Impact of radiotherapy delay on survival in glioblastoma

BACKGROUND: Previous studies in glioblastoma have concluded that there is no decrease in survival with increasing time to initiation of RT up to 6 weeks after surgery. Unfortunately, the number of glioblastoma patients who start RT beyond 6 weeks is not small in some countries. The aim of our study was to evaluate the effect of RT delay beyond 6 weeks on survival of patients who have undergone completed resection of a glioblastoma. METHODS: We reviewed 107 consecutive glioblastoma patients who had a complete surgical resection at our hospital. Clinical data, including delay in initiation of RT, were prospectively collected. The impact of single parameters on overall survival was determined by univariate and multivariate analyses. RESULTS: According to univariate analysis, variables that had a prognostic influence on survival were age (p = 0.036), KPS (p = 0.031), additional treatment with CHT (p < 0.0001), and initiation of RT before 42 days (p = 0.009). Multivariate analysis indicated that Karnofsky performance scale, additional treatment with chemotherapy, and initiation of RT before 6 weeks after surgery were favorable, independent prognostic factors of survival. CONCLUSIONS: Survival is significantly reduced in glioblastoma patients if RT is not initiated within the 6 weeks after complete resection of the tumor (AU)

Simple fMRI postprocessing suffices for normal clinical practice.

BACKGROUND AND PURPOSE: Whereas fMRI postprocessing tools used in research are accurate but unwieldy, those used for clinical practice are user-friendly but are less accurate. We aimed to determine whether commercial software for fMRI postprocessing is accurate enough for clinical practice. METHODS: Ten volunteers underwent fMRI while performing motor and language tasks (hand, foot, and orolingual movements; verbal fluency; semantic judgment; and oral comprehension). We compared visual concordance, image quality (noise), voxel size, and radiologist preference for the activation maps obtained by using Neuro3D software (provided with our MR imaging scanner) and by using the SPM program commonly used in research. RESULTS: Maps obtained with the 2 methods were classified as "partially overlapping" for 70% for motor and 72% for language paradigm experiments and as "overlapping" in 30% of motor and in 15% of language paradigm experiments. CONCLUSIONS: fMRI is a helpful and robust tool in clinical practice for planning neurosurgery. Widely available commercial fMRI software can provide reliable information for therapeutic management, so sophisticated, less widely available software is unnecessary in most cases.

Does gender matter in glioblastoma?

BACKGROUND The clinical outcome of glioblastoma (GBM) patients who receive radiotherapy alone or with chemotherapy is well established. However, little is known about how many patients do not receive this treatment. We consider it is important to investigate why a proportion of operated patients do not receive further treatment after surgery. METHODS We reviewed all consecutive GBM patients operated on in our hospital between January 2000 and December 2008. RESULTS A total of 216 patients with GBM were identified. Fifty-five (25%) did not receive any treatment after surgery. Univariate analysis showed that factors associated with no further treatment after surgery were older than 60 years (p=0.002), of female gender (p=0.03), had a KPS<70 (p<0.001) and had had a biopsy (p<0.001). Multivariate analysis indicated that age =60 years and KPS <70 were independent predictors of no further treatment after surgery. Gender was not an independent variable. However, women in the whole series were older than 60 years (p=0.01), and they had a worse KPS (p=0.02) and more biopsies (p=0.04) than men. In the whole group, median survival time was 10.4 months for men (n=125) vs. 7.2 months for women (n=91), log rank p<0.04. This difference was not observed in the group that was treated after surgery. CONCLUSIONS One out of four patients could not be treated after surgery. Independent predictors were older age and low KPS. These poor risk variables were more frequent in women and their survival was therefore lower than men in our series (AU)

[Intraoperative videoangiography using green indocyanine during aneurysm surgery]. / Videoangiografía intraoperatoria con verde de indocianina durante la cirugía de aneurismas cerebrales. Experiencia inicial en 10 intervenciones quirúrgicas.

