Category: Oncology

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Perioperative Outcomes in Intracranial Pleomorphic Xanthoastrocytoma

Neurosurgery 80:105–111, 2017

Patients with pleomorphic xanthoastrocytoma (PXA) routinely undergo multiple procedures to ensure recurrence-free survival and are resultantly at increased risk of experiencing perioperative complications (regional, medical, and/or neurological), a combination of which has not been recorded in previous studies.

OBJECTIVE: To determine perioperative outcomes in a cohort of patients (adult and pediatric) with intracranial PXA.

METHODS: We retrospectively identified 39 patients who underwent surgery at our insti- tution for intracranial PXA between 1994 and 2011. Demographic factors were recorded along with Karnofsky Performance Status (KPS), complications, and mortality.

RESULTS: Mean patient age was 31 years at the most recent surgery. A majority of patients (24; 62%) had multiple surgeries with a mean of 2 operations per patient. Eleven PXAs (28%) were malignant (grade III or IV). Perioperative complications included permanent neurological worsening in 4 patients (10%), regional complications in 4 (10%), and medical complications in 3 (8%). Preoperative KPS was ≥70 in 34 of 38 patients (89%). Long- term postoperative KPS was ≥70 in 36 of 37 patients (97%), suggesting good functional outcomes. There was no perioperative mortality, but 7 patients (18%) died of tumor progression. Patients with malignant PXAs trended toward higher risk of regional compli- cations (3 of 11 patients [27%]; P = .06), received adjuvant therapy more often (10 of 11 patients [91%]; P < .001), had higher mortality from tumor progression (7 of 11 patients [64%]; P < .001), and were significantly larger (mean, 6.05 ± 0.73 cm standard error of the mean; n = 7; P < .01).

CONCLUSION: Both pediatric and adult PXAs may be resected with good functional outcomes. Perioperative neurological complications are relatively common, but do not affect long-term functional outcome or mortality. Malignant PXAs are higher risk for perioperative complications and, ultimately, death from tumor progression, despite increased use of adjuvant radiation and chemotherapy.

 

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Passive language mapping combining real-time oscillation analysis with cortico-cortical evoked potentials for awake craniotomy

J Neurosurg 125:1580–1588, 2016

Electrocortical stimulation (ECS) is the gold standard for functional brain mapping; however, precise functional mapping is still difficult in patients with language deficits. High gamma activity (HGA) between 80 and 140 Hz on electrocorticography is assumed to reflect localized cortical processing, whereas the cortico-cortical evoked potential (CCEP) can reflect bidirectional responses evoked by monophasic pulse stimuli to the language cortices when there is no patient cooperation. The authors propose the use of “passive” mapping by combining HGA mapping and CCEP recording without active tasks during conscious resections of brain tumors.

Methods Five patients, each with an intraaxial tumor in their dominant hemisphere, underwent conscious resection of their lesion with passive mapping. The authors performed functional localization for the receptive language area, using real-time HGA mapping, by listening passively to linguistic sounds. Furthermore, single electrical pulses were delivered to the identified receptive temporal language area to detect CCEPs in the frontal lobe. All mapping results were validated by ECS, and the sensitivity and specificity were evaluated.

Results Linguistic HGA mapping quickly identified the language area in the temporal lobe. Electrical stimulation by linguistic HGA mapping to the identified temporal receptive language area evoked CCEPs on the frontal lobe. The combination of linguistic HGA and frontal CCEPs needed no patient cooperation or effort. In this small case series, the sensitivity and specificity were 93.8% and 89%, respectively.

Conclusions The described technique allows for simple and quick functional brain mapping with higher sensitivity and specificity than ECS mapping. The authors believe that this could improve the reliability of functional brain mapping and facilitate rational and objective operations. Passive mapping also sheds light on the underlying physiological mechanisms of language in the human brain.

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Comparison between electric-field-navigated and line-navigated TMS for cortical motor mapping in patients with brain tumors

Acta Neurochir (2016) 158:2277–2289

For the navigation of transcranial magnetic stimulation (TMS), various techniques are available. Yet, there are two basic principles underlying them all: electric-fieldnavigated transcranial magnetic stimulation (En-TMS) and line-navigated transcranial magnetic stimulation (Ln-TMS). The current study was designed to compare both methods.

