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Purpose: Glioblastoma often recurs after treatment. Bevacizumab increases progression-free survival in some patients with recurrent glioblastoma. Identifying pretreatment predictors of survival can help clinical decision making. Magnetic resonance texture analysis (MRTA) quantifies macroscopic tissue heterogeneity indirectly linked to microscopic tissue properties. We investigated the usefulness of MRTA in predicting survival in patients with recurrent glioblastoma treated with bevacizumab. Methods: We evaluated retrospective longitudinal data from 33 patients (20 men; mean age 56 ± 13 years) who received bevacizumab on the first recurrence of glioblastoma. Volumes of contrast-enhancing lesions segmented on postcontrast T1-weighted sequences were co-registered on apparent diffusion coefficient maps to extract 107 radiomic features. To assess the performance of textural parameters in predicting progression-free survival and overall survival, we used receiver operating characteristic curves, univariate and multivariate regression analysis, and Kaplan–Meier plots. Results: Longer progression-free survival (>6 months) and overall survival (>1 year) were associated with lower values of major axis length (MAL), a lower maximum 2D diameter row (m2Ddr), and higher skewness values. Longer progression-free survival was also associated with higher kurtosis, and longer overall survival with higher elongation values. The model combining MAL, m2Ddr, and skewness best predicted progression-free survival at 6 months (AUC 0.886, 100% sensitivity, 77.8% specificity, 50% PPV, 100% NPV), and the model combining m2Ddr, elongation, and skewness best predicted overall survival (AUC 0.895, 83.3% sensitivity, 85.2% specificity, 55.6% PPV, 95.8% NPV). Conclusions: Our preliminary analyses suggest that in patients with recurrent glioblastoma pretreatment, MRTA helps to predict survival after bevacizumab treatment.

Purpose: Glioblastoma is the most aggressive brain tumor in adults and has few therapeutic options. The study of molecular subtype classifications may lead to improved prognostic classification and identification of new therapeutic targets. The Cancer Genome Atlas (TCGA) subtype classification has mainly been applied in U.S. clinical trials, while the intrinsic glioma subtype (IGS) has mainly been applied in European trials. Experimental Design: From paraffin-embedded tumor samples of 432 patients with uniformly treated, newly diagnosed glioblastoma, we built tissue microarrays for IHC analysis and applied RNA sequencing to the best samples to classify them according to TCGA and IGS subtypes. Results: We obtained transcriptomic results from 124 patients. There was a lack of agreement among the three TCGA classificatory algorithms employed, which was not solely attributable to intratumoral heterogeneity. There was overlapping of TCGA mesenchymal subtype with IGS cluster 23 and of TCGA classical subtype with IGS cluster 18. Molecular subtypes were not associated with prognosis, but levels of expression of 13 novel genes were identified as independent prognostic markers in glioma-CpG island methylator phenotype–negative patients, independently of clinical factors and MGMT methylation. These findings were validated in at least one external database. Three of the 13 genes were selected for IHC validation. In particular, high ZNF7 RNA expression and low ZNF7 protein expression were strongly associated with longer survival, independently of molecular subtypes. Conclusions: TCGA and IGS molecular classifications of glioblastoma have no higher prognostic value than individual genes and should be refined before being applied to clinical trials.

Glioblastoma is the most aggressive brain tumor in adults and has few therapeutic options. The study of molecular subtype classifications may lead to improved prognostic classification and identification of new therapeutic targets. The Cancer Genome Atlas (TCGA) subtype classification has mainly been applied in U.S. clinical trials, while the intrinsic glioma subtype (IGS) has mainly been applied in European trials.From paraffin-embedded tumor samples of 432 patients with uniformly treated, newly diagnosed glioblastoma, we built tissue microarrays for IHC analysis and applied RNA sequencing to the best samples to classify them according to TCGA and IGS subtypes.We obtained transcriptomic results from 124 patients. There was a lack of agreement among the three TCGA classificatory algorithms employed, which was not solely attributable to intratumoral heterogeneity. There was overlapping of TCGA mesenchymal subtype with IGS cluster 23 and of TCGA classical subtype with IGS cluster 18. Molecular subtypes were not associated with prognosis, but levels of expression of 13 novel genes were identified as independent prognostic markers in glioma-CpG island methylator phenotype-negative patients, independently of clinical factors andTCGA and IGS molecular classifications of glioblastoma have no higher prognostic value than individual genes and should be refined before being applied to clinical trials.

