OBJECTIVE The endoscopic endonasal approach for treating primary skull base malignancies involving the clivus is a formidable task. The authors hypothesized that tumor involvement of nearby critical anatomical structures creates hurdles to endoscopic gross-total resection (GTR). The aim of this study was to retrospectively review the clinical outcomes of patients who underwent an endoscopic endonasal approach to treat primary malignancies involving the clivus and to analyze prognostic factors for GTR. METHODS Between January 2009 and November 2015, 42 patients underwent the endoscopic endonasal approach for resection of primary skull base malignancies involving the clivus at 2 independent institutions. Clinical data; tumor locations within the clivus; and anatomical involvement of the cavernous or paraclival internal carotid artery, cisternal trigeminal nerve, hypoglossal canal, and dura mater were investigated to assess the extent of resection. Possible prognostic factors affecting GTR were also analyzed. RESULTS Of the 42 patients, 37 were diagnosed with chordomas and 5 were diagnosed with chondrosarcomas. The mean (± SD) preoperative tumor volume was 25.2 ± 30.5 cm3 (range 0.8-166.7 cm3). GTR was achieved in 28 patients (66.7%) and subtotal resection in 14 patients (33.3%). All tumors were classified as upper (n = 17), middle (n = 17), or lower (n = 8) clival tumors based on clival involvement, and as central (24 [57.1%]) or paramedian (18 [42.9%]) based on laterality of the tumor. Univariate analysis identified the tumor laterality (OR 6.25, 95% CI 1.51-25.86; p = 0.011) as significantly predictive of GTR. In addition, the laterality of the tumor was found to be a statistically significant predictor in multivariate analysis (OR 41.16, 95% CI 1.12-1512.65; p = 0.043). CONCLUSIONS An endoscopic endonasal approach can provide favorable clinical and surgical outcomes. However, the tumor laterality should be considered as a potential obstacle to total removal.

Total removal of petroclival meningioma is difficult, and aggressive extirpation is often associated with significant surgical morbidity and mortality. The aim of this study was to evaluate the long-term outcome and failure pattern of treatment with Gamma Knife radiosurgery (GKRS) in patients with petroclival meningiomas. Eighty-nine consecutive patients with petroclival meningiomas underwent GKRS between 1998 and 2013. Fifty-eight patients received GKRS as a primary treatment and 31 patients underwent GKRS as a secondary treatment after microsurgery. The mean tumor volume was 6.7 cm3 (range, 0.5-46.3 cm3) and the mean marginal dose was 13.2 Gy (range, 8-17 Gy). At the last radiological follow-up, tumor volume was decreased in 50 patients (56.2%), stationary in 34 patients (38.2%), and increased in 5 patients (5.6%). The actuarial progression-free survival after GKRS was 94.7% at 5 years and 88.9% at 10 years. Favorable cranial nerve outcomes were found in 81 patients (91%). A regrowth pattern was present in all 4 patients of the primary treatment group, whereas cyst formation (3 patients) and regrowth (1 patient) were observed in the secondary treatment group. GKRS is an effective and reasonable option as a primary or secondary treatment for petroclival meningioma. Further studies of failure patterns after GKRS for petroclival meningioma are mandatory.

OBJECTIVE Mannitol is used intraoperatively to induce brain relaxation in patients undergoing supratentorial brain tumor resection. The authors sought to determine the dose of mannitol that provides adequate brain relaxation with the fewest adverse effects. METHODS A total of 124 patients were randomized to receive mannitol at 0.25 g/kg (Group A), 0.5 g/kg (Group B), 1.0 g/kg (Group C), and 1.5 g/kg (Group D). The degree of brain relaxation was classified according to a 4-point scale (1, bulging; 2, firm; 3, adequate; and 4, perfectly relaxed) by neurosurgeons; Classes 3 and 4 were considered to indicate satisfactory brain relaxation. The osmolality gap (OG) and serum electrolytes were measured before and after mannitol administration. RESULTS The brain relaxation score showed an increasing trend in patients receiving higher doses of mannitol (p = 0.005). The incidence of satisfactory brain relaxation was higher in Groups C and D than in Group A (67.7% and 64.5% vs 32.2%, p = 0.011 and 0.022, respectively). The incidence of OG greater than 10 mOsm/kg was also higher in Groups C and D than in Group A (100.0% in both groups vs 77.4%, p = 0.011 for both). The incidence of moderate hyponatremia (125 mmol/L ≤ Na+ < 130 mmol/L) was significantly higher in Group D than in other groups (38.7% vs 0.0%, 9.7%, and 12.9% in Groups A, B, and C; p < 0.001, p = 0.008, and p = 0.020, respectively). Hyperkalemia (K+ > 5.0 mmol/L) was observed in 12.9% of patients in Group D only. CONCLUSIONS The higher doses of mannitol provided better brain relaxation but were associated with more adverse effects. Considering the balance between the benefits and risks of mannitol, the authors suggest the use of 1.0 g/kg of intraoperative mannitol for satisfactory brain relaxation with the fewest adverse effects. Clinical trial registration no.: NCT02168075 ( clinicaltrials.gov ).