Methods To explore whether there is a difference in clinical applicability, workflow, and mapping results of both techniques, we systematically compared motor mapping via EnTMS and Ln-TMS in 12 patients suffering from brain tumors.

Results The number of motor-positive stimulation spots and the ratio of positive spots per overall stimulation numbers were significantly higher for En-TMS (motor-positive spots: EnTMS vs. Ln-TMS: 128.3 ± 35.0 vs. 41.3 ± 26.8, p < 0.0001; ratio of motor-positive spots per number of stimulations: EnTMS vs. Ln-TMS: 38.0 ± 9.2 % vs. 20.0 ± 14.4 %, p = 0.0031). Distances between the En-TMS and Ln-TMS motor hotspots were 8.3 ± 4.4 mm on the ipsilesional and 8.6 ± 4.5 mm on the contralesional hemisphere (p = 0.9124).

Conclusions The present study compares En-TMS and LnTMS motor mapping in the neurosurgical context for the first time. Although both TMS systems tested in the present study are explicitly designed for application during motor mapping in patients with brain lesions, there are differences in applicability, workflow, and results between En-TMS and Ln-TMS, which should be distinctly considered during clinical use of the technique. However, to draw final conclusions about accuracy, confirmation of motor-positive Ln-TMS spots by intraoperative stimulation is crucial within the scope of upcoming investigations.

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Analysis of the surgical benefits of 5-ALA–induced fluorescence in intracranial meningiomas

J Neurosurg 125:1408–1419, 2016

One of the most important causes for recurrence of intracranial meningiomas is residual tumor tissue that remains despite assumed complete resection. Recently, intraoperative visualization of meningioma tissue by 5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PpIX) fluorescence was reported. The aim of this study was to investigate the possible surgical benefits of PpIX fluorescence for detection of meningioma tissue.

Methods 5-ALA was administered preoperatively to 190 patients undergoing resection of 204 intracranial meningiomas. The meningiomas’ PpIX fluorescence status, fluorescence quality (strong or vague), and intratumoral fluorescence homogeneity were investigated during surgery. Additionally, specific sites, including the dural tail, tumor-infiltrated bone flap, adjacent cortex, and potential satellite lesions, were analyzed for PpIX fluorescence in selected cases.

Results PpIX fluorescence was observed in 185 (91%) of 204 meningiomas. In the subgroup of sphenoorbital meningiomas (12 of 204 cases), the dural part showed visible PpIX fluorescence in 9 cases (75%), whereas the bony part did not show any PpIX fluorescence in 10 cases (83%). Of all fluorescing meningiomas, 168 (91%) showed strong PpIX fluorescence. Typically, most meningiomas demonstrated homogeneous fluorescence (75% of cases). No PpIX fluorescence was observed in any of the investigated 89 dural tails. In contrast, satellite lesions could be identified through PpIX fluorescence in 7 cases. Furthermore, tumor-infiltrated bone flaps could be visualized by PpIX fluorescence in all 13 cases. Notably, PpIX fluorescence was also present in the adjacent cortex in 20 (25%) of 80 analyzed cases.

Conclusions The authors’ data from this largest patient cohort to date indicate that PpIX fluorescence enables intraoperatively visualization of most intracranial meningiomas and allows identification of residual tumor tissue at specific sites. Thus, intraoperative detection of residual meningioma tissue by PpIX fluorescence might in future reduce the risk of recurrence.

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Intraoperative Near-Infrared Optical Imaging Can Localize Gadolinium-Enhancing Gliomas During Surgery

Neurosurgery 79:856–871, 2016

Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense.

OBJECTIVE: To propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease.

METHODS: Fifteen patients were identified and administered a Food and Drug Administration-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) before surgical resection. An NIR camera was utilized to localize the tumor before resection and to visualize surgical margins following resection. Neuropathology and magnetic resonance imaging data were used to assess the accuracy and precision of NIR fluorescence in identifying tumor tissue.

RESULTS: NIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low-grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12 of 15 tumors were visualized with the NIR camera. The mean signal-tobackground ratio was 9.5 6 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with signal-to-background ratio (P = .03). Nonenhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71).

