Publications by authors named "Matei A Banu"

29 Publications

  • Page 1 of 1

Protein kinase C and SRC signaling define reciprocally related subgroups of glioblastoma with distinct therapeutic vulnerabilities.

Cell Rep 2021 Nov;37(8):110054

Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA. Electronic address:

We report that atypical protein kinase Cι (PKCι) is an oncogenic driver of glioblastoma (GBM). Deletion or inhibition of PKCι significantly impairs tumor growth and prolongs survival in murine GBM models. GBM cells expressing elevated PKCι signaling are sensitive to PKCι inhibitors, whereas those expressing low PKCι signaling exhibit active SRC signaling and sensitivity to SRC inhibitors. Resistance to the PKCι inhibitor auranofin is associated with activated SRC signaling and response to a SRC inhibitor, whereas resistance to a SRC inhibitor is associated with activated PKCι signaling and sensitivity to auranofin. Interestingly, PKCι- and SRC-dependent cells often co-exist in individual GBM tumors, and treatment of GBM-bearing mice with combined auranofin and SRC inhibitor prolongs survival beyond either drug alone. Thus, we identify PKCι and SRC signaling as distinct therapeutic vulnerabilities that are directly translatable into an improved treatment for GBM.
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http://dx.doi.org/10.1016/j.celrep.2021.110054DOI Listing
November 2021

Synchronous supratentorial and infratentorial oligodendrogliomas with incongruous IDH1 mutations, a case report.

Acta Neuropathol Commun 2021 09 29;9(1):160. Epub 2021 Sep 29.

Department of Neurosurgery, Columbia University Irving Medical Center, New York, USA.

Infratentorial oligodendrogliomas, a rare pathological entity, are generally considered metastatic lesions from supratentorial primary tumors. Here, we report the case of a 23-year-old man presenting with a histopathologically confirmed right precentral gyrus grade 2 oligodendroglioma and a concurrent pontine grade 3 oligodendroglioma. The pontine lesion was biopsied approximately a year after the biopsy of the precentral lesion due to disease progression despite 4 cycles of procarbazine-CCNU-vincristine (PCV) chemotherapy and stable supratentorial disease. Histology and genetic analysis of the pontine biopsy were consistent with grade 3 oligodendroglioma, and comparison of the two lesions demonstrated common 1p/19q co-deletions and TERT promoter mutations but distinct IDH1 mutations, with a non-canonical IDH1 R132G mutation identified in the infratentorial lesion and a R132H mutation identified in the cortical lesion. Initiation of Temozolomide led to complete response of the supratentorial lesion and durable disease control, while Temozolomide with subsequent radiation therapy of 54 Gy in 30 fractions resulted in partial response of the pontine lesion. This case report supports possible distinct molecular pathogenesis in supratentorial and infratentorial oligodendrogliomas and raises questions about the role of different IDH1 mutant isoforms in explaining treatment resistance to different chemotherapy regimens. Importantly, this case suggests that biopsies of all radiographic lesions, when feasible and safe, should be considered in order to adequately guide management in multicentric oligodendrogliomas.
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http://dx.doi.org/10.1186/s40478-021-01265-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482672PMC
September 2021

Rationale and Clinical Implications of Fluorescein-Guided Supramarginal Resection in Newly Diagnosed High-Grade Glioma.

Front Oncol 2021 26;11:666734. Epub 2021 May 26.

Gabriele Bartoli Brain Tumor Laboratory, Department of Neurological Surgery and Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, United States.

Current standard of care for glioblastoma is surgical resection followed by temozolomide chemotherapy and radiation. Recent studies have demonstrated that >95% extent of resection is associated with better outcomes, including prolonged progression-free and overall survival. The diffusely infiltrative pattern of growth in gliomas results in microscopic extension of tumor cells into surrounding brain parenchyma that makes complete resection unattainable. The historical goal of surgical management has therefore been maximal safe resection, traditionally guided by MRI and defined as removal of all contrast-enhancing tumor. Optimization of surgical resection has led to the concept of supramarginal resection, or removal beyond the contrast-enhancing region on MRI. This strategy of extending the cytoreductive goal targets a tumor region thought to be important in the recurrence or progression of disease as well as resistance to systemic and local treatment. This approach must be balanced against the risk of impacting eloquent regions of brain and causing permanent neurologic deficit, an important factor affecting overall survival. Over the years, fluorescent agents such as fluorescein sodium have been explored as a means of more reliably delineating the boundary between tumor core, tumor-infiltrated brain, and surrounding cortex. Here we examine the rationale behind extending resection into the infiltrative tumor margins, review the current literature surrounding the use of fluorescein in supramarginal resection of gliomas, discuss the experience of our own institution in utilizing fluorescein to maximize glioma extent of resection, and assess the clinical implications of this treatment strategy.
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http://dx.doi.org/10.3389/fonc.2021.666734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187787PMC
May 2021

COVID-19 neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital.

Brain 2021 10;144(9):2696-2708

Department of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA.

Many patients with SARS-CoV-2 infection develop neurological signs and symptoms; although, to date, little evidence exists that primary infection of the brain is a significant contributing factor. We present the clinical, neuropathological and molecular findings of 41 consecutive patients with SARS-CoV-2 infections who died and underwent autopsy in our medical centre. The mean age was 74 years (38-97 years), 27 patients (66%) were male and 34 (83%) were of Hispanic/Latinx ethnicity. Twenty-four patients (59%) were admitted to the intensive care unit. Hospital-associated complications were common, including eight patients (20%) with deep vein thrombosis/pulmonary embolism, seven (17%) with acute kidney injury requiring dialysis and 10 (24%) with positive blood cultures during admission. Eight (20%) patients died within 24 h of hospital admission, while 11 (27%) died more than 4 weeks after hospital admission. Neuropathological examination of 20-30 areas from each brain revealed hypoxic/ischaemic changes in all brains, both global and focal; large and small infarcts, many of which appeared haemorrhagic; and microglial activation with microglial nodules accompanied by neuronophagia, most prominently in the brainstem. We observed sparse T lymphocyte accumulation in either perivascular regions or in the brain parenchyma. Many brains contained atherosclerosis of large arteries and arteriolosclerosis, although none showed evidence of vasculitis. Eighteen patients (44%) exhibited pathologies of neurodegenerative diseases, which was not unexpected given the age range of our patients. We examined multiple fresh frozen and fixed tissues from 28 brains for the presence of viral RNA and protein, using quantitative reverse-transcriptase PCR, RNAscope® and immunocytochemistry with primers, probes and antibodies directed against the spike and nucleocapsid regions. The PCR analysis revealed low to very low, but detectable, viral RNA levels in the majority of brains, although they were far lower than those in the nasal epithelia. RNAscope® and immunocytochemistry failed to detect viral RNA or protein in brains. Our findings indicate that the levels of detectable virus in coronavirus disease 2019 brains are very low and do not correlate with the histopathological alterations. These findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but more likely from systemic inflammation, perhaps with synergistic contribution from hypoxia/ischaemia. Further studies are needed to define whether these pathologies, if present in patients who survive coronavirus disease 2019, might contribute to chronic neurological problems.
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http://dx.doi.org/10.1093/brain/awab148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083258PMC
October 2021

Endoscopic endonasal approach for suprasellar meningiomas: introduction of a new scoring system to predict extent of resection and assist in case selection with long-term outcome data.