We present a rare case of radiation-induced osteosarcoma following Gamma Knife® surgery (GKS) for a vestibular schwannoma (VS). A 49-year-old female with sporadic VS underwent GKS. Serial follow-up imaging showed that the tumor size decreased. Six years after GKS, magnetic resonance imaging demonstrated regrowth of the tumor. The tumor was removed via the retrosigmoid approach. Interestingly, the final pathology report confirmed osteosarcoma arising in schwannoma with direct transition (osteosarcoma component: 90 %, schwannoma component: 10 %). The osteosarcoma was considered to be a radiation-induced malignancy. The possibility of this rare complication should be explained to the patient before GKS, and the patient should be screened periodically after GKS.

PURPOSE:Homeobox (HOX) genes are essential developmental regulators that should normally be in the silenced state in an adult brain. The aberrant expression of HOX genes has been associated with the prognosis of many cancer types, including glioblastoma (GBM). This study examined the identity and role of HOX genes affecting GBM prognosis and treatment resistance.MATERIALS AND METHODS:The full series of HOX genes of five pairs of initial and recurrent human GBM samples were screened by microarray analysis to determine the most plausible candidate responsible for GBM prognosis. Another 20 newly diagnosed GBM samples were used for prognostic validation. In vitro experiments were performed to confirm the role of HOX in treatment resistance. Mediators involved in HOX gene regulation were searched using differentially expressed gene analysis, gene set enrichment tests, and network analysis.RESULTS:The underexpression of HOXA11 was identified as a consistent signature for a poor prognosis among the HOX genes. The overall survival of the GBM patients indicated a significantly favorable prognosis in patients with high HOXA11 expression (31±15.3 months) compared to the prognoses in thosewith low HOXA11 expression (18±7.3 months, p=0.03). When HOXA11 was suppressed in the GBM cell lines, the anticancer effect of radiotherapy and/or temozolomide declined. In addition, five candidate mediators (TGFBR2, CRIM1, TXNIP, DPYSL2, and CRMP1) that may confer an oncologic effect after HOXA11 suppression were identified.CONCLUSION:The treatment resistance induced by the underexpression of HOXA11 can contribute to a poor prognosis in GBM. Further investigation will be needed to confirm the value of HOXA11 as a potential target for overcoming the treatment resistance by developing chemo- or radiosensitizers.

OBJECTIVE: Endoscopic transsphenoidal surgery has recently been introduced in pituitary surgery. We investigated outcomes and complications of endoscopic surgery in 2 referral centers in Korea.METHODS: We enrolled 134 patients with acromegaly (microadenomas, n = 15; macroadenomas, n = 119) who underwent endoscopic transsphenoidal surgery at Seoul National University Hospital (n = 74) and Samsung Medical Center (n = 60) between January 2009 and March 2016. Remission was defined as having a normal insulinlike growth factor-1 and a suppressed growth hormone (GH) < 1 ng/mL during an oral glucose tolerance test.RESULTS: Remission was achieved in 73.1% of patients, including 13 of 15 microadenoma patients (86.7%) and 86 of 119 macroadenoma patients (72.3%). A multivariate analysis to determine a predictor of biochemical remission demonstrated that absence of cavernous sinus invasion and immediate postoperative GH levels < 2.5 ng/dL were significant predictors of remission (adjusted odds ratio = OR], 5.14; 95% confidence interval = CI], 1.52e17.3 and OR, 9.60; 95% CI, 3.41e26.9, respectively). After surgery, normal pituitary function was maintained in 34 patients (25.4%). Sixty-four patients (47.7%) presented complete (n = 59, 44.0%) or incomplete (n = 5, 3.7%) recovery of pituitary function. Hypopituitarism persisted in 20 patients (14.9%) and worsened in 16 patients (11.9%). Postoperatively, transient diabetes insipidus was reported in 52 patients (38.8%) but only persisted in 2 patients (1.5%). Other postoperative complications were epistaxis (n = 2), cerebral fluid leakage (n = 4), infection (n = 1), and intracerebral hemorrhage (n = 1).CONCLUSIONS: Endoscopic transsphenoidal surgery for acromegaly presented high remission rates and a low incidence of endocrine deficits and complications. Regardless of surgical techniques, invasive pituitary tumors were associated with poor outcome.