CONCLUSION: With the use of Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity.

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Maximizing safe resection of low- and high-grade glioma

dti-gliomas

J Neurooncol (2016) 130:269–282

Surgical resection plays a central role in the management of gliomas. In this study, we review the evidence in support of extent of resection to improve survival, symptom management, and time to malignant transformation in low- and high-grade gliomas, and summarize the findings from our literature search regarding the role of extent of resection and intraoperative practices to maximize safety.

There is a growing body of evidence supporting improved overall survival, improved progression-free survival, and superior quality of life with greater extent of resection.

Additionally, a better understanding of central nervous system plasticity allows for a staged approach to the surgical management of low- and intermediate-grade gliomas.

A number of intraoperative techniques have been utilized to offer safer glioma surgery with greater extent of resection. Approaches such as awake brain tumor surgery can be safely performed with low failure rates and excellent long-term functional outcomes.

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Reoperation for Recurrent Glioblastoma and Its Association With Survival Benefit

multifocal glioblastoma

Neurosurgery 79:678–689, 2016

Glioblastoma is the most common and aggressive primary brain tumor. Despite current treatment, recurrence is inevitable. There are no clear guidelines for treatment of recurrent glioblastoma.

OBJECTIVE: To investigate factors at initial surgery predictive of reoperation, and the prognostic variables associated with survival, including reoperation for recurrence.

METHODS: A retrospective cohort study was performed, including adult patients diagnosed with glioblastoma between January 2010 and December 2013. Student t test and Fisher exact test compared continuous and categorical variables between reoperation and nonreoperation groups. Univariable and Cox regression multivariable analysis was performed.

RESULTS: In a cohort of 204 patients with de novo glioblastoma, 49 (24%) received reoperation at recurrence. The median overall survival in the reoperation group was 20.1 months compared with 9.0 months in the nonreoperation group (P = .001). Reoperation was associated with longer overall survival in our total population (hazard ratio, 0.646; 95% confidence interval, 0.543-0.922; P = .016) but subject to selection bias. Subgroup analyses excluding patients unlikely to be considered for reoperation suggested a much less significant effect of reoperation on survival, which warrants further study with larger cohorts. Factors at initial surgery predictive for reoperation were younger age, smaller tumor size, initial extent of resection $50%, shorter inpatient stay, and maximal initial adjuvant therapy. When unfavorable patient characteristics are excluded, reoperation is not an independent predictor of survival.

CONCLUSION: Patients undergoing reoperation have favorable prognostic characteristics, which may be responsible for the survival difference observed. We recommend that a large clinical registry be developed to better aid consistent and homogenous data collection.

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Surgery of insular and paralimbic diffuse low-grade gliomas: technical considerations

insular-lgg-2

J Neurooncol (2016) 130:289–298

Once considered a ‘‘no man’s land’’ especially when invaded by a diffuse low grade glioma (DLGG), the insula remains to this day a surgical challenge. Surgery for insular DLGG involves consideration of its hidden location under the potentially eloquent operculae, the proximity to vascular tree and high density of functions not only in the insular cortex but also in the white fiber pathways passing under the insular lobe. The natural history of DLGG and the potential benefits and consequences of the surgical approach also need a close look.

In the last decade, a better knowledge of the functional anatomy and connectivity of this region, as well as an improvement in surgical techniques as direct stimulation mapping, combined with an increasing literature showing a favorable impact of maximal resection for DLGG, were deciding factors in the paradigmatic shift from expectative treatment to early surgical management.

Here, our goal is to discuss the structural and functional aspects of the insula, the specificities of insular and paralimbic DLGG by emphasizing the technical considerations of surgery in this region, as well as its oncological and functional outcomes. In summary, this new strategy based upon early maximal safe surgical resection showed both oncological benefit and preservation of quality of life—or even an improvement thanks to epilepsy relief.