J Neurosurg 2020 Jul 24:1-13. Epub 2020 Jul 24.

Departments of1Neurosurgery and.

Objective: The endoscopic endonasal approach (EEA) has gained increasing popularity for the resection of suprasellar meningiomas (SSMs). Appropriate case selection is critical in optimizing patient outcome. Long-term outcome data are lacking. The authors systematically identified preoperative factors associated with extent of resection (EOR) and determined the relationship between EOR and long-term recurrence after EEA for SSMs.

Methods: In this retrospective cohort study, the authors identified preoperative clinical and imaging characteristics associated with EOR and built on the recently published University of California, San Francisco resectability score to propose a score more specific to the EEA. They then examined the relationship between gross-total resection (GTR; 100%), near-total resection (NTR; 95%-99%), and subtotal resection (STR; < 95%) and recurrence or progression with Kaplan-Meier survival analysis.

Results: A total of 51 patients were identified. Radiographic GTR was achieved in 40 of 47 (85%) patients in whom it was the surgical goal. Significant independent risk factors for incomplete resection were prior surgery (OR 25.94, 95% CI < 2.00 to 336.49, p = 0.013); tumor lateral to the optic nerve (OR 13.41, 95% CI 1.82-98.99, p = 0.011); and complete internal carotid artery (ICA) encasement (OR 15.12, 95% CI 1.17-194.08, p = 0.037). Tumor size and optic canal invasion were not significant risk factors after adjustment for other variables. A resectability score based on the multivariable model successfully predicted the likelihood of GTR; a score of 0 had a positive predictive value of 97% for GTR, whereas a score of 2 had a negative predictive value of 87.5% for incomplete resection. After a mean follow-up of 40.6 ± 32.4 months (mean ± SD), recurrence was 2.7% after GTR (1 patient with atypical histology), 44.4% after NTR, and 80% after STR (p < 0.0001). Vision was stable or improved in 93.5% and improved in 67.4% of patients with a preoperative deficit. There were 5 (9.8%) postoperative CSF leaks, of which 4 were managed with lumbar drains and 1 required a reoperation.

Conclusions: The EEA is a safe and effective approach to SSMs, with favorable visual outcomes in well-selected cases. The combination of postoperative MRI-based EOR with direct endoscopic inspection can be used in lieu of Simpson grade to predict recurrence. GTR dramatically reduces recurrence and can be achieved regardless of tumor size, proximity or encasement of the anterior cerebral artery, or medial optic canal invasion. Risk factors for incomplete resection include prior surgery, tumor lateral to the optic nerve, and complete ICA encasement.
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http://dx.doi.org/10.3171/2020.4.JNS20475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111689PMC
July 2020

Ex vivo multi-electrode analysis reveals spatiotemporal dynamics of ictal behavior at the infiltrated margin of glioma.

Neurobiol Dis 2020 02 12;134:104676. Epub 2019 Nov 12.

Department of Neurology, Columbia University Medical Center, New York, NY, USA.

The purpose of this study is to develop a platform in which the cellular and molecular underpinnings of chronic focal neocortical lesional epilepsy can be explored and use it to characterize seizure-like events (SLEs) in an ex vivo model of infiltrating high-grade glioma. Microelectrode arrays were used to study electrophysiologic changes in ex vivo acute brain slices from a PTEN/p53 deleted, PDGF-B driven mouse model of high-grade glioma. Electrode locations were co-registered to the underlying histology to ascertain the influence of the varying histologic landscape on the observed electrophysiologic changes. Peritumoral, infiltrated, and tumor sites were sampled in tumor-bearing slices. Following the addition of zero Mg solution, all three histologic regions in tumor-bearing slices showed significantly greater increases in firing rates when compared to the control sites. Tumor-bearing slices demonstrated increased proclivity for SLEs, with 40 events in tumor-bearing slices and 5 events in control slices (p-value = .0105). Observed SLEs were characterized by either low voltage fast (LVF) onset patterns or short bursts of repetitive widespread, high amplitude low frequency discharges. Seizure foci comprised areas from all three histologic regions. The onset electrode was found to be at the infiltrated margin in 50% of cases and in the peritumoral region in 36.9% of cases. These findings reveal a landscape of histopathologic and electrophysiologic alterations associated with ictogenesis and spread of tumor-associated seizures.
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http://dx.doi.org/10.1016/j.nbd.2019.104676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147009PMC
February 2020

Cerebral Vasospasm after Open Fenestration of an Arachnoid Cyst in a 4-Year-Old Boy: Case Report and Review of the Literature.

Pediatr Neurosurg 2019 16;54(2):132-138. Epub 2019 Jan 16.

Department of Neurological Surgery, College of Physicians and Surgeons, Neurological Institute of New York, Columbia University, New York, New York, USA,

Cerebral vasospasm is associated with significant morbidity, and most commonly occurs following subarachnoid hemorrhage. Rarely, vasospasm can follow tumor resection and traumatic brain injury. We present the first reported case of a young child who developed diffuse vasospasm following open fenestration of an arachnoid cyst and was promptly treated, with full recovery of neurologic function. Although vasopasm after arachnoid cyst fenestration is rare, it can be included in the differential for a new focal neurologic deficit.
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http://dx.doi.org/10.1159/000495834DOI Listing
April 2019

Endonasal endoscopic transsphenoidal resection of intrinsic third ventricular craniopharyngioma: surgical results.

J Neurosurg 2018 Nov 1:1-11. Epub 2018 Nov 1.

1Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York.

