Category: Oncology

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Insular low-grade glioma and postoperative seizure outcome

Surgery for insular low-grade glioma- predictors of postoperative seizure outcome

J Neurosurg 120:12–23, 2014

Although a number of recent studies on the surgical treatment of insular low-grade glioma (LGG) have demonstrated that aggressive resection leads to increased overall patient survival and decreased malignant progression, less attention has been given to the results with respect to tumor-related epilepsy. The aim of this investigation was to evaluate the impact of volumetric, histological, and intraoperative neurophysiological factors on seizure outcome in patients with insular LGG.

Methods. The authors evaluated predictors of seizure outcome with special emphasis on both the extent of tumor resection (EOR) and the tumor’s infiltrative pattern quantified by computing the difference between the preoperative T2- and T1-weighted MR images (DVT2T1) in 52 patients with preoperative drug-resistant epilepsy.

Results. The 12-month postoperative seizure outcome (Engel class) was as follows: seizure free (Class I), 67.31%; rare seizures (Class II), 7.69%; meaningful seizure improvement (Class III), 15.38%; and no improvement or worsening (Class IV), 9.62%. Poor seizure control was more common in patients with a longer preoperative seizure history (p < 0.002) and higher frequency of seizures (p = 0.008). Better seizure control was achieved in cases with EOR ≥ 90% (p < 0.001) and DVT2T1 < 30 cm3 (p < 0.001). In the final model, DVT2T1 proved to be the strongest independent predictor of seizure outcome in insular LGG patients (p < 0.0001).

Conclusions. No or little postoperative seizure improvement occurs mainly in cases with a prevalent infiltrative tumor growth pattern, expressed by high DVT2T1 values, which consequently reflects a smaller EOR.

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The silent phase of diffuse low-grade gliomas. Is it when we missed the action?

Diffuse low-grade glioma

Acta Neurochir (2013) 155:2237–2242

It is commonly believed that, before being diagnosed after onset of symptoms, diffuse low-grade glioma evolve silently for a long time. The present study aimed to estimate for the first time the exact duration of this silent phase, during which the glioma is radiologically visible but undiscovered.

Methods We retrospectively reviewed our French national database of diffuse low-grade glioma, searching for patients with an MRI-based assessment of their velocity of diameter growth at diagnosis and before any treatment (at least three MRIs over more than 6months). For each patient, the duration of the silent phase was estimated by the formula: duration = initial diameter / initial velocity of growth.

Results A total of 148 patients were included in the study. The mean lead-time duration (i.e., duration of the silent phase) was 14.0±7.8 years (median, 11.6 ; range, 1.6-39.4). The leadtime is statistically not correlated to the tumor volume. It is markedly decreasing with the velocity of diameter expansion.

Conclusions Diffuse low-grade glioma are radiologically detectable but clinically silent for more than a decade. Such a long period of silent evolution could explain our current failure to cure these tumors. It can also be viewed as a window of opportunity to detect these tumors earlier, suggesting the need to set up a screening program.

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Surgical strategy in grade II astrocytoma

Surgical strategy in grade II astrocytoma

Acta Neurochir (2013) 155:2227–2235

We recently demonstrated a survival benefit of early resection in unselected diffuse low-grade gliomas (LGG). However, heterogeneity within the LGG entity warrants investigation in a homogenous subgroup. Astrocytoma represents the largest subgroup of LGG, and is characterized by diffuse growth and inferior prognosis. We aimed to study the effects of early resection compared to biopsy and watchful waiting in this subgroup.

Methods Patient data was retrospectively reviewed in two neurosurgical departments with regional referral practice. In one hospital, initial diagnostic biopsies and watchful waiting was favored, while early resections guided with three-dimensional (3D) ultrasound were advocated in the other hospital. This created a natural experiment with patient management heavy influenced by residential address. In the hospitals’ histopathology databases, all adult patients diagnosed with supratentorial LGG from 1998 through 2009 were screened (n =169) and underwent blinded histopathological review. Histopathological review concluded with 117 patients with grade II astrocytomas that were included in the present study. The primary end-point was overall survival assessed by a regional comparison.

