Full kinetic modeling analysis of [18F]fluorocholine Positron Emission Tomography (PET) at initial diagnosis of high-grade glioma.

PURPOSE: The main objective was to characterize the tracer uptake kinetics of [18F]fluoromethylcholine ([18F]F-CHO) in high-grade gliomas (HGG) through a full PET kinetic modeling approach. Secondarily, we aimed to explore the relationship between the PET uptake measures and the HGG molecular features. MATERIALS AND METHODS: Twenty-four patients with a suspected diagnosis of HGG were prospectively included. They underwent a dynamic brain [18F]F-CHO-PET/CT, from which a tumoral time-activity curve was extracted. The plasma input function was obtained through arterial blood sampling with metabolite correction. These data were fitted to 1- and 2-tissue-compartment models, the best of which was selected through the Akaike information criterion. We assessed the correlation between the kinetic parameters and the conventional static PET metrics (SUVmax, SUVmean and tumor-to-background ratio TBR). We explored the association between the [18F]F-CHO-PET quantitative parameters and relevant molecular biomarkers in HGG. RESULTS: Tumoral time-activity curves in all patients showed a rapid rise of [18F]F-CHO uptake followed by a plateau-like shape. Best fits were obtained with near-irreversible 2-tissue-compartment models. The perfusion-transport constant K1 and the net influx rate Ki showed strong correlation with SUVmax (r = 0.808-0.861), SUVmean (r = 0.794-0.851) and TBR (r = 0.643-0.784), p < 0.002. HGG was confirmed in 21 patients, of which those with methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter showed higher mean Ki (p = 0.020), K1 (p = 0.025) and TBR (p = 0.001) than the unmethylated ones. CONCLUSION: [18F]F-CHO uptake kinetics in HGG is best explained by a 2-tissue-compartment model. The conventional static [18F]F-CHO-PET measures have been validated against the perfusion-transport constant (K1) and the net influx rate (Ki) derived from kinetic modeling. A relationship between [18F]F-CHO uptake rate and MGMT methylation is suggested but needs further confirmation.

Analyzing the role of reoperation in recurrent glioblastoma: a 15-year retrospective study in a single institution.

BACKGROUND: Multiple treatment options at glioblastoma progression exist, including reintervention, reirradiation, additional systemic therapy, and novel strategies. No alternative has been proven to be superior in terms of postprogression survival (PPS). A second surgery has shown conflicting evidence in the literature regarding its prognostic impact, possibly affected by selection bias, and might benefit a sparse subset of patients with recurrent glioblastoma. The present study aims to determine the prognostic influence of salvage procedures in a cohort of patients treated in the same institution over 15 years. METHODS: Three hundred and fifty patients with confirmed primary glioblastoma diagnosed and treated between 2005 and 2019 were selected. To examine the role of reoperation, we intended to create comparable groups, previously excluding all diagnostic biopsies and patients who were not actively treated after the first surgery or at disease progression. Uni- and multivariate Cox proportional hazards regression models were employed, considering reintervention as a time-fixed or time-dependent covariate. The endpoints of the study were overall survival (OS) and PPS. RESULTS: At progression, 33 patients received a second surgery and 84 were treated with chemotherapy only. Clinical variables were similar among groups. OS, but not PPS, was superior in the reintervention group. Treatment modality had no impact in our multivariate Cox regression models considering OS or PPS as the endpoint. CONCLUSIONS: The association of reoperation with improved prognosis in recurrent glioblastoma is unclear and may be influenced by selection bias. Regardless of our selective indications and high gross total resection rates in second procedures, we could not observe a survival advantage.

Use of diffusion tensor imaging to assess the vasogenic edema in traumatic pericontusional tissue / Uso de la resonancia de tensor de difusión para estudiar el edema vasogénico pericontusional