OBJECTIVE: The authors' objective is to report the initial appreciations on the use of the intraoperative near-infrared indocyanine green videoangiography during aneurysm surgery in our center. METHOD: 10 surgical procedures have been made in 9 patients, 5 males and 4 females between 27 and 61 years old with an average of age of 49 years during a time of 10 months between March, 2008 and January, 2009. 10 surgical procedures were performed and 11 aneurysms were clipped. Intravenous indocyanine green and surgical microscope Leica OH4 with module of vascular fluorescence intraoperating Leica FL800, with camera infrared Sony (Heerbrugg-Switzerland) were used. The information offered by this technique during the intervention is compared with the images of the postoperative angiography performed during the first 24 hours. The partial or complete occlusion and the respect to the near vessels were evaluated. RESULTS: The findings of the intraoperative videoangiography were the complete occlusion and absence of complications in all the cases. These results corresponded completely with the postoperative results of the angiography postoperative, except in a case where the angiography demonstrated vasoespasmo moderate without clinical repercussion that during the videoangiografía intraoperatoria was not perceived. Clinically no patient presented neurological added deficits. CONCLUSIONS: The intraoperative videoangiography is a tool of easy application that offers valuable information as for the complete occlusion of the aneurysm and the permeability of the adjacent vessels.

Videoangiografía intraoperatoria con verde de indocianina durante la cirugía deaneurismas cerebrales. Experiencia inicial en 10 intervenciones quirúrgicas / No disponible

Objetivo. El objetivo de los autores es reportar nuestra experiencia inicial sobre la utilización de la videoangiografía intraoperatoria con verde de indocianina durante la cirugía de aneurismas cerebrales en nuestrocentro. Material y métodos. Se han realizado 10 procedimientos quirúrgicos en 9 pacientes, 5 varones y 4 mujeres entre 27 y 61 años con una media de edad de 49 años durante un tiempo de 10 meses entre marzo de 2008 y enero de2009. Se realizaron 10 intervenciones y se cliparon 11aneurismas, de los cuales 5 fueron diagnosticados tras su ruptura y 6 no. Se utilizaron verde de indocianina intravenosa y microscopio quirúrgico Leica OH4 con módulo de fluorescencia vascular intraoperatoria Leica FL800, con cámara infrarroja Sony (Heerbrugg-Suiza).Se recoge la información ofrecida por esta técnica durante la intervención y se compara con las imágenes de la arteriografía postoperatoria a las 24 horas. Se valoraron la oclusión total o parcial de la lesión aneurismática así como la preservación o no de la vascularización adyacente. Resultados. Los hallazgos de la videoangiografía intraoperatoria sobre las lesiones aneurismáticas fueron de oclusión completa en todos los casos y permeabilidad de los vasos vecinos. Estos resultados se corresponden completamente con los de la arteriografía postoperatoria,excepto en un caso donde la arteriografía evidenció vasoespasmo moderado-grave sin repercusión clínica que durante la videoangiografía intraoperatoriano fue percibido. Clínicamente ningún paciente presentó déficits neurológicos añadidos.Conclusiones. La videoangiografía intraoperatoria es una herramienta de fácil aplicación que ofrece información valiosa en cuanto a la oclusión completa del saco aneurismático y la permeabilidad de los vasos adyacentesa éste (AU)

Objective. The authors’ objective is to report the initialappreciations on the use of the intraoperative near infraredindocyanine green videoangiography during aneurysm surgery in our center.Method. 10 surgical procedures have been made in 9 patients, 5 males and 4 females between 27 and 61 years old with an average of age of 49 years during a time of 10 months between March, 2008 and January, 2009. 10 surgical procedures were performed and 11 aneurysms were clipped. Intravenous indocyanine green and surgical microscope LeicaOH4 with module of vascular fluorescence intraoperating Leica FL800, with camera infrared Sony (Heerbrugg-Switzerland)were used. The information offered by this techniqueduring the intervention is compared with the images of the postoperative angiography performed during the first 24hours. The partial or complete occlusion and the respect to the near vessels were evaluated. Results. The findings of the intraoperative videoangiography were the complete occlusion and absence of complications in all the cases. These results corresponded completely with the postoperative results of the angiography postoperative, except in a case where the angiography demonstrated vasoespasmo moderate without clinical repercussion that during the videoangiografía intraoperatoria was not perceived. Clinically no patient presented neurological added deficits.Conclusions. The intraoperative videoangiographyis a tool of easy application that offers valuable informationas for the complete occlusion of the aneurysmand the permeability of the adjacent vessels (AU)