OBJECTIVEIntrinsic third ventricular craniopharyngiomas (IVCs) have been reported by some authors to "pose the greatest surgical challenge" of all craniopharyngiomas (CPAs). A variety of open microsurgical approaches have historically been used for resection of these tumors. Despite increased utilization of the endoscopic endonasal approach (EEA) for resection of CPAs in recent years, many authors continue to recommend against use of the EEA for resection of IVCs. In this paper, the authors present the largest series to date utilizing the EEA to remove IVCs.METHODSThe authors reviewed a prospectively acquired database of the EEA for resection of IVCs over 14 years at Weill Cornell Medical College, NewYork-Presbyterian Hospital. Preoperative MR images were examined independently by two neurosurgeons and a neuroradiologist to identify IVCs. Pre- and postoperative endocrinological, ophthalmological, radiographic, and other morbidities were determined from retrospective chart review and volumetric radiographic analysis.RESULTSBetween January 2006 and August 2017, 10 patients (4 men, 6 women) ranging in age from 26 to 67 years old, underwent resection of an IVC utilizing the EEA. Preoperative endocrinopathy was present in 70% and visual deterioration in 60%. Gross-total resection (GTR) was achieved in 9 (90%) of 10 patients, with achievement of near-total (98%) resection in the remaining patient. Pathology was papillary in 30%. Closure incorporated a "gasket-seal" technique with nasoseptal flap coverage and either lumbar drainage (9 patients) or a ventricular drain (1 patient). Postoperatively, complete anterior and posterior pituitary insufficiency was present in 90% and 70% of patients, respectively. In 4 patients with normal vision prior to surgery, 3 had stable vision following tumor resection. One patient noted a new, incongruous, left inferior homonymous quadrantanopsia postoperatively. In the 6 patients who presented with compromised vision, 2 reported stable vision following surgery. Each of the remaining 4 patients noted significant improvement in vision after tumor resection, with complete restoration of normal vision in 1 patient. Aside from the single case (10%) of visual deterioration referenced above, there were no instances of postoperative neurological decline. Postoperative CSF leakage occurred in 1 morbidly obese patient who required reoperation for revision of closure. After a mean follow-up of 46.8 months (range 4-131 months), tumor recurrence was observed in 2 patients (20%), one of whom was treated with radiation and the other with chemotherapy. Both of these patients had previously undergone GTR of the IVC.CONCLUSIONSThe 10 patients described in this report represent the largest number of patients with IVC treated using EEA for resection to date. EEA for resection of IVC is a safe and efficacious operative strategy that should be considered a surgical option in the treatment of this challenging subset of tumors.
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http://dx.doi.org/10.3171/2018.5.JNS18198DOI Listing
November 2018

Decision-making algorithm for minimally invasive approaches to anterior skull base meningiomas.

Neurosurg Focus 2018 04;44(4):E7

Departments of1Neurological Surgery.

OBJECTIVE Anterior skull base meningiomas are benign lesions that cause neurological symptoms through mass effect on adjacent neurovascular structures. While traditional transcranial approaches have proven to be effective at removing these tumors, minimally invasive approaches that involve using an endoscope offer the possibility of reducing brain and nerve retraction, minimizing incision size, and speeding patient recovery; however, appropriate case selection and results in large series are lacking. METHODS The authors developed an algorithm for selecting a supraorbital keyhole minicraniotomy (SKM) for olfactory groove meningiomas or an expanded endoscopic endonasal approach (EEA) for tuberculum sella (TS) or planum sphenoidale (PS) meningiomas based on the presence or absence of olfaction and the anatomical extent of the tumor. Where neither approach is appropriate, a standard transcranial approach is utilized. The authors describe rates of gross-total resection (GTR), olfactory outcomes, and visual outcomes, as well as complications, for 7 subgroups of patients. Exceptions to the algorithm are also discussed. RESULTS The series of 57 patients harbored 57 anterior skull base meningiomas; the mean tumor volume was 14.7 ± 15.4 cm (range 2.2-66.1 cm), and the mean follow-up duration was 42.2 ± 37.1 months (range 2-144 months). Of 19 patients with olfactory groove meningiomas, 10 had preserved olfaction and underwent SKM, and preservation of olfaction in was seen in 60%. Of 9 patients who presented without olfaction, 8 had cribriform plate invasion and underwent combined SKM and EEA (n = 3), bifrontal craniotomy (n = 3), or EEA (n = 2), and one patient without both olfaction and cribriform plate invasion underwent SKM. GTR was achieved in 94.7%. Of 38 TS/PS meningiomas, 36 of the lesions were treated according to the algorithm. Of these 36 meningiomas, 30 were treated by EEA and 6 by craniotomy. GTR was achieved in 97.2%, with no visual deterioration and one CSF leak that resolved by placement of a lumbar drain. Two patients with tumors that, based on the algorithm, were not amenable to an EEA underwent EEA nonetheless: one had GTR and the other had a residual tumor that was followed and removed via craniotomy 9 years later. CONCLUSIONS Utilizing a simple algorithm aimed at preserving olfaction and vision and based on maximizing use of minimally invasive approaches and selective use of transcranial approaches, the authors found that excellent outcomes can be achieved for anterior skull base meningiomas.
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http://dx.doi.org/10.3171/2018.1.FOCUS17734DOI Listing
April 2018

Order in Chaos: Understanding Intratumoral Heterogeneity in Gliomas by Tracking Tumor Cell Fate.

Neurosurgery 2018 01;82(1):N4-N6

Department of Neurosurgery Columbia University Medical Center New York, New York.

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http://dx.doi.org/10.1093/neuros/nyx538DOI Listing
January 2018

Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of Bcl-xL.

Nat Commun 2017 10 20;8(1):1067. Epub 2017 Oct 20.

Department of Pathology & Cell Biology, Columbia University Medical Center, New York, NY, 10032, USA.

Certain gliomas often harbor a mutation in the activity center of IDH1 (R132H), which leads to the production of the oncometabolite 2-R-2-hydroxyglutarate (2-HG). In six model systems, including patient-derived stem cell-like glioblastoma cultures, inhibition of Bcl-xL induces significantly more apoptosis in IDH1-mutated cells than in wild-type IDH1 cells. Anaplastic astrocytoma samples with mutated IDH1 display lower levels of Mcl-1 than IDH1 wild-type tumors and specific knockdown of Mcl-1 broadly sensitizes glioblastoma cells to Bcl-xL inhibition-mediated apoptosis. Addition of 2-HG to glioblastoma cultures recapitulates the effects of the IDH mutation on intrinsic apoptosis, shuts down oxidative phosphorylation and reduces ATP levels in glioblastoma cells. 2-HG-mediated energy depletion activates AMPK (Threonine 172), blunting protein synthesis and mTOR signaling, culminating in a decline of Mcl-1. In an orthotopic glioblastoma xenograft model expressing mutated IDH1, Bcl-xL inhibition leads to long-term survival. These results demonstrate that IDH1-mutated gliomas are particularly vulnerable to Bcl-xL inhibition.
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http://dx.doi.org/10.1038/s41467-017-00984-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651864PMC
October 2017

FTY720/fingolimod, an oral S1PR modulator, mitigates radiation induced cognitive deficits.

