating the efficacy of emerging treatment paradigms.

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Object Central nervous system (CNS) hemangiopericytomas are relatively uncommon and unique among CNS tumors as they can originate from or develop metastases outside of the CNS. Significant difference of opinion exists in the management of these lesions, as current treatment paradigms are based on limited clinical experience and single-institution series. Given these limitations and the absence of prospective clinical trials within the literature, nationwide registries have the potential to provide unique insight into the efficacy of various therapies. Methods The authors queried the Surveillance Epidemiology and End Results (SEER) database to investigate the clinical behavior and prognostic factors for hemangiopericytomas originating within the CNS during the years 2000–2009. The SEER survival data were adjusted for demographic factors including age, sex, and race. Univariate and multivariate analyses were performed to identify characteristics associated with overall survival. Results The authors identified 227 patients with a diagnosis of CNS hemangiopericytoma. The median length of follow-up was 34 months (interquartile range 11–63 months). Median survival was not reached, but the 5-year survival rate was 83%. Univariate analysis showed that age and radiation therapy were significantly associated with survival. Moreover, young age and supratentorial location were significantly associated with survival on multivariate analysis. Most importantly, multivariate analysis using the Cox proportional hazards model showed a statistically significant survival benefit for patients treated with gross-total resection (GTR) in combination with adjuvant radiation treatment (HR 0.31 [95% CI 0.01–0.95], p = 0.04), an effect not appreciated with GTR alone. Conclusions The authors describe the epidemiology of CNS hemangiopericytomas in a large, national cancer database, evaluating the effectiveness of various treatment paradigms used in clinical practice. In this study, an overall survival benefit was found when GTR was accomplished and combined with radiation therapy. This finding has not been appreciated in previous series of patients with CNS hemangiopericytoma and warrants future investigations into the role of upfront adjuvant radiation therapy.

CSF, cerebrospinal fluidIQR, interquartile rangeSPARCS, Statewide Planning And Research Cooperative System.

OBJECTIVEPatients with medically refractory localization-related epilepsy (LRE) may be candidates for surgical intervention if the seizure onset zone (SOZ) can be well localized. Stereoelectroencephalography (SEEG) offers an attractive alternative to subdural grid and strip electrode implantation for seizure lateralization and localization; yet there are few series reporting the safety and efficacy of SEEG in pediatric patients.METHODSThe authors review their initial 3-year consecutive experience with SEEG in pediatric patients with LRE. SEEG coverage, SOZ localization, complications, and preliminary seizure outcomes following subsequent surgical treatments are assessed.RESULTSTwenty-five pediatric patients underwent 30 SEEG implantations, with a total of 342 electrodes placed. Ten had prior resections or ablations. Seven had no MRI abnormalities, and 8 had multiple lesions on MRI. Based on preimplantation hypotheses, 7 investigations were extratemporal (ET), 1 was only temporal-limbic (TL), and 22 were combined ET/TL investigations. Fourteen patients underwent bilateral investigations. On average, patients were monitored for 8 days postimplant (range 3–19 days). Nearly all patients were discharged home on the day following electrode explantation.There were no major complications. Minor complications included 1 electrode deflection into the subdural space, resulting in a minor asymptomatic extraaxial hemorrhage; and 1 in-house and 1 delayed electrode superficial scalp infection, both treated with local wound care and oral antibiotics.SEEG localized the hypothetical SOZ in 23 of 25 patients (92%). To date, 18 patients have undergone definitive surgical intervention. In 2 patients, SEEG localized the SOZ near eloquent cortex and subdural grids were used to further delineate the seizure focus relative to mapped motor function just prior to resection. At last follow-up (average 21 months), 8 of 15 patients with at least 6 months of follow-up (53%) were Engel class I, and an additional 6 patients (40%) were Engel class II or III. Only 1 patient was Engel class IV.CONCLUSIONSSEEG is a safe and effective technique for invasive SOZ localization in medically refractory LRE in the pediatric population. SEEG permits bilateral and multilobar investigations while avoiding large craniotomies. It is conducive to deep, 3D, and perilesional investigations, particularly in cases of prior resections. Patients who are not found to have focally localizable seizures are spared craniotomies.