Results Early resections were performed in 51 (82 %) versus 12 (22 %) patients in the respective hospitals (p <0.001). The two patient populations were otherwise similar. Median survival was 9.7 years (95 % CI 7.5–11.9) if treated in the hospital favoring early resections compared to 5.6 years (95 % CI 3.5– 7.6) if treated at the hospital favoring biopsy and watchful waiting (p =0.047). No difference in surgical-related neurological morbidity was seen (p =0.843).

Conclusions Early 3D ultrasound guided resections improve survival, apparently without increasedmorbidity, compared to biopsy and watchful waiting in patients with diffuse World Health Organization (WHO) grade II astrocytomas.

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Management and outcome of high-grade multicentric gliomas

Management and outcome of high-grade multicentric gliomas

Acta Neurochir (2013) 155:2245–2251

Multicentric malignant gliomas are wellseparated tumours in different lobes or hemispheres, without anatomical continuity between lesions. The purpose of this study was to explore the clinical features, the pathology and the outcome according to the management strategies in a consecutive series of patients treated at a single institution. In addition, an analysis of the existing literature is presented.

Methods For the institutional analysis, a retrospective review of all patients who underwent treatment for multicentric gliomas in the last 7 years was performed. For the analysis of the literature, a MEDLINE search with no date limitations was accomplished for surgical treatment of multicentric malignant gliomas.

Results Two hundred and thirty-nine patients with glioma were treated in our department. Eighteen patients (7.5%) with a mean age of 64 years (age range, 37–78 years) presented multicentric malignant gliomas. Thirteen patients (72 %) underwent surgical resection of at least one lesion that was followed by adjuvant treatment in all but one case. Five patients (28 %) underwent stereotactic biopsy and thereafter received chemotherapy. A survival advantage was associated with resection of at least one lesion followed by adjuvant treatment (median overall survival 12 months) compared with 4 months for stereotactic biopsy followed by chemotherapy. Similar results were obtained from the review of the literature.

Conclusions Resection of at least one lesion seems to play a significant role in the management of selected patients with multicentric malignant gliomas. Multi-institutional studies on larger series are warranted to define how aggressively the patients with malignant multicentric gliomas should be treated.

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Role of intraoperative neurophysiological monitoring during fluorescence-guided resection surgery

Role of intraoperative neurophysiological monitoring during fluorescence-guided resection surgery

Acta Neurochir (2013) 155:2201–2213

Fluorescence-guided resection (FGR) using 5- aminolevulinic acid (5-ALA) exhibits a potential risk of permanent neurological deficits that can be minimized using intraoperative neurophysiological monitoring (IONM). We assessed the role of IONM in FGR surgery in patients harboring tumors in or near eloquent areas.

Methods IONM and FGR surgeries were performed on 34 patients (49.8±2.4 years) harbored malignant primary gliomas near eloquent cortical areas or semioval center. Different combinations of neurophysiological techniques were used depending on each patient.

Results Gross total resection (GTR) was achieved in 66.7 % of the patients, mean 90.4±3.7 % without neurological deficits. Resection in four patients was stopped by the occurrence of severe warning criteria despite the presence of fluorescence. Hemispheric transcranial electrical stimulation was safe and confident even in cortical surgery. Notably, a significant percentage of patients exhibited clinical improvement after the surgery. One week after surgery, only one patient worsened, and seven patients improved. At 3 months, 27.8 % of the patients improved, and the other patients maintained a similar status to their pre-surgery condition.Warning common criteria (amplitude reduction and/or latency increase) appeared in 68.2 and 50.0 % of patients during cortical or semioval surgery, respectively, with neither a false-negative nor a false-positive clinical outcome. Although 5-ALA exhibits phototoxicity, VEP did not induce any secondary effects in the visual system, including eyelids.

Conclusions IONM can be helpful during surgery to maximize the tumor resection, meanwhile help to avoid neurological deficits and, therefore, to improve the quality of life of these patients.

