Category: Oncology

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Coregistered fluorescence-enhanced tumor resection of malignant glioma: relationships between δ-aminolevulinic acid–induced protoporphyrin IX fluorescence, magnetic resonance imaging enhancement, and neuropathological parameters

J Neurosurg 114:595–603,2011.DOI: 10.3171/2010.2.JNS091322.

The aim of this study was to investigate the relationships between intraoperative fluorescence, features on MR imaging, and neuropathological parameters in 11 cases of newly diagnosed glioblastoma multiforme (GBM) treated using protoporphyrin IX (PpIX) fluorescence-guided resection.

Methods. In 11 patients with a newly diagnosed GBM, δ-aminolevulinic acid (ALA) was administered to enhance endogenous synthesis of the fluorophore PpIX. The patients then underwent fluorescence-guided resection, coregistered with conventional neuronavigational image guidance. Biopsy specimens were collected at different times during surgery and assigned a fluorescence level of 0–3 (0, no fluorescence; 1, low fluorescence; 2, moderate fluorescence; or 3, high fluorescence). Contrast enhancement on MR imaging was quantified using two image metrics: 1) Gd-enhanced signal intensity (GdE) on T1-weighted subtraction MR image volumes, and 2) normalized contrast ratios (nCRs) in T1-weighted, postGd-injection MR image volumes for each biopsy specimen, using the biopsy-specific image-space coordinate transformation provided by the navigation system. Subsequently, each GdE and nCR value was grouped into one of two fluorescence categories, defined by its corresponding biopsy specimen fluorescence assessment as negative fluorescence (fluorescence level 0) or positive fluorescence (fluorescence level 1, 2, or 3). A single neuropathologist analyzed the H & E–stained tissue slides of each biopsy specimen and measured three neuropathological parameters: 1) histopathological score (0–IV); 2) tumor burden score (0–III); and 3) necrotic burden score (0–III).

Results. Mixed-model analyses with random effects for individuals show a highly statistically significant difference between fluorescing and nonfluorescing tissue in GdE (mean difference 8.33, p = 0.018) and nCRs (mean difference 5.15, p < 0.001). An analysis of association demonstrated a significant relationship between the levels of intraoperative fluorescence and histopathological score (χ2 = 58.8, p < 0.001), between fluorescence levels and tumor burden (χ2 = 42.7, p < 0.001), and between fluorescence levels and necrotic burden (χ2 = 30.9, p < 0.001). The corresponding Spearman rank correlation coefficients were 0.51 (p < 0.001) for fluorescence and histopathological score, and 0.49 (p < 0.001) for fluorescence and tumor burden, suggesting a strongly positive relationship for each of these variables.

Conclusions. These results demonstrate a significant relationship between contrast enhancement on preoperative MR imaging and observable intraoperative PpIX fluorescence. The finding that preoperative MR image signatures are predictive of intraoperative PpIX fluorescence is of practical importance for identifying candidates for the procedure. Furthermore, this study provides evidence that a strong relationship exists between tumor aggressiveness and the degree of tissue fluorescence that is observable intraoperatively, and that observable fluorescence has an excellent positive predictive value but a low negative predictive value.

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Gamma Knife radiosurgery for larger-volume vestibular schwannomas

J Neurosurg 114:801–807, 2011.DOI: 10.3171/2010.8.JNS10674

Stereotactic radiosurgery (SRS) is an important management option for patients with small- and medium- sized vestibular schwannomas. To assess the potential role of SRS in larger tumors, the authors reviewed their recent experience.

Methods. Between 1994 and 2008, 65 patients with vestibular schwannomas between 3 and 4 cm in one extracanalicular maximum diameter (median tumor volume 9 ml) underwent Gamma Knife surgery. Seventeen patients (26%) had previously undergone resection.

