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PURPOSE: To analyse feasibility, prognostic factors and patterns of recurrence after concurrent reirradiation and bevacizumab for recurrent high-grade gliomas. PATIENTS AND METHODS: Between 2009 and 2015, 35 patients (median 57-year-old; 21 men, 14 women) with WHO grade III (n=11) or grade IV (n=24) gliomas were included in this retrospective and consecutive single-centre study. All patients received bevacizumab (median number of treatments: 12) concomitant with reirradiation (median dose: 45Gy, median number of fractions: 18) for recurrence with median 22 months (range: 5.6-123.7 months) from first irradiation (median dose: 60Gy). RESULTS: The median follow-up was 9.2 months from reirradiation. The median overall survival from reirradiation was 10.5 months (95% confidence interval [95% CI]: 4.9-16.1) and the progression-free survival from reirradiation was 6.7 months (95% CI: 2.9-10.5). The median overall survival from initial diagnosis was 44.6 months (95% CI: 32-57.1). No grade 3 toxicity or above was reported. Prognostic factors significantly correlated with better overall survival in univariate analysis were: age at least 55 (P=0.024), initial surgery (P=0.003), and 2Gy equivalent dose (EQD2) at least 50Gy at reirradiation (P=0.046). Twenty-two patients bevacizumab-naïve at time of reirradiation had a significantly increased overall survival from reirradiation compared to patients treated with reirradiation after bevacizumab failure (17.7 vs. 5.4 months, P<0.001) as well as overall survival from initial diagnosis (58.9 vs. 33.5 months, P=0.006). This outcome was similar in patients with initial glioblastomas (P=0.018) or anaplastic gliomas (P=0.021). There was no correlation between overall survival and gross tumour volume or planning target volume, frontal localization, or number of salvage therapies before reirradiation (P>0.05). CONCLUSIONS: Concomitant reirradiation with bevacizumab in high-grade recurrent gliomas shows encouraging results in terms of survival and toxicities. Our data suggest that reirradiation should be favoured at initiation of bevacizumab, with EQD2 at least 50Gy.
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Antineoplásicos Inmunológicos/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/terapia , Quimioradioterapia , Glioma/mortalidad , Glioma/terapia , Reirradiación , Adulto , Factores de Edad , Anciano , Neoplasias Encefálicas/patología , Femenino , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Pronóstico , Dosificación Radioterapéutica , Estudios Retrospectivos , Adulto JovenRESUMEN
INTRODUCTION: Surgical resection of supratentorial cavernous angiomas located in eloquent areas poses a significant risk to the patient of postoperative neurological impairment and justifies intraoperative functional monitoring. METHODS: Multicentre retrospective series of adult patients with cavernous angiomas located within eloquent areas and treated with functional-based surgical resection according to functional boundaries under intraoperative functional cortico-subcortical monitoring under awake conditions. RESULTS: Fifty patients (18 males, mean 36.3±10.8 year-old) underwent surgical resection with intraoperative cortico-subcortical functional mapping using direct electrostimulation under awake conditions for a cavernous angioma located in eloquent areas with a mean postoperative follow-up of 21.0±21.2 months. At presentation, the cavernous angioma had previously resulted in severe impairment (neurological deficit in 34%, seizures in 70%, uncontrolled seizures in 34%, reduced Karnofsky Performance Status score of 70 or less in 24%, inability to work in 52%). Functional-based surgical resection allowed complete removal of the cavernous angioma in 98% and of the haemosiderin rim in 82%. Postoperative seizures and other complications were rare, and similarly so across all centres included in this series. Postoperatively, we found functional improvement in 84% of patients (reduced Karnofsky Performance Status score of 70 or less in 6%, uncontrolled seizures in 16%, and inability to work in 11%). CONCLUSION: Functional-based surgical resection aids the safe and complete resection of cavernous angiomas located in eloquent areas while minimizing the surgical risks. Functional mapping has to be considered in such challenging cases.