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Effect of dural detachment on long-term tumor control for meningiomas treated using Simpson Grade IV resection

Effect of dural detachment on long-term tumor control for meningiomas treated using Simpson Grade IV resection

J Neurosurg 119:1373–1379, 2013

Meningiomas treated by subtotal or partial resection are associated with significantly shorter recurrencefree survival than those treated by gross-total resection. The Simpson grading system classifies incomplete resections into a single category, namely Simpson Grade IV, with wide variations in the volume and location of residual tumors, making it complicated to evaluate the achievement of surgical goals and predict the prognosis of these tumors. Authors of the present study investigated the factors related to necessity of retreatment and tried to identify any surgical nuances achievable with the aid of modern neurosurgical techniques for meningiomas treated using Simpson Grade IV resection.

Methods. This retrospective analysis included patients with WHO Grade I meningiomas treated using Simpson Grade IV resection as the initial therapy at the University of Tokyo Hospital between January 1995 and April 2010. Retreatment was defined as reresection or stereotactic radiosurgery due to postoperative tumor growth.

Results. A total of 38 patients were included in this study. Regrowth of residual tumor was observed in 22 patients with a mean follow-up period of 6.1 years. Retreatment was performed for 20 of these 22 tumors with regrowth. Risk factors related to significantly shorter retreatment-free survival were age younger than 50 years (p = 0.006), postresection tumor volume of 4 cm3 or more (p = 0.016), no dural detachment (p = 0.001), and skull base location (p = 0.016). Multivariate analysis revealed that no dural detachment (hazard ratio [HR] 6.42, 95% CI 1.41–45.0; p = 0.02) and skull base location (HR 11.6, 95% CI 2.18–218; p = 0.002) were independent risk factors for the necessity of early retreatment, whereas postresection tumor volume of 4 cm3 or more was not a statistically significant risk factor.

Conclusions. Compared with Simpson Grade I, II, and III resections, Simpson Grade IV resection includes highly heterogeneous tumors in terms of resection rate and location of the residual mass. Despite the difficulty in analyzing such diverse data, these results draw attention to the favorable effect of dural detachment (instead of maximizing the resection rate) on long-term tumor control. Surgical strategy with an emphasis on detaching the tumor from the affected dura might be another important option in resection of high-risk meningiomas not amenable to gross-total resection.

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Recurrent high-grade glioma treated with bevacizumab: prognostic value of MGMT methylation, EGFR status and pretreatment MRI in determining response and survival

Recurrent GBM and bevacizumab

J Neurooncol (2013) 115:267–276

Although bevacizumab represented an important advance in treatment of recurrent high-grade gliomas (HGG), responses occur in fewer than half of patients. There are no validated biomarkers for anti-angiogenic therapy that are available for routine clinical use.

We assessed the prognostic values of imaging and molecular markers in this patient population. MRI scans from 191 patients with recurrent HGG obtained prior to initiating bevacizumab were reviewed for areas of enhancement, necrosis, T2/FLAIR abnormality, and ADC values. Serial MRI scans following the initiation of bevacizumab were evaluated for response and progression. Non-radiographic markers including EGFR and MGMT status were also assessed with respect to response and patient survival.

65 of 191 patients (34 %) showed complete or partial response at the time of their best response MRI and demonstrated longer progression free survival (PFS) and overall survival (OS) compared to the group without response (PFS: 6.9 vs 3.5 months, OS: 10.9 vs 6.1 months). Minimum ADC values within enhancing and non-enhancing regions were lower in responders compared to those of nonresponders (1,099 vs 984 x 10-6 mm2/s, p = 0.006). Smaller enhancing area was associated with longer OS (HR = 1.99, p = 0.017). The ratio of T2/FLAIR to enhancing area was prognostic of OS for only the Grade III HGG subgroup (HR = 0.14, p = 0.004).

Area of enhancing tumor at baseline can stratify survival in patients with recurrent HGG treated with bevacizumab. The extent of edema relative to enhancing area may have a prognostic role specific to Grade III HGG.

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Glioma Spheroids Obtained via Ultrasonic Aspiration Are Viable and Express Stem Cell Markers

Glioma, Immunohistochemistry, Organotypic, Spheroids, Tumor-initiating cells, Ultrasonic aspiration

Neurosurgery 73:868–886, 2013

Ultrasonic aspirators allow safe, rapid, and accurate removal of brain tumors. However, the tissue fragments removed are used surprisingly little in research.

OBJECTIVE: To investigate whether such tissue fragments could be cultured as organotypic multicellular spheroids because access to biopsy tissue is often limited.