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Laser interstitial thermal therapy followed by minimal-access transsulcal resection for the treatment of large and dif cult to access brain tumors

litt

Neurosurg Focus 41 (4):E14, 2016

Laser interstitial thermal therapy (LITT), sometimes referred to as “stereotactic laser ablation,” has demonstrated utility in a subset of high-risk surgical patients with dificult to access (DTA) intracranial neoplasms. However, the treatment of tumors larger than 10 cm3 is associated with suboptimal outcomes and morbidity. This may limit the utility of LITT in dealing with precisely those large or deep tumors that are most dif cult to treat with conventional approaches. Recently, several groups have reported on minimally invasive transsulcal approaches utilizing tubular retracting systems. However, these approaches have been primarily used for intraventricular or paraventricular lesions, and subtotal resections have been reported for intraparenchymal lesions. Here, the authors describe a combined approach of LITT followed by minimally invasive transsulcal resection for large and DTA tumors.

Methoss The authors retrospectively reviewed the results of LITT immediately followed by minimally invasive, trans-sulcal, transportal resection in 10 consecutive patients with unilateral, DTA malignant tumors > 10 cm3. The patients, 5 males and 5 females, had a median age of 65 years. Eight patients had glioblastoma multiforme (GBM), 1 had a previously treated GBM with radiation necrosis, and 1 had a melanoma brain metastasis. The median tumor volume treated was 38.0 cm3.

Results The median tumor volume treated to the yellow thermal dose threshold (TDT) line was 83% (range 76%– 92%), the median tumor volume treated to the blue TDT line was 73% (range 60%–87%), and the median extent of resection was 93% (range 84%–100%). Two patients suffered mild postoperative neurological de cits, one transiently. Four patients have died since this analysis and 6 remain alive. Median progression-free survival was 280 days, and median overall survival was 482 days.

Conclusions Laser interstitial thermal therapy followed by minimally invasive transsulcal resection, reported here for the first time, is a novel option for patients with large, DTA, malignant brain neoplasms. There were no unexpected neurological complications in this series, and operative characteristics improved as surgeon experience increased. Further studies are needed to elucidate any differences in survival or quality of life metrics.

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Accurate Delineation of Glioma Infiltration by Advanced PET/MR Neuro-Imaging (FRONTIER Study)

f1-largeNeurosurgery 79:535–540, 2016

Glioma imaging, used for diagnostics, treatment planning, and followup, is currently based on standard magnetic resonance imaging (MRI) modalities (T1 contrast-enhancement for gadolinium-enhancing gliomas and T2 fluid-attenuated inversion recovery hyperintensity for nonenhancing gliomas). The diagnostic accuracy of these techniques for the delineation of gliomas is suboptimal.

OBJECTIVE: To assess the diagnostic accuracy of advanced neuroimaging compared with standard MRI modalities for the detection of diffuse glioma infiltration within the brain.

METHODS: A monocenter, prospective, diagnostic observational study in adult patients with a newly diagnosed, diffuse infiltrative glioma undergoing resective glioma surgery. Forty patients will be recruited in 3 years. Advanced neuroimaging will be added to the standard preoperative MRI. Serial neuronavigated biopsies in and around the glioma boundaries, obtained immediately preceding resective surgery, will provide histopathologic and molecular characteristics of the regions of interest, enabling comparison with quantitative measurements in the imaging modalities at the same biopsy sites.

DISCUSSION: In this clinical study, we determine the diagnostic accuracy of advanced imaging in addition to standard MRI to delineate glioma. The results of our study can be valuable for the development of an improved standard imaging protocol for glioma treatment.

EXPECTED OUTCOME: We hypothesize that a combination of positron emission tomography, MR spectroscopy, and standard MRI will have a superior accuracy for glioma delineation compared with standard MRI alone. In addition, we anticipate that advanced imaging will correlate with the histopathologic and molecular characteristics of glioma.

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The impact of MGMT methylation and IDH-1 mutation on long-term outcome for glioblastoma treated with chemoradiotherapy

Relationship of glioblastoma multiforme to the subventricular zone is associated with survival

Acta Neurochir (2016) 158:1943–1953

Increasingly, biomarkers have been identified that correlate with improved overall and progression-free survival (OS and PFS) in glioblastoma, including MGMT methylation status and mutations in the IDH1 gene. In this study, we investigated the clinical and biological factors associated with long-term survival in glioblastoma patients treated with chemoradiotherapy.