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Neoplasias Encefálicas/cirugía , Hemangioma Cavernoso/cirugía , Procedimientos Neuroquirúrgicos , Vigilia/fisiología , Adulto , Anciano , Mapeo Encefálico/métodos , Estimulación Eléctrica/métodos , Femenino , Humanos , Monitorización Neurofisiológica Intraoperatoria , Masculino , Persona de Mediana Edad , Neuronavegación/métodos , Procedimientos Neuroquirúrgicos/métodos , Estudios RetrospectivosRESUMEN
INTRODUCTION: Intraoperative application of electrical current to the brain is a standard technique during brain surgery for inferring the function of the underlying brain. The purpose of intraoperative functional mapping is to reliably identify cortical areas and subcortical pathways involved in eloquent functions, especially motor, sensory, language and cognitive functions. MATERIAL AND METHODS: The aim of this article is to review the rationale and the electrophysiological principles of the use of direct bipolar electrostimulation for cortical and subcortical mapping under awake conditions. RESULTS: Direct electrical stimulation is a window into the whole functional network that sustains a particular function. It is an accurate (spatial resolution of about 5mm) and a reproducible technique particularly adapted to clinical practice for brain resection in eloquent areas. If the procedure is rigorously applied, the sensitivity of direct electrical stimulation for the detection of cortical and subcortical eloquent areas is nearly 100%. The main disadvantage of this technique is its suboptimal specificity. Another limitation is the identification of eloquent areas during surgery, which, however, could have been functionally compensated postoperatively if removed surgically. CONCLUSION: Direct electrical stimulation is an easy, accurate, reliable and safe invasive technique for the intraoperative detection of both cortical and subcortical functional brain connectivity for clinical purpose. In our opinion, it is the optimal technique for minimizing the risk of neurological sequelae when resecting in eloquent brain areas.
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Encefalopatías/fisiopatología , Craneotomía/métodos , Estimulación Eléctrica , Vigilia/fisiología , Encéfalo/cirugía , Encefalopatías/cirugía , Mapeo Encefálico , Estimulación Eléctrica/métodos , Humanos , Monitorización Neurofisiológica IntraoperatoriaAsunto(s)
Neoplasias Encefálicas/cirugía , Encéfalo/cirugía , Glioma/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Neoplasias Encefálicas/diagnóstico por imagen , Glioma/diagnóstico por imagen , Humanos , Cuidados Intraoperatorios , Imagen por Resonancia MagnéticaRESUMEN
INTRODUCTION: The aim of brain glioma surgery is to maximize the quality of resection, while minimizing the risk of sequelae. Due to the frequent location of gliomas near or within eloquent areas, owing to their infiltrative feature, and because of major interindividual variability, the anatomofunctional organization and connectivity must be studied individually. Therefore, to optimize the benefit-to-risk ratio of surgery, intraoperative functional mapping is extensively used. MATERIAL AND METHODS: This article aims at describing the rationale, indications and practical aspects of intraoperative direct electrical bipolar electrostimulation for cortical and subcortical mapping under awake conditions using the asleep-awake asleep anaesthetic protocol in the setting of cerebral gliomas. We will address the operative approach, including patient positioning, functional mapping resection strategy, anaesthetic conditions, as well as tips and pitfalls. RESULTS: The intraoperative direct electrical bipolar electrostimulation enables: (i) to study the real-time individual cortical functional organization; (ii) to study the anatomofunctional subcortical connectivity along the resection; (iii) to tailor the resection according to individual corticosubcortical functional boundaries. This is an easy, accurate, reliable, well-tolerated and safe detection technique of both cortical and subcortical functionally essential structures during resection. It should be performed in the context of a standardized protocol involving members of both anaesthesiology and neurosurgery teams at neurosurgical centers specialized in surgical neuro-oncology. CONCLUSION: Intraoperative direct electrical bipolar electrostimulation for cortical and subcortical mapping under awake conditions is currently considered the "gold standard" clinical tool for brain mapping during cerebral resection in neuro-oncology.
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Neoplasias Encefálicas/cirugía , Estimulación Eléctrica , Glioma/cirugía , Monitorización Neurofisiológica Intraoperatoria , Procedimientos Neuroquirúrgicos , Vigilia/fisiología , Mapeo Encefálico/métodos , Neoplasias Encefálicas/patología , Estimulación Eléctrica/métodos , Glioma/complicaciones , Humanos , Procedimientos Neuroquirúrgicos/métodosRESUMEN
OBJECTIVE: Incidentally discovered diffuse low-grade gliomas progress in a fashion similar to their symptomatic counterparts. Their early detection allows more effective pre-emptive and individualized oncological treatment. We assessed the safety and efficacy of maximal safe resection according to functional boundaries for incidental diffuse low-grade gliomas in eloquent areas. MATERIAL AND METHODS: Two-centre retrospective series of adult patients with incidental diffuse low-grade gliomas located within/close to eloquent areas in the dominant hemisphere, treated with maximal surgical resection according to functional boundaries under intraoperative functional cortico-subcortical monitoring under awake conditions, and with a minimal follow-up of 24months. RESULTS: The series included 19 patients (8 men, 11 women) with no preoperative neurological deficit but with a radiologically enlarged glioma. No intraoperative seizure, postoperative infection, haematoma or wound-healing problem was observed. In the immediate postsurgical period, a transient neurological worsening occurred in 10 patients. The resection (mean rate 96.4%; range, 82.4-100) was supratotal in 5 cases, total in 5 cases, subtotal in 7 cases, and partial in 2 cases. Six months after surgery, all patients recovered after functional rehabilitation, with no permanent neurological deficit, Karnofsky Performance Status was 100 (except for one patient who received early postoperative radiotherapy) and no seizures were observed. The survival without progression requiring oncological treatment was significantly longer in patients with a total/supratotal resection than in patients with a partial/subtotal resection. CONCLUSIONS: These results suggest the reproducibility, safety, and effectiveness of an early maximal functionally based resection within cortico-subcortical functional boundaries for incidental diffuse low-grade gliomas in adults in centres hyperspecialized in surgical neuro-oncology.