METHODS: Tissue fragments obtained by ultrasonic aspiration from 10 glioblastomas and tumor biopsy tissue from 7 of these tumors were cultured in serum-containing and serum-free medium. On culturing, the fragments formed spheroids, which were prepared for histology. Two glioblastoma cell lines from ultrasonic fragments and biopsy tissue were established as well.

RESULTS: Hematoxylin and eosin staining showed viable glioma spheroids obtained from both ultrasonic and biopsy tissue in both types of medium. Endothelial growth factor receptor and PTEN/chromosome 10 status was found to be preserved in most spheroids (7-8 of 10 tumors), together with the level of glial fibrillary acidic protein, von Willebrand factor, and Ki-67. The levels of stem cell markers CD133, Bmi-1, nestin, and Sox2 also were preserved. The ultrasonic spheroids had higher levels of glial fibrillary acidic protein and von Willebrand factor and lower levels of Bmi-1, nestin, Sox2, and Olig2 compared with conventional biopsy spheroids. For both types of spheroids, the stem cell medium seemed to favor expression of stem cell markers. The established cell lines were capable of both spheroid formation at clonal density and tumor formation in vivo.

CONCLUSION: Viable organotypic and proliferating spheroids were easily obtained from ultrasonic tissue fragments. The preservation of markers and the establishment of cell lines with tumor-initiating cell properties suggest ultrasonic spheroids as a new tissue resource for glioma research.

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The preoperative use of navigated transcranial magnetic stimulation facilitates early resection of suspected low-grade gliomas in the motor cortex

The preoperative use of navigated transcranial magnetic stimulation facilitates early resection of suspected low-grade gliomas in the motor cortex

Acta Neurochir (2013) 155:1813–1821

Resection is recommended for low-grade gliomas, but often it is not performed if the tumor is suspected of invading the primary motor cortex. The study aim is to assess what influence preoperative navigated transcranial magnetic stimulation (nTMS) has on the treatment strategy and clinical outcome for suspected low-grade gliomas in presumed motor eloquent location.

Methods This paper reports on all our patients with gliomas in the primary motor cortex that were non-enhancing on MRI, since we began using nTMS (n=11). For the comparison group, we identified the 11 most recent such patients just before we started using nTMS.

Results Exact delineation of motor functional versus nonfunctional cortical tissue was provided by nTMS in all cases, also within the area of altered FLAIR signal. In 6 out of 11 cases, the nTMS mapping result changed the treatment plan towards early and more extensive resection. Only one nTMS patient had another seizure within the follow-up period, whereas four patients in the comparison group had further seizures. In the nTMS group, 1 of 4 patients with pre-op neurological deficits improved by one year; whereas the comparison group had increased neurological deficits in 3 of the 8 patients not having surgery. The median (range) change of tumor volume from baseline to 1 year was −83 % (−67 % to −100 %) in the nTMS group, but +12 % (+40 % to −56 %) in the comparison group (p<0.001).

Conclusions nTMS provides accurate motor mapping results also in infiltrative gliomas and enables more frequent and more extensive surgical resection of non-enhancing gliomas in or near the primary motor cortex. The substantial differences observed here in neurological and oncological outcomes suggest that further comparative research is warranted.

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Deformable Anatomic Templates Improve Analysis of Gliomas With Minimal Mass Effect in Eloquent Areas

Deformable Anatomic Templates Improve Analysis of Gliomas With Minimal Mass Effect in Eloquent Areas

Neurosurgery 73:534–542, 2013

Despite improvements in advanced magnetic resonance imaging and intraoperative mapping, cases remain in which it is difficult to determine whether viable eloquent structures are involved by a glioma. A novel software program, deformable anatomic templates (DAT), rapidly embeds the normal location of eloquent cortex and functional tracts in the magnetic resonance images of glioma-bearing brain.

OBJECTIVE: To investigate the feasibility of the DAT technique in patients with gliomas related to eloquent brain.

METHODS: Forty cases of gliomas (grade II-IV) with minimal mass effect were referred for a prospective preoperative and postoperative DAT analysis. The DAT results were compared with the patient’s functional magnetic resonance imaging, diffusion tensor imaging, operative stimulation, and new postoperative clinical deficits.