Study Objectives Patients with isolated rapid eye movement (REM) sleep behavior disorder (IRBD) develop Parkinson disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA). Magnetic resonance imaging (MRI) is abnormal in MSA showing abnormalities in the putamen, cerebellum, and brainstem. Our objective was to evaluate the usefulness of MRI to detect MRI abnormalities in IRBD and predict development of MSA and not PD and DLB. Methods In IRBD patients that eventually developed PD, DLB, and MSA, we looked for the specific structural MRI abnormalities described in manifest MSA (e.g. hot cross-bun sign, putaminal rim, and cerebellar atrophy). We compared the frequency of these MRI changes among groups of converters (PD, DLB, and MSA) and analyzed their ability to predict development of MSA. The clinical and radiological features of the IRBD patients that eventually converted to MSA are described in detail. Results A total of 61 IRBD patients who underwent MRI phenoconverted to PD (n = 30), DLB (n = 26), and MSA (n = 5) after a median follow-up of 2.4 years from neuroimaging. MRI changes typical of MSA were found in four of the five (80%) patients who converted to MSA and in three of the 56 (5.4%) patients who developed PD or DLB. MRI changes of MSA had sensitivity of 80.0%, specificity of 94.6%, positive likelihood ratio of 14.9 (95% CI 4.6–48.8), and negative likelihood ratio of 0.2 (95% CI 0.04–1.2) to predict MSA. Conclusions In IRBD, conventional brain MRI is helpful to predict conversion to MSA. The specific MRI abnormalities of manifest MSA may be detected in its premotor stage.

15 páginas, 7 figuras. Contiene información suplementaria en l aversión online., A mesenchymal transition occurs both during the natural evolution of glioblastoma (GBM) and in response to therapy. Here, we report that the adhesion G-protein-coupled receptor, GPR56/ADGRG1, inhibits GBM mesenchymal differentiation and radioresistance. GPR56 is enriched in proneural and classical GBMs and is lost during their transition toward a mesenchymal subtype. GPR56 loss of function promotes mesenchymal differentiation and radioresistance of glioma initiating cells both in vitro and in vivo. Accordingly, a low GPR56-associated signature is prognostic of a poor outcome in GBM patients even within non-G-CIMP GBMs. Mechanistically, we reveal GPR56 as an inhibitor of the nuclear factor kappa B (NF-κB) signaling pathway, thereby providing the rationale by which this receptor prevents mesenchymal differentiation and radioresistance. A pan-cancer analysis suggests that GPR56 might be an inhibitor of the mesenchymal transition across multiple tumor types beyond GBM., This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) (BFU2009-14616 and RyC-09-389-10-01 to N.d.l.I.), Fundación Ramón Areces (CIVP16A1850 to N.d.l.I.), and an FPI predoctoral fellowship from MINECO (to M. Moreno). This research was also supported by NIH grant R01NS083767 (to I.N.) and the University Cancer Foundation via the Institutional Research Grant program and start-up funds at the University of Texas M.D. Anderson Cancer Center (to K.P.B.). This work was co-funded by the European Regional Development Fund (ERDF) and the CERCA Programme (Generalitat de Catalunya).

Syphilis is a widespread infection with increasing frequency in developed countries, especially among men who have sex with men. We present two cases of oropharyngeal syphilis in two middle-aged men who presented with a painless tonsillar ulcer and progressive enlargement of cervical lymph nodes suspected of being a tonsillar tumour. A pathologic analysis of the ulcer led to an accurate diagnosis. We review the imaging and pathologic findings to emphasize the importance of taking syphilis into account in the differential diagnosis.