Neurosci Lett 2017 Sep 16;658:1-5. Epub 2017 Aug 16.

Department of Radiation Oncology, Stony Brook University Hospital, Stony Brook, NY, United States.

Purpose: This study evaluates FTY720/Fingolimod, modulator of sphingosine-1-phosphate (S1P) receptor, as a potential mitigator of radiation-induced neurocognitive dysfunction.

Methods And Materials: To study radiation-induced neurocognitive deficits, 6 week-old C57/Bl/6J mice received 0 or 7Gy cranial irradiation and were treated with FTY720 or vehicle for seven weeks. Fear conditioning and Morris water maze were then employed to test learning and memory. Immunohistochemical staining for neural progenitor cells (NPCs) and mature neurons was used to assess changes in hippocampal neurogenesis. To test effects on tumor growth, mice harboring brain tumor xenografts were treated with FTY720 or vehicle for six weeks.

Results: In irradiated mice, learning deficits were manifested by significantly longer latency times in the Morris Water Maze compared to non-irradiated controls (p=0.001). The deficits were fully restored by FTY720. In irradiated brains, FTY720 maintained the cytoarchitecture of the dentate gyrus granular cell layer and partially restored the pool of NPC. In mice harboring brain tumor stem cell (BTSC) xenografts FTY720 delayed tumor growth and improved survival (p=0.012).

Conclusions: FTY720 mitigates radiation-induced learning dysfunction. A partial restoration of neurogenesis was observed. Furthermore, FTY720 appears to delay tumor growth and improve survival in a xenograft glioma mouse model.
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http://dx.doi.org/10.1016/j.neulet.2017.08.025DOI Listing
September 2017

Efficacy and outcomes of facial nerve-sparing treatment approach to cerebellopontine angle meningiomas.

J Neurosurg 2017 Dec 10;127(6):1231-1241. Epub 2017 Feb 10.

Departments of1Neurological Surgery and.

OBJECTIVE Advanced microsurgical techniques contribute to reduced morbidity and improved surgical management of meningiomas arising within the cerebellopontine angle (CPA). However, the goal of surgery has evolved to preserve the quality of the patient's life, even if it means leaving residual tumor. Concurrently, Gamma Knife radiosurgery (GKRS) has become an acceptable and effective treatment modality for newly diagnosed, recurrent, or progressive meningiomas of the CPA. The authors review their institutional experience with CPA meningiomas treated with GKRS, surgery, or a combination of surgery and GKRS. They specifically focus on rates of facial nerve preservation and characterize specific anatomical features of tumor location with respect to the internal auditory canal (IAC). METHODS Medical records of 76 patients with radiographic evidence or a postoperative diagnosis of CPA meningioma, treated by a single surgeon between 1992 and 2016, were retrospectively reviewed. Patients with CPA meningiomas smaller than 2.5 cm in greatest dimension were treated with GKRS, while patients with tumors 2.5 cm or larger underwent facial nerve-sparing microsurgical resection where appropriate. Various patient, clinical, and tumor data were gathered. Anatomical features of the tumor origin as seen on preoperative imaging confirmed by intraoperative investigation were evaluated for prognostic significance. Facial nerve preservation rates were evaluated. RESULTS According to our treatment paradigm, 51 (67.1%) patients underwent microsurgical resection and 25 (32.9%) patients underwent GKRS. Gross-total resection (GTR) was achieved in 34 (66.7%) patients, and subtotal resection (STR) in 17 (33.3%) patients. Tumors recurred in 12 (23.5%) patients initially treated surgically, requiring additional surgery and/or GKRS. Facial nerve function was unchanged or improved in 68 (89.5%) patients. Worsening facial nerve function occurred in 8 (10.5%) patients, all of whom had undergone microsurgical resection. Upfront treatment with GKRS for CPA meningiomas smaller than 2.5 cm was associated with preservation of facial nerve function in all patients over a median follow-up of 46 months, regardless of IAC invasion and tumor origin. Anatomical origin was associated with extent of resection but did not correlate with postoperative facial nerve function. Tumor size, extent of resection, and the presence of an arachnoid plane separating the tumor and the contents of the IAC were associated with postoperative facial nerve outcomes. CONCLUSIONS CPA meningiomas remain challenging lesions to treat, given their proximity to critical neurovascular structures. GKRS is a safe and effective option for managing CPA meningiomas smaller than 2.5 cm without associated mass effect or acute neurological symptoms. Maximal safe resection with preservation of neurological function can be performed for tumors 2.5 cm or larger without significant risk of facial nerve dysfunction, and, when combined with GKRS for recurrence and/or progression, provides excellent disease control. Anatomical features of the tumor origin offer critical insights for optimizing facial nerve preservation in this cohort.
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http://dx.doi.org/10.3171/2016.10.JNS161982DOI Listing
December 2017

Response.

J Neurosurg 2016 Apr;124(4):1140-1

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April 2016

Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo.

Oncotarget 2016 Mar;7(11):12791-805

Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.

It remains a challenge in oncology to identify novel drug regimens to efficiently tackle glioblastoma, the most common primary brain tumor in adults. Here, we target deubiquitinases for glioblastoma therapy by utilizing the small-molecule inhibitor WP1130 which has been characterized as a deubiquitinase inhibitor that interferes with the function of Usp9X. Expression analysis data confirm that Usp9X expression is increased in glioblastoma compared to normal brain tissue indicating its potential as a therapeutic. Consistently, increasing concentrations of WP1130 decrease the cellular viability of established, patient-derived xenograft (PDX) and stem cell-like glioblastoma cells. Specific down-regulation of Usp9X reduces viability in glioblastoma cells mimicking the effects of WP1130. Mechanistically, WP1130 elicits apoptosis and increases activation of caspases. Moreover, WP1130 and siRNAs targeting Usp9X reduce the expression of anti-apoptotic Bcl-2 family members and Inhibitor of Apoptosis Proteins, XIAP and Survivin. Pharmacological and genetic interference with Usp9X efficiently sensitized glioblastoma cells to intrinsic and extrinsic apoptotic stimuli. In addition, single treatment with WP1130 elicited anti-glioma activity in an orthotopic proneural murine model of glioblastoma. Finally, the combination treatment of WP1130 and ABT263 inhibited tumor growth more efficiently than each reagent by its own in vivo without detectable side effects or organ toxicity. Taken together, these results suggest that targeting deubiquitinases for glioma therapy is feasible and effective.
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http://dx.doi.org/10.18632/oncotarget.7302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914322PMC
March 2016

Vincent du Vigneaud: following the sulfur trail to the discovery of the hormones of the posterior pituitary gland at Cornell Medical College.

