SUMMARY Glioblastomas (GBMs) are highly vascular and lethal brain tumors that display cellular hierarchies containing self-renewing tumorigenic glioma stem cells (GSCs). As GSCs often reside in perivascular niches and may undergo mensenchymal differentiation, we interrogated GSC potential to generate vascular pericytes. Here we show that GSCs give rise to pericytes to support vessel function and tumor growth. In vivo cell lineage tracing with constitutive and lineage specific fluorescent reporters demonstrated that GSCs generate the majority of vascular pericytes. Selective elimination of GSC-derived pericytes disrupts neovasculature and potently inhibits tumor growth. Analysis of human GBM specimens showed that most pericytes are derived from neoplastic cells. GSCs are recruited toward endothelial cells via the SDF-1/CXCR4 axis and induced to become pericytes predominantly by TGF-β. Thus, GSCs contribute to vascular pericytes that may actively remodel perivascular niches. Therapeutic targeting of GSC-derived pericytes may effectively block tumor progression and improve the anti-angiogenic therapy.

Overexpression of the polycomb group gene Bmi1 promotes cell proliferation and induces leukaemia through repression of Cdkn2a (also known as ink4a/Arf) tumour suppressors. Conversely, loss of Bmi1 leads to haematological defects and severe progressive neurological abnormalities in which de-repression of the ink4a/Arf locus is critically implicated. Here, we show that Bmi1 is strongly expressed in proliferating cerebellar precursor cells in mice and humans. Using Bmi1-null mice we demonstrate a crucial role for Bmi1 in clonal expansion of granule cell precursors both in vivo and in vitro. Deregulated proliferation of these progenitor cells, by activation of the sonic hedgehog (Shh) pathway, leads to medulloblastoma development. We also demonstrate linked overexpression of BMI1 and patched (PTCH), suggestive of SHH pathway activation, in a substantial fraction of primary human medulloblastomas. Together with the rapid induction of Bmi1 expression on addition of Shh or on overexpression of the Shh target Gli1 in cerebellar granule cell cultures, these findings implicate BMI1 overexpression as an alternative or additive mechanism in the pathogenesis of medulloblastomas, and highlight a role for Bmi1-containing polycomb complexes in proliferation of cerebellar precursor cells.

Background Endoscopic skull‐base surgery (ESBS) is employed in the management of diverse skull‐base pathologies. Paralleling the increased utilization of ESBS, the literature in this field has expanded rapidly. However, the rarity of these diseases, the inherent challenges of surgical studies, and the continued learning curve in ESBS have resulted in significant variability in the quality of the literature. To consolidate and critically appraise the available literature, experts in skull‐base surgery have produced the International Consensus Statement on Endoscopic Skull‐Base Surgery (ICAR:ESBS). Methods Using previously described methodology, topics spanning the breadth of ESBS were identified and assigned a literature review, evidence‐based review or evidence‐based review with recommendations format. Subsequently, each topic was written and then reviewed by skull‐base surgeons in both neurosurgery and otolaryngology. Following this iterative review process, the ICAR:ESBS document was synthesized and reviewed by all authors for consensus. Results The ICAR:ESBS document addresses the role of ESBS in primary cerebrospinal fluid (CSF) rhinorrhea, intradural tumors, benign skull‐base and orbital pathology, sinonasal malignancies, and clival lesions. Additionally, specific challenges in ESBS including endoscopic reconstruction and complication management were evaluated. Conclusion A critical review of the literature in ESBS demonstrates at least the equivalency of ESBS with alternative approaches in pathologies such as CSF rhinorrhea and pituitary adenoma as well as improved reconstructive techniques in reducing CSF leaks. Evidence‐based recommendations are limited in other pathologies and these significant knowledge gaps call upon the skull‐base community to embrace these opportunities and collaboratively address these shortcomings.

These modifications of the standard transsphenoidal approach are useful for lesions within the boundaries noted above, they offer excellent alternatives to transcranial approaches for these lesions, and they avoid prolonged exposure time and brain retraction. Technical details are discussed and illustrative cases presented.