RESULTS: Fifteen of the 40 glioma patients had overlap between tumor and eloquent structures. Immediate postoperative neurological deficits were seen in 9 cases in which the DAT showed the eloquent area both within the tumor and within or at the edge of the resection cavity. In 6 cases with no deficits, DAT placed the eloquent area in the tumor but outside the resection cavity.

CONCLUSION: This is proof of concept that DAT can improve the analysis of diffuse gliomas of any grade by efficiently alerting the surgeon to the possibility of eloquent area invasion. The technique is especially helpful in diffuse glioma because these tumors tend to infiltrate rather than displace eloquent structures. DAT is limited by tract displacement in gliomas that produces moderate to severe mass effect.

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Surgical management and outcomes of petroclival meningiomas: a single-center case series of 259 patients

Petroclival meningioma outcomes

Acta Neurochir (2013) 155:1367–1383

Surgical management of petroclival meningiomas is challenging. Various and inconsistent outcome and prognostic factors of the lesions have been evaluated previously. In the present study, the surgical outcome, philosophy, and experience of petroclival meningiomas are detailed based on a large patient series.

Methods A series of 259 patients with petroclival meningiomas (70 males and 189 females) were surgically treated. Clinical charts and radiographs were reviewed. Follow-up results were evaluated.

Results The preoperative Karnofsky Performance Scale (KPS) score was 74.2±10.5. The mean tumor size was 4.3±1.0 cm. The gross total resection (GTR) rate was 52.5 %. During a mean follow-up period of 55.3 months, recurrence/progression (R/P) occurred in 11 patients. The recent KPS score was 78.4±22.7, it improved in 139 (57.2 %) patients and stabilized in 53 (21.8 %) patients, and 201 (82.7 %) patients lived independently. The risk factors affecting the KPS score included (but were not limited to) age≥60, preoperative KPS≤60, and brainstem edema. The adverse factors contributing to R/P-free survival included (but were not limited to) non-total resection and the absence of the subarachnoid space. The R/P-free survival rate was 94.5 % at 5 years and 91.2 % at 9 years. The overall survival rate was 94.7 % at 5 years and 94.7 % at 9 years.

Conclusions Favorable outcomes from petroclival meningiomas could be achieved by microsurgery. Neurological function and quality of life were prioritized, and GTR was attempted. Risk factors should be considered in surgical schemes, and tumor recurrence should be aggressively monitored and treated.

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Pathology of Spinal Ependymomas

Pathology of Spinal Ependymomas

Neurosurgery 73:247–255, 2013

Ependymomas constitute approximately 40% of primary intraspinal tumors. Current World Health Organization (WHO) grading may not correlate with observed progression-free survival (PFS).

OBJECTIVE: This retrospective study of prospectively collected data examines whether PFS is influenced by the histological grade or by the extent of resection. It also analyzes the usage and effectiveness of postoperative adjuvant radiotherapy.

METHODS: We reviewed 134 consecutive patients with ependymomas of all grades. Pathology slides were re-reviewed and the histological grades were confirmed by a single neuropathologist. Postoperative residual or recurrence was evaluated with follow-up magnetic resonance imaging.

RESULTS: There were 85 male and 49 female patients, ranging from 10 to 79 (median 41) years of age. Thirty patients had WHO grade I tumors, 101 had grade II tumors, and 3 had grade III tumors. Kaplan-Meier analysis of PFS demonstrated a mean duration of 6 years for grade I, 14.9 years for grade II, and 3.7 years for grade III (P , .001). In grade II ependymomas, mean PFS was 11.2 years with subtotal resection and 17.8 years with gross total resection (P, .01). PFS of patients who underwent subtotal resection was not significantly changed by adjuvant radiotherapy (P , .36).

CONCLUSION: Patients with grade II ependymoma have significantly longer PFS than patients with grade I ependymoma. The extent of resection did not affect PFS in grade I ependymoma but it did in grade II. Contrary to its higher grade, WHO grade II ependymoma carries a better prognosis than WHO grade I ependymoma.