Background and objective Cerebral edema is a frequent and serious complication of traumatic brain injury (TBI). Diffusion tensor imaging (DTI) is considered a useful technique to assess white matter integrity after TBI. The objective of this prospective, observational study was to assess the characteristics of the vasogenic edema in the traumatic pericontusional tissue and compare it to the vasogenic edema found in brain tumors. We also included a control group. Methods Using DTI, the Apparent diffusion coefficient (ADC) and Fractional anisotropy (FA) were measured in the area of vasogenic edema in both TBI and tumor patients. The measurements in the control group were done in the gray and white matter. We included 15 TBI patients, 18 tumor patients and 15 controls. Results ADC and FA showed no differences between TBI and tumor patients (p=0.27 for AF; p=0.79 for ADC). Compared to healthy controls, TBI and tumor patients presented higher ADC values and lower FA values. The differences between TBI and controls were statistically significant (p<0.05). Conclusions In this prospective observational study using DTI-MRI in a selected group of mild and moderate TBI patients with vasogenic pericontusional edema we have shown that there were no significant differences of the ADC and FA values compared to brain tumor patients. Furthermore, healthy controls showed significant lower ADC values and higher FA values compared to TBI and tumor patients. Future studies, using DTI-MRI, should address whether any therapy has a favorable impact on the vasogenic edema of TBI patients with brain contusions (AU)

Antecedentes y objetivo El edema cerebral es una complicación grave y frecuente en pacientes con traumatismo craneoencefálico (TCE). La resonancia de tensor de difusión (DTI-RM) es considerada como una técnica de imagen muy útil para valorar la integridad de la sustancia blanca tras un TCE. El objetivo de este estudio prospectivo y observacional es valorar las características del edema vasogénico pericontusional de pacientes traumáticos y comparar dichas zonas con el edema vasogénico de pacientes con tumores cerebrales. También se ha incluido un grupo control. Pacientes y métodos Se ha empleado la DTI-RM para cuantificar el coeficiente de difusión aparente (ADC) y la anisotropía fraccional (AF) en las zonas de edema vasogénico en pacientes con contusiones cerebrales traumáticas y tumores cerebrales. Las mediciones del grupo control se hicieron tanto en la sustancia gris como en la sustancia blanca. Se incluyeron 15 pacientes con TCE, 18 pacientes con tumores cerebrales y 15 controles. Resultados Los valores del ADC y de la AF fueron similares en los pacientes con TCE y tumores cerebrales (p=0.27 para los valores de AF; p=0,79 para los valores de ADC). Respecto a los controles, tanto los pacientes con TCE como con tumores cerebrales presentaron valores más elevados del ADC y valores más bajos de la AF. Las diferencias en estas variables entre los pacientes con TCE y los controles fueron estadísticamente significativas (p<0,05) (AU)

Use of diffusion tensor imaging to assess the vasogenic edema in traumatic pericontusional tissue.

BACKGROUND AND OBJECTIVE: Cerebral edema is a frequent and serious complication of traumatic brain injury (TBI). Diffusion tensor imaging (DTI) is considered a useful technique to assess white matter integrity after TBI. The objective of this prospective, observational study was to assess the characteristics of the vasogenic edema in the traumatic pericontusional tissue and compare it to the vasogenic edema found in brain tumors. We also included a control group. METHODS: Using DTI, the Apparent diffusion coefficient (ADC) and Fractional anisotropy (FA) were measured in the area of vasogenic edema in both TBI and tumor patients. The measurements in the control group were done in the gray and white matter. We included 15 TBI patients, 18 tumor patients and 15 controls. RESULTS: ADC and FA showed no differences between TBI and tumor patients (p=0.27 for AF; p=0.79 for ADC). Compared to healthy controls, TBI and tumor patients presented higher ADC values and lower FA values. The differences between TBI and controls were statistically significant (p<0.05). CONCLUSIONS: In this prospective observational study using DTI-MRI in a selected group of mild and moderate TBI patients with vasogenic pericontusional edema we have shown that there were no significant differences of the ADC and FA values compared to brain tumor patients. Furthermore, healthy controls showed significant lower ADC values and higher FA values compared to TBI and tumor patients. Future studies, using DTI-MRI, should address whether any therapy has a favorable impact on the vasogenic edema of TBI patients with brain contusions.

Use of diffusion tensor imaging to assess the vasogenic edema in traumatic pericontusional tissue.

