Preoperative assessment of optic nerve sheath diameter and heart rate variability to predict intraoperative brain condition in patients with supratentorial tumors: a prospective observational study.

Brain relaxation is an important requirement in intracranial neurosurgical procedures and optimal brain relaxation improves the operating conditions. Optic nerve sheath diameter (ONSD) is a non-invasive bedside surrogate marker of intracranial pressure (ICP) status. Elevated ICP is often associated with marked autonomic dysfunction. There is no standard measure to predict intraoperative brain condition non-invasively, considering both anatomical displacement and physiological effects due to raised ICP and brain oedema. This study was aimed to determine the usefulness of heart rate variability (HRV) parameters and ONSD preoperatively in predicting intraoperative brain relaxation in patients with supratentorial tumors undergoing surgery.This prospective observational study was conducted in a tertiary care centre. 58 patients with supratentorial brain tumors undergoing elective surgery were studied. Preoperative clinical presentation, computed tomography (CT) findings, ONSD and HRV parameters were assessed in determining intraoperative brain condition. Intraoperative hemodynamic parameters and brain relaxation score after craniotomy were studied. There was significant difference in CT grade, ONSD and HRV parameters in patients between lax and tight brain. A receiver operating curve was constructed to determine the cut off to predict intraoperative brain bulge. A CT grade more than 2, ONSD of greater than 0.63 cms and ratio of low frequency to high ratio (LF/HF) of more than 1.8 were good predictors of brain bulge. The changes in ONSD and HRV parameters, with the CT findings can be used as surrogate markers of increased ICP to help predict intraoperative brain condition.

Review of ependymomas: assessment of consensus in pathological diagnosis and correlations with genetic profiles and outcome.

We focused on histological and immunohistochemical characteristics of ependymoma (EPN) with molecular profiles to develop more reproducible criteria of the diagnosis. Three expert neuropathologists reviewed the pathology of 130 samples from the Japan Pediatric Molecular Neuro-Oncology Group study. Confirmed cases were assessed for histology, surrogate markers, molecular subgrouping, and survival data. We reached a consensus regarding the diagnosis of EPNs in 100% of spinal cord tumors and 93% of posterior fossa (PF) tumors that had been diagnosed as EPNs by local pathologists, whereas we reached a consensus regarding only 77% of the local diagnosis of supratentorial (ST) EPNs. Among the PF-EPNs, most of anaplastic ependymomas (AEPNs) were defined as EPN-A by methylation profiling, which was significantly correlated with the subgroup assignment. Regarding prognosis, the overall survival of patients with PF-EPN was significantly better than that of patients with PF AEPN (p = 0.01). Histologically, all ependymoma, RELA fusion-positive (EPN-RELA) qualified as Grade III. Both L1 cell adhesion molecule and nuclear factor kappaB p65 antibodies showed good sensitivity for detecting EPN-RELA. This study indicated that the expert consensus pathological diagnosis could correlate well with the molecular classifications in EPNs. ST EPNs should be diagnosed more carefully by histological and molecular analyses.

Quantitative assessment of changes in diffusion tensor imaging (DTI) metrics along the courses of the cortico-ponto-cerebellar tracts secondary to supratentorial human brain glial tumors.

BACKGROUND: The cortico-ponto-cerebellar tract (CPCT) is the largest projection pathway, which synapses at the pons. Remote effects of supratentorial brain tumors have not been evaluated along the infratentorial course of the CPCT. AIM: The purpose of this study is to evaluate the possible lateralization of the diffusion tensor metrics of the affected CPCT in patients with supratentorial brain tumor. METHODS AND RESULTS: We included 39 patients with 29 left-sided tumors (LST) and 10 right-sided tumors, retrospectively. We measured the magnitude of changes of the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of the CPCT prior to the brain surgery at the level of crus cerebri and middle cerebellar peduncle. Regions of interest (ROIs) were placed on the lateral side of crus cerebri, and ROI-1 (anterior 1/3), ROI-2 (middle 1/3), ROI-3 (posterior 1/3), and ROI-4 were placed at the level of middle cerebellar peduncle. We hypothesized that there would be decreased FA and increased ADC values of the ipsilesional CPCT compared with contralesional CPCT. Ipsilesional FA values were decreased with simultaneous increased ADC value along the CPCT compared with contralesional CPCT in following ROIs, ROI-1 (LST FA: P = .005, ADC: P = .037) and ROI-3 (LST FA: P = .049, ADC: P = .049), respectively. Affected ROI-4 in LST cases also showed lower FA values, although not statistically significant. CONCLUSION: We observed a statistically significant FA value decrease and ADC increase along the left ROI-1 and ROI-3 as well as the nonstatistically significant FA decrease of the left ROI-4 at the second neuron level when there was a related supratentorial tumor. These findings are suggestive of presynaptic and postsynaptic microstructural changes of these tracts following the presynaptic involvement by a primary supratentorial brain tumor.