To assess the value of resection in glioblastoma based on pre-surgical tumor characteristics and a subsequent staging system. The lack of a staging system for glioblastoma hinders the analysis of treatment outcome. We classified 292 uniformly treated glioblastoma patients as stage I, II, or III based on tumor size, location, and eloquence and then analyzed the impact of the extent of resection. We classified 62% of patients as stage I, 25.3% as stage II, and 12.7% as stage III. Gross total resection (GTR) was performed mainly in stage I rather than stage II or III patients (79.2% vs. 14.6% vs. 6.3%; P < 0.001). Overall survival (OS) was 17.7, 14.6, and 10.8 months for stage I, II, and III patients, respectively (P = 0.005). Longer OS was significantly associated with greater extent of resection, younger age, KPS >= 70%, MGMT methylation, lower stage, and tumor

Hyperintense perilesional edema in brain masses on T1-weighted images (T1WI) is an unusual radiological finding. We report three cases showing this particular type of edema, one representing cerebral hemorrhagic cavernous malformation (CCM, cavernoma) and the other two, metastases of melanoma. The association between this sign and cavernoma was recently recognized. On the other hand, in melanotic lesions, the relationship with T1WI-hyperintense perilesional edema has not yet been described. Despite being an infrequent sign, it can considerably narrow the differential diagnosis, which gives it a high value for clinical practice. Moreover, given the high prevalence of the entities that manifest this imaging feature, it can be occasionally noticed.

Purpose: Anaplastic gliomas constitute a heterogeneous group of tumors with different therapeutic responses to adjuvant chemotherapy with alkylating agents. O6-Methylguanine-DNA methyltransferase (MGMT), a DNA repair protein, is one of the implicated factors in glioma chemoresistance.The prognostic value of MGMT remains controversial due in part to the fact that previous published studies included heterogeneous groups of patients with different tumor grades. The aim of this study was to evaluate the prognostic significance of MGMT in patients with anaplastic glioma. Experimental Design: Ninety-three patients with anaplastic glioma were analyzed for MGMT protein expression by immunohistochemistry. In addition, for those patients from whom a good yield of DNA was obtained (n = 40), MGMT promoter methylation profile was analyzed by methylation-specific PCR. MGMT prognostic significance was evaluated together with other well-known prognostic factors. Results: Fifty-one tumors (54.8%) showed nuclear staining of MGMT. There was a trend towards longer overall survival for those patients with negative MGMT immunostaining (hazard ratio, 1.66; P = 0.066). In a secondary analysis including those patients who actually received chemotherapy (n = 72), the absence of MGMT expression was independently associated with better survival (hazard ratio, 2.12; P = 0.027). MGMT promoter methylation was observed in 50% of the analyzed tumors. No statistical correlation between MGMT expression and MGMT promoter hypermethylation was observed. Conclusions: Unlike previous studies, we did not find a correlation between MGMT promoter methylation and survival. However, we observed a correlation between MGMT protein expression and survival in those patients who received chemotherapy thus suggesting that the absence of MGMT expression is a positive predictive marker in patients with anaplastic glioma.

A 66-year-old woman with the diagnosis of late-onset Pompe disease, receiving enzyme replacement therapy for the past 3 years, presented with a tongue tumor (figure 1) of uncertain evolution over time. It was soft at palpation and in the MRI study, the tongue looked bright in T1 but also an intense localized fatty degeneration generating a pseudohypertrophy of the tongue could be seen (figure 2). In late-onset Pompe disease, skeletal muscle is the most affected tissue and bright tongue sign is well known in patients with Pompe disease,1,2 but a benign tumor composed of muscle lingual pseudohypertrophy is an unusual finding.