Results. The median follow-up duration was 36 months (range 1–146 months). At the first planned imaging follow-up at 6 months, 5 tumors (8%) were slightly expanded, 53 (82%) were stable in size, and 7 (11%) were smaller. Two patients (3%) underwent resection within 6 months due to progressive symptoms. Two years later, with 63 tumors overall after the 2 post-SRS resections, 16 tumors (25%) had a volume reduction of more than 50%, 22 (35%) tumors had a volume reduction of 10–50%, 18 (29%) were stable in volume (volume change < 10%), and 7 (11%) had larger volumes (5 of the 7 patients underwent resection and 1 of the 7 underwent repeat SRS). Eighteen (82%) of 22 patients with serviceable hearing before SRS still had serviceable hearing after SRS more than 2 years later. Three patients (5%) developed symptomatic hydrocephalus and underwent placement of a ventriculoperitoneal shunt. In 4 patients (6%) trigeminal sensory dysfunction developed, and in 1 patient (2%) mild facial weakness (House-Brackmann Grade II) developed after SRS. In univariate analysis, patients who had a previous resection (p = 0.010), those with a tumor volume exceeding 10 ml (p = 0.05), and those with Koos Grade 4 tumors (p = 0.02) had less likelihood of tumor control after SRS.

Conclusions. Although microsurgical resection remains the primary management choice in patients with low comorbidities, most vestibular schwannomas with a maximum diameter less than 4 cm and without significant mass effect can be managed satisfactorily with Gamma Knife radiosurgery.

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Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study

J Neurosurg 114:613–623, 2011. DOI: 10.3171/2010.3.JNS097

Accumulating data suggest more aggressive surgery in patients with malignant glioma to improve outcome. However, extended surgery may increase morbidity. The randomized Phase III 5-aminolevulinic acid (ALA) study investigated 5-ALA–induced fluorescence as a tool for improving resections. An interim analysis demonstrated more frequent complete resections with longer progression-free survival (PFS). However, marginal differences were found regarding neurological deterioration and the frequency of additional therapies. Presently, the authors focus on the latter aspects in the final study population, and attempt to determine how safety might be affected by cytoreductive surgery.

Methods. Patients with malignant gliomas were randomized for fluorescence-guided (ALA group) or conventional white light (WL) (WL group) microsurgery. The final intent-to-treat population consisted of 176 patients in the ALA and 173 in the WL group. Primary efficacy variables were contrast-enhancing tumor on early MR imaging and 6-month PFS. Among secondary outcome measures, the National Institutes of Health Stroke Scale (NIH-SS) score and the Karnofsky Performance Scale (KPS) score were used for assessing neurological function.

Results. More frequent complete resections and improved PFS were confirmed, with higher median residual tumor volumes in the WL group (0.5 vs 0 cm3, p = 0.001). Patients in the ALA group had more frequent deterioration on the NIH-SS at 48 hours. Patients at risk were those with deficits unresponsive to steroids. No differences were found in the KPS score. Regarding outcome, a combined end point of risks and neurological deficits was attempted, which demonstrated results in patients in the ALA group to be superior to those in participants in the WL group. Interestingly, the cumulative incidence of repeat surgery was significantly reduced in ALA patients. When stratified by completeness of resection, patients with incomplete resections were quicker to deteriorate neurologically (p = 0.0036).

Conclusions. Extended resections performed using a tool such as 5-ALA–derived tumor fluorescence, carries the risk of temporary impairment of neurological function. However, risks are higher in patients with deficits unresponsive to steroids.

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Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in single-center experience

J Neurooncol (2011) 102:105–113.DOI 10.1007/s11060-010-0296-4

We analyzed the efficacy and applicability of surgery guided by 5-aminolevulinic acid (ALA) fluorescence in consecutive patients with glioblastoma multiforme (GBM).

Thirty-six patients with GBM were operated on using ALA fluorescence. Resections were performed using the fluorescent light to assess the right plane of dissection. In each case, biopsies with different fluorescent quality were taken from the tumor center, from the edges, and from the surrounding tissue. These samples were analyzed separately with hematoxylin–eosin examination and immunostaining against Ki67. Tumor volume was quantified with pre- and postoperative volumetric magnetic resonance imaging.

Strong fluorescence identified solid tumor with 100% positive predictive value. Invaded tissue beyond the solid tumor mass was identified by vague fluorescence with 97% positive predictive value and 66% negative predictive value, measured against hematoxylin–eosin examination. All the contrast-enhancing volume was resected in 83.3% of the patients, all patients had resection over 98% of the volume and mean volume resected was 99.8%. One month after surgery there was no mortality, and new or increased neurological morbidity was 8.2%.