Executive Committee François Alesch, Vienna Tipu Aziz, Oxford Alexandre Campos, Lisbon Stephan Chabardès, Grenoble Jean Ciurea, Bucharest Angelo Franzini, Milano Miroslav Galanda, Banska Bystrica Jorge Guridi, Pamplona Kostiantyn Kostiuk, Kiyv Kai Lehtimäki, Tampere Roman Liscák, Prague Ruby Mahesparan, Bergen Ioannis Panourias, Larissa Claudio Pollo, Bern Dirk van Roost, Gent Ali Savas, Ankara Gaston Schechtmann, Stockholm Pawel Sokal, Bydgoszcz Vladimir Shabalov, Moscow Yasin Temel, Maastricht Istvan Valalik, Budapest Jürgen Voges, Magdeburg

OBJECTIVEThe endoscopic endonasal approach (EEA) is commonly used for the treatment of craniopharyngioma; therefore, it is essential to analyze outcomes in order to understand the benefits and drawbacks. The goal of this paper was to evaluate the clinical features and outcomes associated with this treatment approach.METHODSFrom July 2010 to March 2016, 82 adult craniopharyngioma patients underwent an EEA at the authors’ institution. Of these cases, intraoperative records and immediate postoperative MR images were available for 68 patients. The patients underwent systemized endocrinological evaluation. Eighteen of 68 patients who underwent EEA for recurrence or regrowth of residual lesions after previous surgical management were excluded in the analysis of the anatomical tumor classification. The authors retrospectively analyzed preoperative clinical features and previous anatomical classifications, focusing on the relationship of the pituitary stalk and tumor, to determine predictive factors for the clinical outcome, such as the extent of resection, visual function, endocrinological function, recurrence rate, and complications.RESULTSThe mean tumor size was 2.5 cm (3.1 cm for primary tumors and 1.9 cm for recurrent lesions). Gross-total resection (GTR) was achieved in 62 (91.1%) patients (48 [96.0%] patients with primary tumors and 14 [77.8%] patients with recurrent tumors). The rate of GTR was higher in the primary group than in the group with recurrence (p = 0.038). The overall pre- and postoperative visual impairment scale (VIS) scores were 40.8 and 22.1, respectively (50.9 and 14.3 in the primary group and 30.7 and 29.9 in patients with recurrence, respectively). The improvement rate in VIS score was higher in the primary group than in the recurrent group (p = 0.001). Endocrinological function was improved in 4 patients (5.9%) and deteriorated in 32 of 68 patients (47.1%). Tumor invasion into the center of the pituitary stalk affected the postoperative outcomes most significantly. Cognitive dysfunction was observed in 22 patients before surgery and improved in 20 patients (90.9%) after surgery. Hydrocephalus was found in 7 patients and resolved after surgery in all cases. CSF leakage occurred in 2 (2.9%) of 68 patients and was repaired by revision surgery in both patients. Ten patients without CSF leakage also received antibiotics for the treatment of meningitis. The infection rate was higher in the recurrent group. Postoperative endocrinological evaluation showed no deficits in 12 patients and panhypopituitarism in 55 patients. The remaining patient had growth hormone deficiency. Forty-three patients had new-onset diabetes insipidus, and 1 patient had persistent diabetes insipidus after surgery. There were 2 (2.9%) cases of recurrence during the mean 30.7-month follow-up period; one patient underwent radiosurgery and the other underwent reoperation.CONCLUSIONSThe EEA resulted in excellent surgical outcomes and acceptable morbidity rates, regardless of the anatomical location of the tumor. Invasion of the craniopharyngioma into the center of the pituitary stalk has strong predictive power for postoperative endocrinological outcome.