Initial attempts at transcranial approaches to the pituitary gland in the late 1800s and early 1900s resulted in a mortality rate that was generally considered prohibitive. Schloffer suggested the use of a transsphenoidal route as a safer, alternative approach to the sella turcica. He reported the first successful removal of a pituitary tumor via the transsphenoidal approach in 1906. His procedure underwent a number of modifications by interested surgeons, the culmination of which was A. E. Halstead's description in 1910 of a sublabial gingival incision for the initial stage of exposure. From 1910 to 1925, Cushing, combining a number of suggestions made by previous authors, refined the transsphenoidal approach and used it to operate on 231 pituitary tumors, with a mortality rate of 5.6%. As he developed increasing expertise with transcranial surgery, however, Cushing reduced his mortality rate to 4.5%. With the transcranial approach, he was able to verify suprasellar tumors and achieve better decompression of the optic apparatus, resulting in better recovery of vision and a lower recurrence rate. As a result he and most other neurosurgeons at the time abandoned the transnasal in favor of the transcranial approaches. Norman Dott, a visiting scholar who studied with Cushing in 1923, returned to Edinburgh, Scotland, and continued to use the transsphenoidal procedure while others pursued transcranial approaches. Dott introduced the procedure to Gerard Guiot, who published excellent results with the transsphenoidal approach and revived the interest of many physicians throughout Europe in the early 1960s. Jules Hardy, who used intraoperative fluoroscopy while learning the transsphenoidal approach from Guiot, then introduced the operating microscope to further refine the procedure; he thereby significantly improved its efficacy and decreased surgical morbidity. With the development of antibiotic drugs and modern microinstrumentation, the transsphenoidal approach became the preferred route for the removal of lesions that were confined to the sella turcica. The evolution of the transsphenoidal approaches and their current applications and modifications are discussed.

Objective/Hypothesis: The h-index is an objective and easily calculable measure that can be used to evaluate both the relevance and amount of scientific contributions of an individual author. Our objective was to examine how the h-index of academic otolaryngologists relates with academic rank.Study Design: A descriptive and correlational design was used for analysis of academic otolaryngologists' h-indices using the Scopus database.Methods: H-indices of faculty members from 50 otolaryngology residency programs were calculated using the Scopus database, and data was organized by academic rank. Additionally, an analysis of the h-indices of departmental chairpersons among different specialties was performed.Results: H-index values of academic otolaryngologists were higher with increased academic rank among the levels of assistant professor, associate professor, and professor. There was no significant difference between the h-indices of professors and department chairpersons within otolaryngology. H-indices of chairpersons in different academic specialties were compared and were significantly different, suggesting that the use of this metric may not be appropriate for comparing different fields.Conclusions: The h-index is a reliable tool for quantifying academic productivity within otolaryngology. This measure is easily calculable and may be useful when evaluating decisions regarding advancement within academic otolaryngology departments. Comparison of this metric among faculty members from different fields, however, may not be reliable.

In this study, endoscopic resection had a significantly lower intraoperative blood loss and lower recurrence rate when compared to open resection. However, there was no difference in recurrence rate when analyzing the IPD and controlling for Radkowski/Sessions grading. Therefore, further large-scale studies may be required to fully elucidate treatment options.

✓Extradural arachnoid cysts in the spine are rare and are seldom a cause of spinal cord compression. They are thought to arise from congenital defects in the dura mater, and they almost always communicate with the intrathecal subarachnoid space through a small defect in the dura. The mainstay of treatment in patients with neurological symptoms is surgical removal of the cyst together with ligation of the communicating pedicle and closure of the dural defect. In the present paper the authors review the literature and discuss the clinical and pathological features, mechanisms of pathogenesis, neuroimaging characteristics, and surgical management of spinal extradural arachnoid cysts. The surgical technique for removal of these lesions is illustrated in a patient with a large thoracolumbar spinal extradural arachnoid cyst causing neurogenic claudication.