Method Demographic and clinical data were collected for all patients with glioblastoma diagnosed between May 2004 and September 2007, treated with chemoradiotherapy and with associated tissue samples available for biomarker analysis. MGMT methylation was determined by pyrosequencing. IDH1 mutation was identified by R132H immunohistochemistry. Univariate Cox regression analysis of factors associated with survival and Kaplan-Meier survival analysis was performed using the SPSS statistics package.

Results One hundred patients were included in the study. Median follow-up was 12.2 months (range 1.6–102.4). Median OS was 12.1 months (95 % CI: 10.8–13.3) and median PFS was 8.2 months (95%CI: 6.8–9.5). The 2-, 3- and 5- year survival was 18, 9 and 6 % respectively. Three patients are still alive at 7.4, 8.3 and 8.5 years after diagnosis. Cox proportional-hazards regression identified independent prognostic factors for OS, female (p = 0.019), MGMT methylation (p < 0.0001) and IDH1 mutation (p = 0.023), and for PFS, MGMT methylation (p = 0.001) and IDH1 mutation (p = 0.018). Kaplan-Meier survival analysis showed that MGMTmethylated/ IDH1+ve was associated with a significantly longer OS 66.8 months (95 % CI: 0.0–167.8) and PFS 16.9 months (95 % CI: 11.1–22.7) when compared with MGMTmethylated/ IDH1-ve OS 15.5 months (95 % CI: 11.6–19.4) and PFS 9.4 months (95 % CI: 8–10.8) (log-rank, P = 0.000) and MGMTunmethylated/IDH1-ve OS 11.1 months (95 % CI: 8.5– 13.7) and PFS 6.3 months (95 % CI: 4.4–8.3) (log-rank, p=0.000).

Conclusions While the importance of MGMT methylation is well established, we demonstrate that the combination of MGMTmethylated/IDH1+ve is associated with considerably longer OS and PFS in this series of chemoradiotherapy-treated glioblastoma tumours. The long-term cognitive function and quality of life in these long-term survivors warrant investigation.

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Cystic meningioma: radiological, histological, and surgical particularities in 43 patients

cystic-meningioma-radiological-histological-and-surgical-particularities-in-43-patients

Acta Neurochir (2016) 158:1955–1964

The presence of cysts is a rare occurrence for intracranial meningiomas in adults. We report our experience in a large consecutive series of cystic meningiomas.

Method: We prospectively collected data for a dedicated database of cystic meningioma cases between January 2004 and December 2011 in two tertiary neurosurgical centers. Studied data included preoperative imaging, surgical records, and pathology reports.

Results: Among 1214 surgeries for intracranial meningioma, we identified 43 cases of cystic meningioma, corresponding to an incidence of 3.5 %. The most common localization was the hemispheric convexity (17/43 cases). Twenty-eight patients had intratumoral cysts, nine peritumoral, and five mixed intra and extratumoral. In 29 patients with available diffusion imaging, ADC coefficients were significantly lower in grade IIIII tumors compared to grade I (p = 0.01). Complete resection of the cystic components was possible in 27/43 patients (63 %); partial resection in 4/43 (9 %); in 6/43 (14 %) cyst resection was not possible but multiple biopsies were performed from the cystic walls; in another 6/43 (14 %) the cystic wall was not identified during surgery. Cells with neoplastic features were identified within the cyst walls at pathology in 26/43 cases (60 %). All patients were followed-up for 24 months; long-term follow-up was available only in 32 patients for an average period of 49 months (range, 36–96 months). No recurrence requiring surgery was observed.

Conclusions Cystic meningiomas are rare. Cells with neoplastic features are often identified within the cyst walls. Complete cyst resection is recommendable when considered technically feasible and safe.

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Selective 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in Gliomas

selective-5-aminolevulinic-acid-induced-protoporphyrin-ix-fluorescence-in-gliomas

Acta Neurochir (2016) 158:1935–1941

Malignant gliomas are locally invasive tumors that offer a poor prognosis. Evidence shows that complete resection of the tumor at the time of surgery confers a significant improvement in overall survival.

In recent years, 5- aminolevulinic acid (ALA)-induced fluorescence has been used by neurosurgeons to good effect in increasing the rate of complete resection. Despite the considerable interest in the use of 5-ALA in fluorescence-guided neurosurgery, the mechanisms behind the accumulation of Protoporphyrin IX (PpIX) in neoplastic tissue are unclear.