[Importance of monitoring neuroendoscopic intracranial pressure during anesthesia for neuroendoscopic surgery: review of 101 cases]. / Importancia de la monitorización de la "presión intracraneal dentro del neuroendoscopio" durante el tratamiento anestésico de la cirugía neuroendoscópica. Experiencia en 101 casos.

OBJECTIVE: The aim of this study was to describe monitoring, anesthetic management, and risk factors for complications in neuroendoscopic surgery. PATIENTS AND METHODS: Patients who underwent neuroendoscopy between 1994 and 2003 under general anesthesia, with monitoring of intracranial pressure from inside the neuroendoscope, were studied retrospectively. In some patients, the blood flow rate in the middle cerebral artery was monitored using transcranial Doppler ultrasound. Information was collected related to surgical procedure and the development of complications. RESULTS: Of 101 patients included in the study, transcranial Doppler ultrasound images were available for 20. In 75 patients neuroendoscopic intracranial pressure exceeded 20 mm Hg. Forty-five percent of the patients with available transcranial Doppler ultrasound images showed episodes of reduced diastolic flow rate in the middle cerebral artery during ventricular irrigation. Hemodynamic instability was associated with higher neuroendoscopic intracranial pressures (P < .05). An increase of more than 30 mm Hg in neuroendoscopic intracranial pressure was associated with more postoperative complications, the most common of which was delayed awakening. Procedures that were more complicated than a simple ventriculostomy were performed in 58% of the cases. Mean (SD) neuroendoscopic intracranial pressures in such cases were higher (50.5 [30.9] mm Hg vs 31.8 [25.1 mm Hg] in the simpler procedures) and the postoperative complication rate was higher (P = .003). CONCLUSIONS: Neuroendoscopic surgery can causes increases in neuroendoscopic intracranial pressure that are associated with disturbances in cerebral blood flow and complications. This situation demonstrates the importance of monitoring intracranial pressure and cerebral blood flow.

Importancia de la monitorización de la “presión intracraneal dentro del neuroendoscopio” durante el tratamiento anestésico de la cirugía neuroendoscópica. Experiencia en 101 casos / Importance of monitoring neuroendoscopic intracranial pressure during anesthesia for neuroendoscopic surgery: review of 101 cases

OBJETIVOS: El objetivo del estudio es describir la monitorización específica, el manejo anestésico, y los factores predictivos de complicaciones en la cirugía neuroendoscópica.PACIENTES Y MÉTODOS: Estudiamos retrospectivamente a los pacientes sometidos a neuroendoscopia con anestesiageneral, con monitorización del valor de la presiónen el interior del neuroendoscopio, desde 1994 hasta2003. En algunos casos se monitorizó además la velocidaddel flujo sanguíneo de la arteria cerebral mediamediante doppler transcraneal. Se registró el procedimientoquirúrgico y la aparición de complicaciones.RESULTADOS: Se incluyeron 101 pacientes, 20 conregistro de doppler transcraneal. En 75 pacientes, la presiónen el interior del neuroendoscopio presentó valoressuperiores a 20 mmHg. El 45% de los pacientes con dopplertranscraneal presentaron episodios de disminuciónde velocidad diastólica de la arteria cerebral mediadurante la irrigación ventricular. La aparición de alteracioneshemodinámicas se asoció a valores más elevadosde presión en el interior del neuroendoscopio (p < 0,05).El aumento de presión en el interior del neuroendoscopiomayor de 30 mmHg, se asoció con el aumento decomplicaciones postoperatorias, siendo la más frecuenteel retraso en el despertar. En el 58% de los casos se realizaron procedimientos quirúrgicos más complejos queuna ventriculostomía simple. En estos casos, los valores de presión en el interior del neuroendoscopio fueron máselevados comparado con las ventriculostomías simples(50,5 ± 30,9 frente a 31,8 ± 25,1 mmHg; p = 0,001) y se asociaron a una aparición de más complicaciones en elpostoperatorio (p=0,003). CONCLUSIONES: La cirugía neuroendoscópica puede provocar aumentos de presión en el interior del neuroendoscopio que se asocia a alteraciones del flujo sanguíneocerebral y la aparición de complicaciones, lo que apoya la importancia de la monitorización de la presión intracraneal y el flujo sanguíneo cerebral(AU)