BACKGROUND AND OBJECTIVE: Cerebral edema is a frequent and serious complication of traumatic brain injury (TBI). Diffusion tensor imaging (DTI) is considered a useful technique to assess white matter integrity after TBI. The objective of this prospective, observational study was to assess the characteristics of the vasogenic edema in the traumatic pericontusional tissue and compare it to the vasogenic edema found in brain tumors. We also included a control group. METHODS: Using DTI, the Apparent diffusion coefficient (ADC) and Fractional anisotropy (FA) were measured in the area of vasogenic edema in both TBI and tumor patients. The measurements in the control group were done in the gray and white matter. We included 15 TBI patients, 18 tumor patients and 15 controls. RESULTS: ADC and FA showed no differences between TBI and tumor patients (p=0.27 for AF; p=0.79 for ADC). Compared to healthy controls, TBI and tumor patients presented higher ADC values and lower FA values. The differences between TBI and controls were statistically significant (p<0.05). CONCLUSIONS: In this prospective observational study using DTI-MRI in a selected group of mild and moderate TBI patients with vasogenic pericontusional edema we have shown that there were no significant differences of the ADC and FA values compared to brain tumor patients. Furthermore, healthy controls showed significant lower ADC values and higher FA values compared to TBI and tumor patients. Future studies, using DTI-MRI, should address whether any therapy has a favorable impact on the vasogenic edema of TBI patients with brain contusions.

Variability of Clinical and Angiographic Results Based on the Treatment Preference (Endovascular or Surgical) of Centers Participating in the Subarachnoid Hemorrhage Database of the Working Group of the Spanish Society of Neurosurgery.

OBJECTIVES: Since the introduction of endovascular treatment for cerebral aneurysms, hospitals in which subarachnoid hemorrhage is treated show different availability and/or preferences towards both treatment modalities. The main aim is to evaluate the clinical and angiographic results according to the hospital's treatment preferences applied. METHODS: This study was conducted based on use of the subarachnoid hemorrhage database of the Vascular Pathology Group of the Spanish Neurosurgery Society. Centers were classified into 3 subtypes according to an index in the relationship between endovascular and surgical treatment as: endovascular preference, high endovascular preference, and elevated surgical preference. The clinical results and angiographic results were evaluated among the 3 treatment strategies. RESULTS: From November 2004 to December 2017, 4282 subarachnoid hemorrhage patients were selected for the study: 630 (14.7%) patients from centers with surgical preference, 2766 (64.6%) from centers with endovascular preference, and 886 (20.7%) from centers with high endovascular preference. The surgical preference group obtained the best angiographic results associated with a greater complete exclusion (odds ratio: 1.359; 95% confidence interval: 1.025-1.801; P = 0.033). The surgical preference subgroup obtained the best outcome at discharge (65.45%), followed by the high endovascular preference group (61.5%) and the endovascular preference group (57.8%) (odds ratio: 1.359; 95% confidence interval: 1.025-1.801; P = 0.033). CONCLUSIONS: In Spain, there is significant variability in aneurysm exclusion treatment in aneurysmal subarachnoid hemorrhage. Surgical centers offer better results for both surgical and endovascular patients. A multidisciplinary approach and the maintenance of an elevated quality of surgical competence could be responsible for these results.

The tumor suppressor FOXO3a mediates the response to EGFR inhibition in glioblastoma cells.

PURPOSE: Although EGFR activation is a hallmark of glioblastoma (GBM), anti-EGFR therapy has so far not yielded the desired effects. Targeting PI3K/Akt has been proposed as a strategy to increase the cellular sensitivity to EGFR inhibitors. Here we evaluated the contribution of FOXO3a, a key Akt target, in the response of GBM cells to EGFR inhibition. METHODS: FOXO3a activation was assessed by immunofluorescence and gene reporter assays, and by evaluating target gene expression using Western blotting and qRT-PCR. Cellular effects were evaluated using cell viability and apoptosis assays, i.e., Annexin V/PI staining and caspase 3/7 activity measurements. Drug synergism was evaluated by performing isobolographic analyses. Gene silencing experiments were performed using stable shRNA transfections. RESULTS: We found that EGFR inhibition in GBM cells led to FOXO3a activation and to transcriptional modulation of its key targets, including repression of the oncogene FOXM1. In addition, we found that specific FOXO3a activation recapitulated the molecular effects of EGFR inhibition, and that the FOXO3a activator trifluoperazine, a FDA-approved antipsychotic agent, reduced GBM cell growth. Subsequent isobolographic analyses of combination experiments indicated that trifluoperazine and erlotinib cooperated synergistically and that their concomitant treatment induced a robust activation of FOXO3a, leading to apoptosis in GBM cells. Using gene silencing, we found that FOXO3a is essential for the response of GBM cells to EGFR inhibition. CONCLUSIONS: Our data indicate that FOXO3a activation is a crucial event in the response of GBM cells to EGFR inhibition, suggesting that FOXO3a may serve as an actionable therapeutic target that can be modulated using FDA-approved drugs.