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Surgery for low-grade glioma infiltrating the central cerebral region

Surgery for low-grade glioma infiltrating the central cerebral region

J Neurosurg 119:318–323, 2013

A main concern with regard to surgery for low-grade glioma (LGG, WHO Grade II) is maintenance of the patient’s functional integrity. This concern is particularly relevant for gliomas in the central region, where damage can have grave repercussions. The authors evaluated postsurgical outcomes with regard to neurological deficits, seizures, and quality of life.

Methods. Outcomes were compared for 33 patients with central LGG (central cohort) and a control cohort of 31 patients with frontal LGG (frontal cohort), all of whom had had medically intractable seizures before undergoing surgery with mapping while awake. All surgeries were performed in the period from February 2007 through April 2010 at the same institution.

Results. For the central cohort, the median extent of resection was 92% (range 80%–97%), and for the frontal cohort, the median extent of resection was 93% (range 83%–98%; p = 1.0). Although the rate of mild neurological deficits was similar for both groups, seizure freedom (Engel Class I) was achieved for only 4 (12.1%) of 33 patients in the central cohort compared with 26 (83.9%) of 31 patients in the frontal cohort (p < 0.0001). The rate of return to work was lower for patients in the central cohort (4 [12.1%] of 33) than for the patients in the frontal cohort (28 [90.3%] of 31; p < 0.0001).

Conclusions. Resection of central LGG is feasible and safe when appropriate intraoperative mapping is used. However, seizure control for these patients remains poor, a finding that contrasts markedly with seizure control for patients in the frontal cohort and with that reported in the literature. For patients with central LGG, poor seizure control ultimately determines quality of life because most will not be able to return to work.

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Surgical techniques for the dissection of encased perforators in giant clinoidal meningiomas

Encased perforators in giant clinoidal meningiomas

Acta Neurochir (2013) 155:1409–1412

Surgical treatment of giant clinoidal meningiomas remains a challenging task for neurosurgeons. Here, we present details of the surgical techniques for the dissection of encased perforators.

Methods The dissection of encased perforators is summarized as follows: (1) split the tumor above the encased arteries and perforators; (2) find the entrance and exit points of the perforators, and estimate the running course of the perforators within the tumor; (3) dissect and expose the perforators along the estimated line.

Conclusions The surgical techniques described in this article will aid in achieving maximum tumor resection while preserving encased perforators.

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Tolerance of awake surgery for glioma: a prospective European Low Grade Glioma Network multicenter study

awake surgery for glioma

Acta Neurochir (2013) 155:1301–1308

Gross total removal of glioma is limited by proximity to eloquent brain. Awake surgery allows for intraoperative monitoring to safely identify eloquent regions. However, data on adverse psychological effects induced in these patients is limited.

Objective This study explored patients’ perception of awake surgery for glioma, with special focus on intraoperative pain and anxiety.

Methods This study was conducted at five neurosurgical centers within the European Low Grade Glioma Network. Patients underwent awake surgery for glioma according to the protocol of the individual center. Pain and discomfort were measured during the awake phase. Postoperatively, patients answered a questionnaire on aspects of their operation.

Results One hundred five patients were enrolled. Pain levels on a 10-cm visual analogue scale were 1.3 cm at the beginning, 1.9 cm the middle, and 2.1 cm at the end of awake phase. Levels of anxiety were 2.2 cm, 2.5 cm and 2.6 cm, respectively. Women and patients younger than 60 years exhibited highest mean anxiety levels. The patient questionnaire revealed that the majority of patients feel comfortable with the procedure. Discomfort resulted from head fixation or positioning on the operating table.

Conclusions We demonstrate that awake surgery is well tolerated, as neither intraoperative nor postoperative assessment revealed major disadvantages. Concerning practical lessons learned from this study, we emphasize the importance of minimizing pain and preparing patients thoroughly to reduce anxiety and maximize cooperation. Awake surgery is an excellent treatment modality for brain tumors with very positive perception by patients. Keywords

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Venous preservation–guided resection: a changing paradigm in parasagittal meningioma surgery

Venous preservation–guided resection- a changing paradigm in parasagittal meningioma surgery-1

J Neurosurg 119:74–81, 2013

Surgical treatment of parasagittal meningiomas is challenging. Preserving the venous outflow is the key point, but this may preclude radical resection. Different surgical strategies have been proposed. To contribute to the debate on the optimal strategy for treating these tumors, a single-institutional, single-surgeon series of patients with parasagittal meningiomas was analyzed and the available literature reviewed.