In the assessment of supratentorial glioma grade: the combined role of multivoxel proton MR spectroscopy and diffusion tensor imaging.

AIM: To detect a difference in the parameters derived from proton magnetic resonance spectroscopy ((1)H-MRS) and diffusion tensor imaging (DTI) between low-grade and high-grade gliomas, and to evaluate whether the combination of these two techniques can improve the diagnostic accuracy of conventional magnetic resonance imaging (MRI) in supratentorial glioma grading. MATERIALS AND METHODS: Thirty patients with histologically proved supratentorial brain gliomas (12 low grade, 18 high grade) were prospectively evaluated with contrast material-enhanced MRI, DTI, and multivoxel (1)H-MRS (135 ms echo time). The tumour grades determined using the three methods were then compared with those obtained at histopathology. Receiver operating characteristic (ROC) analyses were performed to determine the optimum thresholds for glioma grading. Independent sample t-test, Spearman's rank correlation, and the Fisher's exact test were also carried out for statistical analysis. p<0.05 was considered statistically significant. RESULTS: Statistically significant differences were found between the low-grade and high-grade gliomas for the choline (Cho)/creatine (Cr), N-acetylaspartate (NAA)/Cr, NAA/Cho ratio in the tumours (p<0.01), apparent diffusion coefficient (ADC) value (p<0.01), and fractional anisotropy (FA) value (p<0.05) in the tumours. The NAA/Cr and NAA/Cho ratios and the calculated ADC value significantly correlated with the histological grading of the gliomas (p<0.01). Using a threshold value of 0.66 for tumour NAA/Cr, 0.265 for NAA/Cho, 1118.1×10(-6) mm(2)/s for the calculated ADC value, corresponding to the maximum Youden index from the ROC curve of the above-selected parameters, the resultant sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Kappa values were all higher and the fraction of misclassified tumour was lower when compared with conventional MRI. However, only NAA/Cho and ADC calculation contributed to the significant difference (p<0.01) in the assessment of glioma grade compared to conventional MRI alone, and the grading results of statistical tests comparing those two parameters were highly consistent (kappa value=0.798). CONCLUSION: Thresholds for NAA/Cho and calculated ADC values, corresponding to maximum Youden index from ROC curve analyses, helped to improve the accuracy of supratentorial glioma grading when compared with conventional MRI alone. In addition, a combination of NAA/Cho and ADC calculation were more useful together than each alone in a clinical setting to evaluate glioma grade preoperatively and provide a means for guiding treatment.

Functional mapping-guided resection of low-grade gliomas in eloquent areas of the brain: improvement of long-term survival. Clinical article.

OBJECT: Low-grade gliomas (LGGs) frequently infiltrate highly functional or "eloquent" brain areas. Given the lack of long-term survival data, the prognostic significance of eloquent brain tumor location and the role of functional mapping during resective surgery in presumed eloquent brain regions are unknown. METHODS: We performed a retrospective analysis of 281 cases involving adults who underwent resection of a supratentorial LGG at a brain tumor referral center. Preoperative MR images were evaluated blindly for involvement of eloquent brain areas, including the sensorimotor and language cortices, and specific subcortical structures. For high-risk tumors located in presumed eloquent brain areas, long-term survival estimates were evaluated for patients who underwent intraoperative functional mapping with electrocortical stimulation and for those who did not. RESULTS: One hundred and seventy-four patients (62%) had high-risk LGGs that were located in presumed eloquent areas. Adjusting for other known prognostic factors, patients with tumors in areas presumed to be eloquent had worse overall and progression-free survival (OS, hazard ratio [HR] 6.1, 95% CI 2.6-14.1; PFS, HR 1.9, 95% CI 1.2-2.9; Cox proportional hazards). Confirmation of tumor overlapping functional areas during intraoperative mapping was strongly associated with shorter survival (OS, HR 9.6, 95% CI 3.6-25.9). In contrast, when mapping revealed that tumor spared true eloquent areas, patients had significantly longer survival, nearly comparable to patients with tumors that clearly involved only noneloquent areas, as demonstrated by preoperative imaging (OS, HR 2.9, 95% CI 1.0-8.5). CONCLUSIONS: Presumed eloquent location of LGGs is an important but modifiable risk factor predicting disease progression and death. Delineation of true functional and nonfunctional areas by intraoperative mapping in high-risk patients to maximize tumor resection can dramatically improve long-term survival.

Assessment of angiogenesis by CD105 and nestin expression in peritumor tissue of glioblastoma.

