Olfactory groove meningioma: report of 99 cases surgically treated at the Catholic University School of Medicine, Rome

OBJECTIVE: We reviewed our series of olfactory groove meningiomas (OGMs) with the aim to relate the surgical approach with outcome and to define clinical and pathologic predictors of prognosis. METHODS: Ninety-nine patients who underwent 113 craniotomies at our Institution between 1984 and 2010 were entered this study. The relationship between surgical approach (bifrontal, fronto-orbito-basal, and pterional) and either tumor diameter, extent of tumor resection, complication rate, need of reoperation, and Karnofsky Performance Status (KPS) was analyzed. The impact of age ( 64 70 vs. > 70 years), sex, tumor diameter (< 6 vs. 65 6 cm), pre- and postoperative KPS (< 80 vs. 65 80), Simpson grade (I-II vs. III-IV), and World Health Organization (WHO) histologic grade (I vs. II-III) on survival was assessed. Kaplan-Meier survival curves were plotted and differences in survival between groups of patients were compared. A multivariate analysis adjusted for age, pre- and postoperative KPS, Simpson grade, tumor diameter, and WHO histologic grade also was performed. RESULTS: The fronto-orbito-basal approach (n = 22) allowed a significantly greater percentage of Simpson I-II removals than the bifrontal (n = 70) and pterional approach (n = 21) (P = 0.0354 and P = 0.0485, respectively). The risk of life-threatening complications trended to be lower in patients operated upon either via the fronto-orbito-basal and via the pterional approach than in those treated via the bifrontal approach. Retraction-related brain swelling did not occur in any case after the fronto-orbito-basal approach (P = 0.0384); however, this approach was associated with a greater rate of cerebrospinal fluid leak (P = 0.0011). Among prognostic factors, age 64 70 years (P = 0.0044), tumor diameter <6 cm (P = 0.0455), pre- and postoperative KPS 65 80 (both P < 0.0001), Simpson grade I-II (P = 0.0096), and WHO histologic grade I (P = 0.0112) were significantly associated with longer overall survival. Age (P = 0.0393) and WHO histologic grade (P = 0.0418) emerged as independent prognostic factors for overall survival on multivariate analysis. CONCLUSION: In the largest series of OGMs published to date, the bifrontal approach was associated with a greater risk of life-threatening complications compared with the lateral pterional and fronto-orbito-basal approaches. The fronto-orbito-basal approach provided greater chances of total tumor removal than the bifrontal and pterional approaches. Two independent factors for overall survival of patients with OGM were identified, namely age and WHO grade

A BMP7 variant inhibits tumor angiogenesis in vitro and in vivo through direct modulation of endothelial cell biology

Bone morphogenetic proteins (BMPs), members of the TGF-\u3b2 superfamily, have numerous biological activities including control of growth, differentiation, and vascular development. Using an in vitro co-culture endothelial cord formation assay, we investigated the role of a BMP7 variant (BMP7v) in VEGF, bFGF, and tumor-driven angiogenesis. BMP7v treatment led to disruption of neo-endothelial cord formation and regression of existing VEGF and bFGF cords in vitro. Using a series of tumor cell models capable of driving angiogenesis in vitro, BMP7v treatment completely blocked cord formation. Pre-treatment of endothelial cells with BMP7v significantly reduced their cord forming ability, indicating a direct effect on endothelial cell function. BMP7v activated the canonical SMAD signaling pathway in endothelial cells but targeted gene knockdown using shRNA directed against SMAD4 suggests this pathway is not required to mediate the anti-angiogenic effect. In contrast to SMAD activation, BMP7v selectively decreased ERK and AKT activation, significantly decreased endothelial cell migration and down-regulated expression of critical RTKs involved in VEGF and FGF angiogenic signaling, VEGFR2 and FGFR1 respectively. Importantly, in an in vivo angiogenic plug assay that serves as a measurement of angiogenesis, BMP7v significantly decreased hemoglobin content indicating inhibition of neoangiogenesis. In addition, BMP7v significantly decreased angiogenesis in glioblastoma stem-like cell (GSLC) Matrigel plugs and significantly impaired in vivo growth of a GSLC xenograft with a concomitant reduction in microvessel density. These data support BMP7v as a potent anti-angiogenic molecule that is effective in the context of tumor angiogenesis

Deregulated expression of the imprinted DLK1-DIO3 region in glioblastoma stemlike cells: Tumor suppressor role of lncRNA MEG3