Sobre las complicaciones de las biopsias cerebrales / The complications of brain biopsies

No disponible

"Intrasellar Balloon Technique" in intraoperative MRI guided transsphenoidal endoscopic surgery for sellar region tumors. Usefulness on image interpretation and extent of resection evaluation. Technical note.

BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) is an effective and proven tool in transsphenoidal endoscopic surgery. However, image interpretation is not always easy and can be hindered by the presence of blood, tumor remains or the displacement of surrounding structures. In this article we present a novel technique based on using intrasellar ballons to reduce these difficulties and facilitate the surgeon's intraoperative assessment by iMRI. METHODS: Eighteen patients with pituitary macroadenomas underwent transsphenoidal surgery during 2013-2014 under low-field iMRI control (PoleStar N20, 0.15 T). Intrasellar balloons were used in all of them to assess the presence of tumoral remnants. We compared the findings in iMRI and postoperative high-field MRI control scans and also analyzed the number of intermediate imaging controls needed during surgery using this technique. RESULTS: In total, of the 18 patients, 14 underwent a complete resection. In the remaining four patients, a safe maximal resection was performed, leaving a remnant because of cavernous sinus invasion. In all cases, the balloons were a major help in distinguishing the anatomical structures from the tumoral remnants. Fewer imaging controls were required, and there were no false-positives or negative intraoperative findings. No complications related to the technique were registered. CONCLUSION: The "intrasellar balloon technique" is a useful tool that facilitates surgeons' intraoperative decision making. It is an important contribution to overcome the limitations of low-field iMRI as it provides a precise delineation of the resection margins, reduces false-positives and -negatives, and decreases the number of intermediate imaging controls required.

Direct observation during surgery shows preservation of cerebral microcirculation in patients with traumatic brain injury.

OBJECTIVE: To describe the alterations of the cortical microcirculation of the brain (blood flow and vessel density) in TBI patients who and compare them with a control group. METHODS: Prospective and observational study in a third-level university hospital. Cortical microcirculation in the brain was directly observed using sidestream dark-field (SDF) imaging in 14 patients who underwent surgery: 5 subdural hematomas (SDH) and 9 parenchymal lesions (contusions/hematomas). In this last set of patients, images were recorded in the "pericontusional" areas and in the "surrounding" brain (areas that were as far from the lesion as the craniotomy allowed). These patients were compared to five patients who underwent craniotomy for a disease that did not affect the cortex. RESULTS: There were fewer "pericontusional" images that could be analyzed due to the presence of subarachnoid hemorrhage. The proportion or perfused vessels was similar in all groups: control 99.5% ± 1.3%; SDH 98.6% ± 2.4%; "pericontusional" area 98.2% ± 2.4%; "surrounding" area 98.4% ± 2.5% (p = 0.145). The perfused vessel density index was smaller in the "pericontusional" area: control 6.5 ± 1.6 l/mm; SDH 6.5 ± 2.5 l/mm; "pericontusional" area 5.4 ± 2.6 l/mm; "surrounding" 6.6 ± 2.1 l/mm (p = 0.07). CONCLUSIONS: Although the analysis of pericontusional zone was difficult, there were fewer vessels than in the controls and there was no change in the flow. In the surrounding zone and in patients with SDH, we did not document alterations in the microcirculation. Direct imaging of cerebral microcirculation in TBI patients showed that despite serious brain injury the cerebral microcirculation was remarkably well preserved.

Validation of a prognostic score for early mortality in severe head injury cases.