OBJECTIVE: The aim of this study was to describemonitoring, anesthetic management, and risk factors forcomplications in neuroendoscopic surgery.PATIENTS AND METHODS: Patients who underwentneuroendoscopy between 1994 and 2003 under generalanesthesia, with monitoring of intracranial pressurefrom inside the neuroendoscope, were studiedretrospectively. In some patients, the blood flow rate inthe middle cerebral artery was monitored usingtranscranial Doppler ultrasound. Information wascollected related to surgical procedure and thedevelopment of complications.RESULTS: Of 101 patients included in the study,transcranial Doppler ultrasound images were availablefor 20. In 75 patients neuroendoscopic intracranialpressure exceeded 20 mm Hg. Forty-five percent of thepatients with available transcranial Doppler ultrasoundimages showed episodes of reduced diastolic flow rate inthe middle cerebral artery during ventricular irrigation.Hemodynamic instability was associated with higherneuroendoscopic intracranial pressures (P<.05). Anincrease of more than 30 mm Hg in neuroendoscopicintracranial pressure was associated with morepostoperative complications, the most common of whichwas delayed awakening. Procedures that were morecomplicated than a simple ventriculostomy wereperformed in 58% of the cases. Mean (SD)neuroendoscopic intracranial pressures in such caseswere higher (50.5 [30.9] mm Hg vs 31.8 [25.1 mm Hg] inthe simpler procedures) and the postoperativecomplication rate was higher (P=.003).CONCLUSIONS: Neuroendoscopic surgery can causesincreases in neuroendoscopic intracranial pressure thatare associated with disturbances in cerebral blood flowand complications. This situation demonstrates theimportance of monitoring intracranial pressure andcerebral blood flow(AU)

Cerebrospinal fluid composition modifications after neuroendoscopic procedures.

Normal saline solution is currently used as the ventricular irrigation fluid during neuroendoscopic procedures. The aim of this study is to determine the alterations in the cerebrospinal fluid (CSF) composition after neuroendoscopic interventions. Twenty nine patients who underwent a neuroendoscopic procedure under general anaesthesia were studied. Temperature inside the cerebral ventricle was measured and samples of CSF were taken to determinate oxygen and carbon dioxide partial pressures, pH, base excess, ionised calcium, standard bicarbonate, glucose, sodium, potassium, magnesium, total calcium, proteins, chlorine and osmolality before initiating the irrigation and after the neuronavigation. Patient demographics, neuronavigation time, total fluid volume used and temperature of the irrigation solution and complications that appeared in the first 24 hours were collected. Mean age of the patients was 42+/-18 years. The mean neuronavigation time was 21.5+/-15.4 minutes. The mean amount of saline solution used for irrigation was 919.6+/-994.7 mL. All the values studied in the CSF, except osmolality, showed significant variations. There was a significant correlation between the CSF variation of pH, oxygen and carbon dioxide partial pressures, base excess, standard bicarbonate, glucose and total calcium with respect to the total volume of irrigation solution, but not with respect to the neuronavigation time. A cut-off point of 500 mL of irrigation solution (sensitivity 0.7; specificity 0.87) was related with a CSF pH decrease greater than 0.2. The use of saline as irrigation solution during neuroendoscopic procedures produces important changes in CSF.

Episodic high irrigation pressure during surgical neuroendoscopy may cause intermittent intracranial circulatory insufficiency.