BACKGROUND The clinical evolution of anaplastic glioma (anaplastic astrocytoma, oligodendroglioma, and oligoastrocytoma) is variable. Previous studies merged patients with anaplastic glioma and the much more common glioblastoma multiforme. Therefore, the conclusions on prognostic factors reflected in part the consequences of an analysis in a heterogeneous population. METHODS To identify clinical, neuroradiologic, pathologic, and molecular factors with prognostic significance, we analyzed 95 treated patients with a histologic diagnosis of anaplastic glioma. Variables included age, gender, clinical manifestations at diagnosis (seizures, focal neurologic deficit, and cognitive changes), computed tomographic (CT) scan characteristics (diffuse, ring, and no enhancement), tumor location, extent of resection, histopathology, postoperative Karnofsky performance status (KPS) score, adjuvant chemotherapy, tumor response, proliferation index (Ki-67 expression), and p53, p16, pRb, and epidermal growth factor receptor immunohistochemical expression. RESULTS Ninety-five patients with a histologic diagnosis of anaplastic astrocytoma (73%), anaplastic oligoastrocytoma (16.6%), or anaplastic oligodendroglioma (10.4%) constituted the basis of this study. Median overall survival was 29 months. Multivariate analysis revealed that an age of 49 years or younger (P < 0.03), postoperative KPS score of 80 or higher (P < 0.007), absence of ring enhancement (P = 0.03), and a proliferation index of 5.1% or lower (P = 0.044) were independently associated with longer survival. The presence of an oligodendroglial component was associated with better prognosis in the univariate analysis (P = 0.009), although this lost power in the multivariate analysis. CONCLUSIONS In addition to previously recognized prognostic variables such as age and KPS score, CT ring enhancement and tumor proliferation index were identified as independent predictors of survival in a homogeneous series of patients with anaplastic gliomas. Cancer 2003;97:1063–71. © 2003 American Cancer Society. DOI 10.1002/cncr.11120

Introduction: In glioblastoma, the extent of surgery affects neurological condition, survival, and the efficacy of postsurgical systemic treatment. We analyzed the impact of surgical extent on overall survival in function of baseline tumor radiological characteristics (size, eloquence of adjacent brain, and location) and known prognostic factors. Material and Methods: Patients received standard radiotherapy and concomitant/adjuvant temozolomide (GLIOCAT Study). We used an MRI-based topographical glioblastoma staging system (stages I, II, and III) integrating tumor location (A, B, C), size (≤5 cm or >5cm), and eloquence of adjacent brain. Evaluations were accepted when kappa was near 1; only evaluations of T1Gd sequences are reported. Surgery was classified as complete resection (CR=disease-free postoperative MRI), partial resection (PR), or biopsy (B). Age, Karnofsky performance score (KPS), Mini-Mental State (MMS), isocitrate dehydrogenase mutations (mIDH), and O6-methylguanine-DNA methyltransferase promoter methylation (methMGMT) were recorded. Results: In 280 patients, Location: A = 133 (47.5%) // B = 110 (39.3%) // C = 37 (13.2%); Eloquence: NO=196 (70%)//YES= 84(30%); size: ≤5cm: 150(54.5%) // > 5cm: 125(45.5%); Stage: I: 100(43.9%)//II: (22.8%)//III: 76(33.3%). Clinical factors KPS (

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.