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Neoplasias Encefálicas/cirugía , Epilepsia/cirugía , Glioma/cirugía , Adulto , Encéfalo/cirugía , Mapeo Encefálico/métodos , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico , Estimulación Eléctrica/métodos , Epilepsia/etiología , Femenino , Glioma/complicaciones , Glioma/diagnóstico , Humanos , Monitorización Neurofisiológica Intraoperatoria , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/métodos , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Resultado del Tratamiento , Vigilia/fisiologíaRESUMEN
OBJECTIVE: Glioma survival correlated with the extent of resection and the functional status of the patient. We detailed functional results along with oncological results after a functional-based resection of gliomas located within eloquent regions. MATERIAL AND METHODS: Single centre prospective series of adult patients with gliomas located within eloquent regions, treated with maximal resection according to functional boundaries using intraoperative cortico-subcortical monitoring under awake conditions, with available functional outcomes (language and cognitive assessments, neurological status, ability to work) and oncological outcomes (extent of surgical resection, survivals). RESULTS: The series included 107 awake surgeries (45.8% grade II gliomas, 41.1% grade III gliomas, 13.1% glioblastomas) with 18.7% of preoperative focal neurological deficits, 91.6% of neuropsychological disturbances, and 61.5% of inability to work. A total of 85.7% of grade II gliomas had a resection>90% (mean 86.3±22.6%), 61.4% of grade III gliomas had a resection>90% (mean 78.7±30.4%) and 85.7% of glioblastomas had a resection>90% (mean 89.0±29.5%). Also, 85.0% of patients presented a postoperative worsening of their neurological and/or cognitive status and underwent a personalized rehabilitation. At a 6-month postoperative follow-up, 89.9% of cognitive impairments improved, 30.8% of patients with a preoperative language impairment improved (language postoperative worsening present in 1.9%), and 74.4% resumed their employment activities. The survival rate varied significantly with the extent of resection and with the grade of malignancy. CONCLUSIONS: Maximal functional-based resection improves the onco-functional balance of adult patients harboring a glioma located within eloquent regions by increasing both the survival and the quality of life through functional improvement.
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Neoplasias Encefálicas/cirugía , Glioma/cirugía , Calidad de Vida , Vigilia/fisiología , Adulto , Anciano , Mapeo Encefálico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/fisiopatología , Estimulación Eléctrica/métodos , Femenino , Glioma/patología , Glioma/fisiopatología , Humanos , Monitorización Neurofisiológica Intraoperatoria , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio/métodos , Procedimientos Neuroquirúrgicos/métodos , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Imaging determinations of the spatial extent of diffuse low-grade gliomas (DLGGs) are of paramount importance in evaluating the risk-to-benefit ratio of surgical resection. However, it is not clear how accurately preoperative conventional MRI can delineate DLGGs. METHODS: We report a retrospective histologic and imaging correlation study in 16 adult patients who underwent serial stereotactic biopsies for the diagnosis of untreated supratentorial well-defined and non-contrast-enhanced DLGG, in whom biopsy samples were taken within and beyond (OutBSs) MRI-defined abnormalities. RESULTS: Thirty-seven OutBSs that extended from 10 to 26 mm beyond MRI-defined abnormalities were studied. Immunostaining revealed MIB-1-positive cells (i.e., cycling cells) in all but 2 of the OutBSs. None of the MIB-1-positive cells coexpressed glial fibrillary acidic protein, and all of them coexpressed OLIG2. MIB-1-positive cells were cycling isolated tumor cells, because 1) their morphologic characteristics reflected those of tumor cells, 2) the number of MIB-1-positive cells per square centimeter was significantly higher than that of controls, 3) the number of MIB-1-positive cells per square centimeter was positively correlated with the tumor growth fraction (p = 0.012), and 4) the number of MIB-1-positive cells per square centimeter in OutBSs decreased with distance from the tumor (p = 0.003). CONCLUSIONS: This study demonstrates, using a multiscale correlative approach, that conventional MRI underestimates the actual spatial extent of diffuse low-grade gliomas (DLGGs), even when they are well delineated. These results suggest that an extended resection of a margin beyond MRI-defined abnormalities, whenever feasible in noneloquent brain areas, might improve the outcome of DLGGs.