The fluorescence induced by 5-aminolevulinic can help to achieve near total resection of enhancing tumor volume in most surgical cases of GBM. It is possible during surgery to obtain separate samples of the infiltrating cells from the tumor border.

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Identification of diagnostic serum protein profiles of glioblastoma patients

J Neurooncol (2011) 102:71–80.DOI 10.1007/s11060-010-0284-8

Diagnosis of a glioblastoma (GBM) is triggered by the onset of symptoms and is based on cerebral imaging and histological examination. Serum-based biomarkers may support detection of GBM. Here, we explored serum protein concentrations of GBM patients and used data mining to explore profiles of biomarkers and determine whether these are associated with the clinical status of the patients.

Gene and protein expression data for astrocytoma and GBM were used to identify secreted proteins differently expressed in tumors and in normal brain tissues. Tumor expression and serum concentrations of 14 candidate proteins were analyzed for 23 GBM patients and nine healthy subjects. Datamining methods involving all 14 proteins were used as an initial evaluation step to find clinically informative profiles.

Data mining identified a serum protein profile formed by BMP2, HSP70, and CXCL10 that enabled correct assignment to the GBM group with specificity and sensitivity of 89 and 96%, respectively (p< 0.0001, Fischer’s exact test). Survival for more than 15 months after tumor resection was associated with a profile formed by TSP1, HSP70, and IGFBP3, enabling correct assignment in all cases (p< 0.0001, Fischer’s exact test). No correlation was found with tumor size or age of the patient.

This study shows that robust serum profiles for GBM may be identified by data mining on the basis of a relatively small study cohort. Profiles of more than one biomarker enable more specific assignment to the GBM and survival group than those based on single proteins, confirming earlier attempts to correlate  single markers with cancer. These conceptual findings will be a basis for validation in a larger sample size.

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Stereotactic versus endoscopic surgery in periventricular lesions

Acta Neurochir (2011) 153:517–526.DOI 10.1007/s00701-010-0933-x

Endoscopic and stereotactic surgery have gained widespread acceptance as minimally invasive tools for the diagnosis of intracerebral pathologies. We investigated the specific advantages and disadvantages of each technique in the assessment of periventricular lesions.

Method This study included a retrospective series of 70 patients with periventricular lesions. Endoscopic surgery was performed in 17 patients (mean age, 37 years; range, 4 months–78 years) and stereotactic biopsy in 55 patients (mean age, 63 years; range, 23–80 years), including two patients who underwent both procedures.

Results Hydrocephalus was present in 13/17 patients in the endoscopic group (77%) and in 11/55 patients in the stereotactic group (20%). Diagnosis was achieved in all patients in the endoscopic group and in all but one patient in the stereotactic group, in whom histological diagnosis was obtained by endoscopic biopsy during a second operation. In the endoscopic group, additional procedures performed included ventriculostomy (2/17), cyst fenestration (3/17), endoscopic shunt revision (3/17) and placement of Rickham reservoirs or external cerebrospinal fluid drains (6/17). Adverse events occurred in one patient after endoscopy (chronic subdural hematoma) and in two patients after stereotactic surgery (one mild hemiparesis and one transitory paresis of the contralateral leg).

Conclusions Endoscopic and stereotactic surgery have distinct advantages and disadvantages in approaching periventricular lesions. The advantages of endoscopy encompass the possibility to perform additional surgical procedures during the same session (e.g. tumour reduction, third ventriculostomy, fenestration of a cyst). The visual control reduces the hazard of injury to anatomical structures and allows for a better control of bleeding although there is a considerable blind-out in such situations. The advantages of stereotactic surgery include a smaller approach and precise planning of the trajectory. It is usually performed under local anaesthesia. Both methods provide a safe and efficient therapeutic option in periventricular lesions with low surgical-related morbidity.