In this review, we summarize the evidence in the literature on the mechanisms underlying the selective production of PpIX with a specific focus on gliomas.

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Identification of language area and the pars triangularis

language-area-and-pt

Journal of Neurosurgery Vol. 125 / No. 4 : 803-811

Identification of language areas using functional brain mapping is sometimes impossible using current methods but essential to preserve language function in patients with gliomas located within or near the frontal language area (FLA). However, the factors that influence the failure to detect language areas have not been elucidated. The present study evaluated the difficulty in identifying the FLA in dominant-side frontal gliomas that involve the pars triangularis (PT) to determine the factors that influenced failed positive language mapping.

Methods: Awake craniotomy was performed on 301 patients from April 2000 to October 2013 at Tokyo Women’s Medical University. Recurrent cases were excluded, and patients were also excluded if motor mapping indicated their glioma was in or around the motor area on the dominant or nondominant side. Eighty-two consecutive cases of primary frontal glioma on the dominant side were analyzed for the present study. MRI was used for all patients to evaluate whether tumors involved the PT and to perform language functional mapping with a bipolar electrical stimulator. Eighteen of 82 patients (mean age 39 ± 13 years) had tumors that showed involvement of the PT, and the detailed characteristics of these 18 patients were examined.

Results: The FLA could not be identified with intraoperative brain mapping in 14 (17%) of 82 patients; 11 (79%) of these 14 patients had a tumor involving the PT. The negative response rate in language mapping was only 5% in patients without involvement of the PT, whereas this rate was 61% in patients with involvement of the PT. Univariate analyses showed no significant correlation between identification of the FLA and sex, age, histology, or WHO grade. However, failure to identify the FLA was significantly correlated with involvement of the PT (p < 0.0001). Similarly, multivariate analyses with the logistic regression model showed that only involvement of the PT was significantly correlated with failure to identify the FLA (p < 0.0001). In 18 patients whose tumors involved the PT, only 1 patient had mild preoperative dysphasia. One week after surgery, language function worsened in 4 (22%) of 18 patients. Six months after surgery, 1 (5.6%) of 18 patients had a persistent mild speech deficit. The mean extent of resection was 90% ± 7.1%.

Conclusions: Identification of the FLA can be difficult in patients with frontal gliomas on the dominant side that involve the PT, but the positive mapping rate of the FLA was 95% in patients without involvement of the PT. These findings are useful for establishing a positive mapping strategy for patients undergoing awake craniotomy for the treatment of frontal gliomas on the dominant side. Thoroughly positive language mapping with subcortical electrical stimulation should be performed in patients without involvement of the PT. More careful continuous neurological monitoring combined with subcortical electrical stimulation is needed when removing dominant-side frontal gliomas that involve the PT.

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Identification of language area and the pars triangularis

language-area-and-pt

J Neurosurg 125:803–811, 2016

Identification of language areas using functional brain mapping is sometimes impossible using current methods but essential to preserve language function in patients with gliomas located within or near the frontal language area (FLA). However, the factors that influence the failure to detect language areas have not been elucidated. The present study evaluated the difficulty in identifying the FLA in dominant-side frontal gliomas that involve the pars triangularis (PT) to determine the factors that influenced failed positive language mapping.

Methods: Awake craniotomy was performed on 301 patients from April 2000 to October 2013 at Tokyo Women’s Medical University. Recurrent cases were excluded, and patients were also excluded if motor mapping indicated their glioma was in or around the motor area on the dominant or nondominant side. Eighty-two consecutive cases of primary frontal glioma on the dominant side were analyzed for the present study. MRI was used for all patients to evaluate whether tumors involved the PT and to perform language functional mapping with a bipolar electrical stimulator. Eighteen of 82 patients (mean age 39 ± 13 years) had tumors that showed involvement of the PT, and the detailed characteristics of these 18 patients were examined.