J Neurosurg 2016 May 30;124(5):1538-42. Epub 2015 Oct 30.

Department of Neurosurgery, Sackler Brain and Spine Center;

In 1955, Vincent du Vigneaud (1901-1978), the chairman of the Department of Biochemistry at Cornell University Medical College, was awarded the Nobel Prize for Chemistry for his research on insulin and for the first synthesis of the posterior pituitary hormones-oxytocin and vasopressin. His tremendous contribution to organic chemistry, which began as an interest in sulfur-containing compounds, paved the way for a better understanding of the pituitary gland and for the development of diagnostic and therapeutic tools for diseases of the pituitary. His seminal research continues to impact neurologists, endocrinologists, and neurosurgeons, and enables them to treat patients who had no alternatives prior to du Vigneaud's breakthroughs in peptide structure and synthesis. The ability of neurosurgeons to aggressively operate on parasellar pathology was directly impacted and related to the ability to replace these hormones after surgery. The authors review the life and career of Vincent du Vigneaud, his groundbreaking discoveries, and his legacy of the understanding and treatment of the pituitary gland in health and disease.
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http://dx.doi.org/10.3171/2015.5.JNS141952DOI Listing
May 2016

Sensitivity and specificity of intrathecal fluorescein and white light excitation for detecting intraoperative cerebrospinal fluid leak in endoscopic skull base surgery: a prospective study.

J Neurosurg 2016 Mar 21;124(3):621-6. Epub 2015 Aug 21.

Departments of Neurosurgery.

Objective: The intraoperative detection of CSF leaks during endonasal endoscopic skull base surgery is critical to preventing postoperative CSF leaks. Intrathecal fluorescein (ITF) has been used at varying doses to aid in the detection of intraoperative CSF leaks. However, the sensitivity and specificity of ITF at certain dosages is unknown.

Methods: A prospective database of all endoscopic endonasal procedures was reviewed. All patients received 25 mg ITF diluted in 10 ml CSF and were pretreated with dexamethasone and Benadryl. Immediately after surgery, the operating surgeon prospectively noted if there was an intraoperative CSF leak and fluorescein was identified. The sensitivity, specificity, and positive and negative predictive power of ITF for detecting intraoperative CSF leak were calculated. Factors correlating with postoperative CSF leak were determined.

Results: Of 419 patients, 35.8% of patients did not show a CSF leak. Fluorescein-tinted CSF (true positive) was noted in 59.7% of patients and 0 false positives were encountered. CSF without fluorescein staining (false negative) was noted in 4.5% of patients. The sensitivity and specificity of ITF were 92.9% and 100%, respectively. The negative and positive predictive values were 88.8% and 100%, respectively. Postoperative CSF leaks only occurred in true positives at a rate of 2.8%.

Conclusions: ITF is extremely specific and very sensitive for detecting intraoperative CSF leaks. Although false negatives can occur, these patients do not appear to be at risk for postoperative CSF leak. The use of ITF may help surgeons prevent postoperative CSF leaks by intraoperatively detecting and confirming a watertight repair.
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http://dx.doi.org/10.3171/2014.12.JNS14995DOI Listing
March 2016

Endoscope-assisted endonasal versus supraorbital keyhole resection of olfactory groove meningiomas: comparison and combination of 2 minimally invasive approaches.

J Neurosurg 2016 Mar 14;124(3):605-20. Epub 2015 Aug 14.

Departments of 1 Neurological Surgery, Sackler Brain and Spine Center.

Objective: Although the endonasal endoscopic approach has been applied to remove olfactory groove meningiomas, controversy exists regarding the efficacy and safety of this approach compared with more traditional transcranial approaches. The endonasal endoscopic approach was compared with the supraorbital (eyebrow) keyhole technique, as well as a combined "above-and-below" approach, to evaluate the relative merits of each approach in different situations.

Methods: Nineteen cases were reviewed and divided according to operative technique into 3 different groups: purely endonasal (6 cases); supraorbital eyebrow (microscopic with endoscopic assistance; 7 cases); and combined endonasal endoscopic with either the bicoronal or eyebrow microscopic approach (6 cases). Resection was judged on postoperative MRI using volumetric analysis. Tumors were assessed based on the Mohr radiological classification and the presence of the lion's mane sign.

Results: The mean age at surgery was 61.4 years. The mean tumor volume was 19.6 cm(3) in the endonasal group, 33.5 cm(3) in the supraorbital group, and 37.8 cm(3) in the combined group. Significant frontal lobe edema was identified in 10 cases (52.6%). The majority of tumors were either Mohr Grade II (moderate) (42.1%) or Grade III (large) (47.4%). Gross-total resection was achieved in 50% of the endonasal cases, 100% of the supraorbital eyebrow cases with endoscopic assistance, and 66.7% of the combined cases. The extent of resection was 87.8% for the endonasal cases, 100% for the supraorbital eyebrow cases, and 98.9% for the combined cases. Postoperative anosmia occurred in 100% of the endonasal and combined cases and only 57.1% of the supraorbital eyebrow cases. Excluding anosmia, permanent complications occurred in 83.3% of the cases in the endoscopic group, 0% of the cases in the supraorbital eyebrow group, and 16.7% of cases in the combined group (p = 0.017). There were 3 tumor recurrences: 2 in the endonasal group and 1 in the combined group.

Conclusions: The supraorbital eyebrow approach, with endoscopic assistance, leads to a higher extent of resection and lower rate of complications than the purely endonasal endoscopic approach. The endonasal endoscopic approach by itself may be suitable for a small percentage of cases. The combined above-and-below approaches are useful for large tumors with invasion of the ethmoid sinuses.
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http://dx.doi.org/10.3171/2015.1.JNS141884DOI Listing
March 2016

Endoscopic lumbar foraminotomy.

J Clin Neurosci 2015 Apr 2;22(4):730-4. Epub 2015 Mar 2.