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Hemangiopericytomas grade II are not benign tumors

Acta Neurochir (2011) 153:385–394.DOI 10.1007/s00701-010-0877-1

Hemangiopericytomas (HPs) of the central nervous system are rare tumors and afflicted with a high propensity of recurrences and metastases. Histopathologically, HPs correspond to differentiated (WHO grade II) and anaplastic (WHO grade III) tumors. With respect to the available literature and our own experiences, the aggressiveness, especially of differentiated grade II HPs, seems to be underestimated. Methods Thus, in this retrospective study, we describe tumor behavior and examined the effect of radio- and chemotherapy on tumor control with respect to the WHO classification of grade II and III neoplasms. This study consists of 15 patients with cerebral (n=10) and spinal (n=5) HPs. Results Seven HPs were histopathologically classified as grade II and eight as anaplastic grade III tumors. Complete surgical resection could be achieved in 60% of cerebral and in 25% of spinal HPs. In total, local recurrences occurred in 20% of patients within 17.3 months after the primary operation. Recurrences occurred both from differentiated (n=1) and anaplastic (n=2) neoplasms. Treatment comprised re-operation followed by radio- and chemotherapy. Pointing out the importance of the extent of surgical resection, in this study, we could not detect a single patient showing any recurrences or systemic metastases after complete surgical resection of grade II HPs. During primary diagnostics, four patients showed systemic metastases. Although these tumors could be controlled via surgery, systemic metastases appeared in further four patients within 60.4 months. Interestingly, two of them were classified as differentiated tumors (WHO grade II). To control tumor progress, radiotherapy seemed to be partially effective. On the other hand, however, chemotherapy did not show any effect on tumor control. With respect to these results, screening investigations seem to be indispensable and are highly recommended during primary diagnostics and after the appearance of recurrences or metastases, independent of the histopathological staging of the tumor. Conclusion With respect to our results, radical surgical resection offers the best treatment option to control tumor progress. In case of subtotal resection or histopathologically diagnosed anaplasia (WHO III), radiotherapy seems to be indicated; however, chemotherapy did not show effectiveness to control tumor progress.

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Molecular biology of familial and sporadic vestibular schwannomas: implications for novel therapeutics

J Neurosurg 114:359–366, 2011.DOI: 10.3171/2009.10.JNS091135

Vestibular schwannomas (VSs) are benign tumors arising from the sheath of cranial nerve VIII. The pathogenesis underlying most familial and sporadic VSs has been linked to a mutation in a single gene, the neurofibromin 2 (NF2) gene located on chromosome 22, band q11–13.1.

In this review, the authors summarized what is known about the epidemiology of NF2 mutations and patients with VSs. The authors also discuss the function of the NF2 gene product, merlin, and describe the known and hypothetical effects of genetic mutations that lead to merlin dysfunction on a broad variety of cellular and histological end points.

A better understanding of the molecular pathobiology of VSs may lead to novel therapeutics to augment current modalities of treatment while minimizing morbidity.

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Surgical approaches to hypothalamic hamartomas

Neurosurg Focus 30 (2):E2, 2011.(DOI: 10.3171/2010.11.FOCUS10250)

Hypothalamic hamartomas (HHs) are devastating lesions causing refractory epilepsy, rage attacks, social ineptitude, and precocious puberty. Microsurgical and/or endoscopic resection offers an excellent risk/benefit profile for cure or improvement of epilepsy.

Methods. The authors reviewed a prospective database maintained during the first 7 years of the Barrow Hypothalamic Hamartoma program. They describe and illustrate their surgical methods, and they review data from several previous publications regarding surgical outcome.

Results. To date, the authors have performed surgery in 165 patients for symptomatic HHs. Patients underwent an endoscopic, transcallosal, or skull base approach, or multiple approaches. Twenty-six patients (15.8%) required more than 1 treatment for their HH.

Conclusions. Microsurgical and endoscopic resection of symptomatic HHs are technically demanding but can be performed safely with excellent results and an acceptable risk profile. Meticulous attention to the subtleties of surgical management helps optimize outcomes.

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Endocrinologic, neurologic, and visual morbidity after treatment for craniopharyngioma

J Neurooncol (2011) 101:463–476. DOI 10.1007/s11060-010-0265-y

Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma.