Methods. Clinical charts of patients with parasagittal meningioma, managed at the University of Messina between 1988 and 2008, were retrospectively reviewed. A microsurgical resection, the goal of which was to preserve the venous outflow, was performed. Only if the superior sagittal sinus (SSS) was angiographically occluded, but if alternative venous outflow was clearly recognized, was the tumor resected, together with the sinus without further flow restoration. A MEDLINE review of the literature published between 1955 and 2011 was performed.

Results. Long-term follow-up (mean 80 months) data obtained in 67 patients with meningiomas involving the SSS were analyzed. The recurrence rate was 10.4%; the morbidity and mortality rates were 10.4% and 4.5%, respectively. The authors identified in the literature 19 relevant studies on this issue, and based on their review of the literature, there is no evidence that aggressive management offers an advantage in terms of recurrence rate.

Conclusions. Analysis of the data obtained in the 67 patients confirmed good outcome and long-term tumor control following a surgical strategy aimed to preserve venous outflow. These findings and the results of the authors’ analysis of the literature emphasize that the goal of radical tumor resection should be balanced by an awareness of the increased surgical risk attendant on aggressive management of the SSS and bridging veins.

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Modern surgical outcomes following surgery for sphenoid wing meningiomas

Sphenoid wing meningioma

J Neurosurg 119:86–93, 2013

Cushing and Eisenhardt were the first to describe sphenoid wing meningiomas in detail, categorizing globoid tumors into 3 groups: 1) medial; 2) middle; and 3) lateral. The authors review their experience with resection of sphenoid wing meningiomas at a single center, to examine whether this classification predicts clinical presentation and postsurgical outcome.

Methods. All patients undergoing resection of sphenoid wing meningioma at the authors’ institution over a 9-year period were identified. Clinical data were compared from patients with tumors arising at different points along the sphenoid wing to determine if these tumors behaved differently in terms of symptoms, radiographic characteristics, and postsurgical outcome.

Results. A total of 56 patients underwent microsurgical resection for sphenoid wing meningioma during this period. The rates of optic canal invasion (medial 50% vs middle 5% vs lateral 0%; p < 0.0001, chi-square test), supraclinoid internal carotid artery encasement (medial 32% vs middle 5% vs lateral 0%; p < 0.01, chi-square test), and middle cerebral artery encasement (medial 45% vs middle 24% vs lateral 0%; p < 0.01, chi-square test) were all highest with medial-third tumors. New or worsened neurological deficits occurred in 10 (19%) of 56 patients. Of all the imaging characteristics studied, only location of the tumor along the medial third of the sphenoid wing significantly predicted an increased rate of new or worsened neurological deficit (OR 2.7, p < 0.05).

Conclusions. The authors report outcomes in a large series of sphenoid wing meningiomas that were treated using modern surgical techniques.

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Blood-based biomarkers for malignant gliomas

Blood-based biomarkers for malignant gliomas

J Neurooncol (2013) 113:345–352

Malignant gliomas remain incurable and present unique challenges to clinicians, radiologists and clinical and translational investigators. One of the major problems in treatment of these tumors is our limited ability to reliably assess tumor response or progression.

The most frequently used neuro-imaging studies (contrast-enhanced MRI and CT) rely on changes of blood–brain barrier (BBB) integrity, providing only an indirect assessment of tumor burden. In addition, the BBB can be altered by commonly used interventions including radiation, glucocorticoids and vascular endothelial growth factor inhibitors, further complicating the interpretation of scans. Newer radiologic techniques including PET and magnetic resonance spectroscopy are theoretically promising but thus far have not meaningfully changed the assessment of patients with malignant gliomas. A tumor-specific, bloodbased biomarker would be of immediate use to clinicians and investigators if sufficiently sensitive and specific.

This review discusses the potential utility of such a biomarker, the general classes of tumor-derived blood-based biomarkers and it summarizes the currently available data on circulating tumor cells, circulating nucleic acids and circulating proteins in patients with malignant gliomas. It is unclear which marker or marker class appears to be the most promising for these tumors.