Department of Neurological Surgery, University of Washington Medical Center, Seattle, WA, USA. Electronic address:

Foraminal stenosis frequently causes radiculopathy in lumbar degenerative spondylosis. Endoscopic transforaminal techniques allow for foraminal access with minimal tissue disruption. However, the effectiveness of foraminal decompression by endoscopic techniques has yet to be studied. We evaluate radiographic outcome of endoscopic transforaminal foraminotomies performed at L3-L4, L4-L5, and L5-S1 on cadaveric specimens. Before and after the procedures, three dimensional CT scans were obtained to measure foraminal height and area. Following the foraminotomies, complete laminectomies and facetectomies were performed to assess for dural tears or nerve root damage. L3-L4 preoperative foraminal height increased by 8.9%, from 2.12±0.13cm to 2.27±0.14cm (p<0.01), and foraminal area increased by 24.8% from 2.21±0.18cm(2) to 2.72±0.19cm(2) (p<0.01). At L4-L5, preoperative foraminal height was 1.87±0.17cm and area was 1.78±0.18cm(2). Endoscopic foraminotomies resulted in a 15.3% increase of foraminal height (2.11±0.15cm, p<0.05) and 44.8% increase in area of (2.51±0.21cm(2), p<0.01). At L5-S1, spondylitic changes caused diminished foraminal height (1.26±0.14cm) and foraminal area (1.17±0.18cm(2)). Postoperatively, foraminal height increased by 41.6% (1.74±0.09cm, p<0.05) and area increased by 98.7% (2.08±0.17cm(2), p<0.01). Subsequent inspection via a standard midline approach revealed one dural tear of an S1 nerve root. Endoscopic foraminotomies allow for effective foraminal decompression, though clinical studies are necessary to further evaluate complications and efficacy.
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http://dx.doi.org/10.1016/j.jocn.2014.10.025DOI Listing
April 2015

Tight regulation between cell survival and programmed cell death in GBM stem-like cells by EGFR/GSK3b/PP2A signaling.

J Neurooncol 2015 Jan 26;121(1):19-29. Epub 2014 Oct 26.

Laboratory for Translational Brain Tumor and Stem Cell Research, Department of Neurological Surgery, Weill Cornell Brain Tumor Center, Weill Cornell Medical College, 525 East 68th Street, Box 99, New York, NY, 10021, USA.

Malignant gliomas represent one of the most aggressive forms of cancer, displaying high mortality rates and limited treatment options. Specific subpopulations of cells residing in the tumor niche with stem-like characteristics have been postulated to initiate and maintain neoplasticity while resisting conventional therapies. The study presented here aims to define the role of glycogen synthase kinase 3 beta (GSK3b) in patient-derived glioblastoma (GBM) stem-like cell (GSC) proliferation, apoptosis and invasion. To evaluate the potential role of GSK3b in GBM, protein profiles from 68 GBM patients and 20 normal brain samples were analyzed for EGFR-mediated PI3kinase/Akt and GSK3b signaling molecules including protein phosphatase 2A (PP2A). To better understand the function of GSK3b in GBM, GSCs were isolated from GBM patient samples. Blocking GSK3b phosphorylation at Serine 9 attenuated cell proliferation while concomitantly stimulating apoptosis through activation of Caspase-3 in patient-derived GSCs. Increasing GSK3b protein content resulted in the inhibition of cell proliferation, colony formation and stimulated programmed cell death. Depleting GSK3b in GSCs down regulated PP2A. Furthermore, knocking down PP2A or blocking its activity by okadaic acid inactivated GSK3b by increasing GSK3b phosphorylation at Serine 9. Our data suggests that GSK3b may function as a regulator of apoptosis and tumorigenesis in GSCs. Therapeutic approaches targeting GSK3b in glioblastoma stem-like cells may be a useful addition to our current therapeutic armamentarium.
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http://dx.doi.org/10.1007/s11060-014-1602-3DOI Listing
January 2015

Novel hydrogel application in minimally invasive surgical approaches to spontaneous intracranial hypotension. Report of 2 cases.

J Neurosurg 2014 Oct 1;121(4):976-82. Epub 2014 Aug 1.

Weill Cornell Brain Tumor and Stem Cell Laboratory.

The authors report 2 cases of orthostatic headaches associated with spontaneous intracranial hypotension (SIH) secondary to CSF leaks that were successfully treated with an alternative dural repair technique in which a tubular retractor system and a hydrogel dural sealant were used. The 2 patients, a 63-year-old man and a 45-year-old woman, presented with orthostatic headache associated with SIH secondary to suspected lumbar and lower cervical CSF leaks, respectively, as indicated by bony defects or epidural fluid collection. Epidural blood patch repair failed in both cases, but both were successfully treated with the minimally invasive application of a hydrogel dural sealant as a novel adjunct to traditional dural repair techniques. Both patients tolerated the procedure well. Moreover, SIH symptoms and MRI signs were completely resolved at 1-month follow-up in both patients. The minimally invasive dural repair procedure with hydrogel dural sealant described here offers a viable alternative in patients in whom epidural blood patches have failed, with obscure recalcitrant CSF leaks at the cervical as well as lumbar spinal level. The authors demonstrate that the adjuvant use of sealant is a safe and efficient repair method regardless of dural defect location.
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http://dx.doi.org/10.3171/2014.6.JNS13714DOI Listing
October 2014

Pneumocephalus patterns following endonasal endoscopic skull base surgery as predictors of postoperative CSF leaks.

J Neurosurg 2014 Oct 4;121(4):961-75. Epub 2014 Jul 4.

Departments of Neurological Surgery, Brain and Spine Center.

Objectives: Postoperative pneumocephalus is a common occurrence after endoscopic endonasal skull base surgery (ESBS). The risk of cerebrospinal fluid (CSF) leaks can be high and the presence of postoperative pneumocephalus associated with serosanguineous nasal drainage may raise suspicion for a CSF leak. The authors hypothesized that specific patterns of pneumocephalus on postoperative imaging could be predictive of CSF leaks. Identification of these patterns could guide the postoperative management of patients undergoing ESBS.

Methods: The authors queried a prospectively acquired database of 526 consecutive ESBS cases at a single center between December 1, 2003, and May 31, 2012, and identified 258 patients with an intraoperative CSF leak documented using intrathecal fluorescein. Postoperative CT and MRI scans obtained within 1-10 days were examined and pneumocephalus was graded based on location and amount. A discrete 0-4 scale was used to classify pneumocephalus patterns based on size and morphology. Pneumocephalus was correlated with the surgical approach, histopathological diagnosis, and presence of a postoperative CSF leak.