We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson’s chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model.

In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33– 41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, v2 P<0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05–5.81, P<0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available.

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Categorization and characterization of lesions of the orbital apex

Neuroradiology (2011) 53:89–107. DOI 10.1007/s00234-010-0712-7

The apex of the orbit is formed by the union of the lesser and greater wings of the sphenoid bone and acts as an osseous tunnel for numerous neurovascular structures entering the orbit from the cranial vault. Lesions of the orbital apex are clinically important as they can have an adverse effect on vision. A broad range of lesions can occur here, and our purpose is to organize the pathologic processes which occur in the orbital apex into logical imaging differentials, establish an organized approach to image analysis, and present examples of representative lesions.

Methods We review the anatomy of the orbital apex and categorize and describe the pathologic entities that are encountered most frequently in this anatomically compact region and identify imaging patterns that can help to narrow the differential diagnosis.

Results Categories of orbital apex lesions include neoplasms, inflammatory processes, infections, lesions causing extrinsic compression, and vascular lesions. This categorization provides an organized framework to facilitate a reasonable differential diagnosis. Computed tomography and magnetic resonance imaging are the modalities of choice to evaluate and characterize orbital apex lesions, and imaging examples utilizing these modalities will be presented.

Conclusion The orbital apex is a clinically important anatomical region and hosts diverse pathologic processes. An awareness of common imaging patterns can help to generate a focused differential diagnosis. A systematic categorical approach can be of help to radiologists attempting to accurately characterize lesions in this area.

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Decision analysis of treatment options for vestibular schwannoma

J Neurosurg 114:400–413, 2011. (DOI: 10.3171/2010.3.JNS091802)

Widespread use of MR imaging has contributed to the more frequent diagnosis of vestibular schwannomas (VSs). These tumors represent 10% of primary adult intracranial neoplasms, and if they are symptomatic, they usually present with hearing loss and tinnitus. Currently, there are 3 treatment options for quality of life (QOL): wait and scan, microsurgery, and radiosurgery. In this paper, the authors’ purpose is to determine which treatment modality yields the highest QOL at 5- and 10-year follow-up, considering the likelihood of recurrence and various complications.

Methods. The MEDLINE, Embase, and Cochrane online databases were searched for English-language articles published between 1990 and June 2008, containing key words relating to VS. Data were pooled to calculate the prevalence of treatment complications, tumor recurrence, and QOL with various complications. For parameters in which incidence varied with time of follow-up, the authors used meta-regression to determine the mean prevalence rates at a specified length of follow-up. A decision-analytical model was constructed to compare 5- and 10-year outcomes for a patient with a unilateral tumor and partially intact hearing. The 3 treatment options, wait and scan, microsurgery, and radiosurgery, were compared.

Results. After screening more than 2500 abstracts, the authors ultimately included 113 articles in this analysis. Recurrence, complication rates, and onset of complication varied with the treatment chosen. The relative QOL at the 5-year follow-up was 0.898 of normal for wait and scan, 0.953 for microsurgery, and 0.97 for radiosurgery. These differences are significant (p < 0.0052). Data were too scarce at the 10-year follow-up to calculate significant differences between the microsurgery and radiosurgery strategies.

Conclusions. At 5 years, patients treated with radiosurgery have an overall better QOL than those treated with either microsurgery or those investigated further with serial imaging. The authors found that the complications associated with wait-and-scan and microsurgery treatment strategies negatively impacted patient lives more than the complications from radiosurgery. One limitation of this study is that the 10-year follow-up data were too limited to analyze, and more studies are needed to determine if the authors’ results are still consistent at 10 years.

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Development of Stereotactic Mass Spectrometry for Brain Tumor Surgery

Neurosurgery 68:280–290, 2011 DOI: 10.1227/NEU.0b013e3181ff9cbb

Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue.

OBJECTIVE: To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents.

METHODS: Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity.

RESULTS: Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence.

CONCLUSION: The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of any organ and with a rapidity that allows real-time analysis.