Intermittent high peak pressure values inside the endoscope during neuroendoscopic surgical procedures are associated with postoperative morbidity. Unexpected delay in awakening is the complication most frequently observed by the anesthesiologist as a result of high peak pressure values inside the endoscope. During eight neuroendoscopic procedures the authors continuously monitored cerebral hemodynamic function, using a transcranial doppler (TCD) probe fixed on patients' temporal window. We observed that episodes of high peak pressure values inside the endoscope during neuroendoscopic navigation rinsing periods resulted in changes in the TCD wave profile consistent with "near intracranial circulatory arrestlike" wave. No systemic hemodynamic warning signs accompanied these intermittent episodes of severe decrease in cerebral perfusion pressure. When the rinsing liquid was allowed to escape, the pressure inside the endoscope decreased and the TCD wave immediately returned to its previous value. Neuroendoscopic procedures, although classified as minimally invasive surgery, warrant special monitoring that could alert us to a decrease in cerebral perfusion pressure. Middle cerebral artery TCD recording is a reliable and accurate tool for this purpose.

Factors influencing surgical complications of intra-axial brain tumours.

OBJECT: Extensive surgical resection remains nowadays the best treatment available for most intra-axial brain tumours. However, postoperative sequelae can outweigh the potential benefits of surgery. The goal of this study has been to review the results of this treatment in our Department in order to quantify morbidity and mortality and determine predictive risk factors for each patient. METHOD: We report a retrospective study of 200 patients submitted to a craniotomy for intra-axial brain tumours including gliomas and metastases. Postoperative major complications are analysed and related to different variables. An exhaustive review of the literature concerning the main controversial points about primary and metastatic brain tumours surgery is done. FINDINGS: The overall major complication rate was 27.5%, with neurological complications being the most frequently encountered. We did not find a statistically significant relation between them and the grade of eloquence of the tumoural area. Infratentorial tumour location, previous radiotherapy and reoperations were factors strongly related to the incidence of regional complications. Age over 60 and severe concomitant disease were risk factors for systemic complications. INTERPRETATION: The results from published series concerning surgical complications after craniotomies for brain tumours are not comparable because of the lack of homogeneity between them. The knowledge of the complications rate in each particular neurosurgical department turns out essentially to provide the patient with tailored information about risks before surgery.

Anesthetic management of surgical neuroendoscopies: usefulness of monitoring the pressure inside the neuroendoscope.

Neuroendoscopic procedures are increasing in frequency in neurosurgical practice. We describe the anesthetic technique and the perioperative complications found in 100 neuroendoscopic interventions performed at our institution. Cranial tumor biopsy or retrieval (62%) and cisternostomy for hydrocephalus (33%) were the most frequent indications for neuroendoscopy. The mortality rate was low (1%). Intraoperative complications occurred in 36 patients, with arterial hypertension being the most frequent (53%). Postoperative complications occurred in 52 patients; anisocoria (31%) and delayed arousal (29%) were the most frequent. The pressure inside the endoscope was monitored intraoperatively in the last 47 patients. A saline-filled catheter from a pressure transducer connected to the neuroendoscopy system was used for pressure monitoring. We recorded the highest peak of pressure values measured during each procedure. Twenty-three patients (49%) had peak pressure values >30 mm Hg, 12 patients (25%) >50 mm Hg, and 3 patients >100 mm Hg. Only one patient had hemodynamic changes occurring simultaneously with the pressure changes. We found an association between pressure inside the endoscope >30 mm Hg and postoperative (P = .003) but not intraoperative complications. A relationship was found between surgical duration and postoperative complications (P = .002). Neither the pressure inside the endoscope or the intraoperative morbidity were related to surgical duration. We conclude that there may be a high rate of postoperative complications after neuroendoscopies, namely, new neurologic deficits. High pressure levels inside the endoscope during neuroendoscopic procedures can occur without hemodynamic warning signs. Pressure values >30 mm Hg are associated with postoperative morbidity, especially unexpected delayed recovery. Measuring the pressure inside the endoscope is technically easy and might be beneficial if performed in all neuroendoscopic procedures. Reducing the incidence of episodes of high peak pressure values might decrease the rate of postoperative complications.

Efficacy of radiotherapy for malignant gliomas in elderly patients.