Results: The mean follow-up duration was 56.7 months. Of the 258 patients, 102 (39.5%) demonstrated pneumocephalus on postoperative imaging. The most frequent location of pneumocephalus was frontal (73 [71.5%] of 102), intraventricular (34 [33.3%]), and convexity (22 [21.6%]). Patients with craniopharyngioma (27 [87%] of 31) and meningioma (23 [68%] of 34) had the highest incidence of postoperative pneumocephalus compared with patients with pituitary adenomas (29 [20.6%] of 141) (p < 0.0001). The incidence of pneumocephalus was higher with transcribriform and transethmoidal approaches (8 of [73%] 11) than with a transsellar approach (9 of [7%] 131). There were 15 (5.8%) of 258 cases of postoperative CSF leak, of which 10 (66.7%) had pneumocephalus, compared with 92 (38%) of 243 patients without a postoperative CSF leak (OR 3.3, p = 0.027). Pneumocephalus located in the convexity, interhemispheric fissure, sellar region, parasellar region, and perimesencephalic region was significantly correlated with a postoperative CSF leak (OR 4.9, p = 0.006) and was therefore termed "suspicious" pneumocephalus. In contrast, frontal or intraventricular pneumocephalus was not correlated with postoperative CSF leak (not significant) and was defined as "benign" pneumocephalus. The amount of convexity pneumocephalus (p = 0.002), interhemispheric pneumocephalus (p = 0.005), and parasellar pneumocephalus (p = 0.007) (determined using a scale score of 0-4) was also significantly related to postoperative CSF leaks. Using a series of permutation-based multivariate analyses, the authors established that a model containing the learning curve, the transclival/transcavernous approach, and the presence of "suspicious" pneumocephalus provides the best overall prediction for postoperative CSF leaks.

Conclusions: Postoperative pneumocephalus is much more common following extended approaches than following transsellar surgery. Merely the presence of pneumocephalus, particularly in the frontal or intraventricular locations, is not necessarily associated with a postoperative CSF leak. A "suspicious" pattern of air, namely pneumocephalus in the convexity, interhemispheric fissure, sella, parasellar, or perimesencephalic locations, is significantly associated with a postoperative CSF leak. The presence and the score of "suspicious" pneumocephalus on postoperative imaging, in conjunction with the learning curve and the type of endoscopic approach, provide the best predictive model for postoperative CSF leaks.
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http://dx.doi.org/10.3171/2014.5.JNS132028DOI Listing
October 2014

Corridor-based endonasal endoscopic surgery for pediatric skull base pathology with detailed radioanatomic measurements.

Neurosurgery 2014 Jun;10 Suppl 2:273-93; discussion 293

*Department of Neurological Surgery, Weill Cornell Medical College, New York, New York; ‡Department of Pediatrics, Weill Cornell Medical College, New York, New York; §Department of Otolaryngology, Head and Neck Surgery, Weill Cornell Medical College, New York, New York; ‖Department of Neurology and Neuroscience, Brain and Spine Center, Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York.

Background: Pediatric anatomy is more restricted, and the propagation of endonasal endoscopic approaches in the pediatric population has been limited.

Objective: To demonstrate the feasibility of the endonasal endoscopic approach in a variety of age groups and to perform measurements of the corridors and spaces available for surgery as a guide for case selection.

Methods: Only patients <18 years were included. The choice of operative corridor/approach is described in relation to pathological entity and location. Preoperative/postoperative visual fields and endocrine panels, extent of resection, as well as postoperative long-term complications are described. Prospective magnetic resonance image-based anatomic measurements of key distances were performed to determine age-dependent surgical indications and limitations.

Results: Forty purely endoscopic procedures were performed in 33 pediatric patients (5-18 years of age) harboring a variety of skull base lesions, from benign tumors to congenital malformations. For the 20 patients in whom gross total resection was the intended goal of surgery, gross total resection was attained in 15 (75%). There were 2 infections (5%) and no cerebrospinal fluid leaks. Significant improvement was shown in 58.3% of patients with visual deficits. Hormone overproduction resolved in 75% of patients, while preoperative hormone insufficiency only improved in 29.2%. Wider intercarotid distance at the superior clivus (P = .01) and shorter nare-dens working distance (P = .001) predicted improved outcomes and fewer postoperative complications.

Conclusion: Endonasal endoscopic skull base approaches are viable in the pediatric population, they are not impeded by sphenoid sinus aeration, and they have minimal risk of cerebrospinal fluid leak and meningitis. Outcomes and complications can be predicted based on specific radio anatomical skull base measurements rather than age.
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http://dx.doi.org/10.1227/NEU.0000000000000252DOI Listing
June 2014

Endoscopic endonasal resection of suprasellar meningiomas: the importance of case selection and experience in determining extent of resection, visual improvement, and complications.

World Neurosurg 2014 Sep-Oct;82(3-4):442-9. Epub 2014 Mar 20.

Department of Neurological Surgery, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, New York, USA; Department of Otolaryngology, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, New York, USA; Department of Neurology and Neurosciences, Brain and Mind Institute, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, New York, USA. Electronic address:

Objective: Suprasellar meningiomas have been resected via various open cranial approaches. During the past 2 decades, the endoscopic endonasal approach has been shown to be an option in selected patients. We wished to examine the learning curve for parameters such as extent of resection, visual outcome, and complications.

Methods: We retrospectively reviewed a consecutive series of patients in whom suprasellar meningiomas were resected via an endonasal endoscopic approach between 2005 and 2013 at our institution. After June 2008, our surgical technique matured. Using this time point, we divided our case series into 2 chronological groups, group 1 (n=8) and group 2 (n=12). This cut-off also was used to examine rates of gross total resection (GTR) and visual improvement. Case selection criteria in successful and unsuccessful cases were examined to determine important principals for case selection.

Results: Mean patient age at surgery was 57.05 years (range, 31-81 years). Mean tumor volume was 11.98 cm3 (range, 0.43-28.93 cm3). Overall, GTR was achieved in 80%, and vision improved or normalized in 14 patients (82.4%) with no occurrence of postoperative visual deterioration. Rates of GTR increased from 62.5% (group 1) to 91.7% (group 2). Visual improvement increased from 75% (group 1) to 88.9% (group 2). Rates of cerebrospinal fluid leak were 25% in group 1 and 0% in group 2. Average follow-up was 51.5 month (range, 3-96 months).