Introducción. La cirugía guiada por imagen es uno de los más importantes avances tecnológicos dentro de la cirugía del Raquis ya que permite al cirujano realizar una navegación multiplanar tridimensional en tiempo real en el interior de una vértebra. Material y métodos. Realizamos un estudio clínico prospectivo no randomizado sobre la fiabilidad en la colocación de tornillos pediculares mediante un sistema de navegación optoelectrónico (SurgiGATE Spine 2.1 Medivision). Se estudiaron veintinueve pacientes intervenidos por diferentes patologías en columna toracolumbar incluyendo: degenerativas (54%), espondilolistesis (21%), fracturas (14%), escoliosis (7%) y espondilodiscitis (4%). Un paciente fue eliminado del estudio debido a un fallo técnico en el equipo de navegación. Se obtuvieron imágenes de TC pre y postoperatorias de cada paciente y éstas fueron evaluadas por dos neurorradiólogos independientes. La colocación correcta se definió de acuerdo a la escala de Heary en 5 grados. Resultados. Se colocaron 163 tornillos, 29 en la columna toracolumbar y 134 en la columna lumbosacra. Hemos conseguido una colocación totalmente intraósea (Grado I) en el 99,4% de tornillos en la columna lumbosacra y en un 100% en la columna toracolumbar. Se comprobó el error de colocación (Grado III) en un pedículo de L3 en la concavidad de una escoliosis. No se observaron complicaciones relacionadas con los implantes. Conclusiones. El bajo porcentaje de tornillos mal colocados en este estudio se compara favorablemente con los resultados publicados en la literatura. Nuestros resultados indican que la cirugía guiada por imagen aplicada a la cirugía del raquis es una técnica segura para la fijación transpedicular.

Objective: To analyze the MRI and CSF oligoclonal bands (OB) changes in patients with MS who underwent an autologous hematopoietic stem cell transplantation (AHSCT). Background: AHSCT is evaluated as an alternative therapy in severe MS. In previous series of AHSCT for MS, data on MRI or OB outcome were limited or not provided. Methods: Five patients with a median Kurtzke’s EDSS score of 6.5, more than two attacks, and confirmed worsening of the EDSS in the previous year received an AHSCT. Hematopoietic stem cells were mobilized with cyclophosphamide (3 g/m2) and granulocyte colony-stimulating factor (5 μg/kg/d). The graft was T cell depleted by positive CD 34+ selection. Conditioning regimen included BCNU (300 mg/m 2 ), cyclophosphamide (150 mg/kg in 3 days), and antithymocyte globulin (60 mg/kg in 4 days). MRI scans were scheduled at baseline and 1, 3, 6, and 12 months and OB analysis at baseline and 3 and 12 months post-AHSCT. Results: Four patients had a stable or improved EDSS after a median follow-up of 18 months (range, 12 to 24 months). The fifth patient’s condition deteriorated during AHSCT. She partially improved and remained stable after month 3 after AHSCT. The baseline CSF OB persisted 1 year after AHSCT. MRI studies after AHSCT showed no enhanced T1 lesions and no new or enlarging T2 lesions. The median percentage change of T2 lesion load was −11.8% (range, −26.6 to −4.0%). All patients had a decrease of corpus callosum area at 1 year (median, 12.4%; range, 7.8% to 20.5%) that did not progress in the two patients evaluated at 2 years after AHSCT. Conclusions: Although the persistence of CSF OB suggests the lymphocytes were not eliminated from the CNS, the follow-up MRI studies showed no enhanced T1 brain lesions and a reduction in the T2 lesion load that correlated with the clinical stabilization of MS after AHSCT.