Background: Glioblastoma (GBM) stemlike cells (GSCs) are thought to be responsible for the maintenance and aggressiveness of GBM, the most common primary brain tumor in adults. This study aims at elucidating the involvement of deregulations within the imprinted delta-like homolog 1 gene type III iodothyronine deiodinase gene (DLK-DIO3) region on chromosome 14q32 in GBM pathogenesis. Methods: Real-time PCR analyses were performed on GSCs and GBM tissues. Methylation analyses, gene expression, and reverse-phase protein array profiles were used to investigate the tumor suppressor function of the maternally expressed 3 gene (MEG3). Results: Loss of expression of genes and noncoding RNAs within the DLK1-DIO3 region was observed in GSCs and GBM tissues compared with normal brain. This downregulation is mainly mediated by epigenetic silencing. Kaplan-Meier analysis indicated that low expression of MEG3 and MEG8 long noncoding (lnc)RNAs significantly correlated with short survival in GBM patients. MEG3 restoration impairs tumorigenic abilities of GSCs in vitro by inhibiting cell growth, migration, and colony formation and decreases in vivo tumor growth, reducing infiltrative growth. These effects were associated with modulation of genes involved in cell adhesion and epithelial-to-mesenchymal transition (EMT). Conclusion: In GBM, MEG3 acts as a tumor suppressor mainly regulating cell adhesion, EMT, and cell proliferation, thus providing a potential candidate for novel GBM therapies

Patient-reported outcome measures in patients with familial cerebral cavernous malformations: results from the Treat_CCM trial

BackgroundThe Phase 1/2 Treat_CCM randomized controlled trial for people with familial cerebral cavernous malformations (FCCMs) confirmed the safety of propranolol and suggested beneficial effects on intracerebral hemorrhage or new focal neurological deficits, but the effects on patient-reported outcome measures have not been reported.MethodsParticipants completed self-reported questionnaires at baseline, 1 and 2 years. Depression was assessed with the Beck Depression Inventory-II (BDI-2); Anxiety with the State–Trait Anxiety Inventory X1 and X2 (STAI X-1 and STAI X-2); and Quality of Life with the Short Form 36 (SF-36), split into the physical and mental component scales (PCS and MCS). Differences between treatment groups and the general population were assessed. Change over time by treatment was assessed by means of mixed models.ResultsIn total, 71 participants (48 propranolol and 23 standard care) were enrolled, of whom 61 (73%) completed questionnaires at baseline and 2-year FU. At baseline, no differences between treatment groups for any of the questionnaires were present. Twenty (31.7%) patients were considered depressed at baseline, while this proportion was lower in the propranolol group after 2 years (28.6% vs. 55.5%, p = 0.047). The STAI X-1 and X-2 scores were stable over time. PCS was lower in FCCM patients as compared with the general Italian population, while the MCS was similar to the general population. No effect of propranolol was found for both PCS and MCS.ConclusionDepression is common among patients with FCCM. Patients randomized to propranolol had a lower proportion of participants with depression after 2 years.Clinical trial registration: https://clinicaltrials.gov/, identifier (NCT03589014)

Emerging role for USP1 in glioblastoma stem cell maintenance and radioresistance: A potential target for glioblastoma therapy

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Response to: "Rare serious complications of erlotinib therapy"

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Is deferred use of bevacizumab for glioblastoma associated with prolonged survival?

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Extradural ependymoma: Diagnosis using magnetic resonance imaging

Extradural ependymomas are a non--homogeneous group of tumors located mainly in lumbosacral region, both intraspinally and extraspinally; in the latter case they can extend presacrally in the retrorectal space or retrosacrally in subcutaneous tissue. More rare cases of thoracic intraspinal or of ectopic location (mediastinum, abdomen, pelvis) have been described. Extradural ependymomas are thought to arise from ependymal remnants, mainly from coccygeal medullary vestige. Neuroimaging, particularly MRI, can help in diagnosis and surgical planning; radiological features are however non-specific and a variety of differential diagnoses can be done. Therapy is mainly surgical; a complete excision is the goal, because of the high risk of recurrence. Adjuvant therapies are generally performed but are of doubtful efficacy. Prognosis is good if radical surgery has been achieved. Recurrent or metastatic tumors carry a worse prognosis

O-arm in Endonasal Endoscopic Cranial Base Surgery. Technical Note on Initial Feasibility

Background: In transsphenoidal endoscopic cranial base surgery, a precise navigational support may be crucial. This is particularly evident when tumors extend to the parasellar region or in recurrent tumors whereas normal anatomy has been altered by previous surgery/radiotherapy. Methods: Previous unsatisfactory experiences with various navigation techniques in this type of surgery encouraged us to perform an endoscopic endonasal approach with an O-arm (Medtronic, Inc., Minneapolis, Minnesota, USA) assisted technique for the surgical treatment of 4 patients affected respectively by an orbital tumor and 3 cases of relapse of nonfunctioning pituitary adenoma, 1 of them localized in the infrasellar-clival region. Results: The system O-arm-StealthStation allows for merging intraoperative bone 3-D acquisition with preoperative computed tomography/magnetic resonance imaging and provides the surgeon with an extremely reliable operative navigational tool. Conclusions: This is the first report of an O-arm-assisted endoscopic surgery for cranial base tumors. Here we report on the feasibility and usefulness of such a new application of the O-arm: technical details, setting of the operating room, advantages, and limits of the method are also described. Our overall impression, considering the limited number of patients, is that use of the O-arm may be successfully extended to selected cases of cranial base tumors operated through an endoscopic endonasal approach