Angiogenesis in the peritumor tissue of glioblastoma (GBM) is still an open field of research. This study investigates neovascularization in the tumor surrounding areas by examining CD105 and nestin expression along with microvessel density (MVD) with the aim of establishing their possible prognostic significance. Angiogenesis was also confirmed by investigating, in vessel walls, the presence of pericytes, which are multipotent stem cells, expressing α-smooth muscle actin (α-SMA). In our study, including 40 GBM patients, tissue samples were obtained from tumors (first area) and white matter at a distance <1 cm (second area) and between 1 and 3.5 cm (third area) from the tumor margin. CD105 and nestin were detected by immunohistochemistry in hyperplastic endothelium of GBM and peritumor tissue, and occasionally coexpressed or colocalized. Pericytes encircling hyperplastic endothelium were evident in all three areas. Univariate analysis revealed that patients with a CD105-MVD value ≥8 in the third area have a significantly shorter survival time and Cox analysis indicated an about 3.5-fold increase in death risk in the same patients. These results demonstrate that a tumor neoangiogenesis occurs in GBM peritumor tissue with intimate involvement of pericytes. CD105-MVD in the area located at a greater distance from the tumor margin carries prognostic significance.

[Assessment of the degree of resection of high grade supratentorial gliomas with early postoperative magnetic resonance]. / Valoración del grado de resección de los gliomas supratentoriales de alto grado con resonancia magnética postoperatoria precoz.

UNLABELLED: In this paper we report the results of a prospective study in which we evaluate the degree of tumor removal of 25 supratentorial high grade gliomas by means of an MRI performed in the early postoperative period. In all cases, there was preoperative enhancement 8 patients had been previously operated on while the others had their first operation. In all cases the postoperative early MRI was performed within the first week and in 15 within the first 3 days. In order to evaluate the degree of tumor removal the presence or not of enhancement was considered and if it existed, classified as linear or nodular. RESULTS: To avoid postsurgical artifacts it is important to perform the MRI as soon as possible after surgery, especially within the first 3 days. Generally, linear enhancement disappeared on subsequent follow-up examinations, showing that it probably does no represent residual, tumor while nodular enhancement usually does. Survival with the high-grade tumors was slightly higher in the group without postoperative enhancement or linear one than in the group with nodular enhancement but the difference was not significant.

A comparative survival evaluation and assessment of interclassification concordance in adult supratentorial astrocytic tumors.

Classification and grading of astrocytic tumors has been the subject of several controversies and no universally accepted classification system is yet available. Nevertheless, acceptance of a common system is important for assessing prognosis as well as easy comparative evaluation and interpretation of the results of multi-center therapeutic trials. We report the results of a single center study on comparative survival evaluation along with assessment of inter-classification concordance in 102 cases of supratentorial astrocytic tumors in adults ((3) (3)16 years of age). Hematoxylin and eosin (H&E) stained slides of these 102 cases were reviewed independently by two pathologists and each case classified or graded according to four different classification systems viz. Kernohan, Daumas-Duport (SAM-A), TESTAST-268 and WHO. The histological grading was then correlated with the survival curves as estimated by the Kaplan-Meier method. The most important observation was that similar survival curves were obtained for any one grade of tumor by all the four classification systems. Fifty three of the 102 cases (51.9%) showed absolute grading concordance using all 4 classifications with maximum concordant cases belonging to grades 2 and 4. Intra-classification grade-wise survival analysis revealed a statistically significant difference between grade 2 and grades 3 or 4, but no difference between grades 3 and 4 in any of the classification systems. It is apparent from the results of this study that if specified criteria related to any of the classification systems is rigorously adhered to, it will produce comparable results. Hence, preferential adoption of any one classification system in practice will be guided by the relative ease of histologic feature value evaluation with maximum possible objectivity and reproducibility. We recommend the Daumas-Duport (SAM-A) system since it appears to be the simplest, most objectivized for practical application and highly reproducible with relative ease.

Assessment of the pathological grade of astrocytic gliomas using an MRI score.

To evaluate the usefulness of an MRI score for identifying tumour tissue characteristics, 41 histologically verified supratentorial astrocytic gliomas, including 13 low-grade astrocytomas (LGA) 14 anaplastic astrocytomas (AA) and 14 glioblastoma multiformes (GBM), were examined with a 0.5T superconductive MR imager. Nine MRI criteria were used: heterogeneity (HET), cyst formation or necrosis (CN), haemorrhage (HEM), crossing the midline (CM), oedema or mass effect (EM), border definition (BD), flow void (FV), degree (CE-D) and heterogeneity (CE-HET) of contrast enhancement; Gd-enhanced T1-weighted images were obtained in 32 cases (10 LGA, 10 AA, and 12 GBM). Each of the criteria was scored and analysed statistically. The mean values of LGA, AA and GBM were 0.45 +/- 0.31, 1.18 +/- 0.20, and 1.47 +/- 0.22, respectively. The MRI score increased with the pathological grades (P < 0.01-0.001). LGA had significantly lower values than AA in five (HET, CN, EM, BD, CE-D) of the nine criteria (55.6%) and lower values than GBM in all except HEM (88.9%). Three criteria (33.3%): HET, CN, and FV were significantly higher in GBM than AA. CE-D, HET, EM, CN, and CE-HET proved to be related to the pathological grade by a multiple regression analysis (P < 0.001).