Results: The FLA could not be identified with intraoperative brain mapping in 14 (17%) of 82 patients; 11 (79%) of these 14 patients had a tumor involving the PT. The negative response rate in language mapping was only 5% in patients without involvement of the PT, whereas this rate was 61% in patients with involvement of the PT. Univariate analyses showed no significant correlation between identification of the FLA and sex, age, histology, or WHO grade. However, failure to identify the FLA was significantly correlated with involvement of the PT (p < 0.0001). Similarly, multivariate analyses with the logistic regression model showed that only involvement of the PT was significantly correlated with failure to identify the FLA (p < 0.0001). In 18 patients whose tumors involved the PT, only 1 patient had mild preoperative dysphasia. One week after surgery, language function worsened in 4 (22%) of 18 patients. Six months after surgery, 1 (5.6%) of 18 patients had a persistent mild speech deficit. The mean extent of resection was 90% ± 7.1%.

Conclusions: Identification of the FLA can be difficult in patients with frontal gliomas on the dominant side that involve the PT, but the positive mapping rate of the FLA was 95% in patients without involvement of the PT. These findings are useful for establishing a positive mapping strategy for patients undergoing awake craniotomy for the treatment of frontal gliomas on the dominant side. Thoroughly positive language mapping with subcortical electrical stimulation should be performed in patients without involvement of the PT. More careful continuous neurological monitoring combined with subcortical electrical stimulation is needed when removing dominant-side frontal gliomas that involve the PT.

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Genomic landscape of intracranial meningiomas

genomic-meningiomas

J Neurosurg 125:525–535, 2016

Meningiomas are the most common primary intracranial neoplasms in adults. Current histopathological grading schemes do not consistently predict their natural history. Classic cytogenetic studies have disclosed a progressive course of chromosomal aberrations, especially in high-grade meningiomas. Furthermore, the recent application of unbiased nextgeneration sequencing approaches has implicated several novel genes whose mutations underlie a substantial percentage of meningiomas. These insights may serve to craft a molecular taxonomy for meningiomas and highlight putative therapeutic targets in a new era of rational biology-informed precision medicine.

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Optic nerve pial circulation in tuberculum meningioma surgery

optic-nerve-pial-circulation-in-tuberculum-meningioma-surgery

J Neurosurg 125:565–569, 2016

Tuberculum sellae meningiomas frequently produce visual loss by direct compression from tumor, constriction of the optic nerve (ON) under the falciform ligament, and/or ON ischemia. The authors hypothesized that changes in visual function after tumor removal may be related to changes in blood supply to the ON that might be seen in the pial circulation at surgery. Indocyanine green (ICG) angiography was used to attempt to document these changes at surgery.

The first patient in whom the technique was used had a left-sided, 1.4-cm, tuberculum meningioma. Time-lapse comparison of images was done postsurgery, and the comparison of video images revealed both faster initial filling and earlier complete filling of the ON pial circulation, suggesting improved pial blood flow after surgical decompression. In follow-up the patient had significant improvements in both visual acuity and visual fields function. Intraoperative ICG angiography of the ON can demonstrate measurable changes in pial vascular flow that may be predictive of postoperative visual outcome.

The predictive value of this technique during neurosurgical procedures around the optic apparatus warrants further investigation in a larger cohort.

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The Simpson grading revisited

PSMeningioma

J Neurosurg 125:551–560, 2016

Recent advances in radiotherapy and neuroimaging have called into question the traditional role of aggressive resections in patients with meningiomas. In the present study the authors reviewed their institutional experience with a policy based on maximal safe resections for meningiomas, and they analyzed the impact of the degree of resection on functional outcome and progression-free survival (PFS).

Methods The authors retrospectively analyzed 901 consecutive patients with primary meningiomas (716 WHO Grade I, 174 Grade II, and 11 Grade III) who underwent resections at the University Hospital of Bonn between 1996 and 2008. Clinical and treatment parameters as well as tumor characteristics were analyzed using standard statistical methods.

Results The median follow-up was 62 months. PFS rates at 5 and 10 years were 92.6% and 86.0%, respectively. Younger age, higher preoperative Karnofsky Performance Scale (KPS) score, and convexity tumor location, but not the degree of resection, were identified as independent predictors of a good functional outcome (defined as KPS Score 90– 100). Independent predictors of PFS were degree of resection (Simpson Grade I vs II vs III vs IV), MIB-1 index (< 5% vs 5%–10% vs >10%), histological grade (WHO I vs II vs III), tumor size (≤ 6 vs > 6 cm), tumor multiplicity, and location. A Simpson Grade II rather than Grade I resection more than doubled the risk of recurrence at 10 years in the overall series (18.8% vs 8.5%). The impact of aggressive resections was much stronger in higher grade meningiomas.