OBJECT: Traumatic brain injury (TBI) represents a large health and economic burden. Because of the inability of previous randomized controlled trials (RCTs) on TBI to demonstrate the expected benefit of reducing unfavorable outcomes, the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in TBI) and CRASH (Corticosteroid Randomisation After Significant Head Injury) studies provided new methods for performing prognostic studies of TBI. This study aimed to develop and externally validate a prognostic model for early death (within 48 hours). The secondary aim was to identify patients who were more likely to succumb to an early death to limit their inclusion in RCTs and to improve the efficiency of RCTs. METHODS: The derivation cohort was recruited at 1 center, Hospital 12 de Octubre, Madrid (1990-2003, 925 patients). The validation cohort was recruited in 2004-2006 from 7 study centers (374 patients). The eligible patients had suffered closed severe TBIs. The study outcome was early death (within 48 hours post-TBI). The predictors were selected using logistic regression modeling with bootstrapping techniques, and a penalized reduction was used. A risk score was developed based on the regression coefficients of the variables included in the final model. RESULTS: In the validation set, the final model showed a predictive ability of 50% (Nagelkerke R(2)), with an area under the receiver operating characteristic curve of 89% and an acceptable calibration (goodness-of-fit test, p = 0.32). The final model included 7 variables, and it was used to develop a risk score with a range from 0 to 20 points. Age provided 0, 1, 2, or 3 points depending on the age group; motor score provided 0 points, 2 (untestable), or 3 (no response); pupillary reactivity, 0, 2 (1 pupil reacted), or 6 (no pupil reacted); shock, 0 (no) or 2 (yes); subarachnoid hemorrhage, 0 or 1 (severe deposit); cisternal status, 0 or 3 (compressed/absent); and epidural hematoma, 0 (yes) or 2 (no). Based on the risk of early death estimated with the model, 4 risk of early death groups were established: low risk, sum score 0-3 (< 1% predicted mortality); moderate risk, sum score 4-8 (predicted mortality between 1% and 10%); high risk, sum score 9-12 (probability of early death between 10% and 50%); and very high risk, sum score 13-20 (early mortality probability > 50%). This score could be used for selecting patients for clinical studies. For example, if patients with very high risk scores were excluded from our study sample, the patients included (eligibility score < 13) would represent 80% of the original sample and only 23% of the patients who died early. CONCLUSIONS: The combination of Glasgow Coma Scale score, CT scanning results, and secondary insult data into a prognostic score improved the prediction of early death and the classification of TBI patients.

Tratamiento con estimulación del nervio vago en pacientes con epilepsia resistente a los fármacos: experiencia en el Hospital Universitario Son Espases / Vagal nerve stimulation treatment in patients with drug resistant epilepsy: Son Espases University Hospital experience

Objetivo Presentar la experiencia en el tratamiento de la epilepsia resistente a los fármacos mediante estimulación del nervio vago (ENV) en nuestro centro, valorando el impacto de este tratamiento sobre el control de la enfermedad, así como sobre aspectos relacionados con la calidad de vida de los pacientes y de sus cuidadores principales. Material y métodos Se realizó un análisis retrospectivo de los pacientes implantados desde enero de 2004 hasta diciembre de 2012. Se evaluaron los resultados de encuestas y test completados por los pacientes y sus cuidadores principales. Resultados Se incluyeron 15 pacientes con un seguimiento medio tras la cirugía de 4,41 (0,5-8) años. La edad media en el momento de la cirugía fue de 25 (10-50) años. Más del 66% de los pacientes experimentaron una disminución en la intensidad de las crisis > 25%. El 47% presentó una reducción > 50% en la frecuencia de las mismas. Como efectos adversos indeseables un paciente presentó disfonía persistente, otro tos y molestias cervicales autolimitados, y otro molestias cervicales. En 2 pacientes fue necesaria la explantación por cefalea refractaria al tratamiento médico. No hubo complicaciones derivadas del acto (AU)

OBJECTIVE: To present our experience in treating drug-resistant epilepsy with vagal nerve stimulation in our centre, evaluating its impact on disease control and on different aspects related to the patients and main caretakers' quality of life. MATERIALS AND METHODS: This was a retrospective analysis of patients operated from January 2004 until December 2012. Interviews and tests completed by outpatients and principle caretakers were evaluated. RESULTS: Fifteen patients were included, with a mean postoperative follow-up of 4.41 (0.5-8) years. Mean age at implantation was 25 (10-50) years. Over 66% of the patients perceived a reduction greater than 25% of their crisis intensity. Forty-seven percent of the patients experienced a decrease greater than 50% in the number of crises. As undesired adverse events, one patient presented persistent dysphonia, another self-limited cough and cervical discomfort and another, persistent cervical discomfort. The device had to be removed in 2 patients due to refractory headaches. There were no complications derived from the surgical procedure. CONCLUSIONS: Vagal nerve stimulation is an effective treatment for reducing crisis frequency and intensity. The patients as well as their caretakers experience a subjective improvement in their quality of life. Despite its economic cost, it seems to reduce their care needs to a certain degree and its use may therefore be justified (AU)

[Vagal nerve stimulation treatment in patients with drug resistant epilepsy: Son Espases University Hospital experience]. / Tratamiento con estimulación del nervio vago en pacientes con epilepsia resistente a los fármacos: experiencia en el Hospital Universitario Son Espases.