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Long-term Results of the Neuroendoscopic Management of Colloid Cysts of the Third Ventricle: A Series of 90 Cases

Neurosurgery 68:179–187, 2011 DOI: 10.1227/NEU.0b013e3181ffae71

The endoscopic removal of third ventricular colloid cysts has been developed as an alternative to microsurgical transcortical-transventricular and transcallosal approaches.

OBJECTIVE: To examine the value of endoscopic technique by reviewing the large number of endoscopically treated patients with long-term follow-up in 2 neurosurgical centers.

METHODS: A retrospective chart review was conducted for all patients admitted for resection of a third ventricular colloid cyst to the Radboud University Nijmegen Medical Centre (Nijmegen, the Netherlands) and the Hoˆ pital Henri Mondor (Paris, France) between 1994 and 2007. Both clinical and radiological symptoms and operative results were evaluated.

RESULTS: Postdischarge clinical follow-up was available for 85 patients over a mean period of 4 years 3 months. Permanent morbidity occurred in 1 patient (persisting preoperative memory deficit). Follow-up imaging of 80 evaluable patients showed that total or nearly total cyst removal was possible in 46 individuals (57.5%). Residual cyst was present in 34 patients (42.5%), and 6 required repeated endoscopic surgery for symptomatic regrowth. Recurrent cysts were mainly seen within the first 2 years after surgery.

CONCLUSION: It is debatable whether the higher numbers of recurrent or residual cysts can be justified by the slightly lower complication rates achieved with endoscopic removal. However, results have been improving over the years. Moreover, the modifications observed on control magnetic resonance images justify the need for regular control imaging for at least the first 2 years postoperatively.

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Posterior fossa ependymomas: new radiological classification with surgical correlation

Childs Nerv Syst (2010) 26:1765–1772. DOI 10.1007/s00381-010-1251-6

The key determinant of long-term outcome in infratentorial ependymomas remains the extent of surgical resection. We describe a new radiological classification system which is validated against surgical findings and correlated with risk of post-operative residual tumour.

Methods Twenty-five consecutive patients (12 females, mean age 4.9 years, range 0.5–17 years) with infratentorial ependymomas were studied. Lesions were classified on preoperative MRI according to the pattern of extension, brainstem displacement and involvement of the obex, as lateral-type or midfloor-type tumours. Twenty-one operative records were reviewed with respect to the microanatomical tumour origin by a paediatric neurosurgeon, blinded to MRI findings. Follow-up imaging studies were evaluated for residual tumour.

Results There were 15 cases of midfloor-type tumour (anterior displacement of brainstem, infiltration of obex) and 10 cases of lateral-type tumour (lateral displacement of brainstem, obex free of tumour). Extension into prepontine or cerebellopontine cisterns was more common in lateraltype tumours. Agreement between the radiological classification and tumour origin, as defined by operative records, was seen in 18 out of 20 cases. Risk of residual tumour in lateral-type tumours was more than twice that of midfloortype tumours (80% vs. 33%, p=0.04). Risk of tumour residual was also significantly higher when vessel encasement or prepontine extension was observed.

Conclusions Infratentorial ependymomas can be preoperatively classified as lateral-type or midfloor-type tumours. This correlates well with operative findings. Lateral-type tumours have significantly increased risk of residual tumour compared to midfloor- type tumours and this may influence intensity of imaging surveillance.

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Long-term Outcome After Resection of Intraspinal Ependymomas: Report of 86 Consecutive Cases

Neurosurgery 67:1622–1631, 2010 DOI: 10.1227/NEU.0b013e3181f96d41

Objective: To evaluate progression-free survival, overall survival (OS) and long-term clinical outcome in a consecutive series of 86 patients with intraspinal ependymomas.

METHODS: Medical charts were retrospectively reviewed. Surviving patients voluntarily participated in a clinical history and physical examination that focused on neurological function and current tumor status.