Radiation necrosis in brain tumor patients is often symptomatic, persistent without immediate resolution, and confused with tumor recurrence. Cerebral vascular pericytes are essential for endothelial function, vascular integrity and angiogenesis. Here we show that the loss of pericyte is involved in the pathogenesis of radiation necrosis. From a prospective brain tumor tissue repository since 2011, we identified three patients with surgically-resected and pathologically-confirmed radiation necrosis after the standard treatment of glioblastoma. The radiation necrosis and their pre-radiation glioblastoma tissues were serially processed to Western blotting using cell-type specific antibodies against endothelial (CD31, active RhoA), pericyte [platelet-derived growth factor receptor-beta (PDGFR-β)], astrocyte (GFAP), myelin sheath protein (MBP), and microglial markers (Iba1). Normal brain tissues from a brain bank were used as normal controls. The changes in vascular compositions were confirmed histopathologically. Results showed that the expressions of pericyte marker (PDGFR-β) were remarkably reduced in the radiation necrosis tissues while the levels were preserved in their original glioblastoma. However, the levels of CD31 or RhoA were not different between the two groups, suggesting no change in the amount of endothelial cells or their cytoskelectal assembly. The radiation necrosis tissues showed a decreased ratio of pericyte/endothelial markers and an increased level of Iba1 compared to the glioblastoma and even to the normal brain tissues. The levels of GFAP and MBP were not changed in the radiation necrosis. In the immunohistochemistry, the PDGFR-β-positive pericyte was nearly absent in the radiation necrosis, resulting in pericyte-unsupported endothelial cells. In contrast, the endothelial cells in the glioblastoma tissues were well supported by pericytes. In conclusion, the radiation necrosis was characterized by the loss of pericyte and unsupported endothelial cells. Radiation necrosis might be induced by the pericyte loss rather than endothelial or glial damage, and the pericytes might be more vulnerable to the radiation.

Background: Supratentorial primitive neuroectodermal tumors (PNETs) are highly malignant and rare tumors of the central nervous system. Objectives: The aim of this study was to determine the role of Gamma Knife surgery (GKS) as a salvage treatment option for patients with recurrent or residual supratentorial PNETs. Methods: Between 1998 and 2014, 11 patients with supratentorial PNETs were retrospectively analyzed. This series consisted of 7 male and 4 female patients. The median age was 17 years. All patients received surgical resection followed by adjuvant therapy. The median time from operation to the first GKS treatment was 72.5 months. The median tumor volume was 17.5 cm3, and the median marginal dose was 11.5 Gy. Results: 15 (65%) of the 23 tumors had been controlled. The actuarial local tumor control rate was 91% at 3 months, 73% at 6 months, and 44% at 12 months. At the time of analysis, 9 (82%) of the patients had died. The median survival time after the first GKS session was 17 months. The median survival time from the initial diagnosis was 65 months. No adverse radiation effect after GKS treatment occurred in any patient. Conclusions: GKS treatment might be an effective salvage treatment option for recurrent or residual supratentorial PNETs after multimodal treatment.

Objective : A rare subtype of meningioma, sclerosing meningioma is not included in the current World Health Organization classification of meningiomas and is classified into the category of other morphological variation subtypes. Sclerosing meningioma is often misdiagnosed to other non-benign meningioma or malignant neoplasm, so it is important to diagnose sclerosing type correctly. We analyzed the radiological and clinical characteristics of a series of sclerosing meningiomas.Methods : Twenty-one patients who underwent surgery in one institute with a histopathologically proven sclerosing meningioma were included from 2006 to 2014. Eighteen tumors were diagnosed as a pure sclerosing-type meningioma, and 3 as mixed type. Magnetic resonance image was taken for all patients including contrast enhancement image. Computed tomography (CT) scan was taken for 16 patients. One neuroradiologist and 1 neurosurgeon reviewed all images retrospectively.Results : In the all 16 patients with preoperative CT images, higher attenuation was observed in the meningioma than in the brain parenchyma, and calcification was observed in 11 (69%). In 15 of the 21 patients (71%), a distinctive very low signal intensity appeared as a dark color in T2-weighted images. Nine of these 15 tumors (60%) exhibited heterogeneous enhancement, and 6 (40%) exhibited homogeneous enhancement that was unlike the homogeneous enhancing pattern shown by conventional meningiomas. Ten patients had a clear tumor margin without peritumoral edema.Conclusion : Although these peculiar radiological characteristics are not unique to sclerosing meningioma, we believe that they are distinctive features that may be helpful for distinguishing sclerosing meningioma from other subtypes.

Gliofibroma is an extremely rare biphasic tumor with an astrocytic and benign mesenchymal component, which commonly occurs within the first two decades of life. The exact biological behavior of the tumor is not fully understood. Therefore, it is not listed as a distinct entity in the current World Health Organization classification of central nervous system tumors. Here, we describe a rare case of gliofibroma, which was located on the medial temporal lobe in a 61-year-old woman. Preoperatively, we misdiagnosed it as a meningioma because it was a well-demarcated and well-enhanced extra-axial mass with calcification and bony destruction. On the histopathological and immunohistochemical examination, the tumor consisted of a mixture of glial tissue and mesenchymal tissue and it was finally diagnosed as a gliofibroma. To our knowledge, this case of intracranial gliofibroma is in the oldest patient ever reported.