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Neoplasias Encefálicas/diagnóstico , Encéfalo/patología , Imagen por Resonancia Magnética , Oligodendroglioma/diagnóstico , Adolescente , Adulto , Anticuerpos Antinucleares/metabolismo , Anticuerpos Monoclonales/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Biopsia/métodos , Encéfalo/metabolismo , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Aumento de la Imagen/métodos , Espectroscopía de Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/metabolismo , Proteínas de Neurofilamentos/metabolismo , Factor de Transcripción 2 de los Oligodendrocitos , Protones , Estudios Retrospectivos , Estadística como Asunto , Adulto JovenRESUMEN
The development of inhibitors following factor VIII replacement therapy is a serious complication in severe inherited haemophilia. Whereas significant experience, notably in orthopaedic surgery, is now obtained with the use of bypassing agents in haemophilia with high-titre inhibitor, new surgical challenges might occur due to patients' increasing life expectancy. A 56-year-old severe haemophilia A patient with a high-titre inhibitor was diagnosed for probable right temporoparietal malignant glioneuronal tumour on cerebral magnetic resonance imaging (MRI) (4 cm x 3 cm cerebromeningeal tumour with perilesional oedema and transfalcial herniation) requiring total resection. Then recombinant activated FVII (rFVIIa) was chosen as the haemostatic agent: bolus of 270 microg kg(-1) every 2 h during the first 24 h, 180 microg kg(-1) every 3, 4 and 6 h, respectively, at days 2-3, from days 4-10 and finally from days 11-15. Tranexamic acid was associated. Pre- and postoperative courses were uneventful, the surgical procedure being assessed at optimal haemostatic condition without any unusual haemorrhage on MRI controls, diffuse intravascular coagulation criteria or thromboembolic event. Intensive rFVIIa therapy has shown to be safe and effective in this first reported neurosurgery about a malignant tumour exhibiting to a high-bleeding risk notably in haemophilia with high-titre inhibitor. The use of lower doses of rFVIIa might have been possible; however, in the absence of accurate test for monitoring rFVIIa therapy, the potentially life-threatening complications of this procedure required maximum haemostasis with high rFVIIa doses.
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Inhibidores de Factor de Coagulación Sanguínea/sangre , Neoplasias del Ventrículo Cerebral/cirugía , Factor VIIa/uso terapéutico , Hemofilia A/tratamiento farmacológico , Neoplasias del Ventrículo Cerebral/inmunología , Hemostasis Quirúrgica , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Hemorragia Posoperatoria/prevención & control , Tiempo de Protrombina , Proteínas Recombinantes/uso terapéuticoRESUMEN
BACKGROUND AND PURPOSE: No standard treatment for brainstem cavernoma has been established because of the lack of sufficient data about the natural history of these lesions in a highly functional location with potential difficult surgical accessibility. METHODS: We present a series of 82 brainstem cavernomas managed at the Sainte-Anne Hospital. Surgery was undertaken for 25 with stereotactic biopsy for 9 and direct surgery for 19 (3 after biopsy). RESULTS: Surgical outcome was good or fair for 17 patients. Two patients worsened and one died. Biopsy results were disappointing with high morbidity (4 patients with 2 permanent deficits). Histological diagnostic was possible for all biopsies. CONCLUSION: In light of these results, an active surgical attitude could be proposed for cavernomas in an accessible locations which have produced at least one previous hemorrhage. Stereotactic biopsies for suspect brainstem cavernoma must be avoided.
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Neoplasias del Tronco Encefálico/cirugía , Hemangioma Cavernoso del Sistema Nervioso Central/cirugía , Procedimientos Neuroquirúrgicos , Adolescente , Adulto , Neoplasias del Tronco Encefálico/patología , Niño , Femenino , Francia , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Radiocirugia , Resultado del TratamientoRESUMEN
The WHO classification divides meningiomas in three grades. In grade 1 tumors, by far the most common (90 p. cent), inactivation of the NF2 gene (associated to the loss of chromosome 22) is the most frequent alteration. However, a subset of grade 1 meningiomas does not involve the NF2 gene and is less likely to evolve towards higher grade tumors. After NF2 inactivation, additional events may occur and are related to greater aggressiveness, such as loss of 1p, 14q, 10 q and 9p chromosomes, reactivation of telomerase, inactivation of the p16/CDKN2A gene. All these alterations are much more frequent in grades 2 (atypical) and 3 (malignant) of the WHO classification. In addition to reviewing the available literature, we pooled together the individual cases in order to refine the correlation between genotype and phenotype (histological grading, location) and to propose a model for tumoral progression of meningiomas.