RESULTS: Follow-up data are nearly 100% complete; mean follow-up time was 82 months. Eighty-five patients (99%) had surgery as a first-line treatment; 14 (17%) of these patients received adjuvant radiotherapy. Of the 85 patients who underwent primary surgery, gross total resection was performed in 60 patients (71%) and subtotal resection in 25 patients (29%). Ten-year progression-free survival rate was 75%; 5-year OS, 97%; and 10-year OS, 91%. Reduced preoperative neurological function and older age at diagnosis were significantly associated with increased risk of death. At follow-up, spontaneous regression of residual tumor after primary surgery may have occurred in 7 of 19 patients (37%). More than 75% of patients had neurological function compatible with an independent life at follow-up. Good preoperative neurological function was significantly associated with favorable outcome. It was not possible to evaluate the effect of radiotherapy on progression-free survival and OS.

CONCLUSION: Gross total resection remains the optimal treatment for patients with spinal ependymoma. Patients should be monitored with a clinical examination and magnetic resonance imaging at regular intervals up to 10 years after surgery.

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Vascular Endothelial Growth Factor: The Major Factor for Tumor Neovascularization and Edema Formation in Meningioma Patients

Neurosurgery 67:1703–1708, 2010 DOI: 10.1227/NEU.0b013e3181fb801b

Peritumoral brain edema (PTBE) may be crucial in the clinical outcome of meningioma patients. The underlying pathogenetic key mechanism has so far not been determined. Sex, age, tumor size, location, involvement of other structures, or the histological appearance was not found to sufficiently explain PTBE formation in meningiomas.

OBJECTIVE: As PTBE formation is widely accepted to be vasogenic, we investigated the role of vascular endothelial growth factor (VEGF) and pial supplying vessels in a series of World Health Organization (WHO) grade I meningiomas.

METHODS: A total of 79 patients with WHO grade I meningiomas were immunohistochemically studied for VEGF and MIB-1. Pre- and postoperative magnetic resonance imaging including 3-dimensional reconstruction of 1.3-mm thick layers, with calculation of tumor and edema volume, was performed. Intraoperatively, the vascular supply and arachnoidal state were noted by the neurosurgeon.

RESULTS: VEGF was found to be exclusively confined to meningioma tumor cells. We identified 4 different patterns. VEGF and supplying pial vessels were found in 14 meningioma patients, pial vascular supply only in 3, VEGF expression only in 46, and neither VEGF expression nor supplying pial vessels in 16. Only the occurrence of both pial vascular supply and tumor VEGF expression was found to be correlated with PTBE formation (P , .002).

CONCLUSION: Our data suggest that VEGF may be crucial in angiogenesis and therefore indirectly in PTBE formation in World Health Organization grade I meningiomas

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A Critical Evaluation of Vestibular Schwannoma Surgery for Patients Younger Than 40 Years of Age

Neurosurgery 67:1646–1654, 2010 DOI: 10.1227/NEU.0b013e3181f8d3d3

There are few published prospective data sets specifically focusing on patients younger than 40 years old undergoing microsurgery for vestibular schwannoma.

OBJECTIVE: We describe functional outcomes and long-term tumor control after surgery in patients younger than 40 years old enrolled in a prospectively collected database over a 25-year period.

METHODS: We selected all vestibular schwannoma patients from a prospectively collected database who were younger than 40 years old at the time of surgical resection for a vestibular schwannoma. Rates of tumor control and hearing preservation were analyzed using Kaplan-Meier analysis, and risk factors for facial nerve palsy, hearing loss, and trigeminal neuropathy were analyzed using multivariate logistic regression.

RESULTS: A total of 204 patients younger than 40 years of age met our inclusion criteria and were included in the analysis. Our data indicate that surgical resection leads to durable long-term freedom from tumor recurrence or progression in 89% of young patients at 15 years of follow-up. Consistent with other published series, hearing was preserved in 68% of patients with smaller tumors (,3 cm). Facial nerve function was preserved in 76% of patients with smaller tumors and 52% of patients with larger tumors (P , .001). On multivariate logistic regression, tumor size was a significant predictor of hearing loss, whereas gross total resection was nearly a significant predictor of hearing loss controlling for other variables (P = .06).