Cancer stem cells (CSCs), defined by CD133 expression, harbor heterogeneous subpopulations of cells, including endothelial progenitor cells (EPCs). This study aimed to investigate whether a subpopulation of CSCs could affect the radiographic characteristics of glioblastoma. Tissue samples from 10 patients newly diagnosed with glioblastoma were selected according to the radiographic characteristics of their tumors. The patients were divided into two groups based on preoperative magnetic resonance imaging demonstrating contrast enhancement, necrosis and infiltrative patterns: the enhancement/necrosis group (E/N, n=5) and the non-enhancement/infiltration group (NE/I, n=5). Flow cytometry was used to assess the CSCs while immunohistochemistry was used to study microvessel density and the proliferation index. The EPC (CD34+/CD133+) fraction in CSCs (CD133+) was larger in the NE/I group. However, there was little difference in the angiogenic activity assessed using microvessel density between the two groups. The proliferation index (assessed using the antibody Ki-67) was higher in the E/N group and was negatively correlated with the EPC fraction. The non-EPC (CD34-/CD133+) fraction is a major factor responsible for radiographic characteristics of contrast enhancement, thus establishing an association between a subpopulation fraction of CSCs and radiographic characteristics in glioblastoma. Therefore, the simple non-invasive assessment of studying contrast enhancement lesions in glioblastomas may be used to estimate CSC subpopulations.

OBJECTIVE Gamma Knife surgery (GKS) represents an alternative treatment for patients with tumor-related trigeminal neuralgia (TRTN). However, in previous studies, the primary GKS target was limited to mass lesions. The authors evaluated whether GKS could target both the tumor and the trigeminal root exit zone (REZ) in a single session while providing durable pain relief and minimizing radiation dose-related complications for TRTN patients. METHODS The authors' institutional review board approved the retrospective analysis of data from 15 consecutive patients (6 men and 9 women, median age 67 years, range 45-79 years) with TRTN who had undergone GKS. In all cases, the radiation was delivered in a single session targeting both the tumor and trigeminal REZ. The authors assessed the clinical outcomes, including the extent of pain relief, durability of the treatment response, and complications. Radiation doses to organs at risk (OARs), including the brainstem and the cranial nerve VII-VIII complex, were analyzed as doses received by 2% or 50% of the tissue volume and the tissue volume covered by a dose of 12 Gy (V12Gy). RESULTS The median length of clinical follow-up was 38 months (range 12-78 months). Pain relief with GKS was initially achieved in 14 patients (93.3%) and at the last follow-up in 13 patients (86.7%). The actuarial recurrence-free survival rates were 93%, 83%, and 69% at 1, 3, and 5 years after GKS, respectively. Persistent facial numbness was observed in 3 patients (20.0%). There were no complications such as facial weakness, altered taste function, hearing impairment, and balance difficulties indicating impaired function of the cranial nerve VII-VIII complex. The V12Gy in the brainstem was less than or equal to 0.24 cm3 in all patients. There were no significant differences in any OAR values in the brainstem between patients with and without facial numbness after GKS. CONCLUSIONS The strategy of performing GKS for both tumor and trigeminal REZ in a single session is a safe and effective radiosurgical approach that achieves durable pain control for TRTN patients.

OBJECTIVE This study was aimed to identify the incidence and risk factors of vancomycin-resistant enterococcus (VRE) colonization in neurosurgical practice of field, with particular attention to intensive care unit (ICU). METHODS This retrospective study was carried out on the Neurosurgical ICU (NICU), during the period from January. 2005 to December. 2007, in 414 consecutive patients who had been admitted to the NICU. Demographics and known risk factors were retrieved and assessed by statistical methods. RESULTS A total of 52 patients had VRE colonization among 414 patients enrolled, with an overall prevalence rate of 6.1%. E. faecium was the most frequently isolated pathogen, and 92.3% of all VRE were isolated from urine specimen. Active infection was noticed only in 2 patients with bacteremia and meningitis. Relative antibiotic agents were third-generation cephalosporin in 40%, and vancomycin in 23%, and multiple antibiotic usages were also identified in 13% of all cases. Multivariate analyses showed Glasgow coma scale (GCS) score less than 8, placement of Foley catheter longer than 2 weeks, ICU stay over 2 weeks and presence of nearby VRE-positive patients had a significantly independent association with VRE infection. CONCLUSION When managing the high-risk patients being prone to be infected VRE in the NICU, extreme caution should be paid upon. Because prevention and outbreak control is of ultimate importance, clinicians should be alert the possibility of impending colonization and infection by all means available. The most crucial interventions are careful hand washing, strict glove handling, meticulous and active screening, and complete segregation.