This article provides thoughts on how novel candidate blood-based markers could be discovered and tested in a more comprehensive way and why these efforts should be among the top priorities in neuro-oncologic research in the coming years.

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Risk factor analysis of the development of new neurological deficits following supplementary motor area resection

Supplementary motor area

J Neurosurg 119:7–14, 2013

Supplementary motor area (SMA) resection often induces postoperative contralateral hemiparesis or speech disturbance. This study was performed to assess the neurological impairments that often follow SMA resection and to assess the risk factors associated with these postoperative deficits.

Methods. The records for patients who had undergone SMA resection for pharmacologically intractable epilepsy between 1994 and 2010 were gleaned from an epilepsy surgery database and retrospectively reviewed in this study.

Results. Forty-three patients with pharmacologically intractable epilepsy underwent SMA resection with intraoperative cortical stimulation and mapping while under awake anesthesia. The mean patient age was 31.7 years (range 15–63 years), and the mean duration and frequency of seizures were 10.4 years (range 0.1–30 years) and 14.6 per month (range 0.1–150 per month), respectively. Pathological examination of the brain revealed cortical dysplasia in 18 patients (41.9%), tumors in 16 patients (37.2%), and other lesions in 9 patients (20.9%). The mean duration of the follow-up period was 84.0 months (range 24–169 months). After SMA resection, 23 patients (53.5%) experienced neurological deficits. Three patients (7.0%) experienced permanent deficits, and 20 (46.5%) experienced symptoms that were transient. All permanent deficits involved contralateral weakness, whereas the transient symptoms patients experienced were varied, including contralateral weaknesses in 15, apraxia in 1, sensory disturbances in 1, and dysphasia in 6. Thirteen patients recovered completely within 1 month. Univariate analysis revealed that resection of the SMA proper, a shorter lifetime seizure history (< 10 years), and resection of the cingulate gyrus in addition to the SMA were associated with the development of neurological deficits (p = 0.078, 0.069, and 0.023, respectively). Cingulate gyrus resection was the only risk factor identified on multivariate analysis (p = 0.027, OR 6.530, 95% CI 1.234–34.562).

Conclusions. Resection of the cingulate gyrus in addition to the SMA was significantly associated with the development of postoperative neurological impairment.

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Prognostic Value of Residual Fluorescent Tissue in Glioblastoma Patients After Gross Total Resection in 5-Aminolevulinic Acid-Guided Surgery

Prognostic_Value_of_Residual_Fluorescent_Tissue_in

Neurosurgery 72:915–921, 2013

There is evidence in the literature supporting that fluorescent tissue signal in fluorescence-guided surgery extends farther than tissue highlighted in gadolinium in T1 sequence magnetic resonance imaging (MRI), which is the standard to quantify the extent of resection.

OBJECTIVE: To study whether the presence of residual fluorescent tissue after surgery carries a different prognosis for glioblastoma (GBM) cases with complete resection confirmed by MRI.

METHODS: A retrospective review in our center found 118 consecutive patients with high-grade gliomas operated on with the use of fluorescence-guided surgery with 5-aminolevulinic acid. Within that series, the 52 patients with newly diagnosed GBM and complete resection of enhancing tumor (CRET) in early MRI were selected for analysis. We studied the influence of residual fluorescence in the surgical field on overall survival and neurological complication rate. Multivariate analysis included potential relevant factors: age, Karnofsky Performance Scale, O6-methylguanine methyltransferase methylation promoter status, tumor eloquent location, preoperative tumor volume, and adjuvant therapy.

RESULTS: The median overall survival was 27.0 months (confidence interval = 22.4-31.6) in patients with nonresidual fluorescence (n = 25) and 17.5 months (confidence interval = 12.5-22.5) for the group with residual fluorescence (n = 27) (P = .015). The influence of residual fluorescence was maintained in the multivariate analysis with all covariables, hazard ratio = 2.5 (P = .041). The neurological complication rate was 18.5% in patients with nonresidual fluorescence and 8% for the group with residual fluorescence (P = .267).

CONCLUSION: GBM patients with CRET in early MRI and no fluorescent residual tissue had longer overall survival than patients with CRET and residual fluorescent tissue.

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