CONCLUSION: We present the largest prospectively studied cohort of young patients undergoing microsurgical resection of vestibular schwannoma. These data suggest that surgical resection provides excellent long-term tumor control in these patients

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Prediction of neurological deficits and recovery after surgery in the supplementary motor area: a prospective study in 26 patients

J Neurosurg 113:1152–1163, 2010.(DOI: 10.3171/2010.6.JNS1090)

Resection of lesions involving the supplementary motor area (SMA) may result in immediate postoperative motor and speech deficits that are reversible in most cases. In the present study the authors aimed to determine the critical involvement of SMA in the lesioned and healthy hemispheres in this functional recovery. They hypothesized that compensatory mechanisms take place following surgery in the SMA, and that these mechanisms can involve either the lesioned or the non-lesioned hemisphere. In addition, they hypothesized that a correlation will be present between the functional MR imaging (fMR) imaging–related activation in the SMA and the occurrence of a functional deficit during intraoperative cortical stimulation.

Methods. Twenty-six patients scheduled for resection of space-occupying lesions involving, or in the vicinity of, the SMA were recruited. Patients underwent an fMR imaging examination that included finger-tapping and verbgeneration tests to assess for motor and language functions. Intraoperatively direct cortical stimulation (DCS) of the SMA region was performed while patients were monitored for language and motor functions using tests similar to those used for the fMR imaging. Task dysfunction during DCS assessed the critical involvement of the SMA in the tested functions. Neurological evaluations were performed prior to surgery and at 3 time points within a month following surgery. A region of interest–based approach was used to evaluate fMR imaging blood oxygen level–dependent activation level and asymmetry in the SMA. These measurements were later compared with the intraoperative DCS and neurological findings.

Results. Functional MR imaging showed greater activation and dominance of the SMA in the lesioned hemisphere in patients who exhibited no motor or language dysfunction during DCS. In addition, patients with the highest activation of the SMA in the lesioned hemisphere for language and motor tests showed stronger coupling of this region with ipsilateral motor and language networks. In contrast, activation in the nonlesioned hemisphere did not correspond with DCS results.

Conclusions. The authors’ findings demonstrate the necessity of activation in the vicinity of the lesioned SMA for functional compensation in motor and language tasks. It is possible that more effective functional coupling of the SMA with motor and language areas in the same hemisphere prevents dysfunctions following surgical intervention. Importantly, fMR imaging activation in the unaffected SMA was not sufficient for development of functional compensation and, if anything, indicated decompensation.

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Morbidity of Transcallosal and Transcortical Approaches to Lesions in and Around the Lateral and Third Ventricles: A Single-Institution Experience

Neurosurgery 67:1483–1496, 2010 DOI: 10.1227/NEU.0b013e3181f7eb68

Resection of an intraventricular mass can result in life-altering complications. Many advocate transcallosal rather than transcortical approaches to these lesions, citing differential postoperative seizure risk.

OBJECTIVE: To test the hypothesis that the complication rates and patient outcomes are no different between these ventricular approaches.

METHODS: The medical records of 127 patients (93 adults and 34 children) operated on for intraventricular lesions between 1996 and 2007 were retrospectively analyzed. Risk factors for specific postoperative complications and outcome were assessed by multivariate analysis.

RESULTS: The transcallosal (59%) or transcortical (41%) approach was used. Gross or nearly total resection was achieved in 87% of cases. The permanent neurological complication rate determined by a staff neurologist was 23.6%. Seizure attributable to surgery occurred after 8% of transcortical and 25% of transcallosal operations (P = .01). After controlling for a variety of factors, the transcallosal approach carried a 4.4-fold increased risk of seizure (95% confidence interval, 1.3-18.9). The operative approach was not a risk factor for any other postoperative complication. One year after surgery, 72% of patients had excellent functional outcome (Karnofsky Performance Score $ 70 and Glasgow Outcome Score = 5). High tumor grade and impaired preoperative Karnofsky Performance Score predicted poor outcome. More than 90% of patients operated on for symptomatic colloid cysts (n = 34) had an excellent outcome.

CONCLUSION: Although the 2 traditional approaches to the ventricular system had similar major complication rates, the transcallosal approach was associated with significantly increased seizure risk. Accordingly, the chosen operative corridor should optimize tumor access and the protection of vulnerable neurovascular structures.

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