Conclusions A policy of maximal safe resections for meningiomas prolongs PFS and is not associated with increased morbidity.

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Stereotactic biopsy of brainstem lesions: 21 years experiences of a single center

Stereotactic biopsy of brainstem lesions- 21 years experiences of a single center

J Neurooncol (2016) 129:243–250

Stereotactic biopsies are procedures performed to obtain tumor tissue for diagnostic examinations. Cerebral lesions of unknown entities can safely be accessed and tissue can be examined, resulting in correct diagnosis and according treatment. Stereotactic procedures of lesions in highly eloquent regions such as the brainstem have been performed for more than two decades in our department.

In this retrospective study we focus on results, approaches, modalities of anesthesia, and complications. We performed a retrospective analysis of our prospective database, including 26 patients who underwent stereotactic biopsy of the brainstem between April 1994 and June 2015.

All of the patients underwent preoperative MRI. Riechert– Mundinger-frame was used before 2000, thereafter the Leksell stereotactic frame was used. After 2000 entry and target points were calculated by using BrainLab stereotactic system. We evaluated histopathological results as well as further treatment; additionally we compared complications of local versus general anesthesia and complications of a frontal versus a trans-cerebellar approach. Median age of all patients was 33 years, and median number of tissue samples taken was 12. In all patients a final histopathological diagnosis could be established. 5 patients underwent the procedure under local anesthesia, 21 patients in general anesthesia. In 19 patients a frontal approach was performed, while in 7 patients a trans-cerebellar approach was used. Complications occurred in five patients. Thereby no significant difference was found with regard to approach (frontal versus trans-cerebellar) or anesthesia (local versus general).

Stereotactic biopsies even of lesions in the brainstem are a save way to obtain tumor tissue for final diagnosis, resulting in adequate treatment. Approach can be trans-cerebellar or frontal and procedure can be performed either under local or general anesthesia without significant differences concerning complication rate.

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A study of prognostic factors in 45 cases of atypical meningioma

Radiation Therapy for Residual or Recurrent Atypical Meningioma

Acta Neurochir (2016) 158:1661–1667

Atypical meningioma differs from Grade I meningioma in terms of high recurrence rate and short life expectancy. We evaluated the clinical course of atypical meningioma and investigated prognostic factors affecting its outcomes.

Method: We reviewed 45 patients with atypical meningioma who underwent surgical intervention between January 2000 and December 2013. The mean age of the patients and mean follow-up period was 58.7 years and 81.0 months, respectively. Analyses included factors such as patient age, gender, location and size of tumor, extent of surgical resection (Simpson Grading System), and MIB-1 labeling index (LI). Univariate analysis was used to detect prognostic factors associated with recurrence and survival.

Results: The 5-year recurrence-free rate for all 45 patients was 58.4 %; 5 and 10-year survival rates were 83.2 % and 79.9 %, respectively. In univariate analyses, age >60 years, and MIB-1 LI correlated with disease recurrence, whereas age >60 years, subtotal surgical resection, MIB-1 LI, and indication for radiotherapy correlated with death. MIB-1 LI levels higher than 12.8 % and 19.7 % predicted recurrence and death, respectively. In our cohort, 26 patients received postoperative radiotherapy including conventional radiation (n = 21) or gamma knife radiosurgery (n = 5). Postoperative radiotherapy did not decrease recurrence rates in our cohort (p = 0.63). Six and two patients who died during the study period underwent conventional radiation and radiosurgery, respectively.

Conclusions: Age, male gender, extent of surgical resection, and higher MIB-1 LI influenced the outcome of atypical meningioma. In our cohort, postoperative radiotherapy failed to provide long-term tumor control. Following incomplete surgical resection of atypical meningioma in elderly patients, adjuvant postoperative radiotherapy may not be an ideal treatment option, particularly when MIB-1 LI is higher than 19.7 %.

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