Purpose:To assess the diagnostic accuracy of diffusion kurtosis magnetic resonance imaging parameters in grading gliomas. Materials and Methods:The institutional review board approved this prospective study, and informed consent was obtained from all patients. Diffusion parameters-mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis, and radial and axial kurtosis-were compared in the solid parts of 17 high-grade gliomas and 11 low-grade gliomas (P , .05 significance level, Mann-Whitney-Wilcoxon test, Bonferroni correction). MD, FA, mean kurtosis, radial kurtosis, and axial kurtosis in solid tumors were also normalized to the corresponding values in contralateral normal-appearing white matter (NAWM) and the contralateral posterior limb of the internal capsule (PLIC) after age correction and were compared among tumor grades. Results:Mean, radial, and axial kurtosis were significantly higher in high-grade gliomas than in low-grade gliomas (P = .02, P = .015, and P = .01, respectively). FA and MD did not significantly differ between glioma grades. All values, except for axial kurtosis, that were normalized to the values in the contralateral NAWM were significantly different between high-grade and low-grade gliomas (mean kurtosis, P = .02; radial kurtosis, P = .03; FA, P = .025; and MD, P = .03). When values were normalized to those in the contralateral PLIC, none of the considered parameters showed significant differences between high-grade and low-grade gliomas. The highest sensitivity and specificity for discriminating between high-grade and low-grade gliomas were found for mean kurtosis (71% and 82%, respectively) and mean kurtosis normalized to the value in the contralateral NAWM (100% and 73%, respectively). Optimal thresholds for mean kurtosis and mean kurtosis normalized to the value in the contralateral NAWM for differentiating high-grade from low-grade gliomas were 0.52 and 0.51, respectively. Conclusion:There were significant differences in kurtosis parameters between high-grade and low-grade gliomas; hence, better separation was achieved with these parameters than with conventional diffusion imaging parameters.q RSNA, 2012 1
Summary:The aim of this work was to add to the body of data on the frequency and severity of degenerative radiographic findings at adjacent levels after anterior cervical interbody fusion and on their clinical impact and to contribute to the insights about their pathogenesis. One hundred eighty patients who were treated by anterior cervical interbody fusion and who had a follow-up of >60 months were clinically and radiologically examined by independent investigators. For all patients, the long-term Odom score was compared with the score as obtained 6 weeks after surgery. For myelopathic cases, both the late Nurick and the Odom score were compared with the initial postoperative situation. For the adjacent disc levels, a radiologic "degeneration score" was defined and assessed both initially and at longterm follow-up. At late follow-up after anterior cervical interbody fusion, additional radiologic degeneration at the adjacent disc levels was found in 92% of the cases, often reflecting a clinical deterioration. The severity of this additional degeneration correlated with the time interval since surgery. The similarity of progression to degeneration between younger trauma patients and older nontrauma patients suggests that both the biomechanical impact of the interbody fusion and the natural progression of pre-existing degenerative disease act as triggering factors for adjacent level degeneration.
Clinical success for both studies exceeded the study acceptance criteria of 85%. At 1-year follow-up, the flexion-extension range of motion per level: Discectomy and implantation of the device alleviates neurologic symptoms and signs similar to anterior cervical discectomy and fusion. Radiographic evidence supports maintenance of motion. The procedure is safe and the patients recover quickly. At least 5 years of follow-up will be needed to assess the long-term functionality of the prosthesis and protective influence on adjacent levels.