PURPOSE: Age above 65 years is a strong negative prognostic factor for survival in patients with malignant gliomas (MG) treated with radiotherapy (RT) and its value has been questioned. We analyzed the effect of RT on the survival of elderly patients with malignant gliomas. METHODS AND MATERIALS: We examined 85 consecutive elderly patients with a histological diagnosis of MG. Age ranged from 65 to 81 years (median 70 years). Glioblastoma multiforme (GBM) was diagnosed in 64 patients (75.3%). Surgical treatment included needle biopsy in 32 patients (37.6%). Median postoperative Karnofsky Performance Status (KPS) was 60 (range: 30-100). Survival probability was estimated using Kaplan-Meier method and compared with the log-rank test. Crude and adjusted hazard ratios (HR) were calculated using Cox's regression models. RESULTS: Median survival time for all patients was 18.1 weeks. In multivariate analysis, RT was the only independent prognostic variable for survival (HR: 9.1 [95% CI: 4.5-18.7]). Forty-two patients did not start RT mostly due to low KPS (<50). The median survival of the 43 patients who started RT was 45 weeks. In these patients, Cox multivariate analysis indicated that age was independently associated with prolonged survival (HR: 2.85 [95% CI 1.31-6.19]). Median survival of patients age 70 years and younger was 55 weeks compared with 34 weeks for patients older than 70 years. CONCLUSIONS: The overall survival for elderly patients with MG is poor. RT seems to improve survival in patients up to 70 years, but in older patients treated with RT the survival is significantly shorter.

Neuroendoscopic management of pineal region tumours.

The management of pineal tumours remains controversial. During 1994 we treated four consecutive adults (16-44 yrs) harbouring a pineal tumour with a neuroendoscopic procedure. All of them presented with hydrocephalus. Pre-operative workup included cranial computerized tomography (CT), craniospinal magnetic resonance imaging (MRI) and serum levels of biological tumour markers. The endoscopic procedure consisted of a third ventriculostomy followed by biopsy with a flexible, steerable neuroendoscope. Histological diagnosis was achieved in three patients who no longer required a shunt device. Recorded complications were: bleeding during ventriculostomy that prevented us from obtaining a good sample for biopsy, short-term memory loss that cleared over a two-week period, and transient increase of pre-operative hemiparesis. Complications and morbidity are emphasized so as to be avoided with further technical experience. Neuroendoscopy affords a minimally invasive way of reaching three objectives by one-step surgery in the management of pineal region lesions: 1) CSF sample for analysis of tumour markers. 2) Treatment of hydrocephalus by third ventriculostomy. 3) Several biopsy specimens can be obtained identifying tumours which will require further open surgery or adjuvant radiation and/or chemotherapy.

[Surgical treatment combined with radiotherapy and chemotherapy in an unselected population of patients with malignant glioma]. / Tratamiento quirúrgico combinado con radioterapia y quimioterapia en una población no seleccionada de pacientes con glioma maligno.

BACKGROUND: Malignant gliomas are tumors of bad prognosis with a mean survival of 12 months. In the present report 74 patients diagnosed of malignant glioma were studied with the following aims: 1) evaluate how many could receive combined radiotherapy (RT) and chemotherapy (BCNU) treatment following surgery and 2) analyze whether the patients treated presented a survival similar to that described in the literature. METHODS: The records of 74 patients operated on for malignant glioma between 1987-1990 and consecutively included in a protocol of treatment with RT and BCNU were reviewed. RESULTS: Out of the total of 74 patients, 29 (39%) were considered evaluable. The medians of progression free interval and survival were of 10 and 16 months, respectively in these patients. Forty-five (61%) patients could not fulfill the protocol mainly because of tumoral progression prior to completion of RT and severe post surgical complications. The evaluable patients were significantly younger (p = 0.004) and tumoral exeresis wider (p = 0.0003) than in those who were not evaluable. CONCLUSIONS: Most of the patients operated on for malignant glioma may not receive treatment considered as standard, principally due to tumor progression in the first weeks following surgery and the presence of severe post surgical complications.