Introduccion. La codelecion 1p19q (LOH1p19q) confiere a los tumores oligodendrogliales quimiosensibilidad y un mejor pronostico en relacion con otros gliomas. La investigacion dirigida a identificar caracteristicas radiologicas asociadas a LOH1p19q ha despertado gran interes en los ultimos anos. Objetivos. Confirmar la existencia de heterogeneidad regional de los parametros moleculares en los gliomas oligodendrogliales, valorar la asociacion entre el perfil genetico y determinadas caracteristicas radiologicas y clinicas, y analizar el valor pronostico de estas. Pacientes y metodos. Se incluyeron 54 pacientes tratados segun un protocolo preestablecido comun. Se valoraron las secuencias T1, con/sin gadolinio, y T2 de la resonancia magnetica preoperatoria a ciegas de la informacion molecular y clinica. El analisis de LOH se efectuo sobre muestras pareadas de ADN tumoral y genomico. Resultados. La presencia de LOH1p se hallo fuertemente asociada a LOH19q (p < 0,0001). LOH1p19q resulto mas frecuente en los tumores situados en el lobulo frontal (odds ratio, OR = 5,38; intervalo de confianza del 95%, IC 95% = 1,51-19,13; p = 0,007) y sin necrosis radiologica (OR = 0,17; IC 95% = 0,03-0,80; p = 0,02). La localizacion frontal (riesgo relativo, RR = 4,499; IC 95% = 1,027-193,708; p = 0,046), la necrosis radiologica (RR = 0,213; IC 95% = 0,065-0,700; p = 0,011) y el grado de reseccion (RR = 9,231; IC 95% = 1,737-49,050; p = 0,009) resultaron factores pronosticos independientes de supervivencia global. Conclusiones. En los tumores oligodendrogliales, ademas del analisis histologico y el estudio genetico-molecular, la valoracion de determinadas caracteristicas radiologicas puede resultar de gran utilidad para definir subgrupos de pacientes con pronostico y respuesta al tratamiento similares. Los esfuerzos deben dirigirse, por tanto, hacia la utilizacion combinada de todos los recursos disponibles en cada centro.

BACKGROUND: Glioblastoma (GBM) is the most life-threatening primary brain tumor, especially in elderly. Despite aggressive treatment, median survival among all GBM patients is only 12-15 months and is worse in elderly (6-9 months). The standard of care for elderly remains controversial. The purpose of this study is to assess the benefit of conventional treatment (Stupp regimen) in elderly patients. METHOD: We retrospectively reviewed a prospective database of 209 patients who were diagnosed with GBM at a single center from January 2005 to March 2013. All patients were divided into younger and elderly groups based on the cut-off age of 65 years. RESULTS: Of 209 patients diagnosed with GBM, 122 (58%) patients were younger than 65 years, and 87 (42%) patients were 65 years old or older. No differences were found in basal patient characteristics and neither in grade of resection between age subgroups. However elderly received less active treatment, radio-chemotherapy was less frequent in elderly (51% vs 73%) but radiotherapy alone (18% vs 8%) and non-oncological treatment after surgery was more frequent in elderly (31% vs 18%) (p = 0.002). No differences in median survival were found in elderly patients who received the same approach treatment than young patients. Median OS was 10.8 months in all GBM patients, 8.7 months in older and 13.6 months in younger patients (p = 0.019). Of all, 106 (51%) patients received Stupp regimen, 41 (47%) elderly and 65 (53%) young. Median OS in patients treated with conventional treatment was 18 months, without differences by age, 15.3 months in older and 18 months in younger (p = 0.228), neither differences were found in PFS (global of 8.2 months, 9.7 and 8.2 months, p = 0.307). MGMT status information was available only for 45.5% of patients that received Stupp regimen, 23 MGMT methylated, 25 MGMT unmethylated and 58 patients with MGMT not evaluable or not done. Surprisingly, no differences in OS were found between groups by MGMT status (19.2, 18.1 and 15.7 months respectively, p = 0.405). Significant differences in OS and post-progression survival (PPS) were found if patients received or not treatment at relapse (7.7 versus 20 months, p < 0.0001 and 1.7 versus 8.9 months, p < 0.0001). No differences between age subgroups in receiving it or not. Bevacizumab (BVZ) was the recurrence treatment in 60% of patients treated (31/52). PPS was better in patients treated with BVZ than in those treated with chemotherapy or surgery (12.4, 5.1 and 8.9 months, p < 0.0001). CONCLUSION: Elderly population newly diagnosed with GBM benefit from conventional treatment. Probably, undertreatment is the most important factor associated with poor survival in elderly newly diagnosed with GBM. Therefore, elderly patients should be encouraged to receive conventional active treatment. Recurrence treatment with bevacizumab might be an important factor in improving survival in the last few years.