OBJECTIVE: To present our experience in treating drug-resistant epilepsy with vagal nerve stimulation in our centre, evaluating its impact on disease control and on different aspects related to the patients and main caretakers' quality of life. MATERIALS AND METHODS: This was a retrospective analysis of patients operated from January 2004 until December 2012. Interviews and tests completed by outpatients and principle caretakers were evaluated. RESULTS: Fifteen patients were included, with a mean postoperative follow-up of 4.41 (0.5-8) years. Mean age at implantation was 25 (10-50) years. Over 66% of the patients perceived a reduction greater than 25% of their crisis intensity. Forty-seven percent of the patients experienced a decrease greater than 50% in the number of crises. As undesired adverse events, one patient presented persistent dysphonia, another self-limited cough and cervical discomfort and another, persistent cervical discomfort. The device had to be removed in 2 patients due to refractory headaches. There were no complications derived from the surgical procedure. CONCLUSIONS: Vagal nerve stimulation is an effective treatment for reducing crisis frequency and intensity. The patients as well as their caretakers experience a subjective improvement in their quality of life. Despite its economic cost, it seems to reduce their care needs to a certain degree and its use may therefore be justified.

Patterns of care and outcome for patients with glioblastoma diagnosed during 2008-2010 in Spain.

BACKGROUND: To assess management patterns and outcome in patients with glioblastoma multiforme (GBM) treated during 2008-2010 in Spain. METHODS: Retrospective analysis of clinical, therapeutic, and survival data collected through filled questionnaires from patients with histologically confirmed GBM diagnosed in 19 Spanish hospitals. RESULTS: We identified 834 patients (23% aged >70 years). Surgical resection was achieved in 66% of patients, although the extent of surgery was confirmed by postoperative MRI in only 41%. There were major postoperative complications in 14% of patients, and age was the only independent predictor (Odds ratio [OR], 1.03; 95% confidence interval [CI],1.01-1.05; P = .006). After surgery, 57% received radiotherapy (RT) with concomitant and adjuvant temozolomide, 21% received other regimens, and 22% were not further treated. In patients treated with surgical resection, RT, and chemotherapy (n = 396), initiation of RT ≤42 days was associated with longer progression-free survival (hazard ratio [HR], 0.8; 95% CI, 0.64-0.99; P = .042) but not with overall survival (HR, 0.79; 95% CI, 0.62-1.00; P = .055). Only 32% of patients older than 70 years received RT with concomitant and adjuvant temozolomide. The median survival in this group was 10.8 months (95% CI, 6.8-14.9 months), compared with 17.0 months (95% CI, 15.5-18.4 months; P = .034) among younger patients with GBM treated with the same regimen. CONCLUSIONS: In a community setting, 57% of all patients with GBM and only 32% of older patients received RT with concomitant and adjuvant temozolomide. In patients with surgical resection who were eligible for chemoradiation, initiation of RT ≤42 days was associated with better progression-free survival.

Implantación de la primera resonancia magnética intraoperatoria en un hospital de la red sanitaria pública española: experiencia inicial, viabilidad y dificultades en nuestro entorno / No disponible

Objetivo La resonancia magnética intraoperatoria (RMiop) es considerada el estándar de oro de entre todas las técnicas de imagen intraoperatoria disponibles. Su principal aplicación es la detección de enfermedad residual durante las resecciones tumorales. Presentamos nuestra experiencia inicial en el primer servicio de neurocirugía de un hospital de la red sanitaria pública española que ha dispuesto de una RMiop de bajo campo. Valoramos su utilidad y precisión para detectar enfermedad residual, comparando los resultados de las imágenes intraoperatorias con los de las pruebas de control post-operatorio realizadas con equipos de diagnóstico convencionales. Material y métodos Revisamos retrospectivamente los primeros 21 pacientes intervenidos con ayuda de esta tecnología. En todos se estableció como objetivo quirúrgico la máxima resección segura. Se empleó instrumental convencional y los asistentes convenientes en cada caso. Resultados El número medio de estudios obtenidos en cada intervención fue de 2,3 (rango 2-4). Las imágenes intraoperatorias confirmaron que el objetivo preoperatorio se había logrado en 15 pacientes (71,4%), y condujeron a ampliar la resección tumoral tras detectar la presencia de (..) (AU)

[First intraoperative magnetic resonance imaging in a Spanish hospital of the public healthcare system: initial experience, feasibility and difficulties in our environment]. / Implantación de la primera resonancia magnética intraoperatoria en un hospital de la red sanitaria pública española: experiencia inicial, viabilidad y dificultades en nuestro entorno.