Conclusion: Once the learning curve is overcome, surgeons performing endonasal endoscopic resection of suprasellar meningiomas can achieve high rates of GTR with low complication rates in well-selected cases.
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http://dx.doi.org/10.1016/j.wneu.2014.03.032DOI Listing
March 2015

Low-dose intrathecal fluorescein and etiology-based graft choice in endoscopic endonasal closure of CSF leaks.

Clin Neurol Neurosurg 2014 Jan 16;116:28-34. Epub 2013 Nov 16.

Department of Neurological Surgery, Weill Cornell Medical College, New York, USA.

Objective: Skull base cerebrospinal fluid (CSF) leaks of various etiologies are increasingly repaired through the natural corridor using an endoscopic endonasal approach. Characteristics of the skull base defect significantly correlate with etiology, which should be ascertained to guide surgical management. The objectives of this study were to assess the long-term outcomes of patients that underwent endoscopic endonasal repair of CSF leak using low-dose intrathecal fluorescein (ITF) and an etiology-based algorithm for multi-layer graft closure.

Methods: Patients were divided into 4 groups: A--congenital, B--post-traumatic, C--post-endonasal surgery, D--post-craniotomy. Low-dose ITF was utilized in all case series. Long-term clinical follow-up data, including perioperative complications associated with the use of intrathecal fluorescein and leak closure rates, were obtained retrospectively. Endoscopic visualization of fluorescein-stained CSF as well as the method of skull base closure and graft material is detailed.

Results: We identified a total of 41 patients (N=24 in Group A, N=4 in Group B, N=12 in Group C and N=1 in Group D) that underwent 50 CSF leak repairs using the endoscopic endonasal approach with an average follow-up of 31.6 months. Nine patients (21.9%) had undergone a previous attempt at CSF leak repair. Lumbar drain was used intraoperatively in 26 patients (63.4%) and kept in place for an average duration of 3.25 days. ITF successfully identified the site of leak in 80.5% of cases regardless of etiology. Leaks were successfully closed in 92% of patients. One patient (2.4%) experienced transient leg weakness following lumbar drain placement. Another patient (2.4%) developed hydrocephalus requiring a ventriculoperitoneal shunt.

Conclusion: Low-dose ITF is a safe and useful adjunct to endoscopic endonasal repair of CSF leaks with minimal complications and successful localization of the leak in approximately 80%. An etiology-based approach to graft choice and duration of lumbar drain placement in CSF leak repair may optimize closure rates.
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http://dx.doi.org/10.1016/j.clineuro.2013.11.006DOI Listing
January 2014

Impact of skull base development on endonasal endoscopic surgical corridors.

J Neurosurg Pediatr 2014 Feb 6;13(2):155-69. Epub 2013 Dec 6.

Departments of Neurological Surgery.

Object: Scarce morphometric data exist on the developing skull base as a corridor for endonasal endoscopic approaches (EEAs). Furthermore, the impact of skull base lesions on its development has not been assessed. The authors describe a novel set of anatomical parameters characterizing the developmental process as well as the utility of these parameters in preoperative planning and a feasibility assessment of EEAs for neurosurgical treatment of skull base lesions in children.

Methods: Based on specific MRI sequences in 107 pediatric patients (2-16 years of age) without skull base lesions (referred to here as the normal population), 3 sets of anatomical parameters were analyzed according to age group and sex: drilling distance, restriction sites, and working distance parameters. A separate set of patients undergoing EEAs was analyzed in similar fashion to address the impact of skull base lesions on the developmental process.

Results: The volume of the sphenoid sinus significantly increases with age, reaching 6866.4 mm(3) in the 14-16 years age group, and directly correlates with the pneumatization type (r = 0.533, p = 0.0001). The pneumatization process progresses slowly in a temporal-posterior direction, as demonstrated by the growth trend of the sellar width (r = 0.428, p = 0.0001). Nasal restriction sites do not change significantly with age, with little impact on EEAs. The intercarotid distance is significantly different only in the extreme age groups (3.9 mm, p = 0.038), and has an important impact on the transsphenoidal angle and the intracranial dissection limits (r = 0.443, p < 0.0001). The 14.9° transsphenoidal angle at 2-4 years has a 37.6% significant increase in the 11-13 years age group (p = 0.001) and is highly dependent on pneumatization type. Age-dependent differences between working parameters are mostly noted for the extreme age groups, such as the 8.6-mm increase in nare-vomer distance (p = 0.025). The nare-sellar distance is the only parameter with significant differences based on sex. Skull base lesions induce a high degree of variance in skull base measurements, delaying development and decreasing parameter values. Skull base parameters are interdependent. Nare-sellar distance can be used to assess global skull base development because it highly correlates with the intercarotid distance in both the normal population and in patients harboring skull base lesions.

Conclusions: Skull base development is a slow, gradual, age-dependent, sex-independent process significantly altering endonasal endoscopic corridors. Preoperative MRI measurements of the pediatric skull base are thus a useful adjunct in choosing the appropriate corridor and in assessing working angles and limits during dissection or reparative surgery. Skull base lesions can significantly impact normal skull base development and age-dependent growth patterns.
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http://dx.doi.org/10.3171/2013.10.PEDS13303DOI Listing
February 2014

Industry progress report on neuro-oncology: a biotech update.

J Neurooncol 2013 Apr 20;112(2):315-21. Epub 2013 Feb 20.

Department of Neurological Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY 10021, USA.

With steadily rising revenue and large numbers of clinical trials utilizing novel treatment strategies, the field of neuro-oncology is at the core of the growing cancer therapy industry. In June 2012, the Weill Cornell Brain and Tumor Center hosted the first Brain Tumor Biotech Summit as a forum for fostering and encouraging collaboration between researches and investors to accelerate novel treatments for brain cancer. This event brought together neuro-oncologists, neurosurgeons, academicians, entrepreneurs, non-profits, CEOs and investors in an attempt to bring innovative treatments and concepts to the fore. Specific subjects presented at the meeting included new surgical devices and delivery techniques, targeted therapeutics, immunotherapy, and stem cell biology. The mission of the summit was to provide opportunities for researchers in neuro-oncology to directly interact with leaders from the investment community with insight into the commercial aspects of our work. Our shared goal is to shorten the time for basic science ideas to be translated into the clinical setting. The following serves as a progress report on the biotech industry in neuro-oncology, as presented at the Brain Tumor Biotech Summit.
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http://dx.doi.org/10.1007/s11060-012-1036-8DOI Listing
April 2013
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