Purpose:To investigate the therapeutic role of adjuvant vaccination with autologous mature dendritic cells (DC) loaded with tumor lysates derived from autologous, resected glioblastoma multiforme (GBM) at time of relapse. Experimental Design: Fifty-six patients with relapsed GBM (WHO grade IV) were treated with at least three vaccinations. Children and adults were treated similarly in three consecutive cohorts, with progressively shorter vaccination intervals per cohort. Feasibility and toxicity were assessed as well as effect of age, extent of resection, Karnofsky Performance Score, and treatment cohort on the progression-free (PFS) and overall survival (OS) using univariable and multivariable analysis. Results: Since the prevaccine reoperation, the median PFS and OS of the total group was 3 and 9.6 months, respectively, with a 2-year OS of 14.8%. Total resection was a predictor for better PFS both in univariable analysis and after correction for the other covariates. For OS, younger age and total resection were predictors of a better outcome in univariable analysis but not in multivariable analysis. A trend to improved PFS was observed in favor of the faster DC vaccination schedule with tumor lysate boosting. Vaccine-related edema in one patient with gross residual disease before vaccination was the only serious adverse event. Conclusion: Adjuvant DC-based immunotherapy for patients with relapsed GBM is safe and can induce long-term survival. A trend to PFS improvement was shown in the faster vaccination schedule. The importance of age and a minimal residual disease status at the start of the vaccination is underscored.In spite of multimodal therapy, including maximal safe neurosurgical resection followed by radiochemotherapy and maintenance chemotherapy, malignant or high-grade gliomas (HGG) continue to have a dismal prognosis (1). Prognosis after relapse is even worse (2, 3), with a median progression-free survival (PFS) of 2 months, and virtually all patients being dead 18 months after the relapse. Even in pediatric patients with relapsed HGG, the prognosis is poor (4).The rationale, the preclinical, and the early clinical evidence to develop dendritic cell (DC)-based immunotherapy for HGG has been reviewed by our research group (5, 6) and by others (7 -14). Vaccination is done with autologous mature monocyte-derived ex vivo generated DC loaded with autologous tumor lysate. The characteristics and in vitro function of the vaccine have been analyzed (15, 16). We described some early clinical experience on feasibility and toxicity that we obtained in a small group of patients (17,18).For the implementation of immunotherapy in clinical practice for patients with relapsed HGG, an observational prospective cohort comparison trial, HGG-IMMUNO, was designed, in which adjuvant autologous DC vaccination is done in patients with relapsed HGG after maximal new resection of the relapsed tumor. Except for the time window in cohort A, which was the
Benign peripheral nerve sheath tumors (PNSTs) are a characteristic feature of neurofibromatosis type I (NF1) patients. NF1 individuals have an 8-13% lifetime risk of developing a malignant PNST (MPNST). Atypical neurofibromas are symptomatic, hypercellular PNSTs, composed of cells with hyperchromatic nuclei in the absence of mitoses. Little is known about the origin and nature of atypical neurofibromas in NF1 patients. In this study, we classified the atypical neurofibromas in the spectrum of NF1-associated PNSTs by analyzing 65 tumor samples from 48 NF1 patients. We compared tumor-specific chromosomal copy number alterations between benign neurofibromas, atypical neurofibromas, and MPNSTs (low-, intermediate-, and high-grade) by karyotyping and microarray-based comparative genome hybridization (aCGH). In 15 benign neurofibromas (4 subcutaneous and 11 plexiform), no copy number alterations were found, except a single event in a plexiform neurofibroma. One highly significant recurrent aberration (15/16) was identified in the atypical neurofibromas, namely a deletion with a minimal overlapping region (MOR) in chromosome band 9p21.3, including CDKN2A and CDKN2B. Copy number loss of the CDKN2A/B gene locus was one of the most common events in the group of MPNSTs, with deletions in low-, intermediate-, and high-grade MPNSTs. In one tumor, we observed a clear transition from a benign-atypical neurofibroma toward an intermediate-grade MPNST, confirmed by both histopathology and aCGH analysis. These data support the hypothesis that atypical neurofibromas are premalignant tumors, with the CDKN2A/B deletion as the first step in the progression toward MPNST.
FDG and MET PET studies provide complementary prognostic information in patients with suspected brain tumour recurrence or progression after primary therapy. MET is considered the single agent of choice in the evaluation of these patients because of its sensitivity and clearer delineation of the suspected recurrence.
The anterior temporal lobe and the frontotemporal region contain several important white matter tracts that can be uniquely understood by performing a white matter dissection of the region. Surgical procedures on the anterior temporal lobe differ substantially as to their repercussions on the subcortical white matter tract anatomy, as shown by the findings in this study.
Astrocytic tumors account for 42% of childhood brain tumors, arising in all anatomical regions and associated with neurofibromatosis type 1 (NF1) in 15%. Anatomical site determines the degree and risk of resectability; the more complete resection, the better the survival rates. New biological markers and modern radiotherapy techniques are altering the risk assessments of clinical decisions for tumor resection and biopsy. The increasingly distinct pediatric neuro-oncology multidisciplinary team (PNMDT) is developing a distinct evidence base. A multidisciplinary consensus conference on pediatric neurosurgery was held in February 2011, where 92 invited participants reviewed evidence for clinical management of hypothalamic chiasmatic glioma (HCLGG), diffuse intrinsic pontine glioma (DIPG), and high-grade glioma (HGG). Twenty-seven statements were drafted and subjected to online Delphi consensus voting by participants, seeking >70% agreement from >60% of respondents; where <70% consensus occurred, the statement was modified and resubmitted for voting. Twenty-seven statements meeting consensus criteria are reported. For HCLGG, statements describing overall therapeutic purpose and indications for biopsy, observation, or treatment aimed at limiting the risk of visual damage and the need for on-going clinical trials were made. Primary surgical resection was not recommended. For DIPG, biopsy was recommended to ascertain biological characteristics to enhance understanding and targeting of treatments, especially in clinical trials. For HGG, biopsy is essential, the World Health Organization classification was recommended; selection of surgical strategy to achieve gross total resection in a single or multistep process should be discussed with the PNMDT and integrated with trials based drug strategies for adjuvant therapies.
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