OBJECTIVE: Intraoperative MRI is considered the gold standard among all intraoperative imaging technologies currently available. Its main indication is in the intraoperative detection of residual disease during tumour resections. We present our initial experience with the first intraoperative low-field MRI in a Spanish hospital of the public healthcare system. We evaluate its usefulness and accuracy to detect residual tumours and compare its intraoperative results with images obtained postoperatively using conventional high-field devices. MATERIAL AND METHODS: We retrospectively reviewed the first 21 patients operated on the aid of this technology. Maximal safe resection was the surgical goal in all cases. Surgeries were performed using conventional instrumentation and the required assistance in each case. RESULTS: The mean number of intraoperative studies was 2.3 per procedure (range: 2 to 4). Intraoperative studies proved that the surgical goal had been achieved in 15 patients (71.4%), and detected residual tumour in 6 cases (28.5%). After comparing the last intraoperative image and the postoperative study, 2 cases (9.5%) were considered as "false negatives". CONCLUSIONS: Intraoperative MRI is a safe, reliable and useful tool for guided resection of brain tumours. Low-field devices provide images of sufficient quality at a lower cost; therefore their universalisation seems feasible.

Implicación del patrón radiológico en el pronóstico de los tumores oligodendrogliales: correlación con el perfil genético / Implication of radiological pattern in the prognosis of oligodendroglial tumors: correlation with genetic profile

Introducción. La codeleción 1p19q (LOH1p19q) confiere a los tumores oligodendrogliales quimiosensibilidad y un mejor pronóstico en relación con otros gliomas. La investigación dirigida a identificar características radiológicas asociadas a LOH1p19q ha despertado gran interés en los últimos años. Objetivos. Confirmar la existencia de heterogeneidad regional de los parámetros moleculares en los gliomas oligodendrogliales, valorar la asociación entre el perfil genético y determinadas características radiológicas y clínicas, y analizar el valor pronóstico de éstas. Pacientes y métodos. Se incluyeron 54 pacientes tratados según un protocolo preestablecido común. Se valoraron las secuencias T1, con/sin gadolinio, y T2 de la resonancia magnética preoperatoria a ciegas de la información molecular y clínica. El análisis de LOH se efectuó sobre muestras pareadas de ADN tumoral y genómico. Resultados. La presencia de LOH1p se halló fuertemente asociada a LOH19q (p < 0,0001). LOH1p19q resultó más frecuente en los tumores situados en el lóbulo frontal (odds ratio, OR = 5,38; intervalo de confianza del 95%, IC 95% = 1,51-19,13; p = 0,007) y sin necrosis radiológica (OR = 0,17; IC 95% = 0,03-0,80; p = 0,02). La localización frontal (riesgo relativo, RR = 4,499; IC 95% = 1,027-193,708; p = 0,046), la necrosis radiológica (RR = 0,213; IC 95% = 0,065-0,700; p = 0,011) el grado de resección (RR = 9,231; IC 95% = 1,737-49,050; p = 0,009) resultaron factores pronósticos independientes de supervivencia global.Conclusiones. En los tumores oligodendrogliales, además del análisis histológico y el estudio genético-molecular, la valoración e determinadas características radiológicas puede resultar de gran utilidad para definir subgrupos de pacientes con pronóstico y respuesta al tratamiento similares. Los esfuerzos deben dirigirse, por tanto, hacia la utilización combinada de todos los recursos disponibles en cada centro (AU)

Introduction. 1p19q loss of heterozygosity (LOH1p19q) in oligodendroglial tumors has shown to be prognostic of prolonged survival and predictive of therapeutic responsiveness. During the last years, research is actively being directed to the discovery of radiological characteristics related to LOH1p19q. Aims. To confirm the existence of molecular heterogeneity in oligodendroglial tumors in relation to their anatomic distribution, and to evaluate the correlation between molecular profile and other radiological and clinical characteristics and their prognostic impact. Patients and methods. Fifty-four patients with oligodendroglial tumors managed according to a previously established protocol were included. Preoperative SE T1, T1 post-gadolinium and T2 magnetic resonance images were reviewed by two independent neuroradiologists, blinded to clinical and molecular information. LOH analysis was assessed from paired tumor-blood DNA acid samples. Results. LOH1p was highly associated with LOH19q (p < 0.0001), LOH1p (odds ratio, OR = 6.19; 95% confidence interval, 95% CI = 1.66-22.68; p = 0.004), LOH19q (OR = 7.59; 95% CI = 1.84-31.34; p = 0.006) and LOH1p19q (OR = 5.38; 95% CI = 1.51-19.13; p = 0.007) were found to be more frequent in tumors located in the frontal lobe. Frontal location (hazard ratio, HR = 4.499; 95% CI = 1.027-193.708; p = 0.046), ring enhancement (HR = 0.213; 95% CI = 0.065-0.700; p = 0.011) and extent of resection (HR = 9.231; 95% CI = 1.737-49.050; p = 0.009) resulted independent prognostic factors for overall survival in the multivariate analysis. Conclusions. Glioma classification aims to better define patients prognosis. Besides histological and immunohistochemical analyses, molecular information has become of great importance. Our results indicate that the evaluation of some MR features may also be useful. Efforts must be directed toward the use of every available resource at each institution (AU)

[Implication of radiological pattern in the prognosis of oligodendroglial tumors: correlation with genetic profile]. / Implicación del patrón radiológico en el pronostico de los tumores oligodendrogliales: correlación con el perfil genético.

INTRODUCTION: 1p19q loss of heterozygosity (LOH1p19q) in oligodendroglial tumors has shown to be prognostic of prolonged survival and predictive of therapeutic responsiveness. During the last years, research is actively being directed to the discovery of radiological characteristics related to LOH1p19q. AIMS. To confirm the existence of molecular heterogeneity in oligodendroglial tumors in relation to their anatomic distribution, and to evaluate the correlation between molecular profile and other radiological and clinical characteristics and their prognostic impact. PATIENTS AND METHODS: Fifty-four patients with oligodendroglial tumors managed according to a previously established protocol were included. Preoperative SE T1, T1 post-gadolinium and T2 magnetic resonance images were reviewed by two independent neuroradiologists, blinded to clinical and molecular information. LOH analysis was assessed from paired tumor-blood DNA acid samples. RESULTS: LOH1p was highly associated with LOH19q (p < 0.0001), LOH1p (odds ratio, OR = 6.19; 95% confidence interval, 95% CI = 1.66-22.68; p = 0.004), LOH19q (OR = 7.59; 95% CI = 1.84-31.34; p = 0.006) and LOH1p19q (OR = 5.38; 95% CI = 1.51-19.13; p = 0.007) were found to be more frequent in tumors located in the frontal lobe. Frontal location (hazard ratio, HR = 4.499; 95% CI = 1.027-193.708; p = 0.046), ring enhancement (HR = 0.213; 95% CI = 0.065-0.700; p = 0.011) and extent of resection (HR = 9.231; 95% CI = 1.737-49.050; p = 0.009) resulted independent prognostic factors for overall survival in the multivariate analysis. CONCLUSIONS: Glioma classification aims to better define patients prognosis. Besides histological and immunohistochemical analyses, molecular information has become of great importance. Our results indicate that the evaluation of some MR features may also be useful. Efforts must be directed toward the use of every available resource at each institution.

Quantitative analysis of matrix metalloproteinase-2 mRNA expression in central and peripheral regions of gliomas.

Malignant gliomas are characterized by their invasiveness and angiogenesis. Matrix metalloproteinases (MMPs) degrade extracellular matrix and create a more permissive environment for cell invasion. We aimed to investigate for the presence of inter- and intratumoral heterogeneity in MMP-2 messenger RNA (mRNA) expression by means of quantitative analysis and to evaluate its prognostic impact in glioma patients. Representative sections from the center and periphery of tumors resected en bloc were taken fresh for study, stained with hematoxylin/eosin for histological evaluation, and immunohistochemically analyzed for Ki-67. MMP-2 mRNA expression was evaluated by real-time reverse transcriptase polymerase chain reaction (RT-PCR). There was MMP-2 expression in all analyzed tumors. By topographical dissection of surgical specimens, we found no differences in cell proliferation or density but significant differences with regard to MMP-2 mRNA expression between central and peripheral regions, being highest at the center of malignant gliomas. MMP-2 mRNA expression showed no prognostic influence on overall or disease-free survival. Our results demonstrate that MMP-2 is differentially expressed in central and peripheral regions of gliomas. Further studies are necessary to clarify the significance of these findings and their